Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells

This is the final version of the article. Available from eLife Sciences Publications via the DOI in this record.Type 1 diabetes (T1D) is an autoimmune disease caused by loss of pancreatic β cells via apoptosis while neighboring α cells are preserved. Viral infections by coxsackieviruses (CVB) may contribute to trigger autoimmunity in T1D. Cellular permissiveness to viral infection is modulated by innate antiviral responses, which vary among different cell types. We presently describe that global gene expression is similar in cytokine-treated and virus-infected human islet cells, with up-regulation of gene networks involved in cell autonomous immune responses. Comparison between the responses of rat pancreatic α and β cells to infection by CVB5 and 4 indicate that α cells trigger a more efficient antiviral response than β cells, including higher basal and induced expression of STAT1-regulated genes, and are thus better able to clear viral infections than β cells. These differences may explain why pancreatic β cells, but not α cells, are targeted by an autoimmune response during T1D.Fonds De La Recherche Scientifique – FNRS: FNRS- F 5/4/5.MCF/KP. Project de secherche (PDR) T.0036.13; European Commission (EC): Projects Naimit and BetaBat, in the Framework Programme 7 of the European Community; Federation Wallonie- Bruxelles: the Communaute Franc¸ aise de BelgiqueActions de Recherche Concertees (ARC); Fonds De La Recherche Scientifique – FNRS: FNRS post-doctoral fellowship; Governo Brasil: PDE/CSF Pos-Doutorado no Exterior; Juvenile Diabetes Research Foundation International (JDRF): JDRF Career Development Award; European Commission (EC): European Union’s Seventh Framework Programme [FP7/2007-2013] under grant agreement 261441 PEVNE

The Safety and Feasibility of Transitioning From Transfemoral to Transradial Access Left Ventricular Endomyocardial Biopsy

BACKGROUND: Left ventricular endomyocardial biopsy (LVEMB) is commonly performed via the transfemoral route. Radial access may help reduce vascular access complications, but there are few data on the safety and feasibility of transradial LVEMB. OBJECTIVE: Describe the safety and feasibility of transitioning from transfemoral to transradial access LVEMB. METHODS: This is a single-center, prospective, observational cohort study. Fifty procedures in 49 patients were included, 25 (50%) via the femoral route and 25 (50%) via the radial route. RESULTS: The cohort had a mean age of 47 ± 13 years and the most common indication for LVEMB was myocarditis. From June 2015 until September 2016, all procedures (n = 21) were performed via the femoral approach; thenceforth, there was a gradual transition to the radial approach. More tissue samples were obtained when the procedure was performed via the femoral approach (P<.01). The minimum sampling target of 3 specimens was not met in 4 patients (16%) via the radial approach and in 1 patient (4%) via the femoral approach. Complications occurred in 3/25 transradial procedures (12%; 2 cardiac perforations and 1 forearm hematoma) and 3/25 transfemoral procedures (12%; 1 cardiac perforation, 1 femoral artery pseudoaneurysm, and 1 ventricular fibrillation). Cardiac perforations via the transradial approach occurred during the early transition period. There were no deaths. CONCLUSIONS: Transradial LVEMB is feasible, with a similar complication profile to femoral procedures, but associated with a smaller number of specimens. Transitioning from transfemoral to transradial procedures may initially be associated with a higher risk of complications and potentially a lower diagnostic yield

Impacts of High-Protein Oral Nutritional Supplements Among Malnourished Men and Women with Sarcopenia: A Multicenter, Randomized, Double-Blinded, Controlled Trial.

BACKGROUND: Recent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia. OBJECTIVES: We evaluated the effects of 2 high-quality oral nutritional supplements (ONS) differing in amount and type of key nutrients in older adult men and women. DESIGN: A multicenter, randomized, double-blinded, controlled clinical trial. PARTICIPANTS: Malnourished and sarcopenic men and women, 65 years and older (n = 330). INTERVENTION: A 24-week intervention period with 2 energy-rich (330 kcal) ONS treatment groups: Control ONS (CONS, 14 g protein; 147 IU vitamin D3) versus Experimental ONS (EONS, 20 g protein; 499 IU vitamin D3; 1.5 g CaHMB) taken twice daily. Both ONS also contained other vitamins, minerals, and nutrients in varying amounts. MEASUREMENTS: Isokinetic peak torque (PT, Nm) leg strength, grip strength (kg), and gait speed (m·s-1) were assessed at baseline and 12 and 24 weeks. Left and right leg muscle mass (LMM, kg) were assessed by dual-energy x-ray absorptiometry (DXA). Muscle quality (MQ) was leg strength expressed relative to the tested LMM (Nm·kg-1). Subgroup analyses were performed: severe sarcopenia (low skeletal mass index, low grip strength [ CONS, P = .032) in those with normal grip strength. There were no treatment differences based on sarcopenic severity for either grip strength or gait speed. CONCLUSION: ONS improved strength outcomes in malnourished older adults with sarcopenia. In those with mild-moderate sarcopenia, but not severe sarcopenia, consumption of the EONS improved leg muscle strength and quality compared with the standard CONS