The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth.

Previous studies have implicated DTNBP1 as a schizophrenia susceptibility gene and its encoded protein, dysbindin, as a potential regulator of synaptic vesicle physiology. In this study, we found that endogenous levels of the dysbindin protein in the mouse brain are developmentally regulated, with higher levels observed during embryonic and early postnatal ages than in young adulthood. We obtained biochemical evidence indicating that the bulk of dysbindin from brain exists as a stable component of biogenesis of lysosome-related organelles complex-1 (BLOC-1), a multi-subunit protein complex involved in intracellular membrane trafficking and organelle biogenesis. Selective biochemical interaction between brain BLOC-1 and a few members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) superfamily of proteins that control membrane fusion, including SNAP-25 and syntaxin 13, was demonstrated. Furthermore, primary hippocampal neurons deficient in BLOC-1 displayed neurite outgrowth defects. Taken together, these observations suggest a novel role for the dysbindin-containing complex, BLOC-1, in neurodevelopment, and provide a framework for considering potential effects of allelic variants in DTNBP1--or in other genes encoding BLOC-1 subunits--in the context of the developmental model of schizophrenia pathogenesis

Rituximab plus bendamustine as front-line treatment in frail elderly (>70 years) patients with diffuse large b-cell non-hodgkin lymphoma: A phase ii multicenter study of the fondazione italiana linfomi

We conducted a phase II study to assess activity and safety profile of bendamustine and rituximab in elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) who were prospectively defined as frail using a simplified version of the Comprehensive Geriatric Assessment (CGA). Patients had to be over 70 years of age, with histologically confirmed DLBCL. Frail patients were those younger than 80 years with a frail profile at CGA or older than 80 years with an unfit profile. Treatment consisted of 4-6 courses of bendamustine [90 mg/m 2 days (d)1-2] and rituximab (375 mg/m 2 d1) administered every 28 days. Other main study end points were complete remission rate and the rate of extra-hematologic adverse events. Forty-nine patients were enrolled of whom 45 were confirmed eligible. Overall, 24 patients achieved a complete remission (53%; 95%CI: 38-68%) and the overall response rate was 62% (95%CI: 47-76%). The most frequent grade 3-4 adverse event was neutropenia (37.8%). Grade 3-4 extra-hematologic adverse events were observed in 7 patients (15.6%; 95%CI: 6.5-29.5%); the most frequent was grade 3 infection in 2 patients. With a median follow up of 33 months (range 1-52), the median progression-free survival was ten months (95%CI: 7-25). The study shows promising activity and manageable toxicity profile of BR combination as first-line therapy for patients with DLBCL who are prospectively defined as frail according to a simplified CGA, as adopted in this trial (clinicaltrials.gov identifier: 01990144)

A more fine-grained measure towards animal welfare: a study with regards to gender differences in Spanish students

The environmental issue is nowadays taking more importance in the environmental awareness all around the world, and in this field, animal consideration is more and more spread. A highlighted part in globalisation is the animal welfare awareness. This article presents a study comparing attitudes towards animals among secondary and university students in reference to gender. It was carried out on 1394 Spanish participants from 11 to 26 years. The instrument used in the study is the reviewed version of the Animal Welfare Attitude Scale which was renamed as “Animal Welfare Attitude-Revised Scale” (AWA-R Scale), with a Cronbach a reliability value of 0.85. It is subdivided into four components namely C1: animal abuse for pleasure or due to ignorance; C2: leisure with animals; C3: farm animals; and C4: animal abandonment. These components have been deeply detailed by a confirmatory factor analysis (CFA), which highly contributes to define the position of participants for the different dimensions of animal welfare. It is concluded that significant differences exist between males’ and females’ attitudes in all components of the AWA-R Scale. It is also suggested that two social characteristics—people’s attitudes towards animals and towards environmental protection—are, at the very least, coexistent and may indeed be interdependent. These differences between gender in matters of socialisation could thus be reflected in environmental attitudes, and also in others related to them, i.e. animal welfare attitudes

Learning environments research in English classrooms

Although learning environments research has thrived for decades in many countries and school subjects, English classroom environment research is still in its infancy. This article paves the way for expanding research on English classroom environments by (1) reviewing the limited past research in English classrooms and (2) reporting the first study of English learning environments in Singaporean primary schools. For a sample of 441 grade 6 students, past research in other subjects was replicated in that a modified version of the What Is Happening In this Class? questionnaire was cross-validated, classroom environment was found to vary with the determinants of student sex and ethnicity, and associations emerged between students’ attitudes and the nature of the classroom environment

Coping and sickness absence

Objectives: The aim of this study is to examine the role of coping styles in sickness absence. In line with findings that contrast the reactive-passive focused strategies, problem-solving strategies are generally associated with positive results in terms of well-being and overall health outcomes; our hypothesis is that such strategies are positively related to a low frequency of sickness absence and with short lengths (total number of days absent) and durations (mean duration per spell). Methods: Using a prospective design, employees' (N = 3,628) responses on a self-report coping inventory are used to predict future registered sickness absence (i.e. frequency, length, duration, and median time before the onset of a new sick leave period). Results and conclusions: In accordance with our hypothesis, and after adjustment for potential confounders, employees with an active problem-solving coping strategy are less likely to drop out because of sickness absence in terms of frequency, length (longer than 14 days), and duration (more than 7 days) of sickness absence. This positive effect is observed in the case of seeking social support only for the duration of sickness absence and in the case of palliative reaction only for the length and frequency of absence. In contrast, an avoidant coping style, representing a reactive-passive strategy, increases the likelihood of frequent absences significantly, as well as the length and duration of sickness absence. Expression of emotions, representing another reactive-passive strategy, has no effect on future sickness absenteeism. The median time before the onset of a new episode of absenteeism is significantly extended for active problem-solving and reduced for avoidance and for a palliative response. The results of the present study support the notion that problem-solving coping and reactive-passive strategies are inextricably connected to frequency, duration, length and onset of sickness absence. Especially, active problem-solving decreases the chance of future sickness absence. © Springer-Verlag 2007

Antimicrobial knowledge and confidence amongst final year medical students in Australia

Introduction: Inappropriate use of antimicrobials is one of the major modifiable contributors to antimicrobial resistance. There is currently no validated survey tool available to assess knowledge and confidence of medical students in infectious diseases (ID) compared to other diseases states, and little is known about this topic. Materials and methods: A cross-sectional survey of final year medical students attending universities around Australia was conducted between August and September, 2015. A survey unique from other published studies was developed to survey satisfaction in education, confidence and knowledge in ID, and how this compared to these factors in cardiovascular diseases. Results: Reliability and validity was demonstrated in the survey tool used. Students were more likely to rate university education as sufficient for cardiovascular diseases (91.3%) compared to ID (72.5%), and were more confident in their knowledge of cardiovascular diseases compared to ID (74.38% vs. 53.76%). Students tended to answer more cardiovascular disease related clinical questions correctly (mean score 78%), compared to questions on antimicrobial use (mean score 45%). Conclusions: Poor knowledge and confidence amongst final year medical students in Australia were observed in ID. Antimicrobial stewardship agenda should include the provision of additional training in antimicrobial prescribing to the future medical workforce

Observation of the Decay Λ0b→Λ+cτ−¯ν

The first observation of the semileptonic b-baryon decay Λb0→Λc+τ-ν¯τ, with a significance of 6.1σ, is reported using a data sample corresponding to 3 fb-1 of integrated luminosity, collected by the LHCb experiment at center-of-mass energies of 7 and 8 TeV at the LHC. The τ- lepton is reconstructed in the hadronic decay to three charged pions. The ratio K=B(Λb0→Λc+τ-ν¯τ)/B(Λb0→Λc+π-π+π-) is measured to be 2.46±0.27±0.40, where the first uncertainty is statistical and the second systematic. The branching fraction B(Λb0→Λc+τ-ν¯τ)=(1.50±0.16±0.25±0.23)% is obtained, where the third uncertainty is from the external branching fraction of the normalization channel Λb0→Λc+π-π+π-. The ratio of semileptonic branching fractions R(Λc+)B(Λb0→Λc+τ-ν¯τ)/B(Λb0→Λc+μ-ν¯μ) is derived to be 0.242±0.026±0.040±0.059, where the external branching fraction uncertainty from the channel Λb0→Λc+μ-ν¯μ contributes to the last term. This result is in agreement with the standard model prediction

Measurement of antiproton production from antihyperon decays in pHe collisions at √sNN=110GeV

The interpretation of cosmic antiproton flux measurements from space-borne experiments is currently limited by the knowledge of the antiproton production cross-section in collisions between primary cosmic rays and the interstellar medium. Using collisions of protons with an energy of 6.5 TeV incident on helium nuclei at rest in the proximity of the interaction region of the LHCb experiment, the ratio of antiprotons originating from antihyperon decays to prompt production is measured for antiproton momenta between 12 and 110GeV\!/c . The dominant antihyperon contribution, namely Λ¯ → p¯ π+ decays from promptly produced Λ¯ particles, is also exclusively measured. The results complement the measurement of prompt antiproton production obtained from the same data sample. At the energy scale of this measurement, the antihyperon contributions to antiproton production are observed to be significantly larger than predictions of commonly used hadronic production models