Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect various organs. Juvenile-onset SLE (jSLE) may be more severe than the adult-onset form, but the diagnosis and classification remain challenging due to the complex nature of the condition and its resemblance to other conditions. Antinuclear antibodies (ANA) are the immunological hallmark of SLE, but their limited specificity poses challenges. The 2019 (European Alliance of Associations for Rheumatology/American College of Rheumatology) SLE proposed a weighted multi-criteria system for classifying SLE, with ANA serving as an entry criterion. However, seronegative SLE, in which a patient's clinical features and laboratory values are consistent with SLE but their ANA serology test is negative, is a rare subtype of SLE that has been reported in several cases worldwide. Here, we present two rare cases of jSLE in 13- and 11 years old girls with negative ANA. The first case presented as lupus cerebritis and lupus nephritis (LN) class IV and V which showed improvement with treatment. The other one was also diagnosed as LN class IV but showed poor outcome despite aggressive immunosuppressive treatment. These cases highlight the importance of considering lupus-like symptoms in children with negative serology and the need for further research into current diagnostic protocols and calls for a re-evaluation using a more inclusive set of criteria that does not centralize immunological serology.

Background: and Purpose Acute ischemic stroke (AIS) is a leading cause of disability worldwide. While intravenous thrombolysis is recommended within 4.5 hours of last known well (LKW) time, many patients present beyond this window. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating tenecteplase (TNK) administration in AIS patients within 4.5 to 24 hours of LKW. The primary outcomes assessed functional independence and ordinal modified Rankin Scale (mRS) shift at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Results: Three RCTs were included, comprising 1,054 patients (532 TNK and 522 standard medical therapy) with a mean age of 69 years, 59% males, and median baseline National Institutes of Health Stroke Scale score of 10.5. TNK treatment was associated with mRS 0–2 at 90 days (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.04–1.70, P=0.023), indicating a 33% higher likelihood of achieving functional independence. However, the ordinal mRS shift showed no significant difference (standardized mean difference: 0.01, 95% CI: -0.37–0.39, P=0.09). Safety outcomes indicated no difference in the rates of sICH (OR: 2.07, 95% CI: 0.86–5.00, P=0.1), and no difference in 90-day mortality (OR: 1.08, 95% CI: 0.76–1.53, P=0.67). Conclusion This meta-analysis suggests TNK might be safe and effective for selected AIS patients in the 4.5- to 24-hour time window, offering improved functional outcomes without a significant increase in hemorrhagic complications.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Background: Establishing cost-effective informal care services for lonely older adults living at home in developing countries can be an innovative approach for improving their well-being. This study investigated the effectiveness of an informal home care support intervention program (HoSIP) reducing the loneliness and improving quality of life of lonely community-dwelling older adults. Methods: This quasi-experimental pre-post study employed a non-randomized control group design with a 12-week intervention period and three follow-up points at the end of the HoSIP. Questionnaires were used to measure feelings of loneliness (20-item UCLA Loneliness Scale), quality of life (Control, Autonomy, Self‐Realization and Pleasure Scale), general health (12-item General Health Questionnaire), social network (six-item Lubben Social Network Scale), social support (12-item Multidimensional Scale of Perceived Social Support), and self-care ability (17-item Self-care Ability Scale for the Elderly). Repeated-measures analysis of variance was used to gauge the effect of the intervention program over time and in comparison to the control group. Data analyses were performed using the IBM SPSS Statistics software (IBM Corp., USA). Results: We found a significant relationship between the outcome variables, including feelings of loneliness (P<0.001) and quality of life (P<0.001), at different stages of measurement. Despite the positive feasibility results, the implementation of the HoSIP faced challenges due to a lack of facilities (e.g., place restriction for holding educational classes, educational facilities like computers, video projector, and whiteboard at daycare center) and the absence of supporting organizations. Conclusion Utilizing the existing capabilities of older adults to provide online and face-to-face care services can be a cost-effective way to improve their quality of life and reduce loneliness. The process of facilitating such informal care services for lonely older adults should be managed by either governmental or non-governmental organizations to reduce the rate of social isolation among this vulnerable population.

This report describes an approach to recover SARS-CoV-2 RNA from rapid antigen test kit (RTK-antigen) cassettes for whole-genome sequencing (WGS). RNA samples were recovered from 33 RTK-antigen cassettes for WGS, with 18 samples achieving more than 80% genome coverage. This work provides a proof-of-concept that positive RTK-antigen cassettes can be safely transported, stored and subjected to WGS, enabling swift identification of circulating variants.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Background: Establishing cost-effective informal care services for lonely older adults living at home in developing countries can be an innovative approach for improving their well-being. This study investigated the effectiveness of an informal home care support intervention program (HoSIP) reducing the loneliness and improving quality of life of lonely community-dwelling older adults. Methods: This quasi-experimental pre-post study employed a non-randomized control group design with a 12-week intervention period and three follow-up points at the end of the HoSIP. Questionnaires were used to measure feelings of loneliness (20-item UCLA Loneliness Scale), quality of life (Control, Autonomy, Self‐Realization and Pleasure Scale), general health (12-item General Health Questionnaire), social network (six-item Lubben Social Network Scale), social support (12-item Multidimensional Scale of Perceived Social Support), and self-care ability (17-item Self-care Ability Scale for the Elderly). Repeated-measures analysis of variance was used to gauge the effect of the intervention program over time and in comparison to the control group. Data analyses were performed using the IBM SPSS Statistics software (IBM Corp., USA). Results: We found a significant relationship between the outcome variables, including feelings of loneliness (P<0.001) and quality of life (P<0.001), at different stages of measurement. Despite the positive feasibility results, the implementation of the HoSIP faced challenges due to a lack of facilities (e.g., place restriction for holding educational classes, educational facilities like computers, video projector, and whiteboard at daycare center) and the absence of supporting organizations. Conclusion Utilizing the existing capabilities of older adults to provide online and face-to-face care services can be a cost-effective way to improve their quality of life and reduce loneliness. The process of facilitating such informal care services for lonely older adults should be managed by either governmental or non-governmental organizations to reduce the rate of social isolation among this vulnerable population.

Background: Parkinson’s disease is a debilitating and the second most common neurodegenerative disorder with a high prevalence. Parkinson’s disease has a multifaceted etiology characterized by an altered redox state and an excessive inflammatory response. In this study, we investigated the potential neuroprotective properties of carvacrol in a haloperidol-induced Parkinson’s model. In female Sprague-Dawley rats, the animal Parkinson model was induced by intraperitoneally administering 1 mg / kg of haloperidol once daily for fifteen days. Carvacrol was administered at a dose of 25 and 50 mg / kg once daily for fifteen days before haloperidol administration. In order to further illustrate the vital role of the tumor necrosis factor (TNF-α) pathway, we administered 50 mg / kg of the TNF-α inhibitor thalidomide once daily for 15 days. Results: Our results showed that haloperidol-induced motor deficits, changed endogenous antioxidant enzymes, along with higher levels of inflammasome (NLRP3) and other inflammatory mediators. Moreover, increased levels of lipid peroxidase (LPO) indicated a significant rise in oxidative stress due to haloperidol. Moreover, carvacrol reduced these effects by preventing pyroptosis mediated by the inflammasome (NLRP3) and TNF-α. The administration of thalidomide mitigated oxidative stress and suppresses inflammatory pathways through the augmentation of the intrinsic antioxidant system. Further, co-treatment of carvacrol with thalidomide synergized the neuroprotective effect of carvacrol as demonstrated by various immunoassays and histology analyses. Conclusions Taken together, our findings suggest that carvacrol mitigated haloperidol-induced Parkinson-like symptoms, partially through the downregulation of TNF-α and NLRP3.

Delayed rupture of intracranial aneurysms after endovascular treatment is a rare but serious complication. We report the first documented case of late aneurysmal rupture following treatment with a Contour intrasaccular device. A patient in their 60s with a basilar tip aneurysm underwent endovascular treatment using a 14-mm Contour device. Fifteen months later, the patient presented with a fatal intraventricular hemorrhage, and imaging revealed device displacement and aneurysm growth. This case underscores the importance of meticulous device sizing and follow-up, especially for large aneurysms.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.