A Systematic Review on Participant Diversity in Clinical Trials-Have We Made Progress for the Management of Obesity and Its Metabolic Sequelae in Diet, Drug, and Surgical Trials.

OBJECTIVE: Individuals from Black and Hispanic backgrounds represent a minority of the overall US population, yet are the populations most affected by the disease of obesity and its comorbid conditions. Black and Hispanic individuals remain underrepresented among participants in obesity clinical trials, despite the mandate by the National Institutes of Health (NIH) Revitalization Act of 1993. This systematic review evaluates the racial, ethnic, and gender diversity of clinical trials focused on obesity at a national level. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of clinicaltrials.gov, PubMed, Cochrane Central, and Web of Science was undertaken to locate phase 3 and phase 4 clinical trials on the topic of obesity that met associated inclusion/exclusion criteria. Ultimately, 18 studies were included for review. RESULTS: White non-Hispanic individuals represented the majority of clinical trial participants, as did females. No study classified participants by gender identity. Reporting of race/ethnicity was not uniform, with noted variability among racial/ethnic subgroups. CONCLUSIONS: Our findings suggest that disparities remain in the diverse racial, ethnic, and gender representation of participants engaged in clinical trials on obesity relative to the prevalence of obesity in underrepresented populations. Commitment to inclusive and intentional recruiting practices is needed to increase the representation of underrepresented groups, thus increasing the generalizability of future research.

Mammalian meat allergy emerges after tick bite: the alpha-gal syndrome.

Alpha-gal syndrome (AGS) is a hypersensitivity reaction to mammalian meat that develops after tick bite exposure. AGS was first described in 2009 and testing for the allergy has become available in the last decade. We report the case of a 56-year-old farmer with a history of frequent lone star tick bites who presented with a 7-year history of diffuse urticaria occurring hours after eating red meat. AGS is likely underdiagnosed because of the unusual presentation of the allergy, historic lack of available testing, and deficiency of physician knowledge about the condition. Recognition of AGS is important both to help alleviate symptom burden and to avoid iatrogenesis. Patients with AGS should not receive products containing mammalian products, such as cat-gut suture, porcine-derived heart valves, and bovine-derived vaccines. Patients with AGS may present in a variety of clinical environments and physicians of all kinds should be able to recognise the symptoms.

Relationships Between Short-Term Exposure to an Indoor Environment and Dry Eye (DE) Symptoms.

Air composition influences Dry Eye (DE) symptoms as demonstrated by studies that have linked the outdoor environment to DE. However, there is insufficient data on the effect of short-term exposure to indoor environments on DE symptoms. We conducted a prospective experimental research, in which an older building served as an experimental site, and a newer building served as the control site. Indoor air quality was monitored in both buildings. One-hundred-and-ninety-four randomly selected individuals were interviewed in the afternoon exiting the buildings and de-identified responses were recorded. Self-reported DE symptoms were modeled with respect to experimental and control buildings, adjusting for potential confounders. The experimental site had 2-fold higher concentration of airborne particulate matter (24,436 vs. 12,213 ≥ 0.5 µm/ft3) and microbial colonies (1066 vs. 400/m3), as compared to the control building. DE symptoms were reported by 37.5% of individuals exiting the experimental and 28.4% exiting the control building. In the univariate analysis, subjects exiting the experimental building were 2.21× more likely to report worsening of DE symptoms since morning compared to the control building (p < 0.05). When adjusting for confounders, including a history of eye allergy, subjects from the experimental building were 13.3× more likely to report worsening of their DE symptoms (p < 0.05). Our findings suggest that short-term exposure to adverse indoor environmental conditions, specifically air pollution and bioaerosols, has an acutely negative impact on DE symptoms.

Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase ß and a de novo DNA Methyltransferase.

DNA damage and base excision repair (BER) are actively involved in the modulation of DNA methylation and demethylation. However, the underlying molecular mechanisms remain unclear. In this study, we seek to understand the mechanisms by exploring the effects of oxidative DNA damage on the DNA methylation pattern of the tumor suppressor breast cancer 1 (BRCA1) gene in the human embryonic kidney (HEK) HEK293H cells. We found that oxidative DNA damage simultaneously induced DNA demethylation and generation of new methylation sites at the CpGs located at the promoter and transcribed regions of the gene ranging from -189 to +27 in human cells. We demonstrated that DNA damage-induced demethylation was mediated by nucleotide misincorporation by DNA polymerase ß (pol ß). Surprisingly, we found that the generation of new DNA methylation sites was mediated by coordination between pol ß and the de novo DNA methyltransferase, DNA methyltransferase 3b (DNMT3b), through the interaction between the two enzymes in the promoter and encoding regions of the BRCA1 gene. Our study provides the first evidence that oxidative DNA damage can cause dynamic changes in DNA methylation in the BRCA1 gene through the crosstalk between BER and de novo DNA methylation.