Primary carnitine deficiency (PCD) is an autosomal recessive disorder caused by mutations in the SLC22A5 gene, which encodes the organic cation transporter 2 (OCTN2). These mutations impair carnitine transport and fatty acid metabolism, leading to a wide range of clinical symptoms, from mild fatigue to severe cardiomyopathy. Although over 100 mutations have been identified, the correlation between specific genotypes and pathogenicity remains unclear, necessitating further investigation into their molecular and clinical impacts. This systematic review aims to evaluate the association between SLC22A5 mutations and PCD, with a focus on cardiomyopathy, to characterise the molecular and functional consequences of these variants, and to explore their implications for diagnosis, treatment, and personalised care. A systematic search of PubMed was conducted, focusing on studies reporting genetic, clinical, and biochemical data related to SLC22A5. Variants were classified according to ACMG guidelines and CADD scoring, and the data were synthesised through descriptive analyses. Most reported variants are missense mutations, accounting for approximately 80% of cases, followed by deletions (12.7%), while duplications, insertions, and deletion-insertion variants are rare. According to ACMG classification, the majority of variants are pathogenic or likely pathogenic (≈72%), with VUS comprising about 24%, and benign variants being uncommon. Exons 1 and 8 have the highest frequencies, whereas Exons 5 and 6, despite fewer variants, exhibit higher mean CADD scores, suggesting greater functional impact. The findings revealed that Exons 1 and 8 harboured the most frequent mutations, while Exons 5 and 6 showed the highest pathogenicity. Nonsense variants exhibit the highest pathogenicity and CADD scores, followed by frameshift and missense mutations. Severe truncating mutations were linked to early-onset cardiomyopathy. Intronic variants are infrequent but include sites with high CADD scores, indicating potential regulatory relevance. Overall, these findings demonstrate that variant pathogenicity is influenced more by functional impact than by frequency alone.

Real-time, multiplexed monitoring of sex hormones is essential for managing reproductive health and endocrine disorders. Traditional invasive blood sampling lacks the temporal resolution required to capture the dynamic hormonal fluctuations necessary for personalized clinical insights. Here, we present a wearable microneedle-based electrochemical aptamer platform (WMEP) for the continuous, minimally invasive monitoring of estradiol, progesterone, luteinizing hormone, and testosterone in interstitial fluid. The WMEP integrates a four-channel microneedle electrode array enhanced with gold nanoparticles (∼2.77-fold increase in electroactive area) and a miniaturized wireless potentiostat employing time-staggered acquisition to suppress inter-channel crosstalk. In vivo rat studies demonstrated real-time tracking of hormone dynamics and revealed size-dependent transvascular transport kinetics: small steroids exhibited rapid interstitial partitioning (T_max≈40 min), while luteinizing hormone showed delayed exchange (T_max≈60 min). Quantitative analysis confirmed high concordance with serum ELISA measurements (Pearson's R ≥ 0.932). Clinical validation using 45 human serum samples across healthy controls, pregnancy, polycystic ovary syndrome, and breast cancer cohorts demonstrated robust analytical accuracy. A random forest classifier achieved 95.56% diagnostic accuracy based on multiplexed profiles. Human on-body trials further confirmed the platform's practical utility, reliably tracking testosterone surges during exercise and maintaining signal stability over 5 days of continuous wear. This wearable platform enables personalized, longitudinal endocrine management and decentralized monitoring of reproductive health disorders.

Diosgenin, derived from Dioscorea alata, is a well-known traditional medicinal compound with therapeutic potential against various conditions, including cancer and cardiovascular diseases. This study aimed to synthesize diosgenin polyethylene glycol succinate (DPGS) from diosgenin and evaluate its acute and chronic toxicity in rats. DPGS was designed as a novel amphiphilic excipient for universal solubilization, improving drug delivery and therapeutic performance. The acute toxicity assessment involved administering DPGS to female Albino-Wistar rats, while the chronic toxicity study was conducted over 90 days in both male and female Albino-Wistar rats at doses of 0 (control), 500, 1000, and 2000 mg/kg body weight/day. Additionally, recovery groups from the control and high-dose categories were observed for another 28 days. In the acute toxicity study, no clinical toxicity or mortality was observed at the highest dose of 2000 mg/kg body weight/day. Similarly, in the 90-day chronic study, no mortality or significant treatment-related effects were detected across all dose groups in either sex, based on histopathological, hematological, and clinical chemistry evaluations. These findings suggest that the oral no-observed-adverse-effect level (NOAEL) of DPGS in Albino-Wistar rats is greater than 2000 mg/kg body weight/day. The results support the safety profile of DPGS and its potential application as an excipient in drug formulation and delivery systems.

Central retinal artery occlusion is rare in pediatrics and typically linked to embolic or hematologic disorders. The authors describe a 13-year-old boy with acute central retinal artery occlusion and elevated Bartonella henselae titers following kitten exposure. Extensive evaluation was unrevealing, suggesting a rare inflammatory association between cat scratch disease and pediatric retinal arterial ischemia. The main take-away from this case is to also look for infectious causes, which are rare and not the first to be investigated for during central retinal artery occlusion.

With the widespread use of human epidermal growth factor receptor 2 (HER2) inhibitors in cancer treatment, cardiovascular diseases induced by these agents have become a significant adverse event.

We retrieved reports of HER2 inhibitor-induced cardiovascular adverse events (CVAEs) from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the fourth quarter of 2024. Disproportionality analyses were conducted using reporting odds ratios and proportional reporting ratios. The signals of HER2 inhibitor-related CVAEs were evaluated at both the standardized MedDRA query and preferred term levels.

A total of 12,698 reports associated with CVAEs were identified, with HER2 inhibitors listed as the primary suspected drug, involving 12,398 patients. Most cases were observed in individuals aged 45 and older, with a notably higher proportion in women. The time to onset of HER2 inhibitor-induced CVAEs showed certain variability. Trastuzumab exhibited higher cardiovascular toxicity compared with other HER2 inhibitors. In general, monoclonal antibodies demonstrated greater cardiovascular toxicity, whereas antibody-drug conjugates and HER2-tyrosine kinase inhibitors displayed comparable and lower effects.

This pharmacovigilance analysis reveals a strong association between HER2 inhibitors and CVAEs, providing valuable insights for their prevention and clinical management.

Angiogenesis is a crucial process in ischemia diseases like coronary heart disease, stroke and wound healing. Panasenoside (PSS) is a flavonoid glycoside ioslated from Chinese Materia Medica GINSENG RADIX ET RHIZOMA which has been demonstrated with multiple biological activities. However, the pharmacological activity of PSS and the underlying mechanism are still unclear. We found that PSS promoted sub-intestinal vessel plexus (SIVs) growth in zebrafish. PSS ameliorated vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor II (VRI)-induced deficiency of intersegmental vessels (ISVs) in a concentration dependent manner by downregulation of mRNA expression of VEGF receptors, including Kdr/VEGFR-2 (kdr), VEGFR-1 (flt1), and Kdr-like/VEGFR-2 (kdrl), and up-regulation of VEGF (vegfaa). The angiogenesis effect of PSS on VRI-induced ISVs deficiency was suppressed by PI3K, AKT, MEK, ERK, P38, Sirtuin 1 (SIRT1), Nuclear factor erythroid-2-related factor 2 (NRF2) and Nicotinamide N-methyl transferase (NNMT) inhibitors. Activation of NRF2, SIRT1 and MNA significantly restored VRI-induced ISVs insufficiency. In addition, PSS protected against VRI-induced tube formation deficiency in human umbilical vascular endothelial cells (HUVECs). SIRT1, NRF2 and NNMT inhibitors or siRNA eliminated PSS promoting vascular endothelial cell tube formation. PSS also prevented SIRT1, NRF2 and NNMT inhibitors-induced vascular endothelial cell senescence. Furthermore, PSS upregulated the protein expression level of SIRT1 and downregulated its downstreams P53 and PGC-1α in HUVECs with high potence of activating SIRT1 by binding with its active domine. In conclusion, PSS presented pro-angiogenesis effect by mitigating vascular endothelial cell ageing and the underlying mechanisms were involved in the PI3K/AKT/MAPKs, SIRT1/NRF2 and NNMT/MNA signaling pathway with SIRT1 acting as a key regulator. We identified the pro-angiogenesis and anti-vascular endothelial cell ageing effects of PSS for the first time, and PSS is a promising drug candidate for treating vascular deficiency associated diseases.

The COVID-19 pandemic has imposed unprecedented psychological demands on nurses working in care homes, profoundly affecting their well-being. Thus, this cross-sectional study examined the psychological burden among German care home nurses during the fourth COVID-19 wave and the early phase of the fifth wave in Germany, focusing on posttraumatic stress disorder (PTSD) and burnout, and assessed the availability of workplace psychosocial resources.

A total of 719 nurses completed an online cross-sectional convenience survey between October 2021 and January 2022. Given the voluntary online recruitment, the findings should be interpreted with caution due to the potential for self-selection bias. PTSD symptoms were assessed using the International Trauma Questionnaire (ITQ), and burnout dimensions were assessed using the Copenhagen Burnout Inventory (CBI). Multiple linear regression analyses were conducted to identify factors associated with PTSD and different dimensions of burnout, including personal burnout, work-related burnout and resident-related burnout.

Among nurses, 91.4% fulfilled PTSD screening criteria and/or exceeded the indicative CBI cut-off for at least one burnout dimension, indicating a high psychological burden within the present study sample. Specifically, 29.5% met screening criteria for PTSD, 90.0% exceeded the indicative CBI cut-off for personal burnout, 78.9% for work-related burnout, and 33.4% for resident-related burnout. Only 21.7% reported availability of psychosocial support at work. PTSD was significantly associated with poorer general health, lower job satisfaction, COVID-19-related deaths among residents in care home, dementia-focused care and female gender. Personal burnout was significantly associated with poorer general health, lower job satisfaction, female gender, absence of participatory leadership at care home, younger age, no COVID-19 infection history, and lower posttraumatic growth. Work-related burnout was significantly associated with lower job satisfaction, poorer general health, lower posttraumatic growth, female gender, no COVID-19 infection history, absence of participatory leadership at care home, and full-time employment. Resident-related burnout was significantly associated with lower job satisfaction, poorer general health, lower posttraumatic growth, and no COVID-19 infection history.

The high levels of PTSD and burnout found in the present study likely reflect strain placed by the pandemic as well as constant work-related strain on care home nurses. These findings underscore the urgent need for improved psychosocial support and organizational strategies to strengthen mental health in long-term care settings.

Not applicable.

Adults presenting for autism-related clinical care often report a range of physical and mental health condition histories. This exploratory study examined whether reported conditions formed person-level profiles among adults with documented or self-reported autism seeking autism-affirming telehealth services.

We conducted a retrospective chart review of 640 adults receiving care from a United States-based telehealth organization. Latent class analysis used 30 binary indicators: 28 physical health condition endorsements and two psychiatric diagnostic indicators, anxiety and mood disorder. Supporting analyses included bivariate correlations, logistic regression, class comparisons, covariate analyses, and sensitivity analyses for rare indicators, overlapping indicators, physical-only class structure, and ADHD.

The retained three-class solution identified a Mental and Physical Health class (17.7%), a Mental Health Predominant class (56.3%), and a Minimal Reported Conditions class (26.1%). The Mental and Physical Health class showed high mood and anxiety endorsement alongside elevated multisystem physical concerns, including chronic pain, chronic fatigue, headaches, dizziness, numbness or tingling, irritable bowel symptoms, hormone-related problems, and bone or joint problems. The Mental Health Predominant class showed similarly high psychiatric endorsement but limited physical endorsement. The Minimal Reported Conditions class showed low endorsement across all indicators. Bivariate analyses showed strong clustering among neurological/autonomic, pain/fatigue, and musculoskeletal indicators, with smaller psychiatric-physical associations. Age, diagnostic documentation status, and ADHD history differed across classes, although documented and self-reported autism groups were represented across all three profiles. Sensitivity analyses supported the three-class structure after excluding rare or overlapping indicators; the physical-only analysis favored a two-class higher-versus-lower endorsement structure.

Reported health-condition histories in this clinical service sample were described by three person-level profiles, suggesting physical and mental health conditions may be partially dissociable rather than uniform. These exploratory profiles may inform more individualized care and future research on health variability among autistic adults.

Findings are provisional. Data came from checklist-based clinical intake records that were not independently validated, autism status was not confirmed by standardized assessment, and the treatment-seeking telehealth sample may not generalize to autistic adults with higher support needs or limited telehealth access.

Not applicable; this is an exploratory descriptive study and not a health care intervention.

Peer support is a prominent recovery-oriented innovation in mental healthcare, with implementation efforts to integrate peer support workers reported worldwide. However, its sustainment, including the factors that shape it, remains underexplored. Sustaining evidence-informed innovations and their associated benefits is a global policy priority and a complex challenge for health care systems. Although recent research has advanced theoretical frameworks and tools to support sustainability planning and assessment, there is a growing need for empirical studies that examine how sustainment unfolds in practice. Drawing on qualitative interviews, this study explores the sustainment of peer support two years post-implementation in a mental health service overseeing community housing for adults with mental health challenges in Canada. During 2022 and 2023, nineteen individuals including managers, service providers and peers, and housing proprietors involved in implementing and sustaining peer support were interviewed. Data collection and analysis were guided by the Consolidated Framework for Sustainability Constructs in Healthcare to explore determinants influencing sustainment. Sustainment was influenced by a constellation of factors spanning the design and delivery of peer support, organisational setting and processes, involved actors, available resources, and external contextual conditions. These factors exerted positive, constraining, or ambivalent influences on sustainment. Positive influences included staff belief in peer support values, funding availability, perceived effectiveness of peer support, peer workers' expertise, integration of peer support innovation and peers into organisational policies and routine practices, organisational leadership, and participant satisfaction with being involved in peer support implementation. Key challenges included limited human resources, high staff workload, and union and administrative constraints, particularly those related to the lack of formal employment regulation of peer support workers. The interplay of additional contextual factors, such as provincial (regional) policy guidelines, training efforts, and organisational culture, highlights the context-dependent nature of sustaining peer support. This study advances understanding of peer support sustainment by demonstrating that it emerges from a dynamic interplay of influences across multiple and interrelated levels. By conceptualising sustainability determinants as context-dependent and evolving influences rather than fixed barriers or facilitators, the study offers a refined lens for examining peer support sustainment in practice. These findings have important implications for policy, research and practice in supporting the long-term integration of peer support workers in mental healthcare.

Mental health applications (MHAs) hold promise for expanding access to care, yet user satisfaction varies across cultural contexts. Drawing on value co-creation theory, this study integrates developer and user perspectives to examine cross-country differences between China and the United States. We analyzed platforms and reviews data from leading Chinese and US app markets. On the developer side, US-based applications demonstrated substantially greater engagement in clinical pipelines and public claims than Chinese applications; however, these indicators were not significantly associated with app store ratings in the US sample and could not be meaningfully estimated in the Chinese sample due to very limited disclosure. On the user side, satisfaction drivers differed markedly: Chinese users emphasized core service functions such as online consultation, whereas US users showed stronger preferences for experiential features such as meditation practice. Across both contexts, personalized services were consistently rated as insufficient. Future development should shift MHAs from "digital products" toward "evidence-based, user-centered health tools".