Occupational stress and common mental disorders: how do coping strategies work?

Introduction: Coping strategies are described as devices capable of minimizing the effects of occupational stress on workers' mental health. Objectives: To evaluate the association between occupational stressors and occurrence of common mental disorders and how coping strategies work in this relationship. Methods: This is a cross-sectional study with 3,343 healthcare workers from six municipalities in the state of Bahia, Brazil. Common mental disorders were measured by the Self-Reporting Questionnaire, and occupational stressors by the Job Content Questionnaire. Coping strategies included physical activity, leisure activities, social support at work, alcohol consumption, and smoking. Bivariate and multivariate analyses were performed, stratified by sex. Results: Occupational stressors were associated with common mental disorders, more strongly among women. The practice of physical activity contributed to reduce the prevalence of common mental disorders, regardless of occupational stressors. Leisure activities were associated with lower prevalence of common mental disorders, but without statistical significance, losing relevance in the presence of occupational stressors. Social support and smoking or drinking habits were not associated with common mental disorders and did not influence the relationship with occupational stressors. Conclusions: Occupational stressors are associated with common mental disorders, with emphasis on high demand, even after adjusted for coping strategies. The relationship between occupational stressors and mental is corroborated, with greater female vulnerability, as well as the role of positive coping strategies in protecting mental health. The pertinence of adopting measures that reduce stress at work, promote the adoption of positive coping strategies, and consider gender inequalities in these relationships.

Tethered Cord Syndrome After Myelomeningocele Repair: A Literature Update.

Tethered cord syndrome (TCS) after myelomeningocele (MMC) repair (or secondary TCS) is a challenging condition characterized by neurological, orthopedic, and urological symptoms, which are combined with a low-lying position of the conus medullaris and damage to the stretched spinal cord owing to metabolic and vascular derangements. It has been reported that this syndrome affects, on average, 30% of children with MMC. In this review, we revisit the historical aspects of secondary TCS and highlight the most important concepts of diagnosis, treatment, and outcomes for secondary TCS as well as the current research regarding the impact of fetal MMC repair in the incidence and management of TCS. In the future, the development of synthetic models of TCS could shorten the learning curve of pediatric neurosurgeons, and research into the cellular proapoptotic features and increased inflammation biomarkers associated with TCS will also improve the treatment of this condition and minimize retethering of the spinal cord.

Linagliptin safety profile: A systematic review.

OBJECTIVE: To describe the safety profile of linagliptin. METHODOLOGY: Systematic review using PubMed/MEDLINE, BVS and Web of Science. The search strategy "Linagliptin" AND "safety" was used. The inclusion criteria were clinical trials with a control group composed of conventional DM2 pharmacotherapy. RESULTS: We identified 16 studies, and the most frequent adverse events (AEs) were nasopharyngitis with linagliptin at 5 and 10mg in monotherapy (31.6% and 29.6%, respectively) and gastrointestinal events (>10.0%) with linagliptin in combination. Of the AEs, 14.9 (±3.1)% were associated with the use of linagliptin in monotherapy, and 17.6 (±6.0)% in combination. The linagliptin AEs have a varied occurrence and frequency, ranging from mild to moderate intensity.

The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.

Opportunities for translation: targeting DNA repair pathways in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the poorest prognosis neoplasms. It is typified by high levels of genomic aberrations and copy-number variation, intra-tumoural heterogeneity and resistance to conventional chemotherapy. Improved therapeutic options, ideally targeted against cancer-specific biological mechanisms, are urgently needed. Although induction of DNA damage and/or modulation of DNA damage response pathways are associated with the activity of a number of conventional PDAC chemotherapies, the effectiveness of this approach in the treatment of PDAC has not been comprehensively reviewed. Here, we review chemotherapeutic agents that have shown anti-cancer activity in PDAC and whose mechanisms of action involve modulation of DNA repair pathways. In addition, we highlight novel potential targets within these pathways based on the emerging understanding of PDAC biology and their exploitation as targets in other cancers.

The OPCML tumor suppressor functions as a cell surface repressor-adaptor, negatively regulating receptor tyrosine kinases in epithelial ovarian cancer.

UNLABELLED: Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy, and its molecular basis is poorly understood. We previously demonstrated that opioid binding protein cell adhesion molecule (OPCML) was frequently epigenetically inactivated in epithelial ovarian cancers, with tumor suppressor function in vitro and in vivo. Here, we further show the clinical relevance of OPCML and demonstrate that OPCML functions by a novel mechanism in epithelial ovarian cancer cell lines and normal ovarian surface epithelial cells by regulating a specific repertoire of receptor tyrosine kinases: EPHA2, FGFR1, FGFR3, HER2, and HER4. OPCML negatively regulates receptor tyrosine kinases by binding their extracellular domains, altering trafficking via nonclathrin-dependent endocytosis, and promoting their degradation via a polyubiquitination-associated proteasomal mechanism leading to signaling and growth inhibition. Exogenous recombinant OPCML domain 1-3 protein inhibited the cell growth of epithelial ovarian cancers cell in vitro and in vivo in 2 murine ovarian cancer intraperitoneal models that used an identical mechanism. These findings demonstrate a novel mechanism of OPCML-mediated tumor suppression and provide a proof-of-concept for recombinant OPCML protein therapy in epithelial ovarian cancers. SIGNIFICANCE: The OPCML tumor suppressor negatively regulates a specific spectrum of receptor tyrosine kinases in ovarian cancer cells by binding to their extracellular domain and altering trafficking to a nonclathrin, caveolin-1­associated endosomal pathway that results in receptor tyrosine kinase polyubiquitination and proteasomal degradation. Recombinant OPCML domain 1-3 recapitulates this mechanism and may allow for the implementation of an extracellular tumor-suppressor replacement strategy.