Wound infections are becoming increasingly difficult to treat due to rising antibiotic-resistant bacteria. β-Lactamase-producing bacteria are among the most common pathogens implicated in these infections. Here, we report a bacterial enzyme-responsive hydrogel formulated with a cephalosporin-derived, β-lactamase-cleavable crosslinker that undergoes selective degradation in the presence of bacterial β-lactamases. This degradation triggers the on-demand release of encapsulated ciprofloxacin-loaded liposomes, ensuring that antibiotic delivery occurs only at the site of infection. This selective degradation and release was demonstrated in both ex vivo and in vivo models of Pseudomonas aeruginosa wound infections. In a murine skin abrasion infection model, a single application of the hydrogel led to complete bacterial eradication and enhanced wound healing, outperforming a commercial silver-based hydrogel wound dressing. These responsive hydrogels did not induce ciprofloxacin resistance in non-β-lactamase-producing bacteria. These findings demonstrate that β-lactamase-responsive hydrogels provide a precise, infection-triggered antibiotic delivery platform that can improve the treatment of wound infections and mitigate antimicrobial resistance.
Importance:Millions of children worldwide are experiencing prolonged symptoms after SARS-CoV-2 infection, yet social risk factors for developing long COVID are largely unknown. As child health is influenced by the environment in which they live and interact, adverse social determinants of health (SDOH) may contribute to the development of pediatric long COVID. Objective:To identify whether adverse SDOH are associated with increased odds of long COVID in school-aged children and adolescents in the US. Design, Setting, and Participants:This cross-sectional analysis of a multicenter, longitudinal, meta-cohort study encompassed 52 sites (health care and community settings) across the US. School-aged children (6-11 years; n = 903) and adolescents (12-17 years; n = 3681) with SARS-CoV-2 infection history were included. Those with an unknown date of first infection, history of multisystem inflammatory syndrome in children, or symptom surveys with less than 50% of questions completed were excluded. Participants were recruited via health care systems, long COVID clinics, fliers, websites, social media campaigns, radio, health fairs, community-based organizations, community health workers, and existing research cohorts from March 2022 to August 2024, and surveys were completed by caregivers between March 2022 and August 2024. Exposure:Twenty-four individual social determinant of health factors were grouped into 5 Healthy People 2030 domains: economic stability, social and community context, caregiver education access and quality, neighborhood and built environment, and health care access and quality. Latent classes were created within each domain and used in regression models. Main Outcomes and Measures:Presence of long COVID using caregiver-reported, symptom-based, age-specific research indices. Results:The mean (SD) age among 4584 individuals included in this study was 14 (3) years, and 2330 (51%) of participants were male. The number of latent classes varied by domain; the reference group was the class with the least adversity. In unadjusted analyses, most classes in each domain were associated with higher odds of long COVID. After adjusting for many factors, including age group, sex, timing of infection, referral source, and other social determinant of health domains, economic instability characterized by difficulty covering expenses, poverty, receipt of government assistance, and food insecurity were associated with an increased risk of having long COVID (class 2 adjusted odds ratio [aOR], 1.57; 95% CI, 1.18-2.09; class 4 aOR, 2.39; 95% CI, 1.73-3.30); economic instability without food insecurity (class 3) was not (aOR, 0.93; 95% CI, 0.70-1.23). Poorer social and community context (eg, high levels of discrimination and low social support) was also associated with long COVID (aOR, 2.17; 95% CI, 1.77-2.66). Sensitivity analyses stratified by age group and adjusted for race and ethnicity did not alter or attenuate these results. Conclusions and Relevance:In this study, economic instability that included food insecurity and poor social and community context were associated with greater odds of pediatric long COVID. Those with food security, despite experiencing other economic challenges, did not have greater odds of long COVID. Further study is needed to determine if addressing SDOH factors can decrease the rate of pediatric long COVID.
Linear growth stunting increases a child's risk for mortality and lifelong morbidities. Understanding and preventing the causes of childhood stunting is a global health priority. The leading contributors to stunting are undernutrition and infection. Schistosomiasis, a neglected tropical disease, has long been associated with childhood stunting, but there are limited reviews summarizing the evidence. This narrative review examines cross-sectional associations between infection and linear growth, longitudinal impacts of schistosomiasis treatment on growth and the influence of schistosomiasis on the endocrine system, specifically the growth hormone (GH) and insulin-like growth factor 1 (IGF-1) axis. After reviewing more than 60 years of research, there is evidence for an association between schistosomiasis infection and linear growth measures but mixed results relating to stunting, a categorical outcome based on low height-for-age measures. This may be due to limitations in study design or the length of time required to induce stunting. The reports also support the theory that schistosomiasis disrupts the GH/IGF-1 axis, resulting in reduced IGF-1 and impaired linear growth. These findings reinforce the need for early treatment interventions for children living in schistosomiasis-endemic regions and encourage research to include stunting risk factors and endocrine measures in future schistosomiasis study designs. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.
This study evaluated the extent to which the sleep is disrupted by nighttime awakenings in urban children with and without asthma and examined racial/ethnic differences in sleep outcomes. Three hundred and seventy-nine urban children aged 7 to 9 years with (n = 250) and without (n = 129) asthma were included. Participants were 45% Latino, 34% black, and 21% non-Latino white (NLW). Nighttime awakenings were assessed via actigraphy. Asthma status was assessed by a clinically and via self-report. Children with asthma had significantly more awakenings than those without. Latino children with asthma had more and longer awakenings compared to Latino children without asthma; these effects were not observed among black or NLW participants. Poor asthma control was associated with more awakenings. Urban children face higher risks for poor sleep and asthma outcomes. Multicomponent interventions addressing asthma management and culturally tailored sleep hygiene strategies are necessary to improve asthma and sleep outcomes in this highly burdened population.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the viral spike proteins, which are key structural components that mediate host cell binding and entry and alter downstream signaling through multiple interactions with endothelial surface receptors. Endothelial dysfunction is a central consequence of COVID-19, contributing to vascular inflammation, barrier disruption, thrombosis, and multi-organ injury affecting the pulmonary, cardiovascular, cerebral, and renal systems. Emerging evidence demonstrates that spike protein-mediated effects, independent of productive viral infection, disrupt endothelial homeostasis through angiotensin-converting enzyme 2 (ACE2) dysregulation, integrin engagement, altered calcium signaling, junctional protein remodeling, oxidative stress, and pro-inflammatory and pro-apoptotic pathways. This review is intentionally focused on spike (S) protein-driven mechanisms of endothelial dysfunction; pathogenic vascular effects attributed to other SARS-CoV-2 structural proteins, including the nucleocapsid (N) protein, are beyond the scope of this discussion. In this review, we synthesize current experimental and translational data detailing the molecular mechanisms by which the SARS-CoV-2 spike protein drives endothelial dysfunction across multiple organ systems and discuss potential therapeutic strategies aimed at preserving endothelial integrity in acute COVID-19 and its long-term vascular sequela.
