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Stigmatization and bias in interpreting lichen sclerosus risk factors
Get PDFDear Editors,
The recent article published by Singal et al. investigating the association between prior anogenital infections and subsequent diagnoses of lichen sclerosus (LS) raises important clinical considerations. However, we are concerned about potential misinterpretations that may arise, especially among lay readers and nonspecialist clinicians
Dosing trajectories of antihypertensive agents among preterm neonates: A retrospective, cross-sectional analysis
Get PDFIntroduction Preterm infants are at increased risk for hypertension due to incomplete organ development. With no established guidelines for treating hypertension in this population, clinicians rely on their experience, and little is known regarding those treatment decisions. This study described dosing trajectories for the three most common antihypertensive agents in preterm infants. Methods This retrospective, cross-sectional study examined preterm neonates (gestational age at birth < 37 weeks, postmenstrual age < 44 weeks) treated with antihypertensive medications at the University of Alabama at Birmingham (UAB) Medical Center. The study identified the three most common antihypertensive agents and identified common dosing patterns over time using the functional K-means algorithm. We then compared demographic and clinical information across these clusters. Results The study included 87 patients across 93 visits. The three most common antihypertensive agents were propranolol (61%), captopril (8.8%), and esmolol (12%). Median treatment durations were 292 hours for propranolol, 186 hours for captopril, and 68 hours for esmolol. Propranolol was often initiated at a dose that was maintained with few dosing changes. Patients needing higher doses of propranolol were generally younger gestational age and spent longer in the hospital. Captopril doses started low and increased over time, likely due to safety concerns. Esmolol showed the most variable dosing trajectories. Conclusions Propranolol is often initiated at a target dose and maintained with less titration, while both captopril and esmolol are titrated more often. Younger gestational age patients typically required higher doses of propranolol
Borderline Personality Disorder: A Comprehensive Meta-Analytic Review of Epidemiology, Neurobiology, and Population Dynamics
Get PDFBorderline Personality Disorder (BPD) is a severe, multifaceted psychiatric condition characterized by pervasive instability in affect regulation, interpersonal relationships, self-image, and impulse control. Historically marginalized within psychiatric nosology and stigmatized in clinical practice, BPD is increasingly recognized as a disorder of neuroplasticity and emotional regulation with significant public health implications. This meta-analytic review synthesizes the current body of literature to provide an exhaustive examination of BPD, ranging from its molecular and structural neurobiological underpinnings to its epidemiological distribution across diverse demographic, clinical, and forensic populations
Biomechanical and Physiological Interactions of Footwear in Trail Running: A Systematic Review and Meta-Synthesis
Get PDFBackground
The divergence of trail running from road running has created a distinct biomechanical paradigm that necessitates specialized equipment analysis. While road running research has historically prioritized metabolic efficiency through sagittal plane kinematics and energy return on uniform surfaces, trail running introduces stochastic environmental variables—including irregular terrain, variable friction coefficients, and acute elevation changes—that fundamentally alter the requirements of footwear. The recent introduction of Advanced Footwear Technology (AFT), characterized by high-rebound foams and curved carbon-fiber plates, has revolutionized road performance, yet its transferability to the heterogeneous trail environment remains a subject of intense scientific debate.
Objectives
This systematic review and meta-synthesis aims to exhaustively evaluate the current body of literature regarding trail running footwear. The primary objectives are to: (1) quantify the effects of specific shoe construction elements (midsole properties, longitudinal bending stiffness, traction elements, and upper stability) on Running Economy (RE) and injury kinetics; (2) analyze the metabolic cost of traction loss and slippage; and (3) determine the optimal footwear characteristics for specific trail disciplines, ranging from the high-intensity Vertical Kilometer (VK) to ultra-endurance events exceeding 100 miles.
Methods
A systematic search strategy was employed across academic databases (PubMed, Scopus, Web of Science, SPORTDiscus) adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were selected based on rigorous inclusion criteria focusing on biomechanical analysis, metabolic cost, and performance metrics in ecologically valid off-road or simulated trail environments. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale.
Results
The synthesis reveals that while AFT consistently improves RE on road surfaces by 2-4%, its efficacy on technical trail terrain is equivocal. Increased Longitudinal Bending Stiffness (LBS) frequently degrades performance in steep uphill locomotion due to altered joint mechanics and reduced compliance. Conversely, traction characteristics—specifically lug depth and outsole compound—significantly influence metabolic cost by mitigating slip probability, with a direct correlation between traction loss and increased energetic expenditure. Shoe mass remains the most consistent predictor of metabolic demand, with a ~1% increase in aerobic cost for every 100g of added mass.
Conclusion
Trail running footwear requires a paradigm shift from the pure efficiency models of road running to a "stability-efficiency" trade-off. Optimal footwear selection is highly dependent on event specificity, with Vertical Kilometer events favoring mass reduction and traction, while ultra-distances prioritize cushioning and fit to accommodate physiological swelling and neuromuscular fatigue
Sinus Tarsi Versus Extensile Lateral Approach For Calcaneal Fractures - A Multicenter Study
Get PDFIntroduction: The optimal surgical approach for intraarticular calcaneal fractures remains debated. This study compares deep infection rates between the extended lateral (EL) and sinus tarsi (ST) approaches. Methods: A retrospective review was conducted of 782 patients treated surgically for OTA 82B/C calcaneal fractures across 15 institutions. Deep infection was defined as requiring surgical débridement or treatment for osteomyelitis. Risk factors were identified using univariate and multivariate analyses. Results: Of 782 fractures, 444 were treated with EL and 338 with ST. Deep infections occurred in 6.8% of EL and 3.0% of ST cases (P = 0.017). Multivariate analysis found that surgical approach (P = 0.03) and age (P < 0.001) were independent risk factors. EL had more wound complications; ST had more symptomatic implants. Conclusion: The ST approach was associated with lower rates of deep infection and wound complications, even in higher-risk patients
Participant Experiences in a Kidney Failure Care Intervention in the Navigate-Kidney Study
Get PDFQuestion How did community health workers (CHWs) in the Navigate-Kidney trial support patients receiving dialysis in managing their health and navigating the health care system?
Findings In this qualitative study of 24 Latino individuals, patients described that CHWs fostered trust through empathy and reliability, addressed social and logistical barriers to care, provided culturally and linguistically tailored health education, and enhanced confidence in self-management, medication adherence, and dialysis attendance.
Meaning These findings suggest that CHWs played a vital role in improving patient engagement, emotional well-being, and self-efficacy, suggesting their integration into dialysis care teams may enhance holistic, patient-centered care.This qualitative study examines the perspectives of Latino individuals with dialysis-dependent kidney failure who received the Navigate-Kidney intervention.
Importance Latino individuals with dialysis-dependent kidney failure experience social challenges that render self-management of kidney disease difficult. In the Navigate-Kidney trial, a community health worker (CHW) intervention for Latinos receiving dialysis, intervention recipients experienced a decrease in interdialytic weight gain, a surrogate end point for patient self-management. Understanding how the Navigate-Kidney trial was experienced by participants is important when considering scalability and sustainment of the intervention.Objective To examine participant perspectives on their experience in the Navigate-Kidney intervention.
Design, Setting, and Participants This qualitative study used semistructured interviews with participants receiving the Navigate-Kidney intervention. Participants received care at dialysis centers in Denver, Colorado, between November 2020 and August 2022 and were randomized to receive the Navigate-Kidney intervention. Interview transcripts were deidentified and analyzed using deductive thematic analysis. Data were examined from September 2024 to July 2025.
Main Outcomes and Measures The main outcomes were the themes and subthemes from the interviews.
Results Twenty-four Latino individuals (11 females [46%]; 13 males [54%]; mean [SD] age of 56 [11] years) participated. The identified themes and subthemes were (1) build trust through understanding health experience (cultivating a personalized connection, promoting optimism and resilience, demonstrating consistency and reliability); (2) address multilevel social and structural challenges to facilitate health system navigation (addressing health insurance barriers, improving food security, relieving the stress of administrative and financial tasks, bridging registered dietitian guidance, enabling attendance of and adherence to dialysis sessions and appointments, coordinating nonnephrology clinical care); (3) provide patient-centered education (improving language concordant communication, promoting health and numeracy literacy, providing culturally responsive dietary restriction); and (4) enhance self-management (exploring opportunities for transplant and peritoneal dialysis, facilitating quality of dialysis care and symptom management, encouraging medication adherence, increasing confidence in diet and fluid intake self-management, achieving clinical parameter targets, activating patients).
Conclusions and Relevance In this qualitative study of participants in the Navigate-Kidney trial, participants’ experience with CHWs built trusting relationships through empathy and consistent support, helped them navigate complex health and social systems, provided culturally and linguistically tailored education, and empowered them to manage their care. Understanding participant perspectives about those activities that promoted health and well-being is critical for future patient-centered adaptations of Navigate-Kidney and similar interventions
Improving training on hepatitis B research in Nigeria: Findings from an innovation bootcamp to strengthen capacity
Get PDFWe organized an Innovation Bootcamp for young people in Nigeria to develop strategies promoting the uptake of the hepatitis B birth dose vaccine among newborns, which remains low, with an estimated coverage of 52%. This event was a collaborative, cross-disciplinary capacity-building platform to generate creative solutions addressing barriers to Hepatitis B vaccine uptake. The purpose of this study was to describe the bootcamp activities that address this gap and evaluate the impact of an Innovation Bootcamp designed to build research capacity among young Nigerians. The bootcamp was informed by Participatory Action Research focused at engaging young people as co-researchers to investigate and address issues affecting their respective communities using the PEN-3 cultural model. Qualitative data from the community needs assessment were analyzed using a thematic analysis framework to identify and synthesize emerging themes. Socio-demographic characteristics of the participants were collected, and a pre- and post-survey was administered. The participants’ knowledge of hepatitis B and research skills were compared using the Wilcoxon test. Our results included five teams composed of fifteen participants with a mean age of 25.5 years, originating from the Southern regions of Nigeria. The post-survey showed significant improvements in participants’ knowledge and research skills, with knowledge increasing by 21.6% (mean score: 39.7 to 48.3, p = 0.010) and research skills by 36.4% (mean score: 56.1 to 76.5, p < 0.001). Each team co-designed implementation strategies, including referral pathways from traditional birth attendants to formal health centers, comprehensive training workshops, and trusted community leaders as vaccination ambassadors. In conclusion, the bootcamp demonstrated its effectiveness in strengthening capacity and increasing knowledge (although in a small sample size), which contributed to informing the development of implementation strategies. Findings from the pilot studies will ultimately inform future research focused on promoting and sustaining youth-derived vaccination service delivery strategies in Nigeria
Natural killer cells and IFN-γ protect against liver injury during HAV infection in mice.
Get PDFA limited number of studies on human subjects with type-A hepatitis have found a positive correlation between activated natural killer (NK) cell frequencies in blood and the severity of liver injury. However, without knowledge of differences in viral burdens, it remains unclear whether NK cells are elevated due to hepatitis A virus (HAV) replication and ongoing associated injury, or if NK cell responses directly cause pathogenesis. To gain insight into how NK cells respond during the early stages of hepatitis A virus infection, we generated mice that are permissive for HAV infection in the liver but are otherwise immunocompetent. HAV readily infected the liver of these hepatocyte-specific type-I interferon receptor knockout mice (Ifnar1ΔHep), resulting in fecal virus shedding, elevated serum alanine aminotransferase levels, and immune cell infiltrates in the liver. Single-cell RNA sequencing analyses of liver leukocytes from infected Ifnar1ΔHep mice revealed a rapid accumulation of activated NK cells in the liver within 2 days. HAV infection and liver inflammation were brief and substantially reduced in magnitude in these mice compared to global Ifnar1-/- knockout mice that failed to induce substantial antiviral NK cell responses. NK cells were the principal source of interferon (IFN)-γ in Ifnar1ΔHep mice. Ifnar1ΔHep mice that were experimentally depleted of NK cells or IFN-γ showed greatly increased viral replication and liver damage. Moreover, IFN-γ alone was sufficient to suppress HAV replication in primary mouse hepatocytes. Collectively, these findings establish a critical role for type-I IFN induction of NK cells, their expression of IFN-γ, and protection against hepatitis A.IMPORTANCEHepatitis A virus remains a leading cause of foodborne illness among unvaccinated individuals. Infection can result in severe liver injury that can progress to fatal fulminant viral hepatitis. Despite its clinical significance, the molecular, genetic, and cellular factors influencing infection severity remain poorly understood. Previous studies of patient blood have suggested that natural killer (NK) cells cause liver injury during infection. In this study, we used mouse models of infection to characterize early cellular defenses to infection and identified a critical role for NK cells and interferon-γ in conferring rapid immune protection rather than pathogenesis
Allosteric Modulation of Cannabinoid Type 1 Receptor by ZCZ011: Integration of In Vitro Pharmacology and Molecular Dynamics Simulation
Get PDFOver the years, the cannabinoid type 1 receptor (CB1R) has emerged as a promising therapeutic target for addressing various neurodegenerative diseases including HIV-associated neurocognitive disorders (HAND). However, the therapeutic application of direct CB1R activation is often hindered by undesirable psychoactive side effects. To mitigate this issue, research has focused on utilizing positive allosteric modulators (PAMs) to enhance the CB1R activity indirectly. Preclinical studies have highlighted the efficacy of CB1R PAMs, such as ZCZ011 and GAT211, in mouse models of Huntington’s disease, neuropathic pain, and, more recently, HAND. Building on this evidence, we employed primary frontal cortex neuronal cultures and whole brain microglial cultures to investigate the direct and indirect effects of racemic ZCZ011 against the HIV-1 trans-activator of transcription (Tat)-induced excitotoxicity. In parallel, molecular modeling and molecular dynamics simulations were conducted using the ZCZ011 enantiomers (R)-ZCZ011 and (S)-ZCZ011, to elucidate their binding profiles at CB1R. Our in vitro studies revealed that ZCZ011 demonstrated neuroprotective effects against Tat-induced excitotoxicity in the presence of N-arachidonoylethanolamine (AEA) in a dose-dependent manner. Interestingly, racemic ZCZ011 exhibited neuroprotective properties even in the absence of AEA, deviating from the classical behavior of a true PAM. This prompted further investigation into the binding profiles of the enantiomers. Molecular modeling revealed that (R)-ZCZ011 and (S)-ZCZ011 bind to distinct sites on CB1R, aligning with the binding profiles of other CB1R allosteric modulators, GAT228 and GAT229. Notably, (R)-ZCZ011 exhibited a higher number of hydrogen bonds and both polar and nonpolar interactions with CB1R, enhancing the stabilization of AEA binding to CB1R. In summary, these findings suggest that (R)-ZCZ011 may function as both a PAM and an allosteric agonist, like GAT228, while (S)-ZCZ011 may act as a pure PAM, resembling GAT229. This dual functionality underscores the therapeutic potential of ZCZ011 in modulating CB1R activity for a number of neuroprotective applications
Affective homophily as the dominant organizing principle in online conflict discourse networks
Get PDFThis study develops a diagnostic framework using a Graph Attention Network (GATv2) to uncover the organizing principles of online conflict networks. By modeling link prediction and rigorously comparing GATv2 against multiple baselines, we validate its superior performance and interpretability. Our analysis delivers a “computational verdict”: the model learns to overwhelmingly prioritize affective homophily while systematically discounting users’ structural prestige. Probing the learned embeddings reveals that emotion is the dominant dimension of this homophily, a phenomenon we term “emotional fortresses.” Critically, by analyzing the model’s prediction failures, we identify a novel class of “emergent brokers” who bridge emotional divides through low centrality and affective neutrality. Finally, applying the framework to non-conflict domains empirically establishes the theory’s boundary conditions. This research provides a new theoretical lens and methodological tool for understanding network dynamics in polarized environments