Obesity, Inflammation, and Clinical Outcomes in COVID-19: A Multicenter Prospective Cohort Study.

CONTEXT: Obesity is a risk factor for coronavirus disease 2019 (COVID-19)-related outcomes; however, the mechanism remains unclear. OBJECTIVE: The objective of this analysis was to determine whether inflammation mediates the association between obesity and COVID-19 outcomes. DESIGN: The International Study of Inflammation in Covid-19 (ISIC): A Prospective Multi-Center Observational Study Examining the Role of Biomarkers of Inflammation in Predicting Covid-19 Related Outcomes in Hospitalized Patients. SETTING: Ten hospitals in the United States and Europe. PARTICIPANTS: Adults hospitalized specifically for COVID-19 between February 1, 2020, through October 19, 2022. MAIN OUTCOME MEASURES: Inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), were measured at admission. Associations were examined between body-mass index (BMI, kg/m2) and a composite of death, need for mechanical ventilation, and renal replacement therapy, stratified by pre- and post-Omicron variants. The contribution of inflammation to the relationship between obesity and outcomes was assessed. RESULTS: Among 4644 participants (mean age 59.3, 45.6% male, 21.8% BMI≥35), those with BMI>40 (n=485) had 55% higher odds of the composite outcome (95% CI[1.21 to 1.98]) compared to non-obese individuals (BMI<30, n=2358) in multivariable analysis. In multiple mediation analysis, only suPAR remained a significant mediator between BMI and composite outcome. Associations were amplified for participants younger than 65 years and with pre-Omicron variants. CONCLUSION: Obesity is associated with worse outcomes in COVID-19, notably in younger participants and in the pre-Omicron era. Inflammation, as measured by suPAR, is a significant mediator of the association between obesity and COVID-19 outcomes.

Assessing the interrelationship between stigma, social influence, and cervical cancer prevention in an urban underserved setting: An exploratory study.

In the US, incidence and mortality from cervical cancer disproportionately affects racial/ethnic minorities and low-income women. Despite affordable access to primary and secondary prevention measures at Federally Qualified Health Centers (FQHCs), Human Papillomavirus (HPV) vaccination and screening rates are low, suggesting the presence of non-financial barriers to uptake in this population. This explanatory sequential mixed-methods study sought to explore factors that influence the acceptability of cervical cancer prevention services among parents and legal guardians of vaccine-eligible girls attending an urban FQHC and to assess social influences related to cervical cancer prevention. Participants included eight mothers, one father, and two grandparents/legal guardians. Nine participants self-identified as Black/Afro-Caribbean, or African American, two as Latinx, and one as Native American. The quantitative data suggested discordance between participants' cervical cancer prevention knowledge and their practices. Most indicated that their daughters had received the HPV vaccine but were unsure about HPV transmission modes. Qualitative data revealed that participants were comfortable disclosing information on HPV infection and vaccination status, and most women were likely to share information related to cervical cancer testing and diagnosis. Few comments indicated personal stigma on the part of participants, but there was frequent expression of perceived public stigma (shaming and blaming women), gender differences (men are indifferent to risk), and distrust of the healthcare system. Findings highlight several concepts including the disharmony between knowledge and practice, prevalent perceived public stigma, cumbersome attitudes on the part of men regarding HPV and cervical cancer, and distrust of the healthcare system.

The development of a mouse model of ovarian endosalpingiosis.

Pelvic pain is a common presenting ailment in women often linked to ovulation, endometriosis, early pregnancy, ovarian cancer, and cysts. Clear differential diagnosis for each condition caused by these varied etiologies is difficult and may slow the delivery of therapy that, in the case of ovarian cancer, could be fatal. Ovarian endosalpingiosis, a pelvic condition typified by the presence of cystic glandular structures lined by benign tubal/salpingeal epithelium, is also associated with pelvic pain in women. The exact cellular antecedents of these epithelial lined cystic structures are not known, nor is there a known link to ovarian cancer. A mouse model of ovarian endosalpingiosis has been developed by directing a dominant-negative version of the TGF-beta transcription factor, Smad2, to the ovary using the Müllerian-inhibiting substance promoter (MIS-Smad2-dn). Female mice develop an ovarian endosalpingeal phenotype as early as 3 months of age. Importantly, cysts continuous with the ovarian surface epithelial have been identified, indicating that these cyst cells may be derived from the highly plastic ovarian surface epithelial cell layer. A second transgenic mouse model that causes loss of activin action (inhibin alpha-subunit transgenic mice) develops similar cystic structures, supporting a TGF-beta/activin/Smad2 dependence in the onset of this disease.