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Ultrasensitive discovery regarding hormonal disruptors via superfine plasmonic spectral hair combs.
A high-risk clone ST69 (clonal complex 69) was also observed in the farm environment. This study provides genetic evidence that E. coli antimicrobial resistance factors in farm environments originate in the clinic or in livestock, and suggests that Good Agricultural Practice in farming is important to inhibit the spread of antimicrobial resistance to fresh produce.BACKGROUND Respiratory syncytial virus (RSV) typically causes winter outbreaks in temperate climates. During summer 2017, the Minnesota Department of Health (MDH) received a report of an increased cases of severe RSV-B infection. METHODS We compared characteristics of summer 2017 cases with those from the surrounding 4 summers (2014-2018). To understand the genetic relatedness among viruses, we performed high-throughput sequencing of RSV from patients with a spectrum of illness from multiple clinical sites in Minnesota and Wisconsin. RESULTS From May-Sept. 2017, 58 cases of RSV (43 RSV-B) were reported compared to 20-29 cases (3-7 RSV-B) during the same time frame in other years. The median age and frequency of co-morbidities was similar, but 55% (24/43) were admitted to the ICU in 2017 compared to 12% in preceding 3 years (OR 4.84, p less then 0.01). Sequencing was performed on 137 specimens from March 2016-March 2018. Outbreak cases formed a unique clade sharing a single conserved non-synonymous change in the SH gene. We observed increased cases during the following winter season, during which time the new lineage was the predominant circulating strain. CONCLUSIONS We identified an outbreak of severe RSV-B disease associated with a new genetic lineage among urban Minnesota children during a time of expected low RSV circulation. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected] Metabolic syndrome (MetS) affects cognitive function in late life, particularly in women. But longitudinal research is scarce on associations of MetS with cognitive function during midlife. OBJECTIVE To determine associations between MetS exposure and cognitive function trajectories in midlife women. DESIGN AND SETTING This is a 17-year prospective, longitudinal study of multiracial/ethnic women in 7 US communities, with annual/biennial assessments. PARTICIPANTS Participants were 2149 US women traversing menopause. EXPOSURE Exposure consisted of MetS assessments (median 4 assessments over 4 years). MAIN OUTCOME MEASURES Main outcome measures were assessments of cognitive function in 3 domains perceptual speed (symbol digit modalities test, SDMT), episodic memory (East Boston Memory Test, EBMT), and working memory (Digit Span Backward Test, DSB). RESULTS By their first cognitive assessment (age 50.7 ± 2.9 years), 29.5% met the criteria for MetS. Women completed a median (interquartile range [IQR]) of 6 (IQR 4-7) follow-up cognitive assessments over 11.2 (IQR 9.2-11.5) years. Women with MetS, compared with those without, had a larger 10-year decline in SDMT z-score (estimate -0.087, 95% confidence interval, -0.150 to -0.024; P = 0.007), after adjustment for cognitive testing practice effects, sociodemographics, lifestyle, mood, and menopause factors. As such, MetS accelerated the 10-year loss of perceptual speed by 24%. MetS did not differentially affect the rate of decline in either immediate (P = 0.534) or delayed (P = 0.740) episodic memory or in working memory (P = 0.584). CONCLUSIONS In midlife women MetS exposure was associated with accelerated decline in perceptual speed, but not episodic or working memory. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail [email protected] Pharmacokinetic (PK)-pharmacodynamic (PD) indices relate measures of drug exposure to antibacterial effect. Clinical PK-PD studies aim to correlate PK-PD indices with outcomes in patients. ReACp53 p53 inhibitor Optimization of dosing based on pre-clinical studies means that PK-PD relationships are difficult to establish; therefore studies need to be designed and reported carefully to validate pre-clinical findings. OBJECTIVES To describe the methodological features of clinical antibacterial and antifungal PK-PD studies that reported the relationship between PK-PD indices and clinical or microbiological responses. METHODS Studies published between 1980 and 2015 were identified through systematic searches. Methodological features of eligible studies were extracted. RESULTS We identified 85 publications containing 97 PK-PD analyses. Most studies were small, with fewer than 100 patients. Around a quarter were performed on patients with infections due to a single specific pathogen. In approximately one-third of studies, patients received concurrent antibiotics/antifungals and in some other studies patients received other treatments that may confound the PK-PD-outcome relationship. Most studies measured antimicrobial concentrations in blood/serum and only four measured free concentrations. Most performed some form of regression, time-to-event analysis or used the Hill/Emax equation to examine the association between PK-PD index and outcome. Target values of PK-PD indices that predict outcomes were investigated in 52% of studies. Target identification was most commonly done using recursive partitioning or logistic regression. CONCLUSIONS Given the variability in conduct and reporting, we suggest that an agreed set of standards for the conduct and reporting of studies should be developed. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email [email protected] The dosing regimen of daptomycin for critically ill patients undergoing continuous renal replacement therapy (CRRT) remains controversial. The goal of this study was to provide guidance for optimal daptomycin therapy in CRRT patients with Staphylococcus aureus infections. METHODS Individual concentration data of 32 CRRT subjects pooled from previously published studies were used to construct the population pharmacokinetic model for daptomycin. Model-based simulations were performed to evaluate the efficacy and risk of toxicity for daptomycin doses of 4, 6 and 8 mg/kg, q24h or q48h, under CRRT doses of 25, 30 and 35 mL/h/kg. Efficacy was assessed by the bacteriostatic and bactericidal AUC/MIC targets and drug exposure-based efficacy references. Toxicity was estimated by safety exposure references and the trough concentration threshold. RESULTS A two-compartment model adequately described the pharmacokinetics of daptomycin. Efficacy analysis demonstrated that q48h dosing is associated with an extremely low probability of bactericidal target attainment on every second day after dosing and q24h dosing is preferred for a high probability of bactericidal target attainment.
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