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Precise correction of the CD40LG gene in T cells and hematopoietic stem/progenitor cells (HSPC) holds promise for treating X‐linked hyper‐IgM Syndrome (HIGM1), but its actual therapeutic potential remains elusive. Here, we developed a one‐size‐fits‐all editing strategy for effective T‐cell correction, selection, and depletion and investigated the therapeutic potential of T‐cell and HSPC therapies in the HIGM1 mouse model. Edited patients’ derived CD4 T cells restored physiologically regulated CD40L expression and contact‐dependent B‐cell helper function. Adoptive transfer of wild‐type T cells into conditioned HIGM1 mice rescued antigen‐specific IgG responses and protected mice from a disease‐relevant pathogen. We then obtained ~ 25% CD40LG editing in long‐term repopulating human HSPC. Transplanting such proportion of wild‐type HSPC in HIGM1 mice rescued immune functions similarly to T‐cell therapy. Overall, our findings suggest that autologous edited T cells can provide immediate and substantial benefits to HIGM1 patients and position T‐cell ahead of HSPC gene therapy because of easier translation, lower safety concerns and potentially comparable clinical benefits.

Concern about the use of antimicrobials in food producing animals is increasing. The study objective was to quantify antimicrobial drug usage in calves using antimicrobial treatment records from Irish suckler beef and dairy farms. Antimicrobial treatment records for calves born between 1 July 2014 and 30 June 2015 on 79 suckler beef and 44 dairy farms were analyzed. Calves were followed from birth (day 0) until 6 months of age. According to standard farm protocol, calves exhibiting clinical signs of any disease were identified and antimicrobial treatment was administered. Farmers recorded the following information for each treatment administered: calf identification, age at treatment, disease event, drug name, number of treatment days, and amount of drug administered. In total, 3,204 suckler beef calves and 5,358 dairy calves, representing 540,953 and 579,997 calfdays at risk, respectively, were included in the study. A total of 1,770 antimicrobial treatments were administered to suckler beef (n = 841) and dairy calves (n = 929) between birth and 6 months of age. There was large variation in TI DDDvet and TI DCDvet by farm. This study provides new insights into the time periods and indications for which specific antimicrobial substances are used in Irish dairy and beef suckler calves.

AbstractBackground:There is a paucity of functional data on mid-to-late preterm infants between 30+0 and 34+6 weeks gestation. We aimed to characterise transitional cardiopulmonary and haemodynamic changes during the first 48 hours in asymptomatic mid-to-late preterm infants.Methods:Forty-five healthy preterm newborns (mean ± standard deviation) gestation of 32.7 ± 1.2 weeks) underwent echocardiography on Days 1 and 2. Ventricular mechanics were assessed by speckle tracking-derived deformation, rotational mechanics, tissue Doppler imaging, and right ventricle-focused measures (tricuspid annular plane systolic excursion, fractional area change). Continuous haemodynamics were assessed using the NICOM™ system to obtain left ventricular output, stroke volume, heart rate, and total peripheral resistance by non-invasive cardiac output monitoring.Results:Right ventricular function increased (all measures p < 0.005) with mostly stable left ventricular performance between Day 1 and Day 2. NICOM-derived left ventricular output [mean 34%, 95% confidence interval 21–47%] and stroke volume [29%, 16–42%] increased with no change in heart rate [5%, −2 to 12%]. There was a rise in mean blood pressure [11%, 1–21%], but a decline in total peripheral resistance [−14%, −25 to −3%].Conclusion:Left ventricular mechanics remained persevered in mid-to-late premature infants, but right ventricular function increased. Non-invasive cardiac output monitoring is feasible in preterm infants with an increase in left ventricular output driven by an improvement in stroke volume during the transitional period.