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: 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.

Background/Aims: Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy. Methods: A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I 2 statistics. Results: Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, –50.72; 95% CI, –94.23 to –7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data. Conclusions Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.

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.

Purpose: Despite extensive research on gastric cancer (GC), efforts to consolidate the numerous associations between possible factors and GC risk remain lacking. This systematic review aimed to provide an overview of potential GC-associated pairs. Materials and Methods: We systematically searched PubMed, Embase, and Cochrane databases, from their inception to April 23, 2022, for eligible systematic reviews and metaanalyses to investigate the association between any possible factors and GC risk. After the inclusion of 75 systematic reviews and meta-analyses, 117 association pairs were examined. We reanalyzed the included meta-analyses and produced effect estimates using uniform analytical models. The certainty of the evidence for each association pair was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Results: Iatrogenic factors, including antibacterial drugs, were associated with an increased risk of GC. Epstein-Barr virus and Helicobacter pylori infections were also associated with an increased risk of GC, while human T-lymphotropic virus type 1 (HTLV-1) infections were associated with a reduced risk. Dietary habit was a major factor influencing moderate to high GRADE associations. Positive associations were observed for heavy alcohol consumption (relative risk [RR], 1.13; 95% confidence interval [CI], 1.06–1.12), refined grain consumption (RR, 1.36; 95% CI, 1.21–1.53), and habitual salt intake (RR, 1.41; 95% CI, 1.04–1.91). Conclusions The associations between GC risk and dietary and nutritional factors were considerably heterogeneous, whereas other factors, such as lifestyle and iatrogenic and environmental exposures, were consistent across regions. Therefore, dietary interventions for GC prevention should be tailored specific to regions.

Background: Distal biceps tendon ruptures are rare injuries that predominantly affect active men between the fourth and sixth decades, with a higher incidence in weightlifters and bodybuilders. This study aimed to comprehensively review cases involving distal biceps tendon ruptures, focusing on sociodemographic factors (such as sex, age, occupation, and smoking status), injury mechanisms, postoperative outcomes, and recorded complications. Methods: This retrospective review examines distal biceps injuries at Royal Berkshire Foundation Trust NHS Hospital from 2017 to 2023. Analyzed data encompasses demographic information, injury mechanisms, clinical findings, and complications. Outcomes were assessed using the range of movement and Elbow Oxford Score. Results: The average age of 73 patients (72 men and 1 woman) was 45.6 ± 9.4 years, with 75.3% falling between 36 and 55 years.Manual workers represented 46.6%, and 9.6% reported comorbidities and 6.8% steroid use. Lifting heavy objects and sports injuries were the predominant causes, constituting 43.8% and 13.7%, respectively. Most injuries (91.8%) involved complete tears, and most underwent acute surgery within the initial 4 weeks (84.9%). The most common complications were heterotopic ossification (23.3%) and neurological injury (16.4%). Ongoing weakness and fatigue were reported by 6.8%. At final follow-up, 75.7% of patients demonstrated a range of movement comparable to the contralateral side. However, 13.7% had a limited pronationsupination arch with a mean loss of 20° ± 14°, 11% had an extension lag with a mean of 15° ± 7°, and 2.7% showed a 10° flexion loss compared to the contralateral side. Conclusions Distal biceps injuries are rare but lead to substantial functional loss without operative treatment. Surgical repair yields positive functional outcomes. Our study aligns with existing literature, emphasizing a predominance of middle-aged men and manual workers. It underscores the impact of corticosteroids and smoking, highlights surgical efficacy, and advocates for increased research in distal biceps injury prevention and treatment understanding.