Purpose: Adolescents with asthma often report poor medication adherence and asthma control. Cognitive factors embedded in the social cognitive theory including self-efficacy, outcome expectations, and barrier perceptions may explain poor asthma outcomes in this population. This study was performed to examine the extent to which these cognitive factors are intercorrelated and explain medication adherence and asthma control in urban adolescents. Patients and methods: A total of 373 urban adolescents (12–20 years) with asthma completed questionnaires measuring asthma-related self-efficacy, outcome expectations, barrier perceptions, medication adherence, and asthma control. Multiple linear regression was conducted to examine the extent to which the three cognitive factors predicted medication adherence and asthma control after controlling for covariates including age, sex, household income, and age at diagnosis. Results: Participants’ ages were on average 14.68 (±1.94) years; 50% were female, and most (78.6%) were African American. Higher self-efficacy associated with lower barrier perceptions and higher outcome expectations (r=0.50, p<0.001; r=−0.26, p<0.001, respectively). Self-efficacy predicted better asthma control (B=−0.098, p=0.004) and adherence (B=0.426, p=0.011), whereas barrier perceptions predicted poorer asthma control (B=0.13, p<0.001) and adherence (B=−0.568, p<0.001). Self-efficacy independently predicted fewer missed doses (B=−0.621, p=0.006), and barrier perception independently predicted asthma control (B=0.12, p<0.001) and adherence (B=−0.519, p<0.001).
Conclusion: Improving medication adherence and asthma control among adolescents may require a multifaceted approach. Interventions focused on increasing self-efficacy and addressing barriers, actual or potential, to medication adherence could ameliorate asthma disparities in urban adolescents.

Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal cancer patients often results in individuals that respond well to therapy and those that respond poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide. Our major aim is to identify what factors in the tumor microenvironment drive a fraction of rectal cancer patients to respond to radiotherapy. We also sought to distinguish potential biomarkers that would indicate a positive response to therapy and design combinatorial therapeutics to enhance radiotherapy efficacy. To address this, we developed an orthotopic murine model of rectal cancer treated with short course radiotherapy that recapitulates the bimodal response observed in the clinic. We utilized a robust combination of transcriptomics and protein analysis to identify differences between responding and nonresponding tumors. Our mouse model recapitulates human disease in which a fraction of tumors respond to radiotherapy (responders) while the majority are nonresponsive. We determined that responding tumors had increased damage-induced cell death, and a unique immune-activation signature associated with tumor-associated macrophages, cancer-associated fibroblasts, and CD8⁺ T cells. This signature was dependent on radiation-induced increases of Type I Interferons (IFNs). We investigated a therapeutic approach targeting the cGAS/STING pathway and demonstrated improved response rate following radiotherapy. These results suggest that modulating the Type I IFN pathway has the potential to improve radiation therapy efficacy in RC.

Localized provoked vulvodynia is characterized by chronic vulvar pain that disrupts every aspect of the patient's life. Pain is localized to the vulvar vestibule, a specialized ring of tissue immediately surrounding the vaginal opening involved in immune defense. In this article, we show inflammation is the critical first step necessary for the generation of pain signals in the vulva. Inflammatory stimuli alone or combined with the transient receptor potential cation channel subfamily V member 4 (TRPV4) agonist 4α-phorbol 12,13-didecanoate stimulate calcium flux into vulvar fibroblast cells. Activity is blocked by the TRPV4 antagonist HC067047, denoting specificity to TRPV4. Using lipidomics, we found pro-resolving lipids in the vulvar vestibule were dysregulated, characterized by a reduction in pro-resolving mediators and heightened production of inflammatory mediators. We demonstrate specialized pro-resolving mediators represent a potential new therapy for vulvar pain, acting on 2 key parts of the disease mechanism by limiting inflammation and acutely inhibiting TRPV4 signaling.

Mercury ranks third on the U.S. Agency of Toxic Substances and Disease Registry priority list of hazardous substances, behind only arsenic and lead. We have undertaken uncovering the mechanisms underlying the developmental toxicity of methylmercury (MeHg), inorganic mercury (HgCl₂), lead acetate (Pb), and sodium arsenite (As). To probe these differences, we used the Drosophila model, taking advantage of three developmental transitions—pupariation, metamorphosis, and eclosion—to differentiate potentially unique windows of toxicity. We elaborated dose response profiles for each individual metal administered in food and accounted for internal body burden, also extending analyses to evaluate combinatorial metal mixture effects. We observed all four metals producing larval lethality and delayed pupariation, with MeHg being most potent. Compared to other metals, MeHg’s potency is caused by a higher body burden with respect to dose. MeHg uniquely caused dose-dependent failure in eclosion that was unexpectedly rescued by titrating in HgCl₂. Our results highlight a unique developmental window and toxicokinetic properties where MeHg acts with specificity relative to HgCl₂, Pb, and As. These findings will serve to refine future studies aimed at revealing tissue morphogenesis events and cell signaling pathways, potentially conserved in higher organisms, that selectively mediate MeHg toxicity and its antagonism by HgCl₂.