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etry, as another potential biomarker of impaired muscle function, may provide novel insights for predicting IADL limitations. Future research should continue examining how strength asymmetries, and other aspects of muscle function beyond maximal strength, factor into the disabling cascade.The current coronavirus disease-2019 (COVID-19) pandemic caused 10,541 deaths among nursing home residents in France, by July 17th, 2020. This study reported the results of an urgent pre-hospital intervention in eight French nursing homes. A retrospective study was conducted from March 26th to May 7th, 2020, before and after the intervention of a task force which took action from April 9th to April 11th, 2020. The task force included nurses and specialists of the county general hospital. The intervention had four steps i) daily notification of deaths; ii) audit by infectious diseases and hygiene specialists focused on nursing team reinforcing, tracking of suspected cases, patients' cohorting, review of preventive and protective measures, hydration, thromboembolism prevention; iii) intervention of an emergency team which urgently performed procedures suggested; iv) relay with a geriatric team. There were a total of 770 residents distributed in eight facilities with capacity varying from 53 to 145 residents. The number of deaths peaked at 139 in week 2 and the trough at 0 occurred in weeks 6-7. https://www.selleckchem.com/screening/inhibitor-library.html Comparison between periods (before vs after intervention) showed a significant decrease in number of new deaths (83/770; 11% vs 35/687; 5%, p = 0.0001) and new COVID-19 cases (348/770; 45% vs 123/422; 29%, p less then 0.001). The urgent pre-hospital intervention by a multidisciplinary task force achieved mortality reduction during COVID-19 outbreak in nursing homes. Pre-hospital intervention is a valid alternative to hospitalization in case of hospital saturation. Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infections in Western countries. Risk factors, mortality, and healthcare utilization for CDI in Latin America are poorly understood. This study assessed risk factors and burden associated with nosocomial CDI in four Latin American countries. This retrospective, case-control study used databases and medical records from 8 hospitals in Argentina, Brazil, Chile, and Mexico to identify nosocomial CDI cases from 2014 - 2017. Cases were patients aged ≥18 years with diarrhea and a positive CDI test ≥72 h after hospital admission. Two controls (without diarrhea; length of hospital stay [LOS] ≥3 days; admitted ±14 days from case patient; shared same ward) were matched to each case. CDI-associated risk factors were assessed by univariate and multivariable analyses. CDI burden (LOS, in-hospital mortality) was compared between cases and controls. The study included 481 cases and 962 controls. Mean age and sex were similar bet, preexisting medical conditions, and recent hospital admission were major risk factors for CDI in Argentina, Brazil, Chile, and Mexico. CDI was associated with increased in-hospital risk of death and longer LOS. These findings are consistent with published literature in Western countries. To evaluate levonorgestrel 52 mg intrauterine system (IUS) expulsion risk by menstrual cycle day of insertion (days 1-8 vs days 9 and beyond) in women using the IUS for noncontraceptive indications. We performed a retrospective cohort study of patients with a levonorgestrel IUS inserted for the management of noncontraceptive, gynecologic conditions at Kaiser Permanente-Hawaii between January 2009 and December 2010. We used multivariable logistic regression models to estimate the likelihood of IUS expulsion adjusting for demographic and clinical factors and a Kaplan-Meier curve for survival analysis. Of 176 patients identified, insertion occurred in 42 patients in cycle days 1 to 8 and 87 patients after day 8. Patient follow-up within the Kaiser system ranged from 1 to 71 months. Thirty-nine (22%) patients experienced expulsion, 16 (38%) and 15 (17%) for the 2 timing groups, respectively. Expulsion was more likely if the IUS placement occurred during the menstrual cycle days 1 to 8 (adjusted odds ratio 3.57 [95% confidence interval 1.13, 11.31]), which was consistent with the Kaplan-Meier analysis (p=0.008). Levonorgestrel IUS expulsion among women using the IUS for noncontraceptive indications occurred more frequently if insertion occurred during the first eight days of the menstrual cycle. In women planning to use the levonorgestrel IUS to treat gynecologic conditions such as abnormal uterine bleeding, dysmenorrhea, and endometrial hyperplasia, providers should consider waiting until after cycle day 8 to perform insertion. In women planning to use the levonorgestrel IUS to treat gynecologic conditions such as abnormal uterine bleeding, dysmenorrhea, and endometrial hyperplasia, providers should consider waiting until after cycle day 8 to perform insertion.We recently reported the antisense properties of a DNA/RNA heteroduplex oligonucleotide consisting of a phosphorothioate DNA-gapmer antisense oligonucleotide (ASO) strand and its complementary phosphodiester RNA/phosphorothioate 2'-O-methyl RNA strand. When α-tocopherol was conjugated with the complementary strand, the heteroduplex oligonucleotide silenced the target RNA more efficiently in vivo than did the parent single-stranded ASO. In this study, we designed a new type of the heteroduplex oligonucleotide, in which the RNA portion of the complementary strand was replaced with phosphodiester DNA, yielding an ASO/DNA double-stranded structure. The ASO/DNA heteroduplex oligonucleotide showed similar activity and liver accumulation as did the original ASO/RNA design. Structure-activity relationship studies of the complementary DNA showed that optimal increases in the potency and the accumulation were seen when the flanks of the phosphodiester DNA complement were protected using 2'-O-methyl RNA and phosphorothioate modifications. Furthermore, evaluation of the degradation kinetics of the complementary strands revealed that the DNA-complementary strand as well as the RNA strand were completely cleaved in vivo. Our results expand the repertoire of chemical modifications that can be used with the heteroduplex oligonucleotide technology, providing greater design flexibility for future therapeutic applications.
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