Domains of Chronic Stress, Lifestyle Factors, and Allostatic Load in Middle-Aged Mexican-American Women

Abstract available at publisher's website

Predictors of mental health in female teachers

Objective: Teaching profession is characterised by an above-average rate of psychosomatic and mental health impairment due to work-related stress. The aim of the study was to identify predictors of mental health in female teachers. Material and Methods: A sample of 630 female teachers (average age 47±7 years) participated in a screening diagnostic inventory. Mental health was surveyed with the General Health Questionnaire GHQ-12. The following parameters were measured: specific work conditions (teacher-specific occupational history), scales of the Effort-Reward-Imbalance (ERI) Questionnaire as well as cardiovascular risk factors, physical complaints (BFB) and personal factors such as inability to recover (FABA), sense of coherence (SOC) and health behaviour. Results: First, mentally fit (MH+) and mentally impaired teachers (MH-) were differentiated based on the GHQ-12 sum score (MH+: < 5; MH-: ≥ 5); 18% of the teachers showed evidence of mental impairment. There were no differences concerning work-related and cardiovascular risk factors as well as health behaviour between MH+ and MH-. Binary logistic regressions identified 4 predictors that showed a significant effect on mental health. The effort-reward-ratio proved to be the most relevant predictor, while physical complaints as well as inability to recover and sense of coherence were identified as advanced predictors (explanation of variance: 23%). Conclusion: Contrary to the expectations, classic work-related factors can hardly contribute to the explanation of mental health. Additionally, cardiovascular risk factors and health behaviour have no relevant influence. However, effort-reward-ratio, physical complaints and personal factors are of considerable influence on mental health in teachers. These relevant predictors should become a part of preventive arrangements for the conservation of teachers' health in the future

Laparoscopic liver resection in Caroli disease: a single-centre case series

Background: Liver resection is the treatment of choice for patients with localised Caroli disease. While liver resection was traditionally performed as open procedure, this case series aims to evaluate the safety and efficacy of minimally invasive, laparoscopic liver surgery in these patients. Methods: A systematic review of electronic case files of patients seen between April 2015 and December 2017 at the Department of Surgery, Charité University Hospital Berlin, was conducted. Patients with Caroli disease in whom laparoscopic liver resection had been performed were identified and analysed in this single-centre case series. Results: Seven patients who underwent laparoscopic liver surgery for Caroli syndrome were identified and presented with a median age of 49 (range = 44–66) years, of which four (57%) were female. Preoperatively, six patients were classified as the American Society of Anaesthesiologists (ASA) 2 and one patient as ASA 3. Two operations were performed as single-incision laparoscopic surgery, whereas the others were done as multi-incision laparoscopic surgery. One patient required a conversion to an open procedure. The length of operation varied between patients, ranging from 128 to 758 min (median = 355). The length of stay in the intensive care unit ranged from 0 to 2 days. Two patients presented with post-operative complications (Clavien–Dindo Grade ≥3a), whereas no patient died. In histopathological analysis, all patients demonstrated characteristic findings of Caroli disease and no cholangiocarcinoma was found. Conclusion: These results indicate that minimally invasive, laparoscopic liver surgery is a safe and efficacious treatment option for patients with Caroli disease who require liver resection

Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder

Increased inflammatory activation might only be present in a subgroup of depressed individuals in which immune processes are especially relevant to disease development. We aimed to analyze demographic, depression, and trauma characteristics of major depressive disorder (MDD) patients with regard to inflammatory monocyte gene expression. Fifty-six naturalistically treated MDD patients (32 +/- 12 years) and 57 healthy controls (HC; 31 +/- 11 years) were analyzed by the Inventory of Depressive Symptomatology (IDS) and by the Childhood Trauma Questionnaire (CTQ). We determined the expression of 38 inflammatory and immune activation genes including the glucocorticoid receptor (GR)alpha and GR beta genes in purified CD14(+) monocytes using quantitative-polymerase chain reaction (RT-qPCR). Monocyte gene expression was age-dependent, particularly in MOD patients. Increased monocyte gene expression and decreased GR alpha/beta ratio were only present in MDD patients aged >= 28 years. Post hoc analyses of monocyte immune activation in patients = 15 years) - additionally characterized by the absence of panic symptoms - that exhibited a strongly reduced inflammatory monocyte activation compared to HC. In conclusion, monocyte immune activation was not uniformly raised in MDD patients but was increased only in patients of 28 years and older. (C) 2014 Elsevier Inc. All rights reserved

High symmetry of visual acuity and visual fields in RPGR-linked retinitis pigmentosa

Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause 70% to 90% of X-linked retinitis pigmentosa (XLRP3) cases, making this gene a high-yield target for gene therapy. This study analyzed the utility of relevant clinical biomarkers to assess symmetry and rate of progression in XLRP3.A retrospective, cross-sectional analysis of 50 XLRP3 patients extracted clinical data including visual acuity (VA), visual fields (I4e and III4e targets), foveal thickness, and ERG data points alongside molecular genetic data. Symmetry was assessed by using linear regression analysis. Kaplan-Meier survival curves (KMCs) and generalized linear mixed model calculations were used to describe disease progression.Ninety-six percent of patients exhibited a rod-cone phenotype, and 4% a cone-rod phenotype. Open reading frame 15 (ORF15) was confirmed as a mutational hotspot within RPGR harboring 73% of exonic mutations. Significant variability, but no clear genotype-phenotype relationship, could be shown between mutations located in exons 1-14 versus ORF15. All biomarkers suggested a high degree of symmetry between eyes but demonstrated different estimates of disease progression. VA and foveal thickness, followed by perimetry III4e, were the most useful endpoints to evaluate progression. KMC estimates predicted a loss of 6/6 vision at a mean of 34 years (&#xB1;2.9; 95% confidence interval).XLRP3 affects retinal structure and function symmetrically, supporting the use of the fellow eye as an internal control in interventional trials. VA and kinetic visual fields (III4e) seem promising functional outcome measures to assess disease progression. KMC analysis predicted the most severe decline in vision between the third and fourth decade of life

Codon-optimized RPGR improves stability and efficacy of AAV8 gene therapy in two mouse models of X-linked retinitis pigmentosa

X-linked retinitis pigmentosa (XLRP) is generally a severe form of retinitis pigmentosa, a neurodegenerative, blinding disorder of the retina. 70% of XLRP cases are due to mutations in the&nbsp;retina-specific isoform of the gene encoding retinitis pigmentosa GTPase regulator (RPGRORF15). Despite successful&nbsp;RPGRORF15&nbsp;gene replacement with adeno-associated viral (AAV) vectors being established in a number of animal models of XLRP, progression to human trials has not yet been possible. The inherent sequence instability in the purine-rich region of&nbsp;RPGRORF15&nbsp;(which contains highly repetitive nucleotide sequences) leads to unpredictable recombination errors during viral vector cloning. While deleted RPGR may show some efficacy in animal models, which have milder disease, the therapeutic effect of a mutated RPGR variant in patients with XLRP cannot be predicted. Here, we describe an optimized gene replacement therapy for human XLRP disease using an AAV8 vector that reliably and consistently produces the full-length correct RPGR protein. The glutamylation pattern in the RPGR protein derived from the codon-optimized sequence is indistinguishable from the wild-type variant, implying that codon optimization does not significantly alter post-translational modification. The codon-optimized sequence has superior stability and expression levels in&nbsp;vitro. Significantly, when delivered by AAV8 vector and driven by the rhodopsin kinase promoter, the codon-optimized RPGR rescues the disease phenotype in two relevant animal models (Rpgr&minus;/y&nbsp;and&nbsp;C57BL/6JRd9/Boc) and shows good safety in&nbsp;C57BL6/J&nbsp;wild-type mice. This work provides the basis for clinical trial development to treat patients with XLRP caused by RPGR mutations.</p