CD8+ cells and small viral reservoirs facilitate post-ART control of SIV replication in M3+ Mauritian cynomolgus macaques initiated on ART two weeks post-infection.

Sustainable HIV remission after antiretroviral therapy (ART) withdrawal, or post-treatment control (PTC), remains a top priority for HIV treatment. We observed surprising PTC in an MHC-haplomatched cohort of MHC-M3+ SIVmac239+ Mauritian cynomolgus macaques (MCMs) initiated on ART at two weeks post-infection (wpi). None of the MCMs possessed MHC haplotypes previously associated with SIV control. For six months after ART withdrawal, we observed undetectable or transient viremia in seven of the eight MCMs, despite detecting replication competent SIV using quantitative viral outgrowth assays. In vivo depletion of CD8α+ cells induced rebound in all animals, indicating the observed PTC was mediated, at least in part, by CD8α+ cells. With intact proviral DNA assays, we found that MCMs had significantly smaller viral reservoirs two wpi than a cohort of identically infected rhesus macaques, a population that rarely develops PTC. We found a similarly small viral reservoir among six additional SIV+ MCMs in which ART was initiated at eight wpi, some of whom exhibited viral rebound. These results suggest that an unusually small viral reservoir is a hallmark among SIV+ MCMs. By evaluating immunological differences between MCMs that did and did not rebound, we identified that PTC was associated with a reduced frequency of CD4+ and CD8+ lymphocyte subsets expressing exhaustion markers. Together, these results suggest a combination of small reservoirs and immune-mediated virus suppression contribute to PTC in MCMs. Further, defining the immunologic mechanisms that engender PTC in this model may identify therapeutic targets for inducing durable HIV remission in humans.

TP53 mutations and the association with platinum resistance in high grade serous ovarian carcinoma.

OBJECTIVES: Alterations in the tumor suppressor TP53 gene are the most common mutations in high grade serous ovarian carcinoma. The impact of TP53 mutations on clinical outcomes and platinum resistance is controversial. We sought to evaluate the genomic profile of high grade serous ovarian carcinoma and explore the association of TP53 mutations with platinum resistance. METHODS: Next generation sequencing data was obtained from our institutional database for patients with high grade serous ovarian carcinoma undergoing primary treatment. Sequencing data, demographic, and clinical information was reviewed. The primary outcome analyzed was time to recurrence or refractory diagnosis. Associations between the primary outcome and different classification schemes for TP53 mutations (structural, functional, hot spot, pathogenicity scores, immunohistochemical staining patterns) were performed. RESULTS: 209 patients met inclusion criteria. TP53 mutations were the most common mutation. There were no differences in platinum response with TP53 hotspot mutations or high pathogenicity scores. Presence of TP53 gain-of-function mutations or measure of TP53 gain-of function activity were not associated with platinum resistance. Immunohistochemical staining patterns correlated with expected TP53 protein function and were not associated with platinum resistance. CONCLUSIONS: TP53 hotspot mutations or high pathogenicity scores were not associated with platinum resistance or refractory disease. Contrary to prior studies, TP53 gain-of-function mutations were not associated with platinum resistance. Estimation of TP53 gain-of-function effect using missense mutation phenotype scores was not associated with platinum resistance. The polymorphic nature of TP53 mutations may be too complex to demonstrate effect using simple models, or response to platinum therapy may be independent of initiating TP53 mutation.

Conflicting patterns of cardiovascular reactivity, self-report, and behavior associated with social anxiety during a conversation with a close friend.

Social anxiety (SA) is characterized by anxious symptomology and fear during social situations, but recent work suggests that SA may not necessarily be associated with negative interpersonal and intrapersonal outcomes in support contexts. The current research investigates the discrepancies between self-perceptions, behavior, and physiological responses associated with SA in social support conversations with close friends. Specifically, we examined the associations between SA and positive and negative affect, perceptions of demands and resources, and responsiveness. Additionally, we used the biopsychosocial model of challenge and threat to understand the physiological responses associated with SA. Participants (79.9% White, 9.8% Black or African American, 10.3% Multiple races or other; 78.7% Female), totaling 172 undergraduate friend dyads, completed self-report measures and had physiological responses recorded while they discussed a problem unrelated to the friendship. Trained coders rated responsive behaviors exhibited during the conversation. Results revealed that greater SA was associated with greater negative perceptions of social interactions (greater negative affect, fewer perceived resources, and greater perceived demands). However, cardiovascular reactivity and behavioral responses within the conversation, as well as perceptions of partners' behavior after the conversation, contrasted with these negative perceptions. Indeed, greater SA was associated with greater sympathetic arousal (indicative of greater task engagement), but not with greater challenge or threat, and SA was not associated with perceived partner responsiveness or responsive behaviors. These results add to the growing body of research that suggests people with greater SA show inconsistencies between their conscious appraisals of social situations and their physiological responses.

Ten years after: findings from the medical surveillance program on Health Effects in High-Level Exposure to PCB (HELPcB).

After the detection of high environmental and occupational exposure to polychlorinated biphenyls (PCBs) in a German recycling company for transformers and capacitors in 2010, the multidisciplinary medical surveillance program "HELPcB" (Health Effects in High-Level Exposure to PCB) was established for former PCB-exposed workers of the company, their family members, employees of surrounding companies, and area residents to investigate potential adverse health effects by PCB exposure in a longitudinal study approach with up to seven examination time points between 2010 and 2019. More than 300 individuals were enrolled into the program. Assessments particularly included plasma and urine concentrations of PCB congeners and their metabolites, clinical laboratory parameters, Comet assay, analysis of telomere length, neuropsychological examinations, psychological screening, abdominal and thyroid ultrasound examination. This review summarizes the main results of the studies conducted in the HELPcB program yielding relevant new data on potential adverse effects of PCB exposure in humans and potential mechanisms that underlie these effects. Even larger studies in PCB-exposed individuals are warranted to confirm the results of this program and to further establish causality between PCB exposure and clinical effects in humans.

The moderating effect of social resources on the link between study-related stressors and depressive symptoms among medical students in North Rhine-Westphalia, Germany - a cross-sectional study.

BACKGROUND: Previous research has demonstrated the negative effects of study-related stressors on the mental health of medical students. It has been found that social resources such as social identity, dual identity and social support help buffer negative mental health outcomes. Notably, social status has been found to weaken the connection between stress and depressive symptoms. Based on these findings, the present study investigates how social resources (i.e., social identity, social support, dual identity and status) mitigate the impact of study-related stressors on the mental health of medical students who carry an inordinate stress burden. METHODS: The data collection was based on a questionnaire (online and paper-pencil) which was distributed to medical students in North Rhine-Westphalia, Germany. The sample (224 participants) consisted of 77.2% female and 22.8% male medical students (36.2% human medicine students (HMS) and 63.8% dental medicine students (DMS)). The questionnaire included graphical scales and standardized questionnaires. We investigated demographic data, study-related stressors (i.e. academic performance, clinical practice, faculty relations) and depressive symptoms as outcomes, and social identity, social support, dual identity and status as moderators. The analyses were performed using SPSS 25 for Windows. RESULTS: We found significant positive associations between study-related stressors and depressive symptoms. While dual identity as well as social support by fellow students emerged as buffers in these associations, the other social resources did not. As regards status, it was found to work as a buffer only in HMS, who typically enjoy a significantly higher status than dental medical students. CONCLUSION: It is only social resources such as support from fellow students and dual identity, but not other resource types, that can be effective buffers against depressive symptoms associated with study-related stressors. These findings can be used to promote students' identities in relation to both fellow students and the faculty, or the university as a whole, enabling students to better cope with stress and, thus, suffer less from depressive symptoms. Furthermore, the HMS, who ascribe a relatively high status to themselves, can use their status as a buffering factor in stressful situations, in which little can be done from the outside.

Prostaglandin E2 Induces miR675-5p to Promote Colorectal Tumor Metastasis via Modulation of p53 Expression.

BACKGROUND & AIMS: Prostaglandin E2 (PGE2) promotes colorectal tumor formation and progression by unknown mechanisms. We sought to identify microRNAs (miRNAs) that might mediate the effects of PGE2 on colorectal cancer (CRC) development. METHODS: We incubated LS174T colorectal cancer cells with PGE2 or without (control) and used miRNA-sequencing technology to compare expression patterns of miRNAs. We knocked down levels of specific miRNAs or proteins in cells using small interfering RNAs or genome editing. Cells were analyzed by immunoblot, quantitative polymerase chain reaction, chromosome immunoprecipitation, cell invasion, and luciferase reporter assays; we measured gene expression, binding activity, cell migration and invasion, and transcriptional activity of transcription factors. NOD-scidIL-2Rg-/- mice were given injections of LS174T cells, and growth of primary tumors and numbers of liver and lung metastases were quantified and analyzed by histology. We used public databases to identify correlations in gene expression pattern with patient outcomes. RESULTS: We identified miRNA 675-5p (miR675-5p) as the miRNA most highly up-regulated by incubation of colorectal cancer cells with PGE2. PGE2 increased expression of miR675-5p by activating expression of Myc, via activation of protein kinase B, also known as (AKT), nuclear factor κB, and ß-catenin. PGE2 increased the invasive activities of cultured CRC cells. LS174T cells incubated with PGE2 formed more liver and lung metastases in mice than control LS174T cells. We identified a 3' untranslated region in the TP53 messenger RNA that bound miR675-5p; binding resulted in loss of the p53 protein. Expression of miR675-5p or its precursor RNA, H19, correlated with expression of cyclooxygenase-1 and cyclooxygenase-2 and shorter survival times of patients with CRC. CONCLUSIONS: We found that treatment of mice with PGE2 increased CRC cells invasive activity and ability to form liver and lung metastases. PGE2 down-regulates expression of p53 by increasing expression of miR675-5p, which binds to and prevents translation of TP53 messenger RNA. These findings provide insight into the mechanisms by which PGE2 promotes tumor development and progression. Strategies to target PGE2 might be developed for treatment of CRC.

Expression of Free Fatty Acid Receptor 2 by Dendritic Cells Prevents Their Expression of Interleukin 27 and Is Required for Maintenance of Mucosal Barrier and Immune Response Against Colorectal Tumors in Mice.

BACKGROUND & AIMS: Intestinal microbes and their metabolites affect the development of colorectal cancer (CRC). Short-chain fatty acids are metabolites generated by intestinal microbes from dietary fiber. We investigated the mechanisms by which free fatty acid receptor 2 (FFAR2), a receptor for short-chain fatty acids that can affect the composition of the intestinal microbiome, contributes to the pathogenesis of CRC. METHODS: We performed studies with ApcMin/+ mice, ApcMin/+Ffar2-/- mice, mice with conditional disruption of Ffar2 in dendritic cells (DCs) (Ffar2fl/flCD11c-Cre mice), ApcMin/+Ffar2fl/flCD11c-Cre mice, and Ffar2fl/fl mice (controls); some mice were given dextran sodium sulfate to induce colitis, with or without a FFAR2 agonist or an antibody against interleukin 27 (IL27). Colon and tumor tissues were analyzed by histology, quantitative polymerase chain reaction, and 16S ribosomal RNA gene sequencing; lamina propria and mesenteric lymph node tissues were analyzed by RNA sequencing and flow cytometry. Intestinal permeability was measured after gavage with fluorescently labeled dextran. We collected data on colorectal tumors from The Cancer Genome Atlas. RESULTS: ApcMin/+Ffar2-/- mice developed significantly more spontaneous colon tumors than ApcMin/+ mice and had increased gut permeability before tumor development, associated with reduced expression of E-cadherin. Colon tumors from ApcMin/+Ffar2-/- mice had a higher number of bacteria than tumors from ApcMin/+ mice, as well as higher frequencies of CD39+CD8+ T cells and exhausted or dying T cells. DCs from ApcMin/+Ffar2-/- mice had an altered state of activation, increased death, and higher production of IL27. Administration of an antibody against IL27 reduced the numbers of colon tumors in ApcMin/+ mice with colitis. Frequencies of CD39+CD8+ T cells and IL27+ DCs were increased in colon lamina propria from Ffar2fl/flCD11c-Cre mice with colitis compared with control mice or mice without colitis. ApcMin/+Ffar2fl/flCD11c-Cre mice developed even more tumors than ApcMin/+Ffar2fl/fl mice, and their tumors had even higher numbers of IL27+ DCs. ApcMin/+ mice with colitis given the FFAR2 agonist developed fewer colon tumors, with fewer IL27+ DCs, than mice not given the agonist. DCs incubated with the FFAR2 agonist no longer had gene expression patterns associated with activation or IL27 production. CONCLUSIONS: Loss of FFAR2 promotes colon tumorigenesis in mice by reducing gut barrier integrity, increasing tumor bacterial load, promoting exhaustion of CD8+ T cells, and overactivating DCs, leading to their death. Antibodies against IL27 and an FFAR2 agonist reduce tumorigenesis in mice and might be developed for the treatment of CRC.

Building an allostatic load index from data of occupational medical checkup examinations: a feasibility study.

The allostatic load index (ALI) assesses the physiological adaption to chronic stress by cumulative changes in the circulation, respiration, inflammation, metabolic and anthropometric systems. The ALI thus can function as a risk marker for secondary prevention in occupational medicine. The aim of this study was to investigate the feasibility of creating a predictive marker by using data from an executive checkup program of an international company and to examine its relationship to work-related surrogate health parameters. Datasets from 307 examinations of 151 executives (19 males and 132 females) were available. Each participant attended at least one checkup examination between 2003 and 2015. The mean age was 43.6 (SD ±6.6, 31-64y). We developed four different ALIs with different biomarkers of the cardio-vascular, immune, metabolic and anthropometric systems. As a primary mediator, the thyroid-stimulating hormone was used as a proxy. For each ALI, the associations with the work ability index (WAI) and categories of sick leave days (SLD) were examined. Zero inflation was considered for SLD. One ALI showed a significant negative association with the WAI (B = -0.680, SE =0.266, p = .049). The results of a second ALI had a similar trend (B= -0.355, SE =0.201, p = .081). After adjustment for zero inflation two other ALIs showed a positive association with SLD. This study provides the first hints that biomarkers form a secondary prevention program are useful in calculating a meaningful ALI. Thus, the concept of allostatic load could be used in workplace health-promotion.

Coordinating Outpatient Care for Pregnant and Postpartum Women with Opioid Use Disorder: Implications from the COACHH Program.

Purpose With the rise of opioid use disorder (OUD) among women of childbearing age, effective care models must address the complex needs of pregnant and postpartum women with OUD. This paper describes promising practices and implementation challenges from the Collaborative Outreach and Adaptable Care at Hallmark Health (COACHH) program, which utilizes a collaborative care team to coordinate outpatient care for pregnant and postpartum women with OUD. Description Semi-structured interviews were conducted with members of the COACHH team to discuss program logistics and takeaways. Interviews were coded to analyze themes. Assessment The COACHH team identified the need for specialized, time-intensive care coordination to address the unique needs of pregnant and postpartum women with OUD. First, the team prioritizes forming trusting relationships with patients to holistically understand patients' needs, improve patient engagement, and connect patients with resources. Second, the wide range of patient needs necessitates a team with diverse professional skills, whose members share an understanding of addiction and pregnancy. Third, finding the right quantitative outcome measurements is difficult; instead, success is measured in qualitative terms, stressing relationships and engagement as signals of change. Finally, the team encounters challenges with low referral rates, lack of provider awareness, and fragmented services. Conclusion We identified care delivery and program design considerations that may inform others who wish to coordinate care for pregnant and postpartum women with OUD. The program continues to face challenges enrolling patients and measuring outcomes, reflecting the need for tailored approaches and metrics for this population.

Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. OBJECTIVES: We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. METHODS: Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. RESULTS: Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. CONCLUSIONS: These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium.

The histone methyltransferase EZH2 is a therapeutic target in small cell carcinoma of the ovary, hypercalcaemic type.

Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a rare but aggressive and untreatable malignancy affecting young women. We and others recently discovered that SMARCA4, a gene encoding the ATPase of the SWI/SNF chromatin-remodelling complex, is the only gene recurrently mutated in the majority of SCCOHT. The low somatic complexity of SCCOHT genomes and the prominent role of the SWI/SNF chromatin-remodelling complex in transcriptional control of genes suggest that SCCOHT cells may rely on epigenetic rewiring for oncogenic transformation. Herein, we report that approximately 80% (19/24) of SCCOHT tumour samples have strong expression of the histone methyltransferase EZH2 by immunohistochemistry, with the rest expressing variable amounts of EZH2. Re-expression of SMARCA4 suppressed the expression of EZH2 in SCCOHT cells. In comparison to other ovarian cell lines, SCCOHT cells displayed hypersensitivity to EZH2 shRNAs and two selective EZH2 inhibitors, GSK126 and EPZ-6438. EZH2 inhibitors induced cell cycle arrest, apoptosis, and cell differentiation in SCCOHT cells, along with the induction of genes involved in cell cycle regulation, apoptosis, and neuron-like differentiation. EZH2 inhibitors suppressed tumour growth and improved the survival of mice bearing SCCOHT xenografts. Therefore, our data suggest that loss of SMARCA4 creates a dependency on the catalytic activity of EZH2 in SCCOHT cells and that pharmacological inhibition of EZH2 is a promising therapeutic strategy for treating this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Effects of psychosocial work characteristics on hair cortisol - findings from a post-trial study.

Prolonged work stress, as indicated by the effort-reward imbalance (ERI) model, jeopardizes health. Cortisol represents a candidate mechanism connecting stress to ill health. However, previous findings appear inconclusive, and recommendations were made to assess work stress at multiple time points and also to investigate ERI (sub-)components. This study therefore examines the effects of two single time points, as well as the mean and change scores between time points of ERI and its components on hair cortisol concentration (HCC), a long-term cortisol measurement. Participants were 66 male factory workers (age: 40.68 ± 6.74 years; HCC: 9.00 ± 7.11 pg/mg), who were followed up after a stress management intervention (2006-2008). In 2008 (T1) and 2015 (T2), participants completed a 23-item ERI questionnaire, assessing effort, the three reward components (esteem, job security, job promotion) and over-commitment. In 2015, participants also provided a 3-cm hair segment close to the scalp for HCC analysis, as well as information on relevant confounders (i.e. medication intake, age, work characteristics, socioeconomic and lifestyle factors, number of stressful life events). Linear regressions revealed hardly any cross-sectional or longitudinal effect of ERI and its components on HCC. Only the change scores between T1 and T2 of job security were negatively associated with lower HCC in unadjusted (ß = -.320; p = .009) and adjusted (ß = -.288; p = .044) models. In this study, only a decrease of perceived job security over time was significantly associated with higher HCC, and other predictors were not related to this outcome. Especially after correction for multiple testing, this study revealed just a weak association of different psychosocial work measurements with HCC. Lay summary This study showed that an increase in perceived job insecurity is correlated with higher levels of the stress hormone cortisol. The higher levels of cortisol might represent a biological explanation for the negative health effects of job insecurity. The association was, however, relatively low, and more and more voices are questioning whether cortisol in hair is a reliable marker for perceived work stress.

Polychlorinated biphenyls and depression: cross-sectional and longitudinal investigation of a dopamine-related Neurochemical path in the German HELPcB surveillance program.

BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) is associated with depressive symptomatology. A cause of depressive symptoms is a disturbance in the neurotransmitter system of dopamine (DA). Animal as well as human studies report that PCBs can influence the DA system. This study examined whether PCB-related depressive symptoms are affected by DA metabolites in humans with high PCB body burden. METHODS: This study is part of the German HELPcB surveillance program (Health Effects in high Level exposure to PCB) for occupationally exposed workers and their relatives. Data was collected from 178 participants on two measurement time points (t1 and t2) with a one-year time lag in between the two time points. PCBs were analyzed in plasma via human biomonitoring and a validated questionnaire was used to identify existence and severity of depressive symptoms. As a surrogate for DA, we measured its metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) in urine. Mediation analyses were performed to test whether the association between PCB exposure and severity of depressive symptoms is mediated by urinary concentration of DA metabolites HVA and VMA. The mediation was tested with the SPSS macro MEDIATE. RESULTS: We found a significant mediation over time for lower-chlorinated, higher-chlorinated and dioxin-like PCBs. The positive association between PCB exposure with severity of depressive symptoms was mediated by the main DA metabolite HVA. At t1 a higher exposure with PCBs was associated with lower concentration in urinary HVA. A reduced HVA concentration at t1 was correlated with increased depressive symptoms severity at t2. No meditations were found for VMA. CONCLUSIONS: This work indicates that the association of PCB exposure and an increase of depressive symptoms after one year is mediated by the DA metabolite HVA as a surrogate for DA. These are first steps towards finding an explanation for an underlying neurochemical pathomechanism of PCB-related depressive symptomatology.

Intestinal Epithelial Toll-Like Receptor 4 Signaling Affects Epithelial Function and Colonic Microbiota and Promotes a Risk for Transmissible Colitis.

Evidence obtained from gene knockout studies supports the role of Toll-like receptor 4 (TLR4) in intestinal inflammation and microbiota recognition. Increased epithelial TLR4 expression is observed in patients with inflammatory bowel disease. However, little is known of the effect of increased TLR4 signaling on intestinal homeostasis. Here, we examined the effect of increased TLR4 signaling on epithelial function and microbiota by using transgenic villin-TLR4 mice that overexpress TLR4 in the intestinal epithelium. Our results revealed that villin-TLR4 mice are characterized by increases in the density of mucosa-associated bacteria and bacterial translocation. Furthermore, increased epithelial TLR4 signaling was associated with an impaired epithelial barrier, altered expression of antimicrobial peptide genes, and altered epithelial cell differentiation. The composition of the colonic luminal and mucosa-associated microbiota differed between villin-TLR4 and wild-type (WT) littermates. Interestingly, WT mice cohoused with villin-TLR4 mice displayed greater susceptibility to acute colitis than singly housed WT mice did. The results of this study suggest that epithelial TLR4 expression shapes the microbiota and affects the functional properties of the epithelium. The changes in the microbiota induced by increased epithelial TLR4 signaling are transmissible and exacerbate dextran sodium sulfate-induced colitis. Together, our findings imply that host innate immune signaling can modulate intestinal bacteria and ultimately the host's susceptibility to colitis.

Exposure to polychlorinated biphenyls and the thyroid gland - examining and discussing possible longitudinal health effects in humans.

BACKGROUND: Many previous studies have dealt with the effect of polychlorinated biphenyls (PCBs) on the thyroid gland, but their findings are inconsistent. One problem of these studies has been their use of cross-sectional designs. OBJECTIVES: The aim of the current study is to investigate longitudinal effects of PCBs on the thyroid gland, focusing on: morphological changes in thyroid tissue (i.e. thyroid volume), changes in thyroid hormones and in thyroid antibodies. METHODS: A total of 122 individuals (Mage=44.7) were examined over a period of four years (t(1) until t(4)). Medical history was collected via interviews, an ultrasound examination was performed and blood samples were taken to determine plasma PCB levels, thyroid stimulating hormone (TSH), free triiodthyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOab), thyreoglobulin antibodies (TGab) and thyroid-stimulating hormone receptor antibodies (TSHRab). Rank correlation coefficients and mixed effect models were performed controlling for age and total lipids. RESULTS: There were negative correlations between higher chlorinated biphenyls and fT3, cross-sectionally as well as longitudinally. We also found an interaction effect of higher-chlorinated PCBs over time for fT4 as well as TSHRab. In case of high exposure, a decrease in fT4 and an increase in TSHRab level were found over time. In regards to the other variables, our findings yielded no clear results in the examined time period. CONCLUSION: This is the first study to shows a PCB-related effect on fT3, fT4 and TSHRab over a four year period. The data also suggest that morphological and antibody findings remain inconsistent and do not allow for unambiguous interpretation.

Occupational exposure to polychlorinated biphenyls: Development of neuropsychological functions over time.

Occupational exposure to polychlorinated biphenyls (PCBs) continues to affect the health of exposed individuals until today. This study aims to expand previous findings by examining the development of neuropsychological functions of occupationally exposed participants over time. Especially verbal fluency and sensorimotor processing, found to be impaired in a previous study, were thus of particular interest. A total of 116 participants, who were part of the HELPcB cohort, underwent a neuropsychological test battery covering a multitude of cognitive functions. Plasma PCB levels were determined for each participant and classified as elevated or normal based on comparative values drawn from the German general population. Two structural equation models were then used to examine the effects of elevated PCB levels on neuropsychological functions. Results suggest that participants who displayed increased PCB plasma levels continued to show impairments in verbal fluency but not in sensorimotor processing after a second examination one year after the first measurement. Specifically, low chlorinated PCBs are associated with impaired verbal fluency, as compared to high-chlorinated and dioxin-like congeners. Alteration of dopamine concentration in response to PCB exposure might be a potential explanation of this result.

Patients' and Caregivers' Preferences for Mental Health Care and Support in Atopic Dermatitis.

Background: Atopic dermatitis (AD) has large mental health impacts for patients and caregivers, yet their preferences regarding how to relieve these impacts are poorly understood. Objective: To understand patients' and caregivers' preferences for AD-related mental health care and support. Methods: We surveyed 279 adult AD patients and 154 caregivers of children with AD across 26 countries regarding their AD-related mental health burden, preferred strategies for improving AD-related mental health, and experiences with mental health care in AD. Results: Caregivers reported significantly worse overall mental health (P = 0.01) and anxiety (P = 0.03) than adult patients when controlling for AD severity. Among adult patients, 58% selected treating the AD, 51% managing itch, 44% wearing clothing to cover up skin, 43% avoiding social situations, and 41% spending time alone, as strategies they felt would improve their own AD-related mental health. Caregivers selected managing itch and treating the AD most frequently for both their own (76% and 75%, respectively) and their children's (75% and 61%) mental health. Adult patients were less satisfied with mental health care from mental health providers versus nonmental health providers (P < 0.001). Conclusions: Effective AD management is the preferred method for improving mental health among patients as well as caregivers, who may experience the greatest mental health impacts. Self-care strategies should be considered in a shared decision-making approach.

The incremental effect of psychosocial workplace factors on the development of neck and shoulder disorders: a systematic review of longitudinal studies.

BACKGROUND: To systematically analyse evidence on the incremental effect of work-related psychosocial risk factors on the development of neck and shoulder disorders, as reported in longitudinal studies. METHODS: A systematic literature search was conducted in three data bases (MEDLINE, EMBASE, and PsychINFO) until May 2009. The quality assessment leading to a methodological quality score of the included studies was conducted by two independent reviewers using a standardised checklist. Criteria for the evaluation of evidence were established. Heterogeneity analyses were conducted. RESULTS: Altogether 18 prospective longitudinal studies were included in the analysis. Potential psychosocial risk factors were mainly based on the job demand control (support) model by Karasek (1998). Study results were too heterogeneous to deduce pooled risk estimates. But the weight of evidence was strong for an incremental effect of job demands, job control, social support, and job strain, on the development of neck and/or shoulder disorders. CONCLUSION: While we found evidence for an incremental effect of different psychosocial work factors (in addition to the effect of physical job factors), these results have to be interpreted carefully in order to support the notion that psychological factors can have an independent causal influence on the development of musculoskeletal disorders. Nevertheless, our findings are important for the development of preventive strategies, as they stress the need for preventive approaches that tackle both physical and psychosocial factors. Future research is warranted to consolidate and strengthen the results of this review.

The provision of weight management advice: an investigation into occupational therapy practice.

BACKGROUND/AIM: Obesity affects more than half the Australian population and has become epidemic throughout the world. Little is known regarding occupational therapy interventions with clients who are overweight or obese. This study aimed to identify occupational therapy practice in relation to the provision of weight management. This was part of a larger study investigating health professional practice. METHODS: A cross-sectional study design using a self-administered, purpose-designed survey was employed to identify the current practices of occupational therapists working in a regional area of New South Wales, Australia. Participants were recruited via email or mail as publically available. RESULTS: Fifty-one occupational therapists anonymously completed the survey. Results revealed that 53% (n = 26) of respondents did not consider weight management to be within their scope of practice or their workplace role description. The most common intervention was the provision of physical activity advice (65.2%; n = 30). Dietary advice was provided by 20.8% (n = 10), while 77% (n = 32) referred onto dietitian services. During entry-level occupational therapy education, only 7.8% (n = 4) had received weight management advice education. Completion of postgraduate professional development training in this area was reported by 14% (n = 7) of respondents. CONCLUSION: This study provides insight into the current practices of Australian occupational therapists in relation to the provision of weight management advice. This research displays a need to acknowledge both a generic and a discipline-specific role for the provision of healthy lifestyle interventions. This may be achieved through better access to education during entry-level programmes and in the workplace.

Antecedents, outcomes and measurement of work related-cognition in non-work time: A multistudy report using the work-related rumination questionnaire in two languages.

According to the perseverative cognition hypothesis, prolonged activation for example, via work-related rumination impairs recovery and thereby poses a risk to employee health. The extent to which gender, age, occupation or longitudinal stress exposure may alter work-related rumination is an ongoing debate. Whether group or longitudinal comparisons of work-related rumination are valid, however, has never been tested. In this multistudy report, we therefore investigated measurement invariance of the widely used Work-Related Rumination Questionnaire (WRRQ) across gender, age, occupation, and longitudinal measurements by performing secondary analyses of preexisting data on work-related rumination. We examined the psychometric properties of WRRQ measurements in two languages and expand knowledge about the nomological network of affective rumination, problem-solving pondering and detachment in relation to individual employee characteristics (e.g., personality, work engagement, commitment), job stressors (e.g., work intensity, decision latitude, social relations with colleagues and supervisors) and employee health outcomes (e.g., wellbeing, irritation, somatic symptoms). Multigroup confirmatory factor analyses showed partial scalar invariance of English and German WRRQ measurements and full scalar invariance across gender, age, occupation and over the period of 1 week (Study 1, n = 2,207). Correlation analyses supported criterion, convergent and discriminant validity of WRRQ measurements (Study 2, n = 4,002). These findings represent a prerequisite for comparisons of work-related cognition across groups and further the understanding of the antecedents and outcomes of different types of work-related cognition.