BackgroundOne of the potential strategies to improve health care delivery in understaffed low- and middle-income countries (LMICs) is task sharing, where specific tasks are transferred from more qualified health care cadre to a lesser trained cadre. Dyslipidemia is a major risk factor for cardiovascular disease but often it is not managed appropriately.ObjectiveWe conducted a systematic review with the objective to identify and evaluate the effect of task sharing interventions on dyslipidemia in LMICs.MethodsPublished studies (randomized controlled trials and observational studies) were identified via electronic databases such as PubMed, Embase, Cochrane Library, PsycINFO, and CINAHL. We searched the databases from inception to September 2016 and updated till 30 June 2017, using search terms related to task shifting, and cardiovascular disease prevention in LMICs. All eligible studies were summarized narratively, and potential studies were grouped for meta-analysis.ResultsAlthough our search yielded 2938 records initially and another 1628 in the updated search, only 15 studies met the eligibility criteria. Most of the studies targeted lifestyle modification and care coordination by involving nurses or allied health workers. Eight randomized controlled trials were included in the meta-analysis. Task sharing intervention were effective in lowering low-density lipoprotein cholesterol (−6.90 mg/dL; 95% CI −11.81 to −1.99) and total cholesterol (−9.44 mg/dL; 95% CI −17.94 to −0.93) levels with modest effect size. However, there were no major differences in high-density lipoprotein cholesterol (−0.29 mg/dL; 95% CI −0.88 to 1.47) and triglycerides (−14.31 mg/dL; 95% CI −33.32 to 4.69). The overall quality of evidence based on Grading of Recommendations Assessment, Development and Evaluation was either “low” or “very low”.ConclusionAvailable data are not adequate to make recommendations on the role of task sharing strategies for the management of dyslipidemia in LMICs. However, the studies conducted in LMICs demonstrate the potential use of this strategy especially in terms of reduction in low-density lipoprotein cholesterol and total cholesterol levels. Our review calls for the need of well-designed and large-scale studies to demonstrate the effect of task-sharing strategy on lipid management in LMICs.

Advanced malignant stages of pancreatic cancer have poor prognosis and very few treatment strategies are available. Pancreatic cancer is known to possess unique growth-related receptors that when activated, stimulate tumour proliferation. Gastrin and its related peptide cholecystokinin (CCK) are also significantly involved in the growth of this cancer type as well as other malignancies through activation of the cholecystokinin-B receptor (CCK-BR). New treatment strategies with CCK-BR antagonists are being suggested that suppress the growth promoting effects of gastrin. In this paper, we report the development of two series of quinazolinone derivatives incorporating hydrazinecarbothioamide (compounds ) and the hydrazino group (compounds) as linkers for developing CCK-BR antagonists. The affinities of the compounds were determined using docking into the CCK-BR homology modeled structure. The compounds were tested for CCK-BR binding and gastric acid secretion in an isolated lumen-perfused mouse stomach assay. The compounds exhibited CCK-BR binding activity (IC) in the range of 0.2-975 nM and showed good gastric acid secretion inhibitory activity. Molecular modeling of the compounds was done and pharmacophore mapping results showed good prediction of activity which correlated well with the experimental antagonistic activity. The compounds were further tested for their cytotoxicity on CCK-BR expressing pancreatic cancer cells. The results of the study provided two potent CCK-BR antagonists which also possess good to moderate growth inhibitory activities against pancreatic cancer cells.

Fluorescent labeling has enabled a better understanding of the relationships between receptor location, function, and life cycle. Each of these perspectives contributes new insights into drug action, particularly for G protein-coupled receptors (GPCRs). The aim of this study was to develop a fluorescein derivative, FLUO-QUIN-a novel antagonist of the cholecystokinin-B/gastrin receptor. A radioligand-binding experiment revealed an IC(50) of 4.79 nm, and the antagonist inhibited gastric acid secretion in an isolated lumen-perfused mouse stomach assay (up to 51 % at 100 nm). The fluorescence properties altered upon binding to the receptor, and the fluorophore was quenched to a greater extent when free than in the bound form. FLUO-QUIN specifically bound to human pancreatic carcinoma cells, MiaPaca-2, which are known to express the receptor, as evidenced by rapid clustering followed by time-dependent receptor internalization. This proves the stability of FLUO-QUIN and its ability to penetrate vesicular membranes and reach various cell targets. Hence it might be used as an agent for the detection of CCK-B-receptor-positive tumors by fluorescence imaging.