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Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic available for the treatment of complicated gram-positive skin and skin structure infections, was compared with standard comparators (cefazolin, oxacillin or vancomycin) in one USA and one international trial. These two randomized, open-label trials of virtually identical design enrolled a total of 893 patients (450 quinupristin/dalfopristin, 443 comparator). The majority of patients had erysipelas, traumatic wound infection or clean surgical wound infection. Staphylococcus aureus was the most frequently isolated pathogen in both treatment groups and polymicrobial infection was more common in the quinupristin/dalfopristin group than in the comparator group. The clinical success rate (cure plus improvement) in the clinically evaluable population was equivalent between the two treatment groups (68.2% quinupristin/dalfopristin, 70.7% comparator; 95% CI, -10.1, 5.1) despite a shorter mean duration of treatment for quinupristin/dalfopristin patients. In the bacteriologically evaluable population, by-patient and by-pathogen bacteriological eradication rates were somewhat lower for quinupristin/dalfopristin (65.8% and 66.6%, respectively) than for the comparator regimens (72.7% and 77.7%, respectively). The lower bacteriological response rates in the quinupristin/dalfopristin group were, in part, due to a higher rate of polymicrobial infections and a higher incidence of patients classified as clinical failure, a category which included premature discontinuation of treatment because of local venous adverse events. The bacteriological eradication rate for quinupristin/dalfopristin was higher in monomicrobial infections than in polymicrobial infections (72.6% versus 63.3%, respectively), whereas the corresponding rate for the comparator regimens was lower for monomicrobial infections than polymicrobial infections (70.8% versus 83.1%). This finding was not unexpected, since the spectrum of quinupristin/dalfopristin is focused on gram-positive pathogens and additional antibiotics to treat gram-negative bacteria were not required per protocol. The systemic tolerability of both treatment regimens was qualitatively similar. A higher rate of drug-related venous adverse events was reported for quinupristin/dalfopristin (66.2%) than for the comparator regimen (28.4%). Premature discontinuation of study drug was primarily due to adverse clinical events for quinupristin/dalfopristin (19.1%), whereas the most common reason for discontinuation among those receiving the comparator regimens was treatment failure (11.5%). Quinupristin/dalfopristin is an effective alternative for the treatment of hospitalized patients with complicated skin and skin structure infections due to quinupristin/ dalfopristin-susceptible gram-positive organisms, including methicillin- and erythromycin-resistant S. aureus. [ABSTRACT FROM AUTHOR]

Identifies the characteristics of a slow learner and gives a basic philosophy and techniques for teaching the slow learners in social studies. Includes a list of 11 tips for teaching slow learners and offers a lesson format designed for their instruction. (AEM)

Transferrin, Tf, the protein that transports iron as Fe(III) from the blood to the tissues via endocytosis, is believed to also transport Cr(III). Under physiological conditions, Tf binds and releases Cr(III) rapidly from Cr(III) 2 -Tf; however, the major form of Tf in the bloodstream is mono-ferric Tf (Fe(III)-Tf). Given the low concentration of Cr(III) in the bloodstream, the form of Cr(III)-containing Tf that is transported is probably monochromic, monoferric-Tf (Cr(III),Fe(III)-Tf). Given that Tf has two specific metal-binding sites, one in both its C-terminal and its N-terminal lobe, two forms of Cr(III),Fe(III)-Tf can form. The binding of Cr(III) to mono-ferric Tf to generate both forms of Cr(III),Fe(III)-Tf has been examined in detail for the first time. The addition of Cr(III) to monoferric Tfs in 100 mM HEPES and 25 mM bicarbonate solution, pH 7.4, resulted in a rapid binding of Cr(III) to the open metal-binding site of the Tfs. Titrations of the monoferric Tfs with Cr(III) indicate the tight binding on one Cr(III) in each case. The binding of Cr(III) to monoferric Tfs is accompanied by conformational changes similar to adding two equivalents of Cr(III) to apoTf. Thus, mono-ferric Tfs bind one equivalent of Cr(III) rapidly and tightly to form mixed Cr(III),Fe(III)-Tfs. Cr(III) is probably transported as mixed Cr(III),Fe(III)-Tfs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Simian immunodeficiency virus (SIV) infection of macaques recapitulates many aspects of HIV pathogenesis and is similarly affected by both genetic and environmental factors. Psychosocial stress is associated with immune system dysregulation and worse clinical outcomes in people with HIV. This study assessed the impact of single housing, as a model of psychosocial stress, on innate immune responses of pigtailed macaques ( Macaca nemestrina ) during acute SIV infection., Methods: A retrospective analysis of acute SIV infection of 2- to si6-year-old male pigtailed macaques was performed to compare the innate immune responses of socially ( n = 41) and singly ( n = 35) housed animals. Measures included absolute monocyte count and subsets, and in a subset ( n ≤ 18) platelet counts and activation data., Results: SIV infection resulted in the expected innate immune parameter changes with a modulating effect from housing condition. Monocyte number increased after infection for both groups, driven by classical monocytes (CD14 + CD16 - ), with a greater increase in socially housed animals (227%, p < .001, by day 14 compared with preinoculation time points). Platelet numbers recovered more quickly in the socially housed animals. Platelet activation (P-selectin) increased by 65% ( p = .004) and major histocompatibility complex class I surface expression by 40% ( p = .009) from preinoculation only in socially housed animals, whereas no change in these measures occurred in singly housed animals., Conclusions: Chronic psychosocial stress produced by single housing may play an immunomodulatory role in the innate immune response to acute retroviral infection. Dysregulated innate immunity could be one of the pathways by which psychosocial stress contributes to immune suppression and increased disease severity in people with HIV., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Newborn screening using dried plasma spots offers preanalytical advantages over conventional cards for plasma-associated targets of interest. Herein we present dried plasma spot-based methods for measuring metabolites using a 250+ compound liquid chromatography tandem mass spectrometry library. Quality assurance reduced this library to 134, and from these, 30 compounds determined the normal newborn reference ranges., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although social distancing is a key public health response during viral pandemics, psychosocial stressors, such as social isolation, have been implicated in adverse health outcomes in general [1] and in the context of infectious disease, such as human immunodeficiency virus (HIV) [2, 3]. A comprehensive understanding of the direct pathophysiologic effects of psychosocial stress on viral pathogenesis is needed to provide strategic and comprehensive care to patients with viral infection., Methods: To determine the effect of psychosocial stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly (n = 35) and socially (n = 41) housed simian immunodeficiency virus (SIV)-infected pigtailed macaques (Macaca nemestrina)., Results: Singly housed macaques had a higher viral load in the plasma and cerebrospinal fluid and demonstrated greater CD4 T-cell declines and more CD4 and CD8 T-cell activation compared with socially housed macaques throughout acute SIV infection., Conclusions: These data demonstrate that psychosocial stress directly impacts the pathogenesis of acute SIV infection and imply that it may act as an integral variable in the progression of HIV infection and potentially of other viral infections., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Macaques with self-injurious behavior (SIB) have been used as a model of human SIB and have previously been shown to respond to treatments targeting enhancement of central serotonin signaling, whether by supplementation with tryptophan, or by inhibiting synaptic reuptake. Decreased serotonin signaling in the brain has also been implicated in many human psychopathologies including major depression disorder. A disturbance in tryptophan metabolism that moves away from the production of serotonin and toward the production of kynurenine has been proposed as a major etiological factor of depression. We hypothesized that in macaques with SIB, central tryptophan metabolism would be shifted toward kynurenine production, leading to lower central serotonin (5-hydroxytryptamine). We analyzed tryptophan metabolites in the cerebral spinal fluid (CSF) of macaques with and without SIB to determine whether and where tryptophan metabolism is altered in affected animals as compared with behaviorally normal controls. We found that macaques with SIB had lower CSF concentrations of serotonin than did behaviorally normal macaques, and that these deficits were inversely correlated with the severity of abnormal behavior. However, our results suggest that this decrease is not due to shifting of the tryptophan metabolic pathway toward kynurenine, as concentrations of kynurenine were also low. Concentrations of IL6 were elevated, suggesting central inflammation. Determining the mechanism by which serotonin function is altered in self-injurious macaques could shed light on novel therapies for SIB and other disorders of serotonin signaling.

Background: Additional antibiotic options are needed to treat bone and joint infections caused by penicillin-resistant Gram-positive pathogens., Objective: This subanalysis of the Telavancin Observational Use Registry (TOUR™) aimed to record real-world telavancin usage patterns in patients with bone and joint infections treated with telavancin., Methods: TOUR was a multicenter observational-use registry study conducted at 45 US sites between January 2015 and March 2017. Patient characteristics, infection type, infecting pathogen(s), previous treatment, telavancin dosing and duration, clinical response, and adverse event data were collected by retrospective medical chart reviews. As such, inclusion/exclusion criteria were limited, and any patient receiving at least one dose of telavancin at the discretion of the treating physician was eligible. Patients were assessed as either positive clinical response, failed treatment, or indeterminate outcome., Results: Of the 1063 patients enrolled in TOUR, 27.4% (291/1063) were patients with bone and joint infections including osteomyelitis (with or without prosthetic material), acute septic arthritis, and prosthetic joint infections. Most of these patients had osteomyelitis without prosthetic material (191/291; 66.0%). Among patients assessed at the end of treatment, 211/268 (78.7%) achieved a positive clinical response, 26/268 (9.7%) failed treatment, and 31/268 (11.6%) had an indeterminate outcome. The most frequent pathogen was methicillin-resistant Staphylococcus aureus (110/291; 37.8%). The median (interquartile range [IQR as Q1, Q3]) telavancin dose was 750.0 mg (IQR, 750, 750 mg) or 8.2 mg/kg (IQR, 6.8, 9.7 mg/kg) administered for a median of 26 days (IQR, 12, 42 days). These assessments were recorded in the registry ≥ 30 days after the last dose of telavancin was administered., Conclusions: Real-world data from the TOUR study show that clinicians are using once-daily telavancin with positive clinical outcomes for the treatment of bone and joint infections caused by Gram-positive pathogens., Clinical Trial Registration: This trial was registered with ClinicalTrials.gov (NCT02288234) on 11 November, 2014., (© 2021. The Author(s).)

Objective: Assess workplace vaping as a trigger for tobacco use; examine interest in and prevalence of vaping cessation programs; determine needs of parents whose children vape., Methods: Employees of companies with more than 150 employees, drawn from an opt-in national online panel (N = 1607), ages 18 to 65, completed an online survey in November 2019., Results: Among tobacco users, 46% to 48% reported workplace vaping was a trigger for smoking and vaping, respectively; 7% of former users reported it as a trigger. Quit vaping support is important to 85% of employees; 1/3 of workplaces have such programs, with industry variation. Child vaping results in presenteeism and absenteeism among roughly 1/3 of parents., Conclusions: Workplace vaping is a trigger for smoking and vaping among current and former tobacco users. A gap exists between desired support for vaping cessation and current employer-sponsored cessation programs.