A SUSTAINABLE APPROACH TO THE CONTROL OF PATHOGENS: THE FATE OF STREPTOCOCCI IN EQUINE COMPOST.

Streptococcus equi subspecies equi (S. equi), causes the potentially fatal respiratory disease called “strangles” in horses, while the closely related Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) causes potentially fatal infections in humans. A study was undertaken to determine the survival of these two organisms in equine compost. Compost piles of equine bedding and feed waste were inoculated with 10 x 1010 c.f.u. of S. zooepidemicus and samples taken at 48, 96, 168 and 336 hours relative to samples placed in the pile at 0 hours. No Streptococci were isolated at 48 hours or subsequent time-points. Next, S. equi was similarly inoculated into equine compost, with samples taken at 2, 4, 8, 12, 24, 48, 168 and 336 hours later. No Streptococci were isolated at any time-point. To rule out killing of S. equi by microflora in equine waste, samples of soiled bedding, both autoclaved and un-autoclaved (with water added to match autoclaved moisture) were inoculated with 10 x 1010 c.f.u. of S. zooepidemicus and sampled at 0, 6, 12, 24, 48, 72, 120, 168 and 264 hours. In autoclaved bedding, S. zooepidemicus was isolated from 0 – 120 hours, but replaced by other flora at 264 hours. In un-autoclaved samples, Streptococci were not present after 48 hours. A repeated trial with S. equi yielded similar results. This data suggest that microbial activity of equine waste bedding may eliminate streptococci within 24 - 48 hours, indicating that normal microflora may provide sustainable methods for the control of human and animal pathogens

A SUSTAINABLE APPROACH TO THE CONTROL OF PATHOGENS: THE FATE OF STREPTOCOCCI IN EQUINE COMPOST.

Streptococcus equi subspecies equi (S. equi), causes the potentially fatal respiratory disease called “strangles” in horses, while the closely related Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) causes potentially fatal infections in humans. A study was undertaken to determine the survival of these two organisms in equine compost. Compost piles of equine bedding and feed waste were inoculated with 10 x 1010 c.f.u. of S. zooepidemicus and samples taken at 48, 96, 168 and 336 hours relative to samples placed in the pile at 0 hours. No Streptococci were isolated at 48 hours or subsequent time-points. Next, S. equi was similarly inoculated into equine compost, with samples taken at 2, 4, 8, 12, 24, 48, 168 and 336 hours later. No Streptococci were isolated at any time-point. To rule out killing of S. equi by microflora in equine waste, samples of soiled bedding, both autoclaved and un-autoclaved (with water added to match autoclaved moisture) were inoculated with 10 x 1010 c.f.u. of S. zooepidemicus and sampled at 0, 6, 12, 24, 48, 72, 120, 168 and 264 hours. In autoclaved bedding, S. zooepidemicus was isolated from 0 – 120 hours, but replaced by other flora at 264 hours. In un-autoclaved samples, Streptococci were not present after 48 hours. A repeated trial with S. equi yielded similar results. This data suggest that microbial activity of equine waste bedding may eliminate streptococci within 24 - 48 hours, indicating that normal microflora may provide sustainable methods for the control of human and animal pathogens

Clinical adjudication in acute kidney injury studies: findings from the pivotal TIMP-2*IGFBP7 biomarker study

Background The NEPROCHECK test (Astute Medical, San Diego, CA, USA) combines urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) to identify patients at high risk for acute kidney injury (AKI). In a US Food and Drug Administration registration trial (NCT01573962), AKI was determined by a three-member clinical adjudication committee. The objectives were to examine agreement among adjudicators as well as between adjudicators and consensus criteria for AKI and to determine the relationship of biomarker concentrations and adjudicator agreement. Methods Subjects were classified as AKI 3/3, 2/3, 1/3 or 0/3 according to the proportion of adjudicators classifying the case as AKI. Subjects were classified as Kidney Disease: Improving Global Outcomes (KDIGO) AKI(+) when stage 2 or 3 AKI criteria were met. Results Concordance between adjudicators and between adjudicators and KDIGO criteria were lower for AKI than non-AKI subjects [78.9 versus 97.3% (P \u3c 0.001) and 91.5 versus 97.9% (P = 0.01)]. Subjects who were AKI 3/3 or 2/3 but KDIGO AKI(−) had higher median [TIMP-2]•[IGFBP7] compared with those who were AKI-1/3 or 0/3 but KDIGO AKI(+) {2.78 [interquartile range (IQR) 2.33–3.56] versus 0.52 [IQR 0.26–1.64]; P = 0.008}. [TIMP-2]•[IGFBP7] levels were highest in patients with AKI 3/3 and lowest in AKI 0/3, whereas AKI 2/3 and 1/3 exhibited intermediate values. Conclusions In this analysis, urine [TIMP-2]•[IGFBP7] levels correlated to clinically adjudicated AKI better than to KDIGO criteria. Furthermore, in difficult cases where adjudicators overruled KDIGO criteria, the biomarker test discriminated well. This study highlights the importance of clinical adjudication of AKI for biomarker studies and lends further support for the value of urine [TIMP-2]•[IGFBP7]

Social Security Research at the University of Michigan Retirement and Disability Research Center

In 1998, the Social Security Administration established the Retirement Research Consortium to encourage research on topics related to Social Security and the well-being of older Americans, and to foster communication between the academic and policy communities. The Michigan Retirement Research Center (MRRC) participated in the Consortium from its inception until 2019, when the MRRC expanded and became the Michigan Retirement and Disability Research Center. This article surveys a selection of the MRRC’s output over its second 10 years (2008–2017), summarizes its innovative use of new data sources, and highlights several key themes in the center’s research contributions

Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: Possible refinement by measuring macrophage abundance

BACKGROUND: Immune checkpoint inhibitor (ICI) myocarditis is associated with high morbidity and mortality. While endomyocardial biopsy (EMB) is considered a gold standard for diagnosis, the sensitivity of EMB is not well defined. Additionally, the pathological features that correlate with the clinical diagnosis of ICI-associated myocarditis remain incompletely understood. METHODS: We retrospectively identified and reviewed the clinicopathological features of 26 patients with suspected ICI-associated myocarditis based on institutional major and minor criteria. Seventeen of these patients underwent EMB, and the histopathological features were assessed by routine hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for CD68, a macrophage marker. RESULTS: Only 2/17 EMBs obtained from patients with suspected ICI myocarditis satisfied the Dallas criteria. Supplemental IHC staining and quantification of CD68 CONCLUSIONS: While the Dallas criteria can identify a subset of ICI-associated myocarditis patients, quantification of macrophage abundance may expand the diagnostic role of EMB. Failure to meet the traditional Dallas Criteria should not exclude the diagnosis of myocarditis

A Novel Method for Assessing Proximal and Distal Forelimb Function in the Rat: the Irvine, Beatties and Bresnahan (IBB) Forelimb Scale

Several experimental models of cervical spinal cord injury (SCI) have been developed recently to assess the consequences of damage to this level of the spinal cord (Pearse et al., 2005, Gensel et al., 2006, Anderson et al., 2009), as the majority of human SCI occur here (Young, 2010; www.sci-info-pages.com). Behavioral deficits include loss of forelimb function due to damage to the white matter affecting both descending motor and ascending sensory systems, and to the gray matter containing the segmental circuitry for processing sensory input and motor output for the forelimb. Additionally, a key priority for human patients with cervical SCI is restoration of hand/arm function (Anderson, 2004). Thus, outcome measures that assess both proximal and distal forelimb function are needed. Although there are several behavioral assays that are sensitive to different aspects of forelimb recovery in experimental models of cervical SCI (Girgis et al., 2007, Gensel et al., 2006, Ballerman et al., 2001, Metz and Whishaw, 2000, Bertelli and Mira, 1993, Montoya et al., 1991, Whishaw and Pellis, 1990), few techniques provide detailed information on the recovery of fine motor control and digit movement

Methods to reduce medication errors in a clinical trial of an investigational parenteral medication

AbstractThere are few evidence-based guidelines to inform optimal design of complex clinical trials, such as those assessing the safety and efficacy of intravenous drugs administered daily with infusion times over many hours per day and treatment durations that may span years. This study is a retrospective review of inpatient administration deviation reports for an investigational drug that is administered daily with infusion times of 8–24 h, and variable treatment durations for each patient. We report study design modifications made in 2007–2008 aimed at minimizing deviations from an investigational drug infusion protocol approved by an institutional review board and the United States Food and Drug Administration. Modifications were specifically aimed at minimizing errors of infusion rate, incorrect dose, incorrect patient, or wrong drug administered. We found that the rate of these types of administration errors of the study drug was significantly decreased following adoption of the specific study design changes. This report provides guidance in the design of clinical trials testing the safety and efficacy of study drugs administered via intravenous infusion in an inpatient setting so as to minimize drug administration protocol deviations and optimize patient safety

Heat and dehydration induced oxidative damage and antioxidant defenses following incubator heat stress and a simulated heat wave in wild caught four-striped field mice Rhabdomys dilectus

Heat waves are known for their disastrous mass die-off effects due to dehydration and cell damage, but little is known about the non-lethal consequences of surviving severe heat exposure. Severe heat exposure can cause oxidative stress which can have negative consequences on animal cognition, reproduction and life expectancy. We investigated the current oxidative stress experienced by a mesic mouse species, the four striped field mouse, Rhabdomys dilectus through a heat wave simulation with ad lib water and a more severe temperature exposure with minimal water. Wild four striped field mice were caught between 2017 and 2019. We predicted that wild four striped field mice in the heat wave simulation would show less susceptibility to oxidative stress as compared to a more severe heat stress which is likely to occur in the future. Oxidative stress was determined in the liver, kidney and brain using malondialdehyde (MDA) and protein carbonyl (PC) as markers for oxidative damage, and superoxide dismutase (SOD) and total antioxidant capacity (TAC) as markers of antioxidant defense. Incubator heat stress was brought about by increasing the body temperatures of animals to 39–40.8˚C for 6 hours. A heat wave (one hot day, followed by a 3- day heatwave) was simulated by using temperature cycle that wild four striped field mice would experience in their local habitat (determined through weather station data using temperature and humidity), with maximal ambient temperature of 39˚C. The liver and kidney demonstrated no changes in the simulated heat wave, but the liver had significantly higher SOD activity and the kidney had significantly higher lipid peroxidation in the incubator experiment. Dehydration significantly contributed to the increase of these markers, as is evident from the decrease in body mass after the experiment. The brain only showed significantly higher lipid peroxidation following the simulated heat wave with no significant changes following the incubator experiment. The significant increase in lipid peroxidation was not correlated to body mass after the experiment. The magnitude and duration of heat stress, in conjunction with dehydration, played a critical role in the oxidative stress experienced by each tissue, with the results demonstrating the importance of measuring multiple tissues to determine the physiological state of an animal. Current heat waves in this species have the potential of causing oxidative stress in the brain with future heat waves to possibly stress the kidney and liver depending on the hydration state of animals.S1 Table. The control and stressed PIT animal body temperature recordings inside the incubator throughout the 6 hour period.S2 Table. The body mass before, body mass after and % body mass change of each individual across all experiments.A DSTNRF SARChI research chair for Mammal Behavioural Ecology and Physiology; a University of Pretoria doctoral research bursary and a University of Pretoria department of research and innovation international cooperation postgraduate exchange bursary.http://www.plosone.orgam2021Mammal Research InstituteZoology and Entomolog

Genomic risk scores and oral contraceptive-associated ischemic stroke risk: a call for collaboration

BackgroundOral contraceptives (OCs) are generally safe but vascular risk factors increase OC-associated ischemic stroke risk. We performed a case-control study to evaluate whether a genomic risk score for ischemic stroke modifies OC-associated ischemic stroke risk.MethodsThe Genetics of Early-Onset Stroke study includes 332 premenopausal women (136 arterial ischemic stroke cases and 196 controls) with data on estrogen-containing OC use within 30 days before the index event (for cases) or interview (for controls). Using a previously validated genetic risk score (metaGRS) for ischemic stroke based on 19 polygenic risk scores for stroke and stroke-associated risk factors, we stratified our combined case-control sample into tertiles of genomic risk. We evaluated the association between OC use and ischemic stroke within each tertile. We tested if the association between OC use and ischemic stroke depended on the genomic risk of stroke using logistic regression with an OC use × metaGRS interaction term. These analyses were performed with and without adjustment for smoking, hypertension, diabetes, coronary heart disease, and body mass index.ResultsAfter adjustment for vascular risk factors, the odds ratio of OC use was 3.2 (1.7–6.3) overall and increased from the lower, middle, and upper tertile of genomic risk from 1.6 (0.5–5.4) to 2.5 (0.08–8.2) to 13.7 (3.8–67.3) respectively, and a p-value for interaction of 0.001.ConclusionsOur results suggest that genomic profile may modify the OC-associated ischemic stroke risk. Larger studies are warranted to determine whether a genomic risk score could be clinically useful in reducing OC-associated ischemic stroke