Odgaard Crews (townbeat93)

The potential harmful effects of polypharmacy (concurrent use of 5 or more drugs) are difficult to investigate in an experimental design in humans. Moreover, there is a lack of knowledge on sex-specific differences on the outcomes of multiple-drug use. The present study aims to investigate the effects of an eight-week exposure to a regimen of five different medications (metoprolol, paracetamol, aspirin, simvastatin and citalopram) in young adult female mice. Polypharmacy-treated animals showed significant impairment in object recognition and fear associated contextual memory, together with a significant reduction of certain hippocampal proteins involved in pathways necessary for the consolidation of these types of memories, compared to animals with standard diet. The impairments in explorative behavior and spatial memory that we reported previously in young adult male mice administered the same polypharmacy regimen were not observed in females in the current study. Therefore, the same combination of medications induced different negative outcomes in young adult male and female mice, causing a significant deficit in non-spatial memory in female animals. Overall, this study strongly supports the importance of considering sex-specific differences in designing safer and targeted multiple-drug therapies.GRSF1 is a mitochondrial RNA-binding protein important for maintaining mitochondrial function. We found that GRSF1 is highly expressed in cultured skeletal myoblasts differentiating into myotubes. To understand the physiological function of GRSF1 in vivo, we generated mice in which GRSF1 was specifically ablated in skeletal muscle. The conditional knockout mice (Grsf1cKO) appeared normal until 7-9 months of age. Importantly, however, a reduction of muscle endurance compared to wild-type controls was observed in 16- to 18-month old Grsf1cKO mice. Transcriptomic analysis revealed more than 200 mRNAs differentially expressed in Grsf1cKO muscle at this age. Notably, mRNAs encoding proteins involved in mitochondrial function, inflammation, and ion transport, including Mgarp, Cxcl10, Nfkb2, and Sln mRNAs, were significantly elevated in aged Grsf1cKO muscle. Our findings suggest that GRSF1 deficiency exacerbates the functional decline of aged skeletal muscle, likely through multiple downstream effector proteins. The National Institute of Child Health and Human Development Neonatal Research Network recently proposed new, severity-based diagnostic criteria for bronchopulmonary dysplasia (BPD). This study provides the first benchmark epidemiological data applying this definition. Retrospective cohort study of infants born from 22 to 29 weeks' gestation in 2018 at 715 US hospitals in the Vermont Oxford Network. Rates of BPD, major neonatal morbidities, and common respiratory therapies, stratified by BPD severity, were determined. Among 24 896 infants, 2574 (10.3%) died before 36 weeks' postmenstrual age (PMA), 12 198 (49.0%) did not develop BPD, 9192 (36.9%) developed grade 1 or 2 BPD, and 932 (3.7%) developed grade 3 BPD. Rates of mortality before 36 weeks' PMA and grade 3 BPD decreased from 52.7% and 9.9%, respectively, among infants born at 22 weeks' gestation to 17.3% and 0.8% among infants born at 29 weeks' gestation. Grade 1 or 2 BPD peaked in incidence (51.8%) among infants born at 25 weeks' gestation. The frequency of severe intraventricular hemorrhage or cystic periventricular leukomalacia increased from 4.8% among survivors without BPD to 23.4% among survivors with grade 3 BPD. Similar ranges were observed for late onset sepsis (4.8%-31.4%), surgically treated necrotizing enterocolitis (1.4%-17.1%), severe retinopathy of prematurity (1.2%-23.0%), and home oxygen therapy (2.0%-67.5%). More than one-half of very preterm infants born in the United States died before 36 weeks' PMA or developed BPD. Greater BPD severity was associated with more frequent development of major neonatal morbi