Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index.

Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.

Less disease severity of COVID-19 among smokers: An indication of investigating nicotine as preventive measure.

The study was aimed to mention the epidemiology of smoking in Pakistani COVID-19 infected patients along with the disease severity, oxygen dependency and fatality rate. A cross sectional epidemiological study was carried out on 555 confirmed cases of COVID-19 infection. The median age was 47±16 years. 59% were male and 41% were female. Most of the patients (97.5%) survived, while only 2.5% expired. 25.6% patients required the oxygen. Total 17 (3%) COVID-19 patients with age 20-75 years were identified as smokers. No mortality was observed in smokers. The 1.4% smokers presented with mild disease, 1.2% with moderate disease and 0.4% had severe disease. According to Chi-Square test, there existed an insignificant difference (p-value: 0.38649) between smokers and non-smokers in disease severity levels. Smoking is a precursor for countless diseases, but it behaved differently in COVID-19 infected patients, as its prevalence was significantly low. We found no significant variation of the disease severity among the smokers and non-smokers. Profound experiments should be conducted to recommend whether nicotine can be used as a protective agent to negate COVID-19 infection.

Daptomycin-Induced Eosinophilic Pneumonia: Can an Antibiotic Cause Pneumonia?

We present an interesting case of a patient who was discharged from the hospital on daptomycin and ertapenem in the setting of osteomyelitis. The patient did not have any respiratory symptoms during that hospital stay. A few weeks after discharge, the patient came back to the hospital with complaints of fever and shortness of breath. Chest X-ray showed pulmonary infiltrates. Initially, the patient was treated for acute respiratory distress syndrome (ARDS) vs pneumonia, but she did not improve. When labs showed significant eosinophilia, daptomycin-induced eosinophilic pneumonia became the working diagnosis, and the patient improved significantly when daptomycin was discontinued and steroids were started.