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OBJECTIVES To describe the current constraints, facilitators, and future prospects for addressing mental health and substance use (MHSU) concerns within sexual health clinics in two cities in British Columbia, Canada. METHODS We conducted in-depth interviews with 22 providers (14 nurses, 3 physicians, 3 administrators, 2 other health professionals) from six sexual health clinics. RESULTS Providers consistently affirmed that MHSU-related concerns co-occur with sexual health concerns among clients presenting to sexual health clinics. Three factors constrained the providers’ abilities to effectively address MHSU service needs (1) clinic mandates or funding models (specific to sexually transmitted infections (STI)/HIV or reproductive health); (2) “siloing” (i.e., physical and administrative separation) of services; and (3) limited familiarity with MHSU service referral pathways. Mental health stigma was an additional provider-perceived barrier for sexual health clinic clients. The low barrier, “safe” nature of sexual health clinics, however, facilitated the ability of clients to open up about MHSU concerns, while the acquired experiences of sexual health nurses in counselling enabled clinicians to address clients’ MHSU needs. In response to this context, participants described actionable solutions, specifically co-location of sexual health and MHSU services. CONCLUSION Sexual health clinicians in British Columbia generally affirm the results of previous quantitative and client-focused research showing high rates of MHSU-related needs among sexual health clinic clients. Providers prioritized specific short-term (referral-focused) and long-term (healthcare re-organization, co-location of sexual and MHSU services) solutions for improving access to MHSU services for those using sexual health services.INTRODUCTION The effects of resistance exercise on vascular function are unclear. AIM To investigate the acute haemodynamic (blood pressure and augmentation index) and rate of perceived exertion (RPE) response to two types of resistance exercises of equal workload-a set of unilateral 35% of one repetition maximum (1RM) quadriceps extension and a set of unilateral 70% 1RM quadriceps extension. METHODS Twenty two young healthy males completed both exercises on separate days. Heart rate, central and peripheral systolic and diastolic blood pressure (BP), augmentation pressure, augmentation index (AIx), augmentation index at a heart rate of 75 beats per minute (AIx75), and RPE were measured using applanation tonometry before exercise, immediately after exercise, 5 min after exercise and 15 min after exercise. RESULTS AIx75 was significantly lower 5 min after exercising at 35% of 1RM than 70% of 1RM. Systolic blood pressure was significantly lower at 5 min post exercise for both intensities. There was no significant difference in RPE between conditions or time points. CONCLUSIONS Results suggest that changes in blood pressure and augmentation index vary depending on the intensity of resistance exercise regardless of the volume of exercise carried out. Changes in AIx75 in response to resistance exercise may be independent of changes in BP.PURPOSE FAM83D has been proposed to act as an oncoprotein in several types of human cancer. Its role and mode of action in human non-small cell lung cancer (NSCLC) metastasis and its impact on chemotherapy are as yet, however, poorly understood. METHODS FAM83D expression was measured in NSCLC cells and normal lung epithelial cells, as well as in primary NSCLC tissues and corresponding adjacent non-cancerous tissues, using qRT-PCR, Western blotting and immunohistochemistry. FAM83D was stably overexpressed in BEAS2B cells or silenced in A549 and H1299 cells using retroviral or lentiviral vectors. The growth capacity of NSCLC cells was evaluated using MTT and colony formation assays. Epithelial-mesenchymal transition (EMT) was assessed using Western blotting and immunofluorescence. NSCLC cell invasive capacities were assessed using scratch wound healing and Boyden chamber assays. NSCLC cell viability in response to cisplatin treatment was assessed using MTT assays in vitro and a xenograft model in vivo. RESULTS We found that FAM83D expression levels were significantly elevated in NSCLC cells and tissues, and positively correlated with tumor progression and a poor prognosis. Exogenous FAM83D overexpression promoted, while FAM83D silencing inhibited NSCLC cell proliferation, EMT and invasion. FAM83D silencing also reduced cisplatin resistance. Concordantly, we found that NSCLC patients with a low FAM83D expression benefited most from chemotherapy. Mechanistically, we found that FAM83D activated the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Pharmacological treatment with either AKT or mTOR inhibitors reverted FAM83D-induced tumorigenic phenotypes. CONCLUSIONS Our results suggest a role of FAM83D in NSCLC development. In addition, our results indicate that NSCLC patients exhibiting FAM83D overexpression are likely to benefit from AKT and/or mTOR inhibitor treatment.Differential scanning fluorimetry (DSF) is an accessible, rapid, and economical biophysical technique that has seen many applications over the years, ranging from protein folding state detection to the identification of ligands that bind to the target protein. In this review, we discuss the theory, applications, and limitations of DSF, including the latest applications of DSF by ourselves and other researchers. We show that DSF is a powerful high-throughput tool in early drug discovery efforts. NCB-0846 molecular weight We place DSF in the context of other biophysical methods frequently used in drug discovery and highlight their benefits and downsides. We illustrate the uses of DSF in protein buffer optimization for stability, refolding, and crystallization purposes and provide several examples of each. We also show the use of DSF in a more downstream application, where it is used as an in vivo validation tool of ligand-target interaction in cell assays. Although DSF is a potent tool in buffer optimization and large chemical library screens when it comes to ligand-binding validation and optimization, orthogonal techniques are recommended as DSF is prone to false positives and negatives.