HIV Prevalence Among Hospitalized Patients at the Main Psychiatric Referral Hospital in Botswana

We examined HIV prevalence among patients 18–49 year olds admitted to a psychiatric hospital in Botswana in 2011 and 2012. The retrospective study analyzed females (F) and males (M) separately, comparing proportions with Chi square test and continuous variables with Wilcoxon rank-sum test, assessing significance at the 5% level. HIV seroprevalence among hospitalized psychiatric patients was much more common among females (53%) compared with males (19%) (p < 0.001). These women also appeared more vulnerable to infection compared with females in the general population (29%) (p < 0.017). Among both women and men, HIV-infection appeared most common among patients with organic mental disorders (F:68%, M:41%) and neurotic, stress related and somatoform disorders (F:68%, M:42%). The largest proportion of HIV infections co-occurred among patients diagnosed with schizophrenia, schizotypal and other psychotic disorders (F:48%; M:55%), mood (affective) disorders (F:21%; M:16%) and neurotic, stress-related and somatoform disorders (F:16%; M:20%). Interventions addressing both mental health and HIV among women and men require development.     

Well‐Being and Personal Growth in Mothers of Full‐Term and Pre‐Term Singletons and Twins

The present study examined well‐being and personal growth in mothers (n = 414) 1 year after childbirth. We examined the contribution of the event characteristics (birth of singletons or twins, full‐ or pre‐term babies, first or non‐first child, spontaneous pregnancy or fertility treatments and infant temperament), internal resources (attachment anxiety and avoidance) and external resources (marital quality and maternal grandmother's support). Regressions indicated that having a first child, child's easier temperament, lower attachment anxiety and avoidance, grandmother's emotional support and some aspects of the spousal relationships contributed to well‐being. Personal growth was found to be related to the birth of a pre‐term baby or babies, positively associated with maternal grandmother's support, and the marital quality of parenthood, and negatively with mothers' education. Beyond the findings that well‐being and personal growth are related to the availability of certain resources, the current study demonstrates that the two outcomes are separate phenomena that reveal different patterns of associations with other variables. Several explanations for the findings are proposed, and practical implications are discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Distinct Haplotype in Non-Ashkenazi Gaucher Patients with N370S Mutation

ABSTRACT: A new polymorphism, in intron 7 of glucocerebrosidase gene, has been identified in Gaucher Disease patients. It seems to appear only in Pv1.1^-alleles bearing the N370S mutation. This new sub-haplotype was only identified in Portuguese patients, of origins spanning all of the Portuguese continental territory. This finding indicates that, in the Portuguese, mutation N370S has existed in the context of two slightly different haplotypes and thus must be relatively ancient.     

Combined Effect of Smoking and Occupational Exposure to Dusts,Gases or Fumes on the Incidence of COPD

To assess risk factors related to the development of chronic obstructive pulmonary disease (COPD) including smoking and occupational exposure (OE) to dusts, gases or fumes, we performed a longitudinal 11-year follow-up postal survey. The original study population was a random population sample of 8000 inhabitants of Helsinki aged 20 to 69 years in 1996. Participants of the first postal questionnaire were invited to this follow-up survey in 2007 with 4302 (78%) answers obtained. Cumulative incidence of COPD in 11 years was 3.43% corresponding to an incidence rate of 3.17/1000/year after exclusion of those with self-reported physician-diagnosed COPD and ever COPD in 1996. Smoking and age, but not gender, were associated with incident COPD. Reported family history of COPD increased the cumulative incidence to 8.55% vs 3.04% among those without a family history (p < 0.001). In multivariate analysis, significant independent risk factors for incident COPD were: current smoking in 1996 (OR 4.40 [95% CI 2.89–6.71]), age over 50 (OR 3.42 [95% CI 2.22–5.26]), family history of COPD (OR 2.08 [1.27–3.43]), ever asthma (OR 2.28 [1.35–3.86]), and self-reported OE (OR 2.14 [1.50–3.05]). Occupational exposure to dusts, gases or fumes, assessed both based on self-reported exposure and a job exposure matrix using reported professions, was an independent risk factor for incident COPD. Smoking and OE together yielded an additive effect on incidence of COPD.     

High frequency of BRAF V600E mutations in ameloblastoma

Ameloblastoma is a benign but locally infiltrative odontogenic neoplasm. Although ameloblastomas rarely metastasise, recurrences together with radical surgery often result in facial deformity and significant morbidity. Development of non‐invasive therapies has been precluded by a lack of understanding of the molecular background of ameloblastoma pathogenesis. When addressing the role of ERBB receptors as potential new targets for ameloblastoma, we discovered significant EGFR over‐expression in clinical samples using real‐time RT–PCR, but observed variable sensitivity of novel primary ameloblastoma cells to EGFR‐targeted drugs in vitro. In the quest for mutations downstream of EGFR that could explain this apparent discrepancy, Sanger sequencing revealed an oncogenic BRAF V600E mutation in the cell line resistant to EGFR inhibition. Further analysis of the clinical samples by Sanger sequencing and BRAF V600E‐specific immunohistochemistry demonstrated a high frequency of BRAF V600E mutations (15 of 24 samples, 63%). These data provide novel insight into the poorly understood molecular pathogenesis of ameloblastoma and offer a rationale to test drugs targeting EGFR or mutant BRAF as novel therapies for ameloblastoma. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk     

CYLD deletion triggers nuclear factor-κB-signaling and increases cell death resistance in murine hepatocytes

AIM:To analyze the role of CYLD for receptor-mediated cell death of murine hepatocytes in acute liver injury models.METHODS:Hepatocyte cell death in CYLD knockout mice(CYLD-/-)was analyzed by application of liver injury models for CD95-(Jo2)and tumor necrosis factor(TNF)-α-[D-Gal N/lipopolysaccharide(LPS)]induced apoptosis.Liver injury was assessed by measurement of serum transaminases and histological analysis.Apoptosis induction was quantified by cleaved PARP staining and Western blotting of activated caspases.Nuclear factor(NF)-κB,ERK,Akt and jun amino-terminal kinases signaling were assessed.Primary Hepatocytes were isolated by two step-collagenase perfusion and treated with recombinant TNF-αand with the CD95-ligand Jo2.Cell viability was analyzed by MTT-assay.RESULTS:Livers of CYLD-/-mice showed increased anti-apoptotic NF-κB signaling.In both applied liver injury models CYLD-/-mice showed a significantly reduced apoptosis sensitivity.After D-Gal N/LPS treatment CYLD-/-mice exhibited significantly lower levels of alanine aminotransferase(ALT)(295 U/L vs 859 U/L,P<0.05)and aspartate aminotransferase(AST)(560 U/L vs 1025 U/L,P<0.01).After Jo injection CYLD-/-mice showed 2-fold lower ALT(50 U/L vs 110 U/L,P<0.01)and lower AST(250 U/L vs 435 U/L,P<0.01)serumlevels compared to WT mice.In addition,isolated CYLD-/-primary murine hepatocytes(PMH)were less sensitive towards death receptor-mediated apoptosis and showed increased levels of Bcl-2,XIAP,c IAP1/2,survivin and c-FLIP expression upon TNF-and CD95-receptor triggering,respectively.Inhibition of NF-κB activation by the inhibitor of NF-κB phosphorylation inhibitor BAY 11-7085 inhibited the expression of antiapoptotic proteins and re-sensitized CYLD-/-PMH towards TNF-and CD95-receptor mediated cell death.CONCLUSION:CYLD is a central regulator of apoptotic cell death in murine hepatocytes by controlling NF-κB dependent anti-apoptotic signaling.