Design and implementation of a digital site-less clinical study of serial rapid antigen testing to identify asymptomatic SARS-CoV-2 infection.

Background: Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.

Methods: This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT.

COVID-19 Test Us: A Case for Embedding Ethics and Regulatory Expertise.

A key aspect of the National Institutes of Health (NIH) funded Rapid Acceleration of Diagnostics (RADx) Tech program was an active Clinical Studies Core including Committees with unique expertise to facilitate the development and implementation of studies to test novel diagnostic devices for Covid-19. The Ethics and Human Subjects Oversight Team (EHSO) was tasked to provide ethics and regulatory expertise to stakeholders in the RADx Tech effort. The EHSO developed a set of Ethical Principles to guide the overall effort and provided consultation on a wide range of ethical and regulatory concerns.

Finding a Needle in a Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection.

Background: Rapid antigen tests (Ag-RDT) for SARS-CoV-2 with Emergency Use Authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially.

Objective: To describe a novel study design to generate regulatory-quality data to evaluate serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.

Design: Prospective cohort study using a decentralized approach.

The RADx Tech Clinical Studies Core: A Model for Academic Based Clinical Studies.

The National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADx) Tech initiative to support the development and commercialization of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care test devices. The primary objective of the Clinical Studies Core (CSC) was to perform SARS-CoV-2 device studies involving diverse populations and settings. Within a few months, the infrastructure for clinical studies was developed, including a master protocol, digital study platform, data management system, single IRB, and multi-site partnerships.

Stories of Identity from High Performance Male Boxers in Their Training and Competition Environments.

The current submission was conceived to broaden the discussion around male athletic identities by exploring the stories told by four members of the Canadian National Boxing Team. The athletes' stories were elicited through an arts-based method followed by a conversational interview. Stories were then analyzed using an interpretive thematic analysis.

De novo expression of sodium-glucose cotransporter SGLT2 in Bowman's capsule coincides with replacement of parietal epithelial cell layer with proximal tubule-like epithelium.

In kidney nephron, parietal epithelial cells line the Bowman's capsule and function as a permeability barrier for the glomerular filtrate. Bowman's capsule cells with proximal tubule epithelial morphology have been found. However, the effects of tubular metaplasia in Bowman's capsule on kidney function remain poorly understood.

Novel DNA gyrase inhibitors: microbiological characterisation of pyrrolamides.

Pyrrolamides are a novel class of antibacterial agents that target DNA gyrase, resulting in inhibition of DNA synthesis and bacterial cell death. In these studies, advanced compounds were shown to have potent in vitro activity against selected Gram-positive and Gram-negative pathogens, including meticillin-resistant Staphylococcus aureus, meticillin- and quinolone-resistant S. aureus, vancomycin-resistant enterococci, penicillin-resistant Streptococcus pneumoniae and β-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis.

A novel SGLT is expressed in the human kidney.

Selective inhibitors of sodium-glucose cotransporter 2 (SGLT2)-mediated reabsorption of glucose in the proximal tubule of the kidney are being developed for the treatment of diabetes. SGLT2 shares high degree of homology with SGLT3; however, very little is known about the expression and functional role of SGLT3 in the human kidney. Indeed, the SGLT2 inhibitors that are currently in clinical trials might affect the expression and/or the activity of SGLT3.

Pyrrolamide DNA gyrase inhibitors: fragment-based nuclear magnetic resonance screening to identify antibacterial agents.

DNA gyrase is an essential enzyme in bacteria, and its inhibition results in the disruption of DNA synthesis and, subsequently, cell death. The pyrrolamides are a novel class of antibacterial agents targeting DNA gyrase. These compounds were identified by a fragment-based lead generation (FBLG) approach using nuclear magnetic resonance (NMR) screening to identify low-molecular-weight compounds that bind to the ATP pocket of DNA gyrase.

A fluorescence method for measurement of glucose transport in kidney cells.

Background: Diabetes may alter renal glucose reabsorption by sodium (Na(+))-dependent glucose transporters (SGLTs). Radiolabeled substrates are commonly used for in vitro measurements of SGLT activity in kidney cells. We optimized a method to measure glucose uptake using a fluorescent substrate, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG).

The role of families in youth sport programming in a Canadian aboriginal reserve.

Background: There has been a recent push in the sport psychology literature for sport participants to be approached based on their cultural backgrounds. However, there are few examples where a cultural approach is considered, such as a culturally reflexive version of participatory action research (PAR). In the current study, the role of family is considered in relation to the sport engagement of Canadian Aboriginal youth.

Zinc finger transcription factor Zn3-Sp1 reactions with Cd2+.

Cadmium is a major environmental pollutant that causes kidney failure including the inability to resorb nutrients such as glucose. In a mouse kidney cell culture model, Cd(2+) inhibits Na(+)-dependent glucose uptake mediated by SGLT transporters. This defect has been traced to the down-regulation of SGLT mRNA synthesis mediated by the zinc-finger transcription factor, Zn(3)-Sp1.

Cadmium down-regulation of kidney Sp1 binding to mouse SGLT1 and SGLT2 gene promoters: possible reaction of cadmium with the zinc finger domain of Sp1.

Cadmium (Cd) exposure causes glucosuria (glucose in the urine). Previously, it was shown that Cd exposure of primary cultures of mouse kidney cells (PMKC) decreased mRNA levels of the glucose transporters, SGLT1 and SGLT2 and that Sp1 from Cd-exposed cells displayed reduced binding to the GC boxes of the mouse SGLT1 promoter in vitro. Here, we identified a GC box upstream of mouse SGLT2 gene.

Argument status and PP-attachment.

Prepositional phrase attachment was investigated in temporarily ambiguous sentences. Both attachment site (noun phrase or verb phrase) and argument status (argument or adjunct) were manipulated to test the hypothesis that arguments are processed differently than adjuncts. Contrary to this hypothesis, some previous research suggested that arguments and adjuncts are initially processed in the same manner, following a general bias to attach prepositional phrases to the verb phrase whenever possible [Clifton, Speer, & Abney (1991) Journal of Memory and Language, 30, 251-271].

Utilization of target-specific, hypersensitive strains of Saccharomyces cerevisiae to determine the mode of action of antifungal compounds.

Target-specific hypersusceptible strains of Saccharomyces cerevisiae were used to screen antifungal compounds. Two novel Erg7p inhibitors were identified, providing proof of principle of the approach taken. However, observed hypersensitivities to antifungals acting via other targets imply that use of this tool to identify the mode of action requires significant deconvolution.

Differences in the timing of implausibility detection for recipient and instrument prepositional phrases.

We conducted two word-by-word reading experiments to investigate the timing of implausibility detection for recipient and instrument prepositional phrases (PPs). These PPs differ in thematic role, relative frequency, and possibly in argument status. The results showed a difference in the timing of garden path effects such that the detection of implausible dative recipients (which are clearly arguments) was delayed relative to the detection of implausible instruments (which may not be arguments).

Pyridines and pyrimidines mediating activity against an efflux-negative strain of Candida albicans through putative inhibition of lanosterol demethylase.

The first step in ergosterol biosynthesis in Saccharomyces cerevisiae consists of the condensation of two acetyl coenzyme A (acetyl-CoA) moieties by acetoacetyl-CoA thiolase, encoded by ERG10. The inhibition of the sterol pathway results in feedback activation of ERG10 transcription. A cell-based reporter assay, in which increased ERG10 transcription results in elevated specific beta-galactosidase activity, was used to find novel inhibitors of ergosterol biosynthesis that could serve as chemical starting points for the development of novel antifungal agents.

Oxaliplatin biotransformation and pharmacokinetics: a pilot study to determine the possible relationship to neurotoxicity.

Background: Both oxaliplatin and ormaplatin undergo biotransformation to Pt(dach)Cl2 with studies suggesting a predictive relationship between systemic exposure to Pt(dach)Cl2 and the severity of the delayed sensory neuropathy associated with ormaplatin. Studies characterizing the pharmacokinetic parameters of oxaliplatin and Pt(dach)Cl2 in humans have not been reported. This study was conducted to characterize the pharmacokinetic parameters of oxaliplatin and Pt(dach)Cl2 and to determine the extent to which oxaliplatin undergoes biotransformation to Pt(dach)Cl2 in humans.

Effects of Calcium Salts on the Cranberry Fruit Rot Disease Complex.

Calcium salts were applied during the growing season to fresh-fruit cranberry beds to test their effects on cranberry fruit rot incidence and the incidence of specific fungi isolated from rotten and sound cranberry fruit at the time of harvest and after storage. Calcium salts did not affect fruit rot incidence, nor did they affect the recovery of specific fungi from berries. The field treatments did not result in higher calcium content in mature berries, nor did they affect the force required to penetrate the berry epidermis.

Selecting patients for falls-prevention protocols: an evidence-based approach on a geriatric rehabilitation unit.

Geriatric rehabilitation treatment focuses on maximizing functional independence in older adults to facilitate a return to independent living following hospitalization. Rehabilitation professionals must therefore balance the need to foster increasing activity levels among patients while, at the same time, preventing falls and potential injuries. This study investigated measures of patient cognition and aspects of health as predictors of the risk for falls among geriatric rehabilitation patients.

Influence of exercise mode and carbohydrate on the immune response to prolonged exercise.

The influence of exercise mode and 6% carbohydrate (C) versus placebo (P) beverage ingestion on lymphocyte proliferation, natural killer cell cytotoxicity (NKCA), Interleukin (IL)-1beta production, and hormonal responses to 2.5 hr of intense running and cycling (approximately 75% VO2max) was measured in 10 triathletes serving as their own controls. The C versus P condition (but not exercise mode) resulted in higher plasma glucose concentrations, lower plasma cortisol concentrations, reduced postexercise lymphocytosis and NKCA, and a lessened T-cell reduction during recovery, No condition or mode effects were observed for concanavalin A and phytohemagglutinin-induced lymphocyte proliferation.

Structural and immunochemical characterization of the type VIII group B Streptococcus capsular polysaccharide.

The type VIII capsular polysaccharide has been isolated and purified from a newly described strain of group B Streptococcus which is a leading cause of sepsis and neonatal meningitis in Japan. The polysaccharide contains D-glucose, D-galactose, L-rhamnose, and sialic acid in the molar ratio 1:1:1:1. By means of high resolution 1H nuclear magnetic resonance (1H NMR), 13C NMR, and homo- and heterocorrelated NMR, the repeating unit structure of the type VIII polysaccharide was delineated as the following, [formula: see text] Enzymatic studies established this polysaccharide as the first from which sialic acid, linked to a branched beta-D-galactopyranosyl residue, is known to be removed by bacterial neuraminidase.

Neuroendocrine aspects of primary endogenous depression. III. Cortisol secretion in relation to diagnosis and symptom patterns.

In order to ascertain the extent of hypothalamo-pituitary-adrenal cortical (HPA) hyperactivity in endogenous depression, we determined circadian serum cortisol patterns, cortisol responses to dexamethasone (DEX) administration, and urine free cortisol excretion before and after DEX administration in 40 definite endogenous depressives diagnosed with the Research Diagnostic Criteria. The cortisol measures ranged from normal to clearly elevated. To elucidate the clinical correlates of these hormone measures in the patients, we examined the relationships of the pre- and post-DEX cortisol measures to the diagnosis of endogenous/melancholic depression by different systems and to the overall severity and specific dimensions of depressive symptomatology.

Neuroendocrine aspects of primary endogenous depression. I. Cortisol secretory dynamics in patients and matched controls.

To examine both predexamethasone and postdexamethasone cortisol measures in depression, we determined circadian serum cortisol patterns, cortisol responses to dexamethasone, and 24-hour urinary free cortisol excretion before and after dexamethasone administration in 40 patients with primary, definite endogenous depression diagnosed by Research Diagnostic Criteria and in 40 individually matched normal control subjects. Fifteen patients (38%) were dexamethasone nonsuppressors; they had significantly higher predexamethasone serum and urine cortisol measures than both their matched controls and the 25 suppressor patients. Both the predexamethasone and postdexamethasone cortisol measures were unimodally distributed across the patients and the controls.