👤 Payal Kohli

An increasing number of university students report feeling lonely, a negative experience arising from a mismatch between perceived and actual social relationships. Loneliness has been linked to poorer mental health. However, the relationship between qualitative (sources of loneliness) and quantitative (high or low) differences in loneliness and mental health is under researched. The aims of this research were to (a) identify profiles of loneliness among university students across three indicators of loneliness, namely, social, family, and romantic indicators, using latent profile analysis (LPA); (b) examine the differences among identified profiles based on dimensions of mental health indicators (depression, anxiety, and stress), social support, and life satisfaction; and (c) assess profile membership based on demographic variables (gender, social isolation, relationship status, and education characteristics) and the Big Five personality traits (extraversion, agreeableness, openness, conscientiousness, and neuroticism). A cross-sectional survey was conducted on 912 university students from five cities in Uttar Pradesh, India. Participants completed questionnaires covering demographic details and validated measures assessing loneliness, depression, stress, anxiety, social support, life satisfaction, and the Big Five personality traits. Data were analyzed using the latent profile module in Jamovi and fit indices, namely, BIC, AIC, and BLRT, and entropy was used to select the best profile. The latent profile analysis identified four profiles for university student loneliness, including Social and emotional lonely (31.4%), Moderate romantic lonely (23.8%), Moderate social lonely (8.2%), and Severe romantic lonely (36.6%). Moreover, the Social and emotional lonely profile scored the highest on depression, anxiety, and stress. The Moderate romantic lonely profile scored the highest on life satisfaction and social support. Being in a relationship decreased the likelihood of being categorized as Severe romantic lonely. In terms of personality, neuroticism was the strongest predictor of profile membership. This study is a step towards identifying at-risk lonely individuals with varying sources of loneliness. Identifying different profiles of lonely individuals will have direct implications for designing interventions that cater to a particular group rather than a one-size-fits-all approach. Show less

Cumulative exposure to low-density lipoprotein cholesterol (LDL-C) is a key driver of atherosclerotic cardiovascular disease (ASCVD) risk. An armamentarium of therapies to achieve robust and sustained reduction in LDL-C can reduce ASCVD risk. The gold standard for LDL-C assessment is ultracentrifugation but in routine clinical practice LDL-C is usually calculated and the most accurate calculation is the Martin/Hopkins equation. For primary prevention, consideration of estimated ASCVD risk frames decision making regarding use of statins and other therapies, and tools such as risk enhancing factors and coronary artery calcium enable tailoring of risk assessment and decision making. In patients with diabetes, lipid lowering therapy is recommended in most patients to reduce ASCVD risk with an opportunity to tailor therapy based on other risk factors. Patients with primary hypercholesterolemia and familial hypercholesterolemia (FH) with baseline LDL-C greater than or equal to 190 mg/dL are at elevated risk, and LDL-C lowering with high-intensity statin therapy is often combined with non-statin therapies to prevent ASCVD. Secondary prevention of ASCVD, including in patients with prior myocardial infarction or stroke, requires intensive lipid lowering therapy and lifestyle modification approaches. There is no established LDL-C level below which benefit ceases or safety concerns arise. When further LDL-C lowering is required beyond lifestyle modifications and statin therapy, additional medications include oral ezetimibe and bempedoic acid, or injectables such as PCSK9 monoclonal antibodies or siRNA therapy. A novel agent that acts independently of hepatic LDL receptors is evinacumab, which is approved for patients with homozygous FH. Other emerging agents are targeted at Lp(a) and CETP. In light of the expanding lipid treatment landscape, this manuscript reviews the importance of early, intensive, and sustained LDL-C-lowering for primary and secondary prevention of ASCVD. Show less

Melanocortin-4 receptor (MC4R) has been investigated as a potential drug target for the treatment of neuropathic pain. The objective of the study was to systematically identify the effects of MC4R antagonists on hypersensitivity in rat models of neuropathic pain. A systematic search was conducted using the following databases: WoS, PubMed, SCOPUS, and MEDLINE. Inclusion criteria were: rat hypersensitivity induced by models of neuropathic pain with reported effects of MC4R antagonist. Two researchers performed the selection process and data extraction. SYRCLE risk of bias tool was used. Standard mean differences (SMD) were calculated and pooled by meta-analysis using random effect models. Ten articles met the eligibility criteria and were included in the systematic review and meta-analysis. The results reveal that, in animals exposed to neuropathic pain, administration of MC4R antagonists significantly increased paw withdrawal threshold (SHU9119 SMD = 1.67, 95% CI: [0.91, 2.44], I Show less

Functional characterization of disease-causing variants at risk loci has been a significant challenge. Here we report a high-throughput single-nucleotide polymorphisms sequencing (SNPs-seq) technology to simultaneously screen hundreds to thousands of SNPs for their allele-dependent protein-binding differences. This technology takes advantage of higher retention rate of protein-bound DNA oligos in protein purification column to quantitatively sequence these SNP-containing oligos. We apply this technology to test prostate cancer-risk loci and observe differential allelic protein binding in a significant number of selected SNPs. We also test a unique application of self-transcribing active regulatory region sequencing (STARR-seq) in characterizing allele-dependent transcriptional regulation and provide detailed functional analysis at two risk loci (RGS17 and ASCL2). Together, we introduce a powerful high-throughput pipeline for large-scale screening of functional SNPs at disease risk loci. Show less