Investigating the leading reasons for primary health care encounters and its implications for health care in Trinidad and Tobago. A systematic review.

This systematic review aims at offering a comparative analysis of the leading reasons for encounters (RFEs) of patients presenting to primary care facilities. A systemic search was carried out using MEDLINE/PUBMED, CINAHL, Google Scholar, LILACS, and PROQUEST to identify the studies relevant to RFEs in primary health care in June 2020. Fifteen studies met the eligibility criteria which included originality, published between 2015 and 2020, listed two to five RFEs at a primary health care facility, and included patients with acute and/or chronic conditions. The mean total RFEs recorded were 6753.07 (Standard deviation = 17446.38, 95% Confidence Interval 6,753.0667 ± 8,829.088 [± 130.74%]). The most common RFE chapters recorded were Respiratory and Digestive chapters. The patients recorded fever as the most frequently reported RFE while cough was ranked as most common. The physicians reported hypertension as the most frequently reported and most common RFE. The most frequently physician and patient reported RFEs to the primary health care are hypertension and fever. Respiratory and Digestive were the most frequently reported chapters. The findings are useful for the proper implementation of services, facilities, and equipment utilized in Trinidad and Tobago primary health care.

Targeting the Wnt pathway in zebrafish as a screening method to identify novel therapeutic compounds.

Activating mutations in the Wnt signaling pathway account for the initiation of greater than 90% of all colorectal cancers and this pathway has been implicated in numerous other diseases. Therefore, identifying small molecule inhibitors of this pathway is of critical importance towards identifying clinically relevant drugs. Numerous screens have been employed to identify therapeutic reagents, but none have made it to advanced clinical trials, suggesting that traditional screening methods are ineffective at identifying clinically relevant targets. Here, we describe a novel in vivo screen to identify small molecule inhibitors of the Wnt pathway. Specifically, treatment of zebrafish embryos with LiCl inhibits GSK3 kinase function, resulting in hyperactivation of the signaling pathway and an eyeless phenotype at 1 day post fertilization. Using the small molecule XAV939, a known inhibitor of Wnt signaling, we rescued the LiCl induced eyeless phenotype, confirming efficacy of the screen. We next tested our assay with 400 known small molecule kinase inhibitors, none of which should inhibit Wnt signaling below the level of GSK3 based on their known targets. Accordingly, none of these small molecules rescued the eyeless phenotype, which demonstrates the stringency of the assay. However, several of these small molecule kinase inhibitors did generate a non-Wnt phenotype in accordance with the kinase they targeted. Therefore, combining the efficacy, sensitivity, and stringency of this preliminary screen, this model will provide an alternative to the traditional in vitro screen, generating potentially clinical relevant drugs in a rapid and cost-effective way.