A 47-year-old woman with Parkinson disease (PD) complicated by severe motor fluctuations had been treated with deep brain stimulation (DBS) for 11 years and intestinal carbidopa/levodopa infusion for 5 years. Three months after her most recent clinic visit, at which both the DBS and infusion pump systems were confirmed to be functioning appropriately, she presented to the emergency department with abnormal movements. On examination, she had continuous, generalized, involuntary hyperkinetic movements with an erratic, dance-like quality, consistent with levodopa-associated dyskinesia. Evaluation revealed rhabdomyolysis, subcutaneous emphysema, and pneumomediastinum. She required admission to the intensive care unit for sedation and airway protection. After a key surgical intervention, she rapidly returned to her previous neurologic status and was discharged home. This case highlights the approach to acute dyskinesia and underscores the challenges of managing severe motor fluctuations in patients with PD.

H5Nx clade 2.3.4.4b viruses are evolving rapidly, expanding host ranges and threatening animal and public health. In the US, genotype B3.13 dominates dairy outbreaks, while D1.1 is linked to fewer cases. In the UK, an asymptomatic ewe infected with genotype DI.2 raised concerns about ruminant susceptibility. We inoculated lactating and nonlactating sheep with D1.1 (H5N1) and A6 (H5N5) viruses. Intramammary inoculation in lactating sheep caused clinical mastitis, high viral loads in milk, and transmission to suckling lambs, which further spread infection to the uninoculated mammary glands. Both ewes and their lambs seroconverted. Aerosol exposure of nonlactating sheep led to transient respiratory infection, with low-level viral replication, and seroconversion. In vitro, both viruses replicated in sheep mammary epithelial cells. These findings establish sheep as a viable ruminant model for H5N1 and H5N5 infection and highlight previously unidentified transmission dynamics, including milk-mediated and lamb-to-ewe spread, relevant for surveillance and biosecurity in ruminant populations.

Pleuroparenchymal fibroelastosis (PPFE) is a progressive interstitial lung disease (ILD) with defining histology of intra-alveolar fibrosis with septal elastosis (AFE), suggesting unique cellular disease processes. Here, we present a binational single-nucleus RNA sequencing atlas of PPFE, based on explanted lungs from 40 patients. Immunofluorescence microscopy, RNA in situ hybridization, micro-computed tomography (CT), and hierarchical phase-contrast (HiP) synchrotron CT provided spatial context. We identify PPFE-associated adventitial and elastofibrotic fibroblasts as key drivers of elastotic remodeling within an inflammatory microenvironment, maintained by immune cells forming tertiary lymphoid structures. Spatial mapping reveals an intriguing zonation of AFE, maintained by intercellular circuits between PPFE-associated cell types. Comparative analysis with idiopathic pulmonary fibrosis highlights CTHRC1+ fibrotic fibroblasts and aberrant basaloid cells as conserved profibrotic cellular machinery mediating collagen deposition across ILDs. This integrative atlas defines the cellular landscape of PPFE and dissects elastotic from fibrotic remodeling, providing a molecular rationale for niche-specific therapeutic strategies.

Primary ciliary dyskinesia (PCD) is a rare multi-system cilia-related disorder, and approximately 50% of individuals with PCD exhibit left-right asymmetry disorder. The dynein axonemal heavy chain 11 gene (DNAH11) pathogenic variants are responsible for primary ciliary dyskinesia 7, with or without left-right asymmetry disorder. This study aimed to detect the pathogenic variants in three unrelated patients diagnosed with PCD or left-right asymmetry disorder based on the clinical and imaging examinations. Whole exome sequencing, Sanger sequencing, and comprehensive bioinformatics analyses were performed. Seven DNAH11 heterozygous variants, which involved evolutionarily conserved residues and were predicted to exert deleterious effects, reduce protein stability, change protein conformation, and affect non-covalent residue's interactions, were identified as potential pathogenic factors responsible for these patients, respectively. In patient 1, three variants in compound heterozygotes, c.[3541A > G];[4334G > A;12428T > C] (p.[(Ser1181Gly)];[(Arg1445Gln;Met4143Thr)]), were confirmed. In patient 2, two variants in potential compound heterozygotes, c.2912A > G(;)7980A > T (p.(Asp971Gly)(;)(Gln2660His)), were detected. In patient 3, two variants in compound heterozygotes, c.[845T > C];[11402C > G] (p.[(Met282Thr)];[(Pro3801Arg)]), were confirmed. The phenotypes observed in these patients are consistent with typical/probably atypical PCD or DNAH11-associated ciliopathy, although functional validation is needed to confirm variant pathogenicity. These findings expand the phenotypic spectrum of DNAH11 variants and may facilitate more accurate genetic diagnosis and counseling.

The severe acute respiratory syndrome coronavirus 2 spike glycoprotein enables infection through a key conformational transition that exposes its receptor binding domain (RBD). Experimental evidence indicates that spike mutations, particularly the early D614G variant, alter the rate of this conformational shift, potentially increasing viral infectivity. We conducted extensive weighted ensemble simulations of the Ancestral, Delta, and Omicron BA.1 spike strains to investigate relationships between sequence mutations and RBD opening dynamics. We observe that Ancestral, Delta, and Omicron BA.1 spike RBDs open differently. Via dynamical network analysis, we identified two allosteric communication networks connecting all S1 domains: the established N2R linker and a newly investigated antiparallel R2N linker. In Delta and Omicron BA.1 variant spikes, RBD opening is facilitated by both linkers, while the Ancestral strain relies predominantly on the N2R linker. In the Ancestral spike, the D614-K854 salt bridge impedes allosteric communication through the R2N linker, whereas the loss of this salt bridge in all subsequent variants of concerns allows for increased local flexibility, thereby accelerating RBD opening. Hydrogen-deuterium mass spectrometry experiments validate these altered dynamics in the D614 region. This study unveils a "hidden" network, connecting the N-terminal domain to the RBD via the 614-proximal region, and the D614G mutation reshapes the fitness landscape of these critical viral glycoproteins.

Previous studies have highlighted the relationship between socioeconomic inequalities and the general population's risk of contracting or dying from COVID-19 during the 2020-2023 pandemic. In France, socioeconomic inequalities vary across metropolitan areas; few studies have investigated whether this variation explains the spatial disparities observed in COVID-19 incidence and testing rates during the pandemic. We examined the relationship between socioeconomic profiles and these two rates across all 22 metropolitan areas in France for eight of the country's nine epidemic waves.

For each metropolitan area, we used socioeconomic variables from census data to define socioeconomic profiles through principal component clustering. We then used spatialized generalised additive mixed models to analyze associations between these profiles and both testing and incidence rates, for each epidemic wave from July 2020 to March 2023. Finally, we performed meta-regressions to study the distribution of testing and incidence rate ratios among the various socioeconomically deprived and privileged profiles within each of the 22 metropolitan areas, according to COVID-19 vaccination rate.

Testing rates were lower in socioeconomically deprived metropolitan areas than in privileged ones, except during wave 4 (July-October-2021), when testing rates were more similar. Incidence rates were higher in deprived areas (waves 2-4, July-2020 to October-2021), but this pattern reversed between waves 6-9 (March-2022 to March-2023). Meta-regressions indicated that high vaccination coverage was associated with a narrower gap in testing between deprived and privileged areas. Moreover, for each metropolitan area, the higher the level of deprivation in a zone within the deprived profile, the greater the deprived-privileged gap in under-testing.

The impact of socioeconomic inequalities on testing and incidence patterns during the COVID-19 pandemic in each metropolitan area in France was driven by the most deprived zones; this impact varied across epidemic waves. Higher vaccination rates and government health measures (lockdowns, mandatory health pass) may have reduced this variation.

The venous excess ultrasound score (VExUS) is a promising method to assess venous congestion in adults, but evidence in children is scarce. This study aimed to evaluate the feasibility, reproducibility, and clinical usefulness of VExUS in pediatric patients. We also explored whether portal venous Doppler (PVD) alone could serve as a faster alternative and assessed the role of inferior vena cava (IVC) measurements. In this prospective single-center study, 35 pediatric patients were enrolled between 2022 and 2024. Associations between clinical variables and VExUS grades at admission (VExUS-0), 24 h (VExUS-24 h), and 48 h (VExUS-48 h), as well as PVD at corresponding time points, were analyzed. The relationship between IVC diameter and VExUS was also evaluated. VExUS demonstrated perfect reproducibility (κ coefficient and intraclass correlation coefficient = 1). Patients with VExUS-0 or VExUS-24 h grades 2-3 had longer aortic cross-clamp times (p = 0.03; 0.04) and higher vasoactive-inotropic scores (p = 0.01) than those graded 0-1. A higher incidence of acute kidney injury was observed in VExUS-24 h grades 2-3 (p = 0.04). Similar associations were found with PVD. Most patients with VExUS grades 2-3 had non-dilated IVCs according to pediatric reference values.

 VExUS is a feasible, reproducible, and clinically relevant bedside tool for detecting venous congestion in children. Its association with morbidity markers suggests prognostic potential, with optimal performance 24 h after PICU admission. PVD may provide comparable information in less time, while IVC diameter appears unreliable for this purpose.

• VExUS enables bedside assessment of venous congestion and is associated with adverse outcomes in adults, particularly after cardiac surgery. • However, pediatric evidence is limited, and its clinical applicability remains uncertain.

• This study shows that VExUS is feasible, reproducible, and associated with morbidity after pediatric cardiac surgery, with the highest prognostic value at 24h. • Portal Doppler may provide comparable performance, whereas IVC diameter is is not a reliable marker of venous congestion in this population.

To estimate the short-term effect of rosuvastatin versus atorvastatin on the corrected QT interval (QTc) by emulating a published randomized controlled trial (RCT) using electronic health record (EHR) data, and to assess whether target trial emulation (TTE) can replicate RCT findings for a pharmacological safety outcome at substantially greater scale.

Retrospective cohort study emulating a target trial, reported according to the Transparent Reporting of Observational Studies Emulating a Target Trial (TARGET) guideline.

Single tertiary A teaching hospital in China, March 2012 to September 2024.

Of 619,216 cardiology hospitalizations, 165,460 new statin users with suspected coronary artery disease met all eligibility criteria. After 1:1 propensity score matching, 98,860 patients (49,430 per group) constituted the analytic cohort. All standardized mean differences were below 0.013 after matching.

The primary outcome was the change in Fridericia-corrected QT interval (ΔQTcF) from baseline to first follow-up electrocardiogram (24-72 h). Secondary outcomes included newly emerged QTc prolongation, any QTc increase, clinically significant increase (> 30 ms), severe QTc prolongation, and a composite cardiac safety endpoint. Both intention-to-treat and per-protocol effects were estimated.

The mean ΔQTcF in the rosuvastatin group was + 7.71 ms (SD 20.41) versus + 0.31 ms (SD 22.30) in the atorvastatin group, yielding a between-group difference of 7.40 ms (95% CI 7.13 to 7.67; P < 0.001). Newly emerged QTc prolongation occurred in 14.7% versus 10.5% (risk ratio 1.40, 95% CI 1.35 to 1.45). The composite cardiac safety endpoint did not differ (0.4% versus 0.5%; P = 0.24). Results were consistent across eight subgroups and six sensitivity analyses. The TTE estimate was concordant with the published RCT finding of 7.40 ms (heterogeneity P = 1.00), with a 14-fold narrower confidence interval. The negative control outcome analysis showed no residual bias.

Rosuvastatin was associated with a 7.40 ms greater short-term QTcF prolongation than atorvastatin in a cohort 212 times larger than the emulated RCT, without excess clinical cardiac events over a mean follow-up of 48 h. Target trial emulation successfully replicated the RCT finding for a short-term drug safety outcome, demonstrating the framework's value for pharmacovigilance research using routine clinical data.

The optimal timing for reinitiating antiplatelet therapy after treatment of chronic subdural hematoma (cSDH) remains uncertain, especially when middle meningeal artery embolization (MMAE) is used as an adjunct to surgery. This study evaluated the safety and outcomes of early antiplatelet reinitiation in patients undergoing combined surgical evacuation and MMAE, and compared outcomes in antiplatelet-treated patients receiving surgery with versus without MMAE. Adult cSDH patients from the TriNetX database (May 2020-May 2025) were identified using ICD-10 and RXNORM codes. Two propensity score-matched analyses were performed: (1) patients receiving surgery with adjunct MMAE, stratified by antiplatelet initiation within 30 days; and (2) antiplatelet-treated patients undergoing surgery with adjunct MMAE versus surgery alone. Outcomes included rescue surgery and 6-month mortality. After matching, early antiplatelet use in surgery + MMAE patients (n = 163 per group) was not associated with higher rescue surgery rates (OR 0.68, 95% CI 0.32-1.48) or mortality (OR 1.52, 95% CI 0.73-3.20). Among antiplatelet-treated patients, surgery + MMAE (n = 176) had similar rescue surgery rates to surgery alone (n = 176) but significantly lower mortality (10.8% vs. 21.0%; OR 0.46, 95% CI 0.25-0.83, p = 0.009). Early antiplatelet reinitiation appeared safe after cSDH evacuation with adjunct MMAE. The associated lower 6-month mortality with adjunct MMAE in antiplatelet-treated patients is observational and hypothesis-generating, and warrants prospective confirmation.

This review examines the unique cardiovascular disease patterns in older women, focusing on sex and age-specific pathophysiology, diagnostic challenges, and disparities in management. We aim to clarify how aging and hormonal transitions influence disease presentation and outcomes among women, and to identify gaps in cardiovascular care.

Emerging data demonstrate that older women are disproportionately affected by HFpEF, coronary microvascular dysfunction, atrial fibrillation, and valvular heart disease. These conditions are influenced by vascular stiffness, myocardial remodeling, and systemic inflammation and often present with atypical symptoms leading to diagnosis delays. Contemporary studies highlight persistent gaps in timely diagnosis, referral for advanced therapies, and representation in clinical trials. Increasing attention is being directed toward frailty, multimorbidity, and patient-centered care models in this population. Recognizing age and sex-specific characteristics, increasing representation of older women in clinical trials, improving equitable access to diagnostic and therapeutic resources, and aligning treatment decisions with patient priorities are critical to narrowing existing gaps and improving long-term outcomes for older women with cardiovascular disease.