Multi-level drivers of tobacco use and purchasing behaviors during COVID-19 "lockdown": A qualitative study in the United States.

BACKGROUND: The COVID-19 pandemic and associated public health prevention measures (e.g., "stay at home" orders) may impact tobacco supply and demand among consumers. This qualitative study identified multi-level drivers of shifts in inhaled tobacco product use and access patterns during the initial COVID-19 "lockdown" period in the United States. METHODS: Between April and May 2020, we conducted semi-structured telephone interviews (n = 44) with adults who use cigarettes and/or electronic nicotine delivery systems (ENDS). Transcripts were thematically analyzed using a socioecological framework. RESULTS: Nearly all participants reported changes in their product use during lockdown, though patterns varied. Increased use was most common and was predominantly driven by individual-level factors: pandemic-related anxiety, boredom, and irregular routines. Decreased use was common among social users who cited fewer interpersonal interactions and fear of sharing products. At the community level, retail access impacted cigarette and ENDS use differently. While cigarettes were universally accessible, ENDS access was more limited, driving some to purchase products online. Delayed deliveries led some ENDS users to compensate with readily-available cigarettes. CONCLUSION: To mitigate ways that the COVID-19 pandemic may exacerbate an existing public health crisis, multi-level policy strategies, such as expanded virtual cessation services and implementation and enforcement of smoke-free home rules, can better support population health during this critical period. Policies that facilitate access to lower risk products can help minimize harm among those who cannot or do not want to quit smoking.

Engulfment and cell motility protein 1 potentiates diabetic cardiomyopathy via Rac-dependent and Rac-independent ROS production.

Engulfment and cell motility protein 1 (ELMO1) is part of a guanine nucleotide exchange factor for Ras-related C3 botulinum toxin substrate (Rac), and ELMO1 polymorphisms were identified to be associated with diabetic nephropathy in genome-wide association studies. We generated a set of Akita Ins2C96Y diabetic mice having 5 graded cardiac mRNA levels of ELMO1 from 30% to 200% of normal and found that severe dilated cardiomyopathy develops in ELMO1-hypermorphic mice independent of renal function at age 16 weeks, whereas ELMO1-hypomorphic mice were completely protected. As ELMO1 expression increased, reactive oxygen species indicators, dissociation of the intercalated disc, mitochondrial fragmentation/dysfunction, cleaved caspase-3 levels, and actin polymerization increased in hearts from Akita mice. Cardiomyocyte-specific overexpression in otherwise ELMO1-hypomorphic Akita mice was sufficient to promote cardiomyopathy. Cardiac Rac1 activity was positively correlated with the ELMO1 levels, and oral administration of a pan-Rac inhibitor, EHT1864, partially mitigated cardiomyopathy of the ELMO1 hypermorphs. Disrupting Nox4, a Rac-independent NADPH oxidase, also partially mitigated it. In contrast, a pan-NADPH oxidase inhibitor, VAS3947, markedly prevented cardiomyopathy. Our data demonstrate that in diabetes mellitus ELMO1 is the "rate-limiting" factor of reactive oxygen species production via both Rac-dependent and Rac-independent NADPH oxidases, which in turn trigger cellular signaling cascades toward cardiomyopathy.

HDL deficiency due to a new insertion mutation (ApoA-INashua) and review of the literature.

A 61-year-old white man of European ancestry with significant coronary heart disease since age 42 years and marked high-density lipoprotein (HDL) deficiency (HDL cholesterol 1 mg/dL) was evaluated. His fasting low-density lipoprotein cholesterol level was 42 mg/dL, and his triglycerides were 417 mg/dL on therapy with rosuvastatin 40 mg/day, ezetimibe 10 mg/day, fenofibrate 145 mg/day, and extended-release niacin 2 g/day. Further analysis of his plasma revealed an apolipoprotein (apo) A-I level of 23.5 mg/dL (approximately 20% of normal), and the absence of small alpha-4 HDL, medium alpha-3 HDL, and very large alpha-1 HDL, with only very small pre-beta-1 HDL and large alpha-2 HDL being present. APOA-I gene sequencing revealed a novel heterozygous in-frame insertion mutation with duplication of nucleotides 1535 through 1552 inserted at position 1553, causing a new amino acid glycine at codon 157 and a duplication of amino acids alanine, arginine, alanine, histidine, and leucine at codons 158-162. This novel apoA-I mutation results in the formation of apoA-I that appears to have abnormal lipid binding properties, resulting in impaired reverse cholesterol transport, probable enhanced clearance, and premature coronary heart disease.