Symptoms associated with victimization in patients with schizophrenia and related disorders

Background: Patients with psychoses have an increased risk of becoming victims of violence. Previous studies have suggested that higher symptom levels are associated with a raised risk of becoming a victim of physical violence. There has been, however, no evidence on the type of symptoms that are linked with an increased risk of recent victimization. Methods: Data was taken from two studies on involuntarily admitted patients, one national study in England and an international one in six other European countries. In the week following admission, trained interviewers asked patients whether they had been victims of physical violence in the year prior to admission, and assessed symptoms on the Brief Psychiatric Rating Scale (BPRS). Only patients with a diagnosis of schizophrenia or related disorders (ICD-10 F20–29) were included in the analysis which was conducted separately for the two samples. Symptom levels assessed on the BPRS subscales were tested as predictors of victimization. Univariable and multivariable logistic regression models were fitted to estimate adjusted odds ratios. Results: Data from 383 patients in the English sample and 543 patients in the European sample was analysed. Rates of victimization were 37.8% and 28.0% respectively. In multivariable models, the BPRS manic subscale was significantly associated with victimization in both samples. Conclusions: Higher levels of manic symptoms indicate a raised risk of being a victim of violence in involuntary patients with schizophrenia and related disorders. This might be explained by higher activity levels, impaired judgement or poorer self-control in patients with manic symptoms. Such symptoms should be specifically considered in risk assessments

A mathematical modelling tool for predicting survival of individual patients following resection of glioblastoma: a proof of principle

The prediction of the outcome of individual patients with glioblastoma would be of great significance for monitoring responses to therapy. We hypothesise that, although a large number of genetic-metabolic abnormalities occur upstream, there are two ‘final common pathways' dominating glioblastoma growth – net rates of proliferation (ρ) and dispersal (D). These rates can be estimated from features of pretreatment MR images and can be applied in a mathematical model to predict tumour growth, impact of extent of tumour resection and patient survival. Only the pre-operative gadolinium-enhanced T1-weighted (T1-Gd) and T2-weighted (T2) volume data from 70 patients with previously untreated glioblastoma were used to derive a ratio D/ρ for each patient. We developed a ‘virtual control' for each patient with the same size tumour at the time of diagnosis, the same ratio of net invasion to proliferation (D/ρ) and the same extent of resection. The median durations of survival and the shapes of the survival curves of actual and ‘virtual' patients subjected to biopsy or subtotal resection (STR) superimpose exactly. For those actually receiving gross total resection (GTR), as shown by post-operative CT, the actual survival curve lies between the ‘virtual' results predicted for 100 and 125% resection of the T1-Gd volume. The concordance between predicted (virtual) and actual survivals suggests that the mathematical model is realistic enough to allow precise definition of the effectiveness of individualised treatments and their site(s) of action on proliferation (ρ) and/or dispersal (D) of the tumour cells without knowledge of any other clinical or pathological information

Tandem quadruplication of HMA4 in the zinc (Zn) and cadmium (Cd) hyperaccumulator noccaea caerulescens

Zinc (Zn) and cadmium (Cd) hyperaccumulation may have evolved twice in the Brassicaceae, in Arabidopsis halleri and in the Noccaea genus. Tandem gene duplication and deregulated expression of the Zn transporter, HMA4, has previously been linked to Zn/Cd hyperaccumulation in A. halleri. Here, we tested the hypothesis that tandem duplication and deregulation of HMA4 expression also occurs in Noccaea. A Noccaea caerulescens genomic library was generated, containing 36,864 fosmid pCC1FOSTM clones with insert sizes ~20–40 kbp, and screened with a PCR-generated HMA4 genomic probe. Gene copy number within the genome was estimated through DNA fingerprinting and pooled fosmid pyrosequencing. Gene copy numbers within individual clones was determined by PCR analyses with novel locus specific primers. Entire fosmids were then sequenced individually and reads equivalent to 20-fold coverage were assembled to generate complete whole contigs. Four tandem HMA4 repeats were identified in a contiguous sequence of 101,480 bp based on sequence overlap identities. These were flanked by regions syntenous with up and downstream regions of AtHMA4 in Arabidopsis thaliana. Promoter-reporter b-glucuronidase (GUS) fusion analysis of a NcHMA4 in A. thaliana revealed deregulated expression in roots and shoots, analogous to AhHMA4 promoters, but distinct from AtHMA4 expression which localised to the root vascular tissue. This remarkable consistency in tandem duplication and deregulated expression of metal transport genes between N. caerulescens and A. halleri, which last shared a common ancestor >40 mya, provides intriguing evidence that parallel evolutionary pathways may underlie Zn/Cd hyperaccumulation in Brassicaceae

Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production

© 2014 Pandit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SPD against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection. © 2014 Pandit et al.The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/)

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

Characterizing Family Physicians Who Refer to Telepsychiatry in Ontario

INTRODUCTION: Telepsychiatry can improve access to psychiatric services for those who otherwise cannot easily access care. Family physicians are gatekeepers to specialized care in Ontario, so it is essential to understand predictors relating to referrals to telepsychiatry to better plan services and increase telepsychiatry adoption. METHODS: This study used an annual retrospective cross-sectional study design to compare physicians who referred their patients to telepsychiatry each year from fiscal year (FY) 2008 to FY 2016. A 1-year (FY 2016) comparison of family physicians who referred to telepsychiatry (FPTs) compared to family physicians who did not refer to telepsychiatry (FPNTs) matched (1:2) by region was also conducted. Finally, we used statistical modeling to understand the predictors of referring to telepsychiatry among physicians. RESULTS: Between FY 2008 and FY 2016, the number of patients receiving telepsychiatry increased from 925 visits to 13,825 visits. Thirty-two percent of Ontario primary care physicians referred to telepsychiatry in 2016. Several characteristics were notably different between FPTs and FPNTs: FPTs were more likely to be from a residence with less than 10,000 people, to have more nurse practitioners in the practice, and to be from a family health team than FPNTs. Rostered patients of FPTs were more likely to reside in rural areas, have more clinical complexity, and to utilize more mental health services compared to FPNTs. CONCLUSIONS: There has been an increase in the use of telepsychiatry by patients and family physicians over the study period, although there remains opportunity for significant growth. Family physicians who live in rural areas, are part of an FHT, have more NPs, with more rural and complex patients were more likely to refer to telepsychiatry. As recent pro-telemedicine policies support the growth of telepsychiatry, this study will serve as an important baseline

Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia

BACKGROUND: There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation, a recognized index of medication effectiveness in the treatment of schizophrenia. METHODS: We used data from a large, 3-year, observational, non-randomized, multisite study of schizophrenia, conducted in the U.S. between 7/1997 and 9/2003. Patients who were initiated on oral atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone) or oral typical antipsychotics (low, medium, or high potency) were compared on time to all-cause medication discontinuation for 1 year following initiation. Treatment group comparisons were based on treatment episodes using 3 statistical approaches (Kaplan-Meier survival analysis, Cox Proportional Hazards regression model, and propensity score-adjusted bootstrap resampling methods). To further assess the robustness of the findings, sensitivity analyses were performed, including the use of (a) only 1 medication episode for each patient, the one with which the patient was treated first, and (b) all medication episodes, including those simultaneously initiated on more than 1 antipsychotic. RESULTS: Mean time to all-cause medication discontinuation was longer on atypical (N = 1132, 256.3 days) compared to typical antipsychotics (N = 534, 197.2 days; p < .01), and longer on atypicals compared to typicals of high potency (N = 320, 187.5 days; p < .01), medium potency (N = 140, 213.5 days; p < .01), and low potency (N = 74, 208.7 days; p < .01). Among the atypicals, only clozapine, olanzapine, and risperidone had significantly longer time to all-cause medication discontinuation compared to typicals, regardless of potency level, and compared to haloperidol with prophylactic anticholinergic treatment. When compared to perphenazine, a medium-potency typical antipsychotic, only clozapine and olanzapine had a consistently and significantly longer time to all-cause medication discontinuation. Results were confirmed by sensitivity analyses. CONCLUSION: In the usual care of schizophrenia patients, time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level. Findings were primarily driven by clozapine and olanzapine, and to a lesser extent by risperidone. Furthermore, only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine, a medium-potency typical antipsychotic