Gregersenbertelsen5290

To analyze the effects of a tailored exercise intervention in acutely hospitalized elderly diabetic patients.

This is an ancillary analysis of a randomized controlled trial (RCT). A total of 103 acutely hospitalized elderly adults (mean age ~87 years) with type II diabetes were randomized to an intervention (exercise, n = 54) or control group (usual care, n = 49). The primary endpoint was change in functional status from baseline to hospital discharge as assessed with the Barthel Index and the Short Physical Performance Battery (SPPB). Secondary endpoints comprised cognitive function and mood status, quality of life (QoL), incidence of delirium, and handgrip strength. Exercise-related side effects, length of hospital stay, and incidence of falls during hospitalization were also assessed, as well as transfer to nursing homes, hospital readmission, and mortality during a 3-month follow-up.

The median length of stay was 8 days (interquartile range, 4) for both groups. The intervention was safe and provided significant benefits over usual care on SPPB (2.7 [95% confidence interval (CI) 1.8, 3.5]) and Barthel Index (8.5 [95% CI 3.9, 13.1]), as well as on other secondary endpoints such as cognitive status, depression, QoL, and handgrip strength (all P < 0.05). No significant between-group differences were found for the remainder of secondary endpoints.

An in-hospital individualized multicomponent exercise intervention was safe and effective for the prevention of functional and cognitive decline in acutely hospitalized elderly diabetic patients, although it had no influence on other endpoints assessed during hospitalization or at the 3-month follow-up after discharge.

An in-hospital individualized multicomponent exercise intervention was safe and effective for the prevention of functional and cognitive decline in acutely hospitalized elderly diabetic patients, although it had no influence on other endpoints assessed during hospitalization or at the 3-month follow-up after discharge.The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) less then 0.1% after induction and less then 0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD less then 0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. Metabolism activator The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.

Granulosa cells (GCs) are the major cellular component in a follicular microenvironment and play an indispensable role in ovarian function. This study was conducted to investigate the effects of ethanol exposure on the cellular and transcriptional changes of ovarian GCs.

For this purpose, bovine GCs were exposed to different concentrations of ethanol (0, 50, 100, 200, 500 and 1000) to mimic the effects of alcohol in in vitro. Subsequently, 100 and 1000mM concentrations were discarded from further experiments, as 100mM was not different from 50mM, and 1000mM was supertoxic to the cells.

The results showed that there was a gradual loss of cell viability with the increase of the ethanol concentration, i.e. lowest viability was observed at the highest concentration (1000mM), which is further supported by cell proliferation assay. Mitochondrial activity decreased significantly at higher concentrations. The expression of NRF2 decreased significantly (P<0.05) in ethanol-exposed cells compared with the cells in the control group at the 6-h time point, whereas the expression was increased in 500mM concentration at the 24-h time point. The expression of antioxidant genes, downstream to Nrf2-pathway activation, showed that overall expression pattern similar to NRF2.

The result of this study prompted us to postulate that ethanol exposure decreases the ability of GCs to handle stress by downregulating the expression of genes involved in Nrf2-pathway.

The result of this study prompted us to postulate that ethanol exposure decreases the ability of GCs to handle stress by downregulating the expression of genes involved in Nrf2-pathway.

In Portugal, carbapenem-resistant Acinetobacter baumannii (CRAB) has been associated with ST98, ST103 and ST208 (Oxford Scheme, Oxf) and a clone has usually been associated with a particular period of time. These clonal shifts were primarily explained by an increased antimicrobial resistance profile. Here we explore genomic and biochemical differences among these and more recent clones, which could further explain the diversity and evolution of this species.

A total of 116 CRAB isolates (2010-15), together with representatives of a previously described CRAB collection (4 isolates, 2001-06) were characterized by attenuated total reflection Fourier transform infrared spectroscopy (FTIR-ATR) and MLST. Representatives of different FTIR-ATR/MLST clusters were selected for WGS (n = 13), which allowed the in silico extraction of resistance and virulence genes, capsule locus and SNP analysis.

A. baumannii clonal shifts of OXA-58-producing ST103Oxf (2001-04), OXA-40-producing ST98Oxf (2002-06), OXA-23-producing tive virulence and AMR gene pool enlargement, together with features increasing pathogen-host adaptation. Worldwide dominance of ST218Oxf is supported by the combination of high AMR and virulence levels.

Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), is associated with an increased risk of osteoporotic fractures. It is unknown whether RYGB or sleeve gastrectomy (SG) have different effects on bone health.

To compare changes in bone mineral density and markers of bone turnover 1 year after SG and RYGB.

Randomized, triple-blind, single-center trial at a tertiary care center in Norway. The primary outcome was diabetes remission. Patients with severe obesity and type 2 diabetes were randomized and allocated (11) to SG or RYGB.

Changes in areal bone mineral density (aBMD) and bone turnover markers.

Femoral neck, total hip, and lumbar spine aBMD, but not total body aBMD, decreased significantly more after RYGB (n = 44) than after SG (n = 48) (mean [95% confidence interval] between group differences -2.8% [-4.7 to -0.8], -3.0% [-5.0 to -0.9], -4.2% [-6.4 to -2.1], and -0.5% [-1.6 to 0.6], respectively). The increase in procollagen type 1 N-terminal propeptide (P1NP) and C-telopeptide of type I collagen (CTX-1) were approximately 100% higher after RYGB than after SG (between group difference at 1 year, both P < 0.001). The changes in femoral neck, total hip, and lumbar spine aBMDs and the changes in P1NP and CTX-1 were independently associated with the surgical procedure (all P < 0.05) and not weight change.

Roux-en-Y gastric bypass was associated with a greater reduction in aBMD and a greater increase in bone turnover markers compared with SG. This finding could suggest greater skeletal fragility after RYGB.

Roux-en-Y gastric bypass was associated with a greater reduction in aBMD and a greater increase in bone turnover markers compared with SG. This finding could suggest greater skeletal fragility after RYGB.Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% has shown to be efficacious with an acceptable safety profile in people with hemophilia A (PwHA). The PROPEL trial compared safety and efficacy of 2 target FVIII troughs in PwHA aged 12 to 65 years, with severe disease, annualized bleeding rate ≥2, and previous FVIII treatment. PwHA were randomized to 12 months' pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1% to 3% (reference arm) or 8% to 12% (elevated arm); first 6 months was treatment-adjustment period. The primary endpoint was absence of bleeds during the second 6 months, analyzed using multiple imputations (full analysis set [FAS]). In the 1% to 3% and 8% to 12% arms, respectively, point estimates (95% confidence interval) of proportions of PwHA with zero total bleeds were 42% (29% to 55%) and 62% (49% to 75%) in FAS (N = 115; P = .055) and 40% (27% to 55%) and 67% (52% to 81%) in per-protocol analysis set (N = 95; P = .015). Dosing frequency and consumption varied in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA; serious AEs in 7/115 (6%) PwHA, including 1 treatment-related in 8% to 12% arm (transient anti-FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms. No new safety signals were observed in the 8% to 12% arm. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. This trial was registered at www.clinicaltrials.gov as #NCT02585960.We expand on existing understandings of health disparities among middle-class African Americans by examining how the postsecondary educational context gives rise to the unequal distribution of health. We used panel data (1994-2009) from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to estimate whether the risk of developing metabolic syndrome by midlife significantly differs for African Americans who attended Historically Black College or Universities (HBCUs) versus predominantly White institutions. We found that HBCU enrollment was associated with a 35% reduction in the odds of metabolic syndrome. Furthermore, we demonstrate that HBCU attendees who grew up in more segregated environments experienced the greatest reductions in the likelihood of developing metabolic syndrome. Our results underscore the important role that HBCUs play in the lives of African Americans and suggest their impacts go far beyond traditional benchmarks of socioeconomic achievement to include key health outcomes.Hematopoietic stem cells (HSC) self-renew to sustain stem cell pools and differentiate to generate all types of blood cells. HSCs remain in quiescence to sustain their long-term self-renewal potential. It remains unclear whether protein quality control is required for stem cells in quiescence when RNA content, protein synthesis, and metabolic activities are profoundly reduced. Here, we report that protein quality control via endoplasmic reticulum-associated degradation (ERAD) governs the function of quiescent HSCs. The Sel1L/Hrd1 ERAD genes are enriched in the quiescent and inactive HSCs, and conditional knockout of Sel1L in hematopoietic tissues drives HSCs to hyperproliferation, which leads to complete loss of HSC self-renewal and HSC depletion. Mechanistically, ERAD deficiency via Sel1L knockout leads to activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, we identify Ras homolog enriched in brain (Rheb), an activator of mTOR, as a novel protein substrate of Sel1L/Hrd1 ERAD, which accumulates upon Sel1L deletion and HSC activation.