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Factor VIIa–released extracellular vesicles attenuate joint bleed–induced hemophilic arthropathy
Abstract Repeated bleeding into joints in hemophilia leads to chronic inflammation that plays a central role in the pathogenesis of hemophilic arthropathy (HA). Our recent studies revealed that factor VIIa (FVIIa) treatment releases extracellular vesicles from endothelial cells (eEVs) and FVIIa-released eEVs exhibit anti-inflammatory and barrier-protective functions. The present study was undertaken to investigate the effect of FVIIa-released eEVs on HA and the mechanism of their protective effect. Joint bleeding in hemophilia (F8–/–) mice was induced by a needle puncture injury. Injured mice were treated with saline, control eEVs, or FVIIa-released eEVs, and the changes in the knee joints were analyzed by gross examination of knees as well as histological and immunohistochemical analysis. Joint tissues were examined for evidence of synovial hyperplasia, macrophage infiltration, neoangiogenesis, cartilage degeneration, and chondrocyte apoptosis. The data showed that treatment of mice with control eEVs had no significant effect on the development of HA, whereas treatment with FVIIa-released eEVs markedly reduced all pathological features of joint bleed–induced HA. Incorporation of microRNA10a (miR10a) inhibitor into FVIIa-released eEVs abrogated the protective effect of FVIIa-released eEVs on HA. More importantly, loading miR10a mimic into control eEVs conferred a protective effect. Administration of miR10a-containing FVIIa-released eEVs or control eEVs loaded with miR10a mimic was found to abrogate joint bleed–induced interleukin-6 production in the synovium. miR10a in eEVs had no effect on hemostasis. Cumulatively, our data indicate that EVs containing miR10a that effectively suppress synovial inflammation would have immense therapeutic value in treating HA.
Resistance is not futile: RAS inhibition resensitizes AML
Time to say adieu to FISH in myeloma diagnostics
Prior transplantation and idecabtagene vicleucel in multiple myeloma: a secondary analysis of CIBMTR data
Abstract Recent analyses have suggested a possible negative impact of prior autologous stem cell transplantation on outcomes with idecabtagene vicleucel (ide-cel) chimeric antigen receptor T-cell therapy in relapsed/refractory multiple myeloma. Our registry-based analysis of >800 ide-cel recipients did not identify any such association.
Effects of plyometric jump training on measures of physical fitness and lower-limb asymmetries in male soccer players according to maturity: A randomized controlled trial
The purpose of this study was to determine the effects plyometrics on dynamic balance, muscle power and lower limb asymmetries in youth soccer players according to maturity. 43 youth soccer players (23 pre pubertal and 20 post pubertal) were classified according to their peak height velocity (PHV) and participated in a 8-week progressive plyometrics training program or an active control with two weekly sessions, alongside three regular soccer-specific training sessions per week. Participants’ training and performance caliber was rated Tier 2. While plyometrics training groups performed jumping and hopping exercises such as maximal and submaximal hopping on stable ground, active control groups performing passing skills. Pre and post training, tests included the Y balance test, single leg hop and 505 change-of-direction speed (CoD) tests; and lower limb asymmetries were calculated based upon these tests. The main findings were that plyometrics significantly improved these physical attributes, with greater enhancements observed in the post-Peak Height Velocity (PHV) group compared to both the pre-PHV group and the active control group. However, asymmetry did not improve after the training intervention and even increased for balance test in the post-PHV training groups compared with the pre-PHV groups at the post test. Plyometrics effectively enhances jumps, CoD and dynamic balance, with greater benefits observed in post- PHV male soccer players. While overall lower-limb asymmetry largely remained unchanged, a notable finding was an increase in balance asymmetry specifically within the post-PHV group, attributed to a differential enhancement of left and right limb balance.
Lethal effect of heterologous Haemonchus contortus α- and β-tubulin expression in Leishmania tarentolae
Benzimidazoles are widely used anthelmintics that target β-tubulin and disrupt microtubule formation, yet the precise mode of action and resistance mechanisms in parasitic nematodes remains incompletely understood. To investigate the processes, heterologous expression of Haemonchus contortus isotype-1 α-tubulin and isotype-1 β-tubulin linked to the selection markers nourseothricin and hygromycin, respectively, was attempted following integration into Leishmania tarentolae ssu(18S) loci. Transcription of both tubulin genes was confirmed by RT-PCR two days post-transfection. However, transgenic L. tarentolae failed to recover or enter exponential growth under antibiotic selection. In contrast, control constructs containing scrambled open reading frame integrated successfully and yielded viable and proliferating lines expressing the corresponding mRNAs. These findings indicate that translation of functional H. contortus tubulins is toxic to L. tarentolae , likely due to incompatibility with native tubulins and disruption of the native microtubule network, resulting in loss of motility and cell death. The study provides experimental evidence that cross-species tubulin expression can be lethal due to cytoskeletal interference, underscoring the functional specificity of tubulin subunits. This incompatibility represents a barrier to heterologous tubulin expression and suggests that controlled or inducible eukaryotic expression systems may be necessary for the functional production of nematode tubulins.
Investigating the influence of the physical environment on psychiatric nurses wellbeing and professional interactions: A convergent parallel mixed-method study protocol
Nurses in psychiatric hospitals face demanding working conditions, where high emotional burdens, unpredictable patient behavior, and safety concerns contribute to stress. Research highlights the significant impact of the physical environment on healthcare workers’ experiences, with environmental factors either reducing or increasing stress levels, affecting professional interactions, and influencing job satisfaction and well-being. Despite growing recognition of these effects, there remains a need for robust, evidence-based methodologies to systematically examine how specific spatial features impact psychiatric nurses’ experiences. This study protocol aims to develop and test scalable and structured methods to evaluate the influence of the physical environment on stress levels, professional interactions, and spatial perceptions among psychiatric nurses. Conducting research in psychiatric hospitals presents unique challenges, requiring methodologies that consider the sensitive nature of the setting. Issues such as patient confidentiality, changeable work dynamics, and psychological demands on staff require a carefully tailored data collection approach. This study protocol addresses outlined concerns by selecting methods and equipment that minimize disruptions while ensuring reliable and meaningful data collection. Observations are conducted unobtrusively, and the study design prioritizes ethical considerations, ensuring participant comfort and patient privacy. The study employs a convergent parallel mixed methods design, simultaneously collecting and analyzing qualitative and quantitative data. Quantitative measures include wearable sensors tracking heart rate variability, light exposure, and physical activity alongside surveys and systematic in-person observations of professional interactions. Qualitative data, gathered through semi-structured interviews, explores nurses’ perceptions of their work environment and stress levels. The study aims to provide new insights relevant to interdisciplinary research, demonstrating the value of integrating architectural and healthcare perspectives to improve the design of therapeutic and work-friendly environments.
Lifestyle factors and prevalence of semen abnormalities among men undergoing infertility evaluation at oak specialist hospital: A retrospective cohort study
Background Male infertility constitutes a notable health burden in Sub-Saharan Africa, contributing to approximately 40–50% of all infertility cases, compounded by cultural stigma and a grave knowledge issue. The study aimed to apply the updated World Health Organisation (WHO) 6th Edition (2021) criteria to a Ghanaian cohort, generating contemporary prevalence data on semen abnormalities. Methods A retrospective cohort study design was employed, analysing the medical and laboratory records of 221 men who underwent semen analysis as part of an infertility investigation at Oak Specialist Hospital, Kumasi, Ghana. A consecutive sampling method was used to include all eligible patient records from September 1, 2022, to August 31, 2024. Key variables included semen parameters (volume, concentration, motility, morphology, leukocytes) analysed per WHO 2021 guidelines, and associated lifestyle and demographic factors. Data were analysed using descriptive statistics, prevalence rates, and regression analysis. Results The study identified high prevalence rates of oligozoospermia (38.91%) and teratozoospermia (38.46%). A critically high prevalence of leukocytospermia was the most striking finding, affecting 80.54% of the cohort. Regression analysis revealed significant negative associations between sugary drink consumption and sperm motility (p = 0.038) and a positive association between caffeine intake and sperm morphology (p = 0.011). Paradoxically, the cohort’s median values for semen volume, concentration, and motility were significantly above the WHO 2021 lower reference limits. Conclusion Using current international standards, this study provides updated baseline data on male infertility patterns in urban Ghana. The findings reveal a high burden of specific abnormalities, particularly in sperm morphology and leukocyte concentration, which may be more clinically relevant than simple concentration or motility deficits in this population. Modifiable lifestyle factors, such as diet, represent viable targets for public health intervention. These results are vital for clinical benchmarking, guiding targeted health strategies, and establishing a foundation for future comparative studies in similar resource-constrained settings.
Subretinal Photovoltaic Implant to Restore Vision in Geographic Atrophy Due to AMD
Global, regional, and national burden of hip dislocation, 1990–2021, and Bayesian age-period-cohort predictions: Systematic analysis of the Global Burden of Disease study, 2021
Background Hip dislocation is a severe, clinically rare trauma. The global incidence, trends, and causes of hip dislocation have not been precisely documented. We aimed to explore the burden of hip dislocation from 1990 to 2021 and predict the trends over the next two decades. Methods Data from the Global Burden of Disease (GBD) Study 2021 were used to describe the incidence, years lived with disability (YLD), and the corresponding age-standardized rates (ASRs) of hip dislocation for 1990 and 2021, stratified by sex, age, and the Socio-Demographic Index (SDI) across 21 GBD regions and 204 countries and territories. Joinpoint regression analysis was employed to investigate the temporal trends in incidence. Correlations between ASRs and SDI at the regional and national levels were assessed using Pearson correlation analysis. A Bayesian Age-Period-Cohort (BAPC) model was constructed to predict the disease burden for hip dislocation for the next 20 years. Results In 2021, 2,429,935 new cases (95% uncertainty interval [UI] 1,634,456–3,549,251) of hip dislocation were recorded globally, with 109,146 YLDs (95% UI 57,181–190,161) attributable to hip dislocation. Between 1990 and 2021, the incidence of hip dislocation increased by 18.4% (95% UI 8.5–30.5%) and the YLDs increased by 57.2% (95% UI 50.9–66.4%). The corresponding average annual percentage changes (AAPC) in the age-standardized incidence rate and YLD were −0.712 (95% UI −0.79 to −0.634) and −0.535 (95% UI −0.59 to −0.481), respectively. The highest disease burden occurred in regions with high-SDI. Yemen and Afghanistan had the highest age-standardized incidence rates (ASIRs). At both regional and national levels, statistically significant non-linear relationships were observed between the ASRs of hip dislocation and SDI. The highest incidence occurred in young adulthood for males and old age for females. The leading cause was falls. The BAPC model predicts an increasing burden of hip dislocation among females over the next 20 years. Conclusion The global burden of hip dislocation has increased over the last three decades, and is relatively larger in some high-SDI regions and low-income countries. The burden of hip dislocation is expected to increase, particularly among elderly females, due to population aging. Therefore, appropriate preventive measures should be developed to mitigate this trend.
Financing Telehealth — Moving Beyond Payment Parity
Impact of COVID-19 restrictions on thyroid cancer diagnoses in a comprehensive cancer center (2017–2023)
Introduction The Coronavirus 2019 (COVID-19) pandemic disrupted healthcare delivery across the United States, leading to a sharp decline in outpatient visits. Given that thyroid nodule evaluation and diagnosis typically occur in outpatient settings, we hypothesized that these disruptions would reduce thyroid cancer incidence. This study evaluates trends in thyroid cancer diagnosis, treatment, and outcomes at a U.S. comprehensive cancer center from 2017 to 2023. Methods We included adults with pathologically confirmed thyroid cancer diagnosis between January 1, 2017, and December 31, 2023. Primary analyses assessed (1) annual percent change (APC) in thyroid cancer incidence from 2017–2023 and (2) incidence trends across three periods: pre-pandemic (Jan 2017–Mar 2020), pandemic (Apr 2020–Mar 2021), and COVID-years (Apr 2021–Dec 2023). Annual incidence rates were calculated using the total number of individuals cared for within our health system each year as the denominator. Secondary outcomes included tumor size, extent and timing of surgery, and 1-year all-cause mortality across time periods. Results Among 1,031 patients (68% women, 92% White, mean age 52 ± 15.5), age- and sex-adjusted thyroid cancer incidence declined from 34 to 15.6 per 100,000 persons between 2017 and 2022, with an average APC of –14.4%. Diagnoses rose slightly in 2023 (21 per 100,000) compared to 2022 but remained 38% below 2017 levels. No significant differences were observed in tumor size, surgical treatment, gender ratio, or 1-year all-cause mortality across timeframes. Conclusion Age- and sex-adjusted annual incidence of thyroid cancer declined steadily from 2017 to 2022. The annual decrease in thyroid cancer continued through the pandemic years. Tumor size and mortality remained stable across all years evaluated. The increase in diagnoses noted in 2023 may be a correction due to missed cases during the years of the pandemic or could represent a new steady state incidence after years of decline.
Advancing Diagnostic Excellence through Medical Education in Diagnostic Equity
Effects of an information shock on registry-based health indicators: Evidence from a Swedish PFAS crisis
This study investigates how the public announcement of very high levels of the toxic chemicals PFAS in the drinking water in Kallinge, Sweden, impacted the health of local residents. By leveraging the unexpected timing of the announcement and utilizing high-frequency individual-level healthcare data, we can isolate the effects of the information shock independently of any toxic effects of PFAS exposure. Despite numerous reports of distress and concern among those affected, our analysis reveals no significant increase in health care utilization following the announcement, as measured by prescription drug use and specialist healthcare visits. This finding holds true even when specifically examining mental health-related care, prescriptions of antidepressants, and sleeping medications. Overall, our results suggest that both the affected community and public authorities managed the situation effectively, mitigating potential health consequences related to anxiety.
The Things We Carry
Author Correction: Cryo-EM structure of a natural RNA nanocage
Inhibition of HER2 signaling and breast cancer cell growth with a novel antibody targeting HER2 ECD III/IV
Human epidermal growth factor receptor 2 (HER2), a ligand-independent tyrosine kinase receptor belonging to the EGFR family, serves as a key oncogenic driver in breast, gastric, and several other solid tumors. Although anti-HER2 therapies have substantially improved survival outcomes—particularly in breast and gastric cancers—treatment resistance and cancer recurrence remain major clinical challenges. Thus, developing novel antibodies exhibiting complementary effects to the current anti-HER2 therapies could provide additional therapeutic benefits. Here, we describe two novel HER2-targeting monoclonal antibodies, m66 (murine-derived) and r40 (rabbit-derived), which inhibit breast cancer cell proliferation in vitro . Of the two, antibody r40 exhibits stronger suppression of the PI3K/AKT and MAPK signaling pathways compared to m66. Moreover, the addition of r40 to the combination of trastuzumab and pertuzumab leads to a significantly enhanced inhibitory effect. We also determined the cryo-EM structures of the HER2-m66-trastuzumab ternary complex and the HER2-r40-trastuzumab-pertuzumab tetrameric complex, at overall resolutions of 3.2 Å and 3.1 Å, respectively. Structural analyses reveal that m66 recognizes an epitope overlapping with that of pertuzumab, whereas r40 binds within the HER2 ECD III/IV—a region distinct from the binding sites of both trastuzumab and pertuzumab. These findings identify r40 as a promising therapeutic candidate for use in combination with trastuzumab and pertuzumab in the treatment of HER2-positive breast cancer.
Medical Management and Revascularization for Asymptomatic Carotid Stenosis
From law enforcement to public safety: Police officer experiences of naloxone administration to reverse opioid overdose in New York City
The overdose epidemic has reshaped law enforcement’s relationship with public health, as police increasingly adopt overdose response measures, including naloxone training and use. This study analyzed 15 interviews with New York Police Department (NYPD) officers to examine their experiences administering naloxone in their duties. Naloxone was seen as facilitating a shift from traditional law enforcement to a broader public safety role, and officers noted its potential to improve public perceptions of police. However, tensions emerged as officers navigated dual roles in enforcement and health, with concerns that overdose reversal might enable continued drug use or crime. Additionally, officers expressed frustrations about naloxone’s limitations, particularly its inability to address systemic barriers to addiction recovery. These findings underscore the need for clear policies, comprehensive training, and stronger interagency partnerships to enhance the integration of public health strategies within policing and better support officers in responding to the overdose crisis.