Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection

IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: PASC and 44 participant-reported symptoms (with severity thresholds). RESULTS: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. CONCLUSIONS AND RELEVANCE: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC

Researching COVID to Enhance Recovery (RECOVER) Adult Study Protocol: Rationale, Objectives, and Design

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options

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Formulation and Evaluation of Transdermal Patches of Salbutamol

ABSTRACT Transdermal drug delivery system of Salbutamol using sodium carboxy methyl cellulose and other additives was prepared by solvent casting technique. Salbutamol, a β 2 adrenergic receptor agonist used as an antiasthmatic agent. Propylene glycol (10%) was used as permeation enhancer and Dibutyl pthalate (5%) as plasticizer. The prepared films exhibited satisfactory physicochemical characters such as thickness, weight, drug content, percentage dissolution and swelling inde

Investigation of Different Configurations in GeSe Solar Cells for Their Performance Improvement

Thin-film-based photovoltaics offer affordable solar panels (high energy output per unit cost). Various materials have been used for thin-film solar cells, and still, new materials are being tested. In this work, the overall performance of GeSe is enhanced theoretically from a generic solar structure to a configuration that yields a whopping 33.12% efficiency along with an open circuit voltage of 1.04 V by optimizing various active layers using solar cell capacitance simulator SCAPS. The results have been explained most simply, utilizing the physics behind introducing hole transport layers in solar cells. The work also shows how certain contradictions in parameter values in the literature of GeSe can influence the cell’s performance. The result shows why the substrate structure is better than the superstrate structure. Most of the reported results are on superstrate structure, which might have caused poor performance in previously experimentally produced GeSe solar cells

Vasicinone, a pyrroloquinazoline alkaloid from Adhatoda vasica Nees enhances memory and cognition by inhibiting cholinesterases in Alzheimer's disease

Background: Alzheimer's disease (AD) is a neurodegenerative disease with cognitive and memory decline. Due to the lack of effective treatment for AD, there is an interest in finding novel compounds to treat AD. The leaves of Adhatoda vasica Nees (AV) exhibited anti-AD effects and known to be rich in pyrroloquinazoline alkaloids. However, the role of pyrroloquinazoline alkaloids as an anti-AD was not explored. Therefore, the present study aimed to isolate active pyrroloquinazoline alkaloids through bioactivity guided fractionation from AV to explore their anti-AD effect. Method: Column chromatography of dichloromethane (DCM) fraction of methanolic extract was used to isolate the alkaloids from AV. The isolated compounds were characterized by TLC, HPLC, ATR, HRMS, and NMR techniques. In-silico, studies were performed to investigate the interaction of the isolated compounds with cholinesterase enzymes (AChE and BuChE). Further, in-vitro assays were carried out to evaluate the AChE, BuChE, and Aβ inhibition properties. Propidium iodide displacement assay was performed to know the selectivity of isolated compounds at AChE PAS site. Furthermore, in-vivo studies were performed to evaluate memory and cognitive improvement against scopolamine-induced amnesia and Aβ induced neurotoxicity in rats. Results: A couple of leads were identified through bioactivity guided fractionation, such as vasicinone (VAS) and vasicine (VA) were responsible for the cholinesterase inhibition in DCM fraction. In-silico studies identified that both compounds exhibited stable interactions at AChE and BuChE active sites. VAS and VA inhibited the AChE, BuChE, and Aβ aggregation in-vitro studies and effectively displaced the propidium iodide at AChE PAS site. Further, in-vivo studies showed that administration of VAS and VA significantly improved the memory and cognitive dysfunction in scopolamine and Aβ induced cognitive and memory impairments in rats. Besides, both VAS and VA recovered the hippocampal cell density in AD rats. Moreover, VAS and VA did not show any sign of toxicity. Conclusions: The present study revealed that VAS acts as potent anti-AD agent from Adhatoda vasica Nees and it showed similar potency profile to VA against memory and cognitive impairment in AD. Both compounds VAS and VA possess strong potential in the preclinical development as natural drugs for anti-AD

The Possibility of Site Effects: The Anjar Case, following Past Earthquakes in Gujarat, India

by Sudhir Kumar Jain et al.