N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection.

The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. There remains an ongoing need for high-performance SARS-CoV-2 tests which may be broadly deployed for infection monitoring. Here we report a highly sensitive single molecule array (Simoa) immunoassay in development for detection of SARS-CoV-2 nucleocapsid protein (N-protein) in venous and capillary blood and saliva.

Probing Anti-inflammatory Properties Independent of NF-κB Through Conformational Constraint of Peptide-Based Interleukin-1 Receptor Biased Ligands.

Interleukin-1β (IL-1β) binds to the IL-1 receptor (IL-1R) and is a key cytokine mediator of inflammasome activation. IL-1β signaling leads to parturition in preterm birth (PTB) and contributes to the retinal vaso-obliteration characteristic of oxygen-induced retinopathy (OIR) of premature infants. Therapeutics targeting IL-1β and IL-1R are approved to treat rheumatoid arthritis; however, all are large proteins with clinical limitations including immunosuppression, due in part to inhibition of NF-κB signaling, which is required for immuno-vigilance and cytoprotection.

Examination of the active secondary structure of the peptide 101.10, an allosteric modulator of the interleukin-1 receptor, by positional scanning using β-amino γ-lactams.

The relationship between the conformation and biological activity of the peptide allosteric modulator of the interleukin-1 receptor 101.10 (D-Arg-D-Tyr-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH₂) has been studied using (R)- and (S)-Bgl residues. Twelve Bgl peptides were synthesized using (R)- and (S)-cyclic sulfamidate reagents derived from L- and D-aspartic acid in an optimized Fmoc-compatible protocol for efficient lactam installment onto the supported peptide resin.

Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease.

Epidemiological studies have shown that cardiovascular disease (CVD) is less common in pre-menopausal women (Pre-MW) compared to men of the same age or post-menopausal women (Post-MW), suggesting cardiovascular benefits of estrogen. Estrogen receptors (ERs) have been identified in the vasculature, and experimental studies have demonstrated vasodilator effects of estrogen/ER on the endothelium, vascular smooth muscle (VSM) and extracellular matrix. Several natural and synthetic estrogenic preparations have been developed for relief of menopausal vasomotor symptoms.

Estrogen receptor-mediated enhancement of venous relaxation in female rat: implications in sex-related differences in varicose veins.

Background: A greater incidence of varicose veins has been reported in premenopausal women than in men. We hypothesized that the sex differences in venous function reflect reduced constriction and enhanced venous dilation in women due to direct venous relaxation effects of estrogen on specific estrogen receptors (ER).

Methods: Circular segments of inferior vena cava (IVC) from male and female Sprague-Dawley rats were suspended between two wires, and isometric contraction (in mg/mg tissue) to phenylephrine, angiotensin II (AngII), and 96 mM KCl was measured.

Functional adaptation of venous smooth muscle response to vasoconstriction in proximal, distal, and varix segments of varicose veins.

Background: Varicose veins (VarVs) are a common disorder of venous dilation and tortuosity with unclear mechanism. The functional integrity and the ability of various regions of the VarVs to constrict is unclear. This study tested the hypothesis that the different degrees of venodilation in different VarV regions reflect segmental differences in the responsiveness to receptor-dependent vasoconstrictive stimuli and/or in the postreceptor signaling mechanisms of vasoconstriction.

Insertion of multiple alpha-amino gamma-lactam (Agl) residues into a peptide sequence by solid-phase synthesis on synphase lanterns.

The insertion of lactams into peptide analogs can enhance potency and improve receptor selectivity. The synthesis of lactam-bridged peptide sequences has been accomplished by a solid-phase approach on SynPhase lanterns using cyclic (R)- and (S)-oxathiazinane ester (2) to annulate the amino lactam residue onto the peptide chain. Parallel synthesis of alpha-amino gamma-lactam analogs of the allosteric modulator of IL-1 receptor 101.

VRQ397 (CRAVKY): a novel noncompetitive V2 receptor antagonist.

Vasopressin type 2 receptor (V2R) exhibits mostly important properties for hydroosmotic equilibrium and, to a lesser extent, on vasomotricity. Drugs currently acting on this receptor are analogs of the natural neuropeptide, arginine vasopressin (AVP), and hence are competitive ligands. Peptides that reproduce specific sequences of a given receptor have lately been reported to interfere with its action, and if such molecules arise from regions remote from the binding site they would be anticipated to exhibit noncompetitive antagonism, but this has yet to be shown for V2R.

Positional scanning for peptide secondary structure by systematic solid-phase synthesis of amino lactam peptides.

Incorporation of amino lactams into biologically active peptides has been commonly used to restrict conformational mobility, enhance selectivity, and increase potency. A solid-phase method using a Fmoc-protection strategy has been developed for the systematic synthesis of peptides containing configurationally defined alpha- and beta-amino gamma-lactams. N-Alkylation of N-silyl peptides with five- and six-member cyclic sulfamidates 9 and 8 minimized bis-alkylation and provided N-alkyl peptides, which underwent lactam annulation under microwave heating.

Sensitivity of household reported medical conditions in the medical expenditure panel survey.

Introduction: Accurate survey data on medical conditions are critical for health care researchers. Although medical condition data are complex and are subject to reporting error, little information exists on the quality of household reported condition data.

Methods: We used pooled data from 4 years (2002-2005) of the Medical Expenditure Panel Survey (MEPS) to estimate the extent to which household respondents may underreport 23 types of medical conditions.

Patient safety, elephants, chickens, and mosquitoes.

Five years after the landmark report by the Institute of Medicine, To Err is Human (2000), many of us still grapple with making care safer for patients. This article broadly describes how patient safety fits into the picture of quality, concepts in patient safety, and practical safety processes you can implement today.

Patient safety: mindful, meaningful, and fulfilling.

Five years after the landmark report of the Institute of Medicine To Err Is Human (Kohn, Corrigan, and Donaldson 2000), many are asking, "Is U.S. healthcare safer?" A number of articles addressing this question have been written, interviews with nationally recognized patient safety leaders have been published, and governing boards of many healthcare organizations are examining reports of care provided by their institutions.

Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization.

Immunofluorescence and other methods have been used to probe the self-assembly and internalization of the binary toxin, anthrax lethal toxin (LeTx), in primary murine macrophages. Proteolytic activation of protective antigen (PA; 83 kDa, the B moiety of the toxin) by furin was the rate-limiting step in internalization of LeTx and promoted clearance of PA from the cell surface. A furin-resistant form of PA remained at the cell surface for at least 90 min.

Nitric oxide production by coelomocytes of Asterias forbesi.

Vertebrate mononuclear phagocytes produce a plethora of molecules involved in host defense. Among the most potent are the reactive oxygen and nitrogen intermediates. Coelomocytes from invertebrates subserve many of the same functions.

Anthrax toxin entry into polarized epithelial cells.

We examined the entry of anthrax edema toxin (EdTx) into polarized human T84 epithelial cells using cyclic AMP-regulated Cl- secretion as an index of toxin entry. EdTx is a binary A/B toxin which self assembles at the cell surface from anthrax edema factor and protective antigen (PA). PA binds to cell surface receptors and delivers EF, an adenylate cyclase, to the cytosol.

Turning up the contrast: self-enhancement motives prompt egocentric contrast effects in social judgments.

Contrast effects occur when people judge the behavior and attitudes of others relative to their own. We tested a motivational account suggesting that these effects arise because people tailor their judgments of others to affirm their own self-worth. Consistent with that interpretation, participants displayed more egocentric contrast in their judgments of another person's intelligence (i.

Anthrax toxin-mediated delivery in vivo and in vitro of a cytotoxic T-lymphocyte epitope from ovalbumin.

We reported earlier that a nontoxic form of anthrax toxin was capable of delivering a cytotoxic T-lymphocyte (CTL) epitope in vivo, such that a specific CTL response was primed against the epitope. The epitope, of bacterial origin, was fused to an N-terminal fragment (LFn) from the lethal-factor component of the toxin, and the fusion protein was injected, together with the protective antigen (PA) component, into BALB/c mice. Here we report that PA plus LFn is capable of delivering a different epitope--OVA(257-264) from ovalbumin.

pH-dependent perforation of macrophage phagosomes by listeriolysin O from Listeria monocytogenes.

The pore-forming toxin listeriolysin O (LLO) is a major virulence factor implicated in escape of Listeria monocytogenes from phagocytic vacuoles. Here we describe the pH-dependence of vacuolar perforation by LLO, using the membrane-impermeant fluorophore 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) to monitor the pH and integrity of vacuoles in mouse bone marrow-derived macrophages. Perforation was observed when acidic vacuoles containing wild-type L.

The effect of universal coverage on health expenditures for the uninsured.

Objectives: Universal coverage will trigger an increase in health-care spending, because the uninsured will use more services after they are insured. The effect of insurance status on expenditures is estimated here from a multivariate statistical model.

Methods: The model is estimated with data from the 1987 National Medical Expenditure Survey, aged to 1994 using population projections from the US Bureau of the Census and expenditure projections from the Health Care Financing Administration.

Gene cloning and production of active recombinant Brugia malayi microfilarial chitinase.

Canlas and coworkers [Canlas et al. (1984) Am. J.

Expression of recombinant microfilarial chitinase and analysis of domain function.

A family of chitinase isozymes was previously characterized from the microfilariae of Brugia malayi and Brugia pahangi. The expression of these enzymes correlates with the onset of microfilarial infectivity for the mosquito vector. To study the role of chitinase activity in filarial transmission, the p70 chitinase from Brugia malayi was cloned and expressed in two forms: a full-length product of approximately 62 kDa and a truncated product of 43 kDa containing only the N-terminal catalytic domain.