COVID-19 is a disease triggered by SARS-CoV-2 and some individuals develop a severe form that can progress to multiple organ failure. Neutrophils have been described as responsible for the release of neutrophil extracellular traps (NETs). The role of the elastase and myeloperoxidase (MPO) in NET release by neutrophils stimulated by SARS-CoV-2 infection was not addressed, and it was the aim of the present study. The NET release by human neutrophils infected with SARS-CoV-2 depends on elastase/MPO migration to the nucleus. Moreover, elastase/MPO migration is a consequence of PKC and PI3K kinase activation, leading to reactive oxygen species generation by the neutrophil mitochondria and NOX-2. We also reanalyzed the single-cell RNA sequencing data available in a database and demonstrated that neutrophils from bronchoalveolar lavage (BAL) fluid of patients with COVID-19 present increased expression of genes involved in the formation of the NOX2 complex, PKC delta and members of the PI3K family. In summary, the release of NETs by neutrophils in response to SARS-CoV-2 infection depends on the sequential activation of the PKC/PI3K/ROS pathway, inducing elastase/MPO migration to the nucleus triggering the NET formation. Thus, our study demonstrates new insights into the signaling pathways that induce NETs in response to SARS-CoV-2, highlighting new targets for studies and therapies for COVID-19.

With increasing H5 avian influenza cases reported globally and the potential for pandemic emergence, induction of cross-reactive antibody responses may represent an important attribute of an effective vaccine. This phase 2 extension study evaluated immunogenicity and safety of MF59-adjuvanted, cell culture-derived H5N6 vaccine (aH5N6c) in adults primed with MF59-adjuvanted, cell culture-derived H5N1 vaccine (aH5N1c) and in unprimed adults. Adults previously primed with two doses of aH5N1c in the parent study V89_18 were randomized to receive two aH5N6c doses (Group 1) or one aH5N6c and one placebo (Group 2) 3 weeks apart. Unprimed adults received two aH5N6c doses (Group 3). Immunogenicity was assessed by hemagglutination inhibition (HI) and microneutralization (MN) assays against the priming (H5N1) and booster (H5N6) strains on Days 1, 8, 22, 43, and 202. Among 258 exposed participants, primed subjects (Groups 1 and 2) showed higher HI geometric mean titers against both strains than unprimed (Group 3) subjects, with MN responses similarly enhanced. Heterologous H5N1 responses were robust in primed subjects (Day 43 HI GMTs: 333-343; seroconversion rates >89%) but minimal in unprimed subjects, with responses persisting to Day 202. Solicited adverse events were mild or moderate, comparable between groups, and consistent with other MF59-adjuvanted pandemic vaccines; no vaccine-related serious adverse events occurred. Heterologous H5N6 booster vaccination in H5N1-primed adults elicited strong cross-reactive immunity against the priming strain, demonstrating long-lasting immune memory for at least 6 y and supporting heterologous prime-boost strategies for pandemic preparedness against emerging H5 outbreaks.

Stroke frequently results in long-term motor impairments, making effective rehabilitation essential for functional recovery. However, the development of intelligent rehabilitation systems is hindered by the lack of large-scale kinematic data from stroke patients. Here, we present REHAB, a wearable sensor-based kinematic dataset collected from 120 post-stroke patients during a two-week rehabilitation program. The dataset comprises signals recorded from 27 standardized assessment movements and 16 rehabilitation training movements, providing comprehensive limb kinematics together with corresponding task annotations and clinical labels. Detailed descriptions of the data acquisition protocol, sensor configuration, and data organization are provided to ensure reproducibility and facilitate reuse. In addition, systematic quality-control procedures, including clinician-guided acquisition, sensor calibration, signal inspection, and preprocessing standardization, were implemented throughout the data collection pipeline to ensure data quality and consistency. REHAB provides a comprehensive and clinically relevant kinematic resource for stroke rehabilitation research and may support future studies in rehabilitation assessment, movement analysis, wearable sensing, and data-driven intelligent rehabilitation systems.

A retrospective analysis was conducted on the baseline characteristics, clinical symptoms and signs, laboratory and imaging findings, and treatment prognosis of 10 PAVF patients from Northern Jiangsu People's Hospital from February 2013 to November 2024. The age of onset was between 16 and 79 years, with 3 cases in men and 7 cases in women. Among the 10 patients, 9 had pulmonary arteriovenous fistula and 1 bronchial artery-pulmonary vein fistula. Clinically, there were 4 cases of dyspnea and chest tightness, 3 cases of cough and sputum production, 1 case of chest pain, 2 cases of hemoptysis, 1 case of dizziness, 2 cases of nosebleeds, 1 case of multiple red nevi on the skin, 3 cases of asymptomatic findings upon physical examination, and 3 cases of acute cerebral infarction as the onset. Patients are mainly diagnosed with PAVF based on chest contrast-enhanced CT and/or pulmonary artery CT angiography (CTA). In terms of treatment, 6 cases underwent interventional embolization; 2 patients underwent surgical treatment: one underwent thoracotomy to remove the diseased lob, and one underwent video-assisted thoracoscopic lobectomy; 2 patients received conservative treatment. 10 patients improved and were discharged after treatment, with follow-up lasting 2.1-4.5 years. Among them, one complex PAVF patient was admitted one year after surgery for a second interventional treatment. During follow-up, 10 patients had stable conditions with no related complications, and no recurrence or signs of vascular embolization or recanalization were observed. Clinical manifestations of PAVF patients are diverse, diagnosis requires chest contrast-enhanced CT and pulmonary artery CTA, treatment methods include interventional embolization therapy and surgical treatment, follow-up is required after surgery to evaluate treatment effectiveness.

The use of agents to prevent and treat thromboembolism in pregnancy continues to increase, likely a reflection of greater burden of comorbid conditions in pregnant people, increased awareness of venous thromboembolism prevention efforts, and enhanced access to diagnostic testing. For this reason, obstetricians commonly find themselves involved in the management of patients who are receiving anticoagulation during pregnancy. Here, we summarize the features of anticoagulants used in pregnancy. Despite the advent of newer agents, the most common anticoagulant used in pregnancy remains heparin derivatives (primarily the low-molecular-weight forms).

Chronic limb-threatening ischemia is the most advanced stage of peripheral arterial disease and typically requires revascularization to prevent limb-loss. The choice of open surgical bypass versus endovascular therapy should be individualized based on patients' anatomy, operative risk, and conduit availability. Patients who are suitable candidates for both bypass and endovascular intervention and have an adequate single-segment great saphenous vein should undergo open surgical bypass based on level 1 evidence.

Macular disease is the leading cause of vision loss in the United Kingdom, affecting nearly 1.5 million people. Vascular endothelial growth factor (VEGF) has a major role in the onset and progression of vision-threatening macular conditions such as neovascular age-related macular degeneration, diabetic macular oedema and retinal vein occlusion. Anti-VEGF treatments, given by intravitreal injection, can prevent vision loss and may improve vision but must be started quickly before sight loss is irreversible. Informed by an observational study using Hospital Episode Statistics and the Emergency Care Data Set in England and a Costed Integrated Patient Scenario, we identify issues within the current pathway in England. Our key recommendations to optimise care and improve patient outcomes include: (1) increasing public awareness of macular disease to reduce late presentation; (2) ensuring the right patients are seen in the right place at the right time by improving quality and priority of optometrist referrals and by specialists directing patients with conditions such as diabetes and hypertension to community optometrists in the first instance; (3) planning for current and future demand and capacity using innovative solutions to manage expected increases in medical retina conditions and (4) ensuring patient-centred care. Our evidence should encourage National Health Service organisations at all levels to review macular disease pathways to address immediate issues and plan for the future. A shift in care delivery is needed, embracing scalable sustainable solutions, earlier diagnosis and treatment, improved access to more durable therapies, wider adoption of digital technologies and care closer to home.

Cerebral amyloid angiopathy (CAA) is associated with intracerebral hemorrhage, cognitive decline, and dementia. We examined (1) associations between CAA, cognitive impairment, and depressive symptoms; (2) whether depressive symptoms mediate the relationship between CAA and cognition; and (3) whether CAA neuroimaging markers predict depressive symptom severity.

Recruitment occurred through memory and stroke prevention clinics across 2 sites. Cross-sectional data from probable CAA and controls were analyzed. Neuropsychological tests were grouped into episodic memory, executive function, and processing speed domains. Scores ≥5 on the Geriatric Depression Scale: Short Form (GDS-15) defined "possible depression." Regression and mediation analyses examined associations among CAA status, cognition, and depressive symptoms, and in CAA, associations between neuroimaging biomarkers and GDS-15.

In 85 CAA (mean age 73.5; 35.3% female) and 83 controls (mean age 68.8; 62.7% female), CAA status was associated with poorer performance across cognitive domains. Higher GDS-15 scores were associated with poorer performance across domains. CAA participants had higher odds of "possible depression" (odds ratio 15.71; 95% CI 4.26-80.05, p < 0.001) and scored 2.71 times higher on the GDS-15 than controls (95% CI 2.10-3.51, p < 0.001). In mediation, "possible depression" accounted for significant proportions of the effect of CAA on episodic memory (11%; β = -0.14, 95% CI -0.30 to -0.03, p = 0.014) and executive function (9%; β = -0.14, 95% CI -0.30 to -0.02, p = 0.016), but not processing speed (2%; β = -0.04, 95% CI -0.18 to 0.08, p = 0.56). In 81 CAA participants, higher GDS-15 scores were associated with lower mean cortical thickness (count ratio [CR] 1.33 per SD decrease in thickness, 95% CI 1.09-1.62, p = 0.005), presence of cortical superficial siderosis (CR 2.04, 95% CI 1.35-3.09, p < 0.001), and higher CAA small vessel disease total score (CR 1.16, 95% CI 1.00-1.35, p = 0.047).

CAA participants exhibited greater depressive symptoms and poorer cognition than controls. Depressive symptoms mediated a small portion of the association between CAA and cognition. Cerebral cortex damage may underlie some depressive symptoms. Interventions targeting CAA-related neurodegeneration and treatment of depressive symptoms may support cognitive health in CAA.

Background and objectives A considerable proportion of the older populations have been suffering from stroke multimorbidity. Post-stroke complications often affect the overall well-being of individuals. This study assesses the trends, patterns, and determinants of stroke multimorbidity. Methods We used data from three waves of the World Health Organization study on global ageing and adult health (WHO-SAGE) and analysed individuals aged 50 and above years (Wave I, 7,150 individuals, Wave II, 6,823 individuals, and Wave III, 6,719 individuals) who reported a physician diagnosis of stroke. We analysed trends and patterns of stroke multimorbidity across three waves of WHO-SAGE. Stroke multimorbidity was also analysed with respect to the socioeconomic characteristics of study participants. Results We found a significant increase in the prevalence of stroke multimorbidity over one and a half decade (1,050 per 100,000 to 2,410 per 100,000). The burden of stroke multimorbidity increased steadily, mainly among individuals suffering from two or more long-term conditions. Prevalence of stroke multimorbidity was much higher among older people aged 80 yr and above in wave 3 as compared with wave 1, a relative increase of around 200%. An older individual with no formal education showed an increased prevalence of stroke multimorbidity, a relative change of 102% in last one and a half decade. Interpretation and conclusions This study demonstrated a significant increase in the prevalence of stroke multimorbidity over the last one and a half decade (2007-2020), which considerably varied by age group, sex, place of residence, education, and wealth quintile.

The presence of a patent foramen ovale (PFO) in the heart is a risk factor for stroke due to the potential for paradoxical embolism. Given the implication of the heart in PFO-associated stroke and transcatheter closure, there may be unique factors that prevent patients from returning to physical activity.

To elicit patient perceptions of physical activity after PFO-associated stroke and transcatheter closure.

A purposive sample of 48 individuals who had a PFO-associated stroke participated in this study. Data were collected using semi-structured interviews and data were analyzed using Braun and Clarke's thematic analysis methodology. NVivo software was used to manage data, code, and generate themes.

Participants were on average 47.7 years of age (SD = 8.2). All participants were diagnosed with ischemic stroke or transient ischemic attack and 44 participants received transcatheter PFO closure. The main themes (and sub themes) related to perceptions of physical activity after stroke and closure were: (1) psychological barriers (fear and anxiety, and closure device apprehension); (2) variability in fitness performance (subjective fitness improvement and decline in physical activity compared to before their stroke); and (3) variability in physical recovery (lingering fatigue/neuro-fatigue, residual physical symptoms, and cardiac irregularities after closure).

PFO-associated stroke survivors reported several significant and unique barriers (e.g., cardiac irregularities) to engaging in physical activity after PFO-associated stroke and closure. Some participants also reported improved fitness after their closure procedure. These findings highlight the need for further research to better support patient recovery and reduce uncertainty surrounding return-to-activity recommendations.