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Plain English Summary The main aim of this study was to explore doctors' experiences and perceptions of providing sexual and reproductive health care services at Catholic hospitals in a conflict affected area in Cameroon. In Cameroon, sexual, and reproductive health services are lacking, thereby contributing to a very high maternal mortality rate of about 456/100000 live births, far from the Sustainable Development Goal Agenda 2030. The Catholic Church remains one of the largest suppliers of health care services in Cameroon and receives huge funding from donors, but their role in providing sexual and reproductive health care is restricted by religious norms. This study therefore uses in-depth interviews with doctors from Catholic hospitals in the North-West region to explore their experiences in providing sexual and reproductive health services in a conflict region. Qualitative coding was done with NVivo, and data analysed using thematic analysis. The respondents described strict rules and a broad range of challenges to providing comprehensive sexual and reproductive health care services. Nonetheless, there is evidence of doctors overcoming obstacles to providing sexual and reproductive health (SRH) care despite the religious and political climate. However, while attempting to overcome challenges, participants describe numerous examples of poor SRH care and poor health outcomes. The study highlights the importance of understanding the intersect between religion and women's health, particularly in improving access to SRH for vulnerable populations in conflict affected areas. It further provides insight into doctors' motivations for practicing medicine, and how doctors cope and make efforts to provide care and minimize harm. Background Sexual and reproductive health (SRH) care services are essential to improving the lives of women and achieving the Sustainable Development Goals. In Cameroon, the Catholic Church is one the largest non-governmental suppliers of health care, but its role in providing SRH care is restricted by religious norms. Methods This study explored doctors' experiences and perceptions of providing SRH care at Catholic hospitals in a conflict-affected area in Cameroon by using 10 in-depth interviews with doctors from three Catholic hospitals in the North-West region. Qualitative coding was done with NVivo, and data were analysed using thematic analysis. Results Three themes and seven categories were identified. The respondents described strict rules and a broad range of challenges to providing comprehensive sexual and reproductive health care services. Nonetheless, there is evidence of doctors overcoming obstacles to providing SRH care despite the religious and political climate. However, whilst attempting to overcome challenges, participants described numerous examples of poor SRH care and health outcomes. Conclusion The study highlights the importance of understanding the intersect between religion and women's health, particularly in improving access to SRH for vulnerable populations in conflict-affected areas. It further provides insight into doctors' motivations in practicing medicine and how doctors cope and make efforts to provide care and minimize harm.

Microsomal prostaglandin E synthase-1 (mPGES-1) inhibition has been suggested as an alternative to cyclooxygenase (COX) inhibition in the treatment of pain and inflammation. We characterized a selective inhibitor of mPGES-1 activity (compound III) and studied its impact on the prostanoid profile in various models of inflammation. Compound III is a benzoimidazole, which has a submicromolar IC50 in both human and rat recombinant mPGES-1. In cellular assays, it reduced PGE2 production in A549 cells, mouse macrophages and blood, causing a shunt to the prostacyclin pathway in the former two systems. Lastly, we assayed compound III in the air pouch model to verify its impact on the prostanoid profile and compare it to the profile obtained in mPGES-1 k.o. mice. As opposed to mPGES-1 genetic deletion, which attenuated PGE2 production and caused a shunt to the thromboxane pathway, mPGES-1 inhibition with compound III reduced PGE2 production and tended to decrease the levels of other prostanoids.

Microsomal prostaglandin E(2) synthase-1 (MPGES1) catalyzes the formation of prostaglandin E(2) from the endoperoxide prostaglandin H(2). MPGES1 expression is induced in inflammatory diseases, and this enzyme is regarded as a potential drug target. To aid in the drug discovery effort, a simple method for determination of inhibition mechanism and potency toward both prostaglandin H(2) and glutathione (GSH) has been developed. Using an assay with thiobarbituric acid-based detection, the inhibitory effects of six MPGES1 inhibitors were evaluated. The IC(50) values obtained at three substrate (S) concentrations ([S]K(M), [S]≈K(M), [S]K(M)) were used to estimate inhibition modality and inhibition constant values. This facilitated strategy is a useful and general screening method to evaluate the inhibitory effects of new drug compounds.

Patients with diseases characterized by chronic inflammation, caused by infection or cancer, have T cells and NK cells with impaired function. The underlying molecular mechanisms are diverse, but one of the major mediators in this immune suppression is oxidative stress caused by activated monocytes, granulocytes, or myeloid-derived suppressor cells. Reactive oxygen species can seriously hamper the efficacy of active immunotherapy and adoptive transfer of T and NK cells into patients. In this study, we have evaluated whether enhanced expression of the antioxidant enzyme catalase in human T cells can protect them against reactive oxygen species. Human CD4+ and CD8+ T cells retrovirally transduced with the catalase gene had increased intracellular expression and activity of catalase. Catalase transduction made CD4+ T cells less sensitive to H2O2-induced loss-of-function, measured by their cytokine production and ability to expand in vitro following anti-CD3 stimulation. It also enhanced the resistance to oxidative stress-induced cell death after coculture with activated granulocytes, exposure to the oxidized lipid 4-hydroxynonenal, or H2O2. Expression of catalase by CMV-specific CD8+ T cells saved cells from cell death and improved their capacity to recognize CMV peptide-loaded target cells when exposed to H2O2. These findings indicate that catalase-transduced T cells potentially are more efficacious for the immunotherapy of patients with advanced cancer or chronic viral infections.

An HbA1c threshold of ≥ 42 mmol/mol has been proposed to diagnose prediabetes. The sensitivity, specificity and positive predictive value of the proposed threshold for detection of individuals with prediabetes was examined in a study of 573 randomly selected individuals from Vara and Skövde. In addition, the utility of the FINDRISC questionnaire and of a fasting glucose test in combination with three short questions concerning BMI, heredity for type 2 diabetes and known hypertension was examined. Results from an oral glucose tolerance test were used as reference. The sensitivity of HbA1c and FINDRISC to detect individuals with IGT was 16 and 26 per cent respectively. Questions regarding BMI, heredity and hypertension together with a fasting glucose test yielded a sensitivity of 50%, but a lower specificity and positive predictive value. We conclude that HbA1c inefficiently detected individuals with impaired glucose tolerance and that oral glucose tolerance tests can still preferably be recommended.

Much new information on C-peptide physiology has appeared during the past 20 years. It has been shown that C-peptide binds specifically to cell membranes, elicits intracellular signaling via G-protein and Ca2+ -dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+, K+ -ATPase and several transcription factors of importance for anti-inflammatory, anti-oxidant and cell protective mechanisms. Studies in animal models of diabetes and early clinical trials in patients with type 1 diabetes demonstrate that C-peptide in replacement doses elicits beneficial effects on early stages of diabetes-induced functional and structural abnormalities of the peripheral nerves, the kidneys and the retina. Much remains to be learned about C-peptide's mechanism of action and long-term clinical trials in type 1 diabetes subjects will be required to determine C-peptide's clinical utility. Nevertheless, even a cautious evaluation of the available evidence presents the picture of a bioactive endogenous peptide with therapeutic potential.

Quartz crystal microbalance with dissipation (QCM-D) measurements were used to investigate the adsorption of human fibrinogen, human serum albumin, bovine hemoglobin, horse heart cytochrome c, human immunoglobulin (hIgG), and 10% fetal bovine serum on supported bilayers of egg-phosphatidylcholine (eggPC) lipids. For comparison the adsorption of fibrinogen and hIgG to eggPC bilayers was also studied with surface plasmon resonance (SPR). The supported bilayers were formed in situ by vesicle adhesion and spontaneous fusion onto a SiO(2) surface. The supported lipid bilayer is highly protein resistant: The irreversible adsorption measured with the QCM-D technique was below the detection level, while reversible protein adsorption was detected for all the proteins in the range 0.3-4% of the saturation coverage on a hydrophobic thiol monolayer on gold. The adsorbed amounts were slightly higher for the SPR measurements. Possible mechanisms for the protein resistance of eggPC bilayers are briefly discussed.

Background and Purpose In order to improve the physiotherapeutic treatment of patients with long-standing knee pain, it it important to identify osteoarthritis (OA) of the knee at an early stage. The aim of the present study was to test the value of single functional measurement variables with the focus on the lower extremities for the association to early radiographic signs of OA of the knee. The classification by Ahlback grade I (joint space narrowing) was used in a cohort of 204 individuals aged 35–54 years with long-standing knee pain. Methods The following five selected tests were employed: three tests of static and dynamic balance (Balance I–III); one test of muscle strength (one-leg-rising-test, OLR); and one test of walking ability (time for walking 300 m indoors). Odds ratios (ORs) were calculated with a 95% confidence interval. Results and Conclusions Results revealed that the selected tests of functional capacity due to rather low sensitivity (0.15–0.81), specificity (0.21–0.86) and inconclusive odds ratios (0.78–1.62) are probably of limited value as assessment tools to find radiographic knee OA in a younger population with mild OA. However, it is also possible to conclude that in middle-aged individuals with chronic knee pain, the diagnosis of radiographic OA is not related to the functional capacity as measured in the present study. Copyright © 1998 Whurr Publishers Ltd.

Microsomal prostaglandin E synthase (mPGES)-1 inhibition has been proposed as an alternative to cyclooxygenase (COX) inhibition in the treatment of pain and inflammation. This novel approach could potentially mitigate the gastro-intestinal and cardiovascular side effects seen after long-term treatment with traditional non-steroidal anti-inflammatory drugs (NSAIDs) and Coxibs respectively. Several human mPGES-1 inhibitors have been developed in the recent years. However, they were all shown to be considerably less active on rodent mPGES-1, precluding the study of mPGES-1 inhibition in rodent models of inflammation and pain. The aim of this study was to characterize the new mPGES-1 inhibitor compound II, a pyrazolone that has similar potency on rat and human recombinant mPGES-1, in experimental models of inflammation. In cell culture, compound II inhibited PGE2 production in synovial fibroblasts from patients with rheumatoid arthritis (RASF) and in rat peritoneal macrophages. In vivo, compound II was first characterized in the rat air pouch model of inflammation where treatment inhibited intra-pouch PGE2 production. Compound II was also investigated in a rat adjuvant-induced arthritis model where it attenuated both the acute and delayed inflammatory responses. In conclusion, compound II represents a valuable pharmacological tool for the study of mPGES-1 inhibition in rat models.