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Twenty insulin pump-treated adults (10 women) with type 1 diabetes completed the study. The baseline median (range) age was 48 (24-64) years, glycated hemoglobin 55 (44-66) mmol/mol, diabetes duration 24 (8-57) years, and body mass index 28.4 (22.3-35.8) kg/m

. No differences were observed between 5S and 2S in the percentage (mean±SD) of time spent below 3.9 mmol/L (3.5%±2.8% vs 4.5%±4.2%, p=0.28), time spent in 3.9-10.0 mmol/L (65.3%±15.0% vs 68.5%±13.6%, p=0.31), time spent above 10.0 mmol/L (31.2%±16.4% vs 27.3%±14.5%, p=0.15), mean glucose (8.7±1.3 mmol/L vs 8.5±1.2 mmol/L, p=0.33) and glycemic variability (35.8%±5.3% vs 35.8%±6.6%, p=0.97).

Time spent in hypoglycemia was comparable between the two 5-day periods with different duration and frequency of physical activity.

NCT04089462.

NCT04089462.

Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. THAL-SNS-032 inhibitor Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk.

We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D (n=232) and without either T1D or T2D (n=247). We used factor analysis to generate summary scores of cognitive domains and used regression analyses to examine the associations between sex and cognition adjusting for sociodemographic and cardiovascular confounders.

We included 1237 participants (630 women and 607 men) with mean age 68 years. By design, the distribution of men and women in T1D, T2her these differences change over time or in older cohorts and to understand their relationship to subsequent dementia.A key controversy in the COVID-19 pandemic has been over staff safety in health and social care settings. Anaesthetists and intensivists were anticipated to be at the highest risk of work-related infection due to involvement in airway management and management of critical illness and therefore wear the highest levels of personal protective equipment (PPE) in the hospital. However, the data clearly show that those working in anaesthesia and critical care settings are at lower risk of infection, harm and death from COVID-19 than colleagues working on the wards. The observed safety of anaesthetists and intensivists and increased risk to those in other patient-facing roles has implications for transmission-based infection control precautions. The precautionary principle supports extending training in and use of airborne precaution PPE to all staff working in patient-facing roles who have close contact with coughing patients. This will both reduce their risk of contracting COVID-19, maintain services and reduce nosocomial transmission to vulnerable patients. The emergence of a new variant of the SARS-CoV-2 virus with significantly higher transmissibility creates urgency to addressing this matter.The minor spliceosome mediates splicing of the rare but essential U12-type precursor messenger RNA. Here, we report the atomic features of the activated human minor spliceosome determined by cryo-electron microscopy at 2.9-angstrom resolution. The 5' splice site and branch point sequence of the U12-type intron are recognized by the U6atac and U12 small nuclear RNAs (snRNAs), respectively. Five newly identified proteins stabilize the conformation of the catalytic center The zinc finger protein SCNM1 functionally mimics the SF3a complex of the major spliceosome, the RBM48-ARMC7 complex binds the γ-monomethyl phosphate cap at the 5' end of U6atac snRNA, the U-box protein PPIL2 coordinates loop I of U5 snRNA and stabilizes U5 small nuclear ribonucleoprotein (snRNP), and CRIPT stabilizes U12 snRNP. Our study provides a framework for the mechanistic understanding of the function of the human minor spliceosome.

End-stage kidney disease (ESKD) is a life-threatening complication of diabetes that can be prevented or delayed by intervention. Hence, early detection of people at increased risk is essential.

From a population-based cohort of 5,460 clinically diagnosed Danish adults with type 1 diabetes followed from 2001 to 2016, we developed a prediction model for ESKD accounting for the competing risk of death. Poisson regression analysis was used to estimate the model on the basis of information routinely collected from clinical examinations. The effect of including an extended set of predictors (lipids, alcohol intake, etc.) was further evaluated, and potential interactions identified in a survival tree analysis were tested. The final model was externally validated in 9,175 adults from Denmark and Scotland.

During a median follow-up of 10.4 years (interquartile limits 5.1; 14.7), 303 (5.5%) of the participants (mean [SD] age 42.3 [16.5] years) developed ESKD, and 764 (14.0%) died without having developed ESKD. The final ESKD prediction model included age, male sex, diabetes duration, estimated glomerular filtration rate, micro- and macroalbuminuria, systolic blood pressure, hemoglobin A

, smoking, and previous cardiovascular disease. Discrimination was excellent for 5-year risk of an ESKD event, with a C-statistic of 0.888 (95% CI 0.849; 0.927) in the derivation cohort and confirmed at 0.865 (0.811; 0.919) and 0.961 (0.940; 0.981) in the external validation cohorts from Denmark and Scotland, respectively.

We have derived and validated a novel, high-performing ESKD prediction model for risk stratification in the adult type 1 diabetes population. This model may improve clinical decision making and potentially guide early intervention.

We have derived and validated a novel, high-performing ESKD prediction model for risk stratification in the adult type 1 diabetes population. This model may improve clinical decision making and potentially guide early intervention.

Therapeutic strategies silencing and reducing the hepatitis B virus (HBV) reservoir, the covalently closed circular DNA (cccDNA), have the potential to cure chronic HBV infection. We aimed to investigate the impact of small interferring RNA (siRNA) targeting all HBV transcripts or pegylated interferon-α (peg-IFNα) on the viral regulatory HBx protein and the structural maintenance of chromosome 5/6 complex (SMC5/6), a host factor suppressing cccDNA transcription. In particular, we assessed whether interventions lowering HBV transcripts can achieve and maintain silencing of cccDNA transcription in vivo.

HBV-infected human liver chimeric mice were treated with siRNA or peg-IFNα. Virological and host changes were analysed at the end of treatment and during the rebound phase by qualitative PCR, ELISA, immunoblotting and chromatin immunoprecipitation. RNA in situ hybridisation was combined with immunofluorescence to detect SMC6 and HBV RNAs at single cell level. The entry inhibitor myrcludex-B was used during the rebound phase to avoid new infection events.

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