Mechanical forces impair antigen discrimination by reducing differences in T-cell receptor/peptide-MHC off-rates.

T cells use their T-cell receptors (TCRs) to discriminate between lower-affinity self and higher-affinity foreign peptide major-histocompatibility-complexes (pMHCs) based on the TCR/pMHC off-rate. It is now appreciated that T cells generate mechanical forces during this process but how force impacts the TCR/pMHC off-rate remains debated. Here, we measured the effect of mechanical force on the off-rate of multiple TCR/pMHC interactions. Unexpectedly, we found that lower-affinity TCR/pMHCs with faster solution off-rates were more resistant to mechanical force (weak slip or catch bonds) than higher-affinity interactions (strong slip bonds). This was confirmed by molecular dynamics simulations. Consistent with these findings, we show that the best-characterized catch bond, involving the OT-I TCR, has a low affinity and an exceptionally fast solution off-rate. Our findings imply that reducing forces on the TCR/pMHC interaction improves antigen discrimination, and we suggest a role for the adhesion receptors CD2 and LFA-1 in force-shielding the TCR/pMHC interaction.

An update on tinea capitis in children.

Tinea capitis presents a significant public health care challenge due to its contagious nature, and potential long-term consequences if unrecognized and untreated. This review explores the prevalence, risk factors, diagnostic methods, prevention strategies, impact on quality of life, and treatment options for pediatric tinea capitis. Epidemiological analysis spanning from 1990 to 1993 and 2020 to 2023 reveals prevalence patterns of pediatric tinea capitis influenced by geographic, demographic, and environmental factors. Notably, Trichophyton species is most prevalent in North America; however, Microsporum species remain the primary causative agent globally, with regional variations. Risk factors include close contact and environmental conditions, emphasizing the importance of preventive measures. Accurate diagnosis relies on clinical evaluation, microscopic examination, and fungal culture. Various treatment modalities including systemic antifungals show efficacy, with terbinafine demonstrating superior mycological cure rates particularly for Trichophyton species. Recurrent infections and the potential development of resistance can pose challenges. Therefore, confirming the diagnosis, appropriately educating the patient/caregiver, accurate drug and dose utilization, and compliance are important components of clinical cure. Untreated or poorly treated tinea capitis can lead to chronic infection, social stigma, and psychological distress in affected children. Prevention strategies focus on early detection and healthy lifestyle habits. Collaborative efforts between healthcare providers and public health agencies are important in treating pediatric tinea capitis and improving patient outcomes. Education and awareness initiatives play a vital role in prevention and community-level intervention to minimize spread of infection. Future research should explore diagnostic advances, novel treatments, and resistance mechanisms in order to mitigate the disease burden effectively.

Fibrosis in burns: an overview of mechanisms and therapies.

Scar development remains a common occurrence and a major healthcare challenge affecting the lives of millions of patients annually. Severe injuries to the skin, such as burns can lead to pathological wound healing patterns, often characterized by dermal fibrosis or excessive scarring, and chronic inflammation. The two most common forms of fibrotic diseases following burn trauma are hypertrophic scars (HSCs) and keloids, which severely impact the patient's quality of life. Although the cellular and molecular mechanisms are similar, HSC and keloids have several distinct differences. In this review, we discuss the different forms of fibrosis that occur postburn injury, emphasizing how the extent of burn influences scar development. Moreover, we highlight how a systemic response induced by a burn injury drives wound fibrosis, including both the role of the inflammatory response, as well as the fate of fibroblast during skin healing. Finally, we list potential therapeutics aimed at alleviating pathological scar formation. An understanding of the mechanisms of postburn fibrosis will allow us to effectively move studies from bench to bedside.

Pattern hair loss and health care professionals: How well are we connecting with our audience?

BACKGROUND: Pattern hair loss, the most common form of hair loss, affects millions in the United States. Americans are increasingly seeking health information from social media. It would appear that healthcare professionals contribute relatively minimally to pattern hair loss content, thereby posing serious concerns for credibility and quality of information available to the general public. OBJECTIVES: This study evaluates popular pattern hair loss-related content on Instagram, TikTok, and YouTube, aiming to understand effective engagement strategies for healthcare professionals on social media. METHODS: The top 60 short-form videos were extracted from Instagram, TikTok, and YouTube, using the search term "pattern hair loss" and inclusion of USA-based accounts only. Videos were categorized by creator type (healthcare vs. non-healthcare professional), content type (informational, interactional, and transactional), and analyzed for user engagement and quality, using engagement ratios and DISCERN scores, respectively. CONCLUSIONS: Healthcare professionals, especially dermatologists, play a crucial role in delivering credible information on social media, supported by higher DISCERN scores. Multi-platform presence, frequent activity, and strategic content creation contributes to increased reach and engagement. Duration of short-form videos does not impact engagement. The "Duet" or "Remix" options on TikTok, Instagram, and YouTube serve as a valuable tool for healthcare professionals to counter misinformation. Our study underscores the importance of optimizing educational impact provided by health care professionals at a time when the public increasingly relies on social media for medical information.

BURNS INDUCE ALTERATIONS IN THE ACYL PROTEOME OF MICE AND HUMANS.

ABSTRACT: Hypermetabolic reprogramming triggered by thermal injury causes substantial morbidity and mortality. Despite the therapeutic potential of targeting this response, the underlying mechanisms remain poorly understood. Interestingly, protein S-acylation is a reversible posttranslational modification induced by metabolic alterations via DHHC acyltransferases. While this modification aids in the regulation of cellular functions, deregulated S-acylation contributes to various diseases by altering protein structure, stability, and localization. However, whether and how S-acylation may impact morbidity and mortality during postburn hypermetabolism is unknown. In this study, we discovered that alterations in the acyl proteome play a key role in mediating adverse outcomes that occur after burn injury. Using a murine model, we show that burn injury induces profound changes in the expression of various DHHC isoforms in metabolic organs central to regulating postburn hypermetabolism, the adipose tissue, and liver. This was accompanied by increased levels of S-acylated proteins in several pathways involved in mediating the adverse hypermetabolic response, including ER stress, lipolysis, and browning. In fact, similar results were also observed in adipose tissue from severely burned patients, as reflected by increased S-acylation of ERK1/2, eIF2a, ATGL, FGF21, and UCP1 relative to nonburn controls. Importantly, pharmacologically targeting this posttranslational modification using a nonselective DHHC inhibitor effectively attenuated burn-induced ER stress, lipolysis, and browning induction in an ex vivo explant model. Together, these findings suggest that S-acylation may facilitate the protein activation profile that drives burn-induced hypermetabolism and that targeting it could potentially be an effective strategy to restore metabolic function and improve outcomes after injury.

No association between the presence of periodontal disease and poor IVF outcomes: a pilot study.

Background: Periodontal disease can lead to bacteremia with release of cytokines, affecting implantation in women trying to conceive through in vitro fertilization (IVF). A potential association between maternal periodontal disease and poor IVF outcomes has been described. Objective: The aim of the study is to assess whether pre-existing periodontal disease has any effect on IVF parameters. Method: A pilot study composed of 34 women was conducted at a tertiary care center. Prior to IVF, dental examination, IVF parameters were collected. Results: Thirty-four women participated in the study. The outcomes of 28 women (82.3%) were analyzed. Out of the 28 patients, 17 patients had a positive pregnancy test (60.7%) with a total of 13 live births (46.4%) and 4 pregnancy losses (14.3%). Plaque and bleeding index scores were both lower in patients who achieved pregnancy after IVF yet did not reach statistical significance (p=0.309 and 0.422). Comparison of mean values for the different infertility parameters showed no significant differences among women with different IVF outcomes (p>0.05). Different degrees of inflammation of the gingiva did not have an effect on the different clinical parameters and the live birth rates. Conclusion: The evidence provided by the present study does not support the hypothesis. Addressing the status of oral health before any infertility treatment remains to be elucidated.