RESUMO
The recent development and mass administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines allowed for disease control, reducing hospitalizations and mortality. Most of these vaccines target the SARS-CoV-2 Spike (S) protein antigens, culminating with the production of neutralizing antibodies (NAbs) that disrupt the attachment of the virus to ACE2 receptors on the host cells. However, several studies demonstrated that the NAbs typically rise within a few weeks after vaccination but quickly reduce months later. Thus, multiple booster administration is recommended, leading to vaccination hesitancy in many populations. Detecting serum anti-SARS-CoV-2 NAbs can instruct patients and healthcare providers on correct booster strategies. Several in vitro diagnostics kits are available; however, their high cost impairs the mass NAbs diagnostic testing. Recently, we engineered an ACE2 mimetic that interacts with the Receptor Binding Domain (RBD) of the SARS-2 S protein. Here we present the use of this engineered mini-protein (p-deface2 mut) to develop a detection assay to measure NAbs in patient sera using a competitive ELISA assay. Serum samples from twenty-one patients were tested. Nine samples (42.8%) tested positive, and twelve (57.1%) tested negative for neutralizing sera. The data correlated with the result from the standard commercial assay that uses human ACE2 protein. This confirmed that p-deface2 mut could replace human ACE2 in ELISA assays. Using bacterially expressed p-deface2 mut protein is cost-effective and may allow mass SARS-CoV-2 NAbs detection, especially in low-income countries where economical diagnostic testing is crucial. Such information will help providers decide when a booster is required, reducing risks of reinfection and preventing the administration before it is medically necessary.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Enzima de Conversão de Angiotensina 2 , COVID-19/diagnóstico , Anticorpos Antivirais , Anticorpos Neutralizantes , Glicoproteína da Espícula de CoronavírusRESUMO
CONTEXT: Supraspinatus tendinopathy and shoulder pain are common in competitive youth swimmers; however, no studies have investigated clinical and structural factors contributing to shoulder pain and disability in master level swimmers. OBJECTIVE: The objectives of this study were: 1) to determine the prevalence of shoulder pain and disability in master level swimmers, 2) to identify the most provocative special tests for shoulder pain, and 3) to determine if shoulder clinical and tissue specific measures, training variables and volume vary between those with and without shoulder pain, dissatisfaction and disability. DESIGN: Cross-sectional. SETTING: Collegiate swimming facilities. PATIENTS OR OTHER PARTICIPANTS: Thirty-nine adult masters level swimmers were evaluated and included in the data analysis. MAIN OUTCOME MEASURES: A survey of demographics, training, and pain and disability ratings using the Penn Shoulder Score and Disability of Arm Shoulder Hand sports module. Swimmers underwent a clinical exam including shoulder passive range of motion (PROM), posterior shoulder endurance test (PSET), supraspinatus tendon structure and posterior capsule thickness. One-way ANOVAs were used to compare demographics, clinical and structural findings between those with significant pain, dissatisfaction and disability (+PDD) and those without (-PDD). RESULTS: Fifteen percent of subjects reported pain at rest, 28% with normal activities (eating, dressing), and 69% with strenuous activities (sports) and 50% reported disability. The +PDD group had less shoulder internal rotation (10°), less ER (8°), and completed less yardage per day and per year. There were significant differences in the supraspinatus tendon structure between the +PDD and -PDD groups. CONCLUSION: Masters swimmers with pain and disability are able to self-limit yardage and likely why they recorded less yardage. The reduced shoulder motion (IR and ER) without posterior capsule differences may be due to rotator cuff muscle/tendon restrictions and the supraspinatus tendon structure may indicate degeneration caused by previous overuse resulting in pain.
RESUMO
Chronic exposure to manganese (Mn) positively correlates with the occurrence of Parkinsonism but little is known about mechanisms of its neurotoxicity. In the present study, we determined the clearance of Mn from rat substantia nigra after its nigral injection and correlated it with the establishment of apomorphine-induced rotational behaviour and loss of striatal tyrosine hydroxylase (TH) immunoreactivity. Our results suggest that Mn is slowly cleared from the substantia nigra, following a first-order kinetics with a t(1/2) of 3 days. Appearance of apomorphine-induced rotational behaviour and loss of TH immunoreactivity within the striatum follows metal clearance were both detected 24 hours after intra-nigral Mn microinjection and maximal 72 hours after injection. The present data suggest that the cellular mechanisms induced by Mn and leading to dopaminergic cell death, occurred shortly after its injection and that the metal concentration needs to reach a threshold value to induce neurotoxic effects. This would indicate that nigral damages are a direct consequence of Mn accumulation.