A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice.

BACKGROUND: While the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice. RESULTS: We weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy. We measured liver gene expression with RNA-seq (using 21 total libraries, each pooled with 2 mice of the same sex and diet) and DNA methylation with MRE-seq and MeDIP-seq (using 8 total libraries, each pooled with 4 mice of the same sex and diet). There were 4356 genes with expression differences associated with diet, with 184 genes exhibiting a sex-by-diet interaction. Dietary fat dysregulated several pathways, including those involved in cytokine-cytokine receptor interaction, chemokine signaling, and oxidative phosphorylation. Over 7000 genes had differentially methylated regions associated with diet, which occurred in regulatory regions more often than expected by chance. Only 5-10% of differentially methylated regions occurred in differentially expressed genes, however this was more often than expected by chance (p = 2.2 × 10- 8). CONCLUSIONS: Discovering the gene expression and methylation changes associated with a high-fat diet can help to identify new targets for epigenetic therapies and inform about the physiological changes in obesity. Here, we identified numerous genes with altered expression and methylation that are promising candidates for further study.

Impact of COVID-19 on emergency oral health care in New Jersey.

BACKGROUND: The COVID-19 pandemic led to reduced services of private dental practices. The public emergency clinic of Rutgers School of Dental Medicine (RSDM) (Newark, NJ) faced changing demands during various periods of the pandemic. METHODS: Records of patients visiting the emergency clinic at RSDM during 3 distinct periods (prelockdown, lockdown, teledentistry) from January 10, 2020, through June 30, 2020, were retrospectively reviewed. Qualitative and quantitative attributes pertaining to patient encounters were reviewed and analyzed. RESULTS: A total of 1,799 records were included in this study. Patient visits increased during the early lockdown but were reduced after the implementation of teledentistry. Trends were noted in patient volume, reasons for visits, treatment needs, symptoms, diagnostic methodology, prescription use, and final disposition of patients. CONCLUSIONS: The lockdown affected emergency dental clinic services at RSDM. Teledentistry visits played a key role in screening patients and in facilitating the delivery of oral health care and timely follow-ups to patients who needed urgent in-person emergency visits. PRACTICAL IMPLICATIONS: Data gathered will lead to a better understanding of patients seen in the emergency clinic and can help with long-term planning for both institutional and smaller outpatient clinics during public health emergencies.

Study of Clinical Outcome and Healthcare Modalities of COVID-19 Patients Treated With Remdesivir at a Tertiary Care Teaching Hospital.

Background Effective treatment for COVID-19 infection is still under evaluation. Remdesivir is an approved drug for COVID-19 treatment and major countries have released guidelines on the use of remdesivir. Still, many factors are under evaluation which can determine the future use of remdesivir. Aim To study the clinical outcome and healthcare modalities of COVID-19 patients treated with remdesivir. Materials and methods A retrospective study was conducted through the clinical records of patients admitted to the tertiary care hospital between August 2020 and December 2020. All the patients who were administered remdesivir intravenously as per standard protocol were included in the study. Data were analyzed for statistical association between health care modalities and patient characteristics. Results Among 166 patients included, the mean age of patient who received remdesivir was 57.51 ± 12.98 years (95% confidence interval (CI), 30-84). The mean duration of stay and duration of oxygen requirement were 12.80 ± 5.99 (95% CI, 5-30) and 9.41 ± 7.47 (95% CI, 0-39) days, respectively. A total of 12 (7.23%) required assisted ventilation and the cure rate was 89.76% (149/166). Out of 166 patients, 105 (63.25%) had comorbidities, among which hypertension and diabetes were the most common. Significantly >60 year age group had a higher duration of oxygen requirement (u=2,639.5, p=0.01), while ≤60 year age group had a higher cure rate (X2=4.23, p=0.03) and a higher requirement for assisted ventilation (X2=4.77, p=0.02). Differences and associations in the above-mentioned health care modalities were not statistically significant for gender and comorbidity except that non-comorbid had a higher cure rate (X2=3.97, p=0.04). The odds ratio of comorbidity and cure rate was 1.07, while the association of the number of comorbidities with the duration of stay (p=0.62) and duration of oxygen requirement (p=0.35) was not statistically significant. Conclusion In remdesivir-treated patients, age affects utilization of health care modalities. Female, non-comorbid, and younger patients have better clinical outcomes.

The effect of dietary fat on behavior in mice.

PURPOSE: Obesity is linked to cognitive dysfunction in humans and rodents, and its effects can be passed on to the next generation. However, the extent of these effects is not well understood. The purpose of this study was to determine the effect of a prenatal maternal high-fat diet and an individual high-fat diet in inbred mice. METHODS: We varied maternal diet and offspring diet to test the hypothesis that a high-fat diet would increase anxiety, reduce activity levels, and impair nest-building. First, we fed a high-fat (HF) or low-fat (LF) diet to genetically identical female Small (SM/J) mice and mated them with LF males. We cross-fostered all offspring to LF-fed SM/J nurses and weaned them onto an HF or LF diet. We weighed the mice weekly and we tested anxiety with the Open Field Test, activity levels with instantaneous scan sampling, and nest building using the Deacon Scale. RESULTS: Diet significantly affected weight, with HF females weighing 28.2 g (± 1.4 g SE) and LF females weighing 15.1 g (± 1.6 g SE) at 17 weeks old. The offspring's own diet had major behavioral effects. HF mice produced more fecal boli and urinations in the Open Field Test, built lower-quality nests, and had lower activity in adulthood than LF mice. The only trait that a prenatal maternal diet significantly affected was whether the offspring built their nests inside or outside of a hut. CONCLUSIONS: Offspring diet, but not prenatal maternal diet, affected a wide range of behaviors in these mice.

Maternal high-fat diet associated with altered gene expression, DNA methylation, and obesity risk in mouse offspring.

We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts. Maternal diet particularly affected genes involved in RNA processing, immune response, and mitochondria. Between one-quarter and one-third of differentially expressed genes contained a differentially methylated region associated with maternal diet. An offspring high-fat diet reduced overall variation in DNA methylation, increased body weight and organ weights, increased long bone lengths and weights, decreased insulin sensitivity, and changed the expression of 3,908 genes in the liver. Although the offspring were more affected by their own diet, their maternal diet had epigenetic effects lasting through adulthood, and in the daughters these effects were accompanied by phenotypic changes relevant to obesity and diabetes.

Prescription drug monitoring programs and other interventions to combat prescription opioid abuse.

The Center for Disease Control and Prevention (CDC) has published significant data and trends related to opioid prescription pain relievers (OPR). In 2008, 20,044 deaths were attributed to prescription drug overdose of which 14,800 (73.8%) were due to OPR, an amount greater than the number of overdose deaths from heroin and cocaine combined. The majority of these deaths were unintentional. Between 1999-2008, overdose deaths from OPR increased almost four-fold. Correspondingly, sales of OPR were four times greater in 2010 than in 1999. Most significant to emergency physicians is the estimate that 39% of all opioids prescribed, administered or continued come from the emergency department (ED). We present findings from the CDC's Morbidity and Mortality Weekly Report (MMWR) with commentary on current recommendations and policies for curtailing the OPR epidemic.1.