The pathogenesis of type 2 diabetes (T2D) might change with increasing age. Here, we used a stratification based on age of diagnosis to gain insight into the genetics and causal risk factors of T2D across different age-groups. We performed genome-wide association studies (GWAS) on T2D and T2D subgroups based on age of diagnosis (70 years) (total of 24,986 cases). As control subjects, participants were at least 70 years of age at the end of follow-up without developing T2D (N =187,130). GWAS identified 208 independent lead single nucleotide polymorphism (SNPs) mapping to 69 loci associated with T2D (P less then 1.0e-8). Among others, SNPs mapped to CDKN2B-AS1 and multiple independent SNPs mapped to TCF7L2 were more strongly associated with cases diagnosed after age 70 years than with cases diagnosed before age 50 years.  https://www.selleckchem.com/products/zongertinib.html  Based on the different case groups, we performed two-sample Mendelian randomization. Most notably, we observed that of the investigated risk factors, the association between BMI and T2D attenuated with increasing age of diagnosis. Collectively, our results indicate that stratification of T2D based on age of diag-nosis reveals subgroup-specific genetics and causal determinants, supporting the hypothesis that the pathogenesis of T2D changes with increasing age.
  To investigate the efficacy of automated control of inspired oxygen (FiO2) by Predictive Intelligent Control of Oxygenation (PRICO) on the Fabian ventilator in maintaining oxygen saturation (SpO2) in preterm infants on high flow nasal cannula (HFNC) support.
 
  Single-centre randomised two-period crossover study.
 
  Tertiary neonatal intensive care unit.
 
  27 preterm infants (gestational age (GA) <30 weeks) on HFNC support with FiO2 >0.25.
 
  A 24-hour period on automated FiO2-control with PRICO compared with a 24-hour period on routine manual control (RMC) to maintain a SpO2 level within target range of 88%-95% measured at 30 s intervals.
 
  Primary outcome time spent within target range (88%-95%).
 
  time spent above and below target range, in severe hypoxia (SpO2 <80%) and hyperoxia (SpO2 >98%), mean SpO2 and FiO2 and manual FiO2 adjustments.
 
  15 patients received PRICO-RMC and 12 RMC-PRICO. The mean time within the target range increased with PRICO 10.8% (95% CI 7.6 to 13.9). There was a decrease in time below target range 7.6% (95% CI 4.2 to 11.0), above target range 3.1% (95% CI 2.9 to 6.2) and in severe hypoxia 0.9% (95% CI 1.5 to 0.2). We found no difference in time spent in severe hyperoxia. Mean FiO2 was higher during PRICO 0.019 (95% CI 0.006 to 0.030). With PRICO there was a reduction of manual adjustments 9/24 hours (95% CI 6 to 12).
 
  In preterm infants on HFNC support, automated FiO2-control by PRICO is superior to RMC in maintaining SpO2 within target range. Further validation studies with a higher sample frequency and different ventilation modes are needed.
 In preterm infants on HFNC support, automated FiO2-control by PRICO is superior to RMC in maintaining SpO2 within target range. Further validation studies with a higher sample frequency and different ventilation modes are needed.Advances in neonatal-perinatal medicine have resulted in increased survival at lower gestations. Although the incidence of germinal matrix haemorrhage-intraventricular haemorrhage and cystic periventricular leucomalacia is reducing, a new phenotype of preterm brain injury has emerged consisting of a combination of destructive and dysmaturational effects. Consequently, severe neurological disability is reported at a lower rate than previously, but the overall morbidity associated with premature birth continues to present a large global burden and contributes significantly to increased financial costs to health systems and families. In this review, we examine the developmental milestones of fetal brain development and how preterm birth can disrupt this trajectory. We review common morbidities associated with premature birth today. Although drug-based and cell-based neuroprotective therapies for the preterm brain are under intense study, we outline basic, sustainable and effective non-medical, family-centred and developmental care strategies which have the potential to improve neurodevelopmental outcomes for this population and need to be considered part of the future neuroprotection care bundle.
  The COVID-19 pandemic has led to an unprecedented global research effort to build a body of knowledge that can inform mitigation strategies. We carried out a bibliometric analysis to describe the COVID-19 research output in Africa in terms of setting, study design, research themes and author affiliation.
 
  We searched for articles published between 1 December 2019 and 3 January 2021 from various databases including PubMed, African Journals Online, medRxiv, Collabovid, the WHO global research database and Google. All article types and study design were included.
 
  A total of 1296 articles were retrieved. 46.6% were primary research articles, 48.6% were editorial-type articles while 4.6% were secondary research articles. 20.3% articles used the entire continent of Africa as their study setting while South Africa (15.4%) was the most common country-focused setting. The most common research topics include 'country preparedness and response' (24.9%) and 'the direct and indirect health impacts of the pandemic' (2vaccines and therapeutics are needed to inform local development. In addition, the uneven distribution of research productivity among African countries emphasises the need for increased investment where needed.For Mycobacterium avium complex pulmonary disease (MAC-PD), current treatment regimens yield low cure rates. To obtain an evidence-based combination therapy, we assessed the in vitro activity of six drugs, namely, clarithromycin (CLR), rifampin (RIF), ethambutol (EMB), amikacin (AMK), clofazimine (CLO), and minocycline (MIN), alone and in combination, against Mycobacterium avium and studied the contributions of individual antibiotics to efficacy. The MICs of all antibiotics against M. avium ATCC 700898 were determined by broth microdilution. We performed kinetic time-kill assays of all single drugs and clinically relevant two-, three-, four-, and five-drug combinations against M. avium. Pharmacodynamic interactions of these combinations were assessed using area under the time-kill curve-derived effect size and Bliss independence. Adding a second drug yielded an average increase of the effect size (E) of 18.7% ± 32.9%, although antagonism was seen in some combinations. Adding a third drug showed a smaller increase in effect size (+12.