Objective Impaired expansion of peripheral fat contributes to the pathogenesis of insulin resistance and Type 2 Diabetes (T2D). We aimed to identify novel disease–gene interactions during adipocyte differentiation. Methods Genes in disease-associated loci for T2D, adiposity and insulin resistance were ranked according to expression in human adipocytes. The top 125 genes were ablated in human pre-adipocytes via CRISPR/CAS9 and the resulting cellular phenotypes quantified during adipocyte differentiation with high-content microscopy and automated image analysis. Morphometric measurements were extracted from all images and used to construct morphologic profiles for each gene. Results Over 10 7 morphometric measurements were obtained. Clustering of the morphologic profiles accross all genes revealed a group of 14 genes characterized by decreased lipid accumulation, and enriched for known lipodystrophy genes. For two lipodystrophy genes, BSCL2 and AGPAT2, sub-clusters with PLIN1 and CEBPA identifed by morphological similarity were validated by independent experiments as novel protein–protein and gene regulatory interactions. Conclusions A morphometric approach in adipocytes can resolve multiple cellular mechanisms for metabolic disease loci; this approach enables mechanistic interrogation of the hundreds of metabolic disease loci whose function still remains unknown.

Metformin is the first line management for patients with Type 2 diabetes mellitus. Metformin-induced lactic acidosis (MALA) is a severe side effect of metformin in high doses. However, there have not been many reported cases of MALA. The threshold metformin concentration needed to induce lactic acidosis is still not fully understood. It is important for physicians to measure metformin levels upon admission in Type 2 diabetes patients who take metformin and present with suspected lactic acidosis. We present a case of a 40-year-old Caucasian male who presented with severe lactic acidosis shortly after overdosing on metformin.

Quality of Healthcare and corruption eradication are the two vital Sustainable Development Goals (SDGs). It states that transparent institutional performance supports the quality of public services. This study explores the HealthCare System regarding facilities, human resources, and governance in Pakistan's corruption and transparency of public services (healthcare). This descriptive and theoretical study has used longitudinal data from 2008 to 2020 for analysis and discussion. Transparency International Pakistan's (TIP) healthcare corruption variables surveyed in 2010, inadequate healthcare facilities, inadequate hospital beds, and hospital mismanagement, have been taken under consideration. The analysis shows that the HCS has been showing uneven progress toward eradicating corruption. It further states that institutional governance has deteriorated with time in Pakistan. However, despite low resources, and institutional accountability failures, HealthCare System has shown marginal improvement in Pakistan. This study concludes that the Government of Pakistan (GOP) should focus on health budget allocation and human resource training and counseling to improve HCS standards. Moreover, healthcare quality and service delivery will help Pakistan combat COVID-19 and other future health crises. Furthermore, GOP should achieve healthcare and institutional sustainability by using prudent corruption control and institutional enhancement measures.

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