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1%±0.14% (mean±SE), from baseline 9.2%±1.0% to 8.1%±1.1%, p≤0.0001, with moderate to high heterogeneity between sites (Q=43.9, I<br /><br /> =74.9, p&lt;0.0001) explained by differences in baseline HbA1c between sites.The HbA1c improvement in both groups was observed by age group, body mass index, duration of insulin use and sex at birth.<br /><br /> In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of ﬂash glucose monitoring technology.<br /><br />In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of ﬂash glucose monitoring technology.Over half of all spinal cord injuries (SCIs) are cervical, which can lead to paralysis and respiratory compromise, causing significant morbidity and mortality. Effective treatments to restore breathing after severe upper cervical injury are lacking; thus, it is imperative to develop therapies to address this. Epidural stimulation has successfully restored motor function after SCI for stepping, standing, reaching, grasping, and postural control. We hypothesized that closed-loop stimulation triggered via healthy hemidiaphragm EMG activity has the potential to elicit functional neuroplasticity in spinal respiratory pathways after cervical SCI (cSCI). To test this, we delivered closed-loop, electrical, epidural stimulation (CLES) at the level of the phrenic motor nucleus (C4) for 3 d after C2 hemisection (C2HS) in freely behaving rats. A 2 × 2 Latin Square experimental design incorporated two treatments, C2HS injury and CLES therapy resulting in four groups of adult, female Sprague Dawley rats C2HS + CLES (n = 8), C2HS (n = 6), intact + CLES (n = 6), intact (n = 6). In stimulated groups, CLES was delivered for 12-20 h/d for 3 d. After C2HS, 3 d of CLES robustly facilitated the slope of stimulus-response curves of ipsilesional spinal motor evoked potentials (sMEPs) versus nonstimulated controls. To our knowledge, this is the first demonstration of CLES eliciting respiratory neuroplasticity after C2HS in freely behaving animals. These findings suggest CLES as a promising future therapy to address respiratory deficiency associated with cSCI.Autonomic parasympathetic preganglionic neurons (PGNs) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be because of recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within Lamina VII, where PGN are situated, by combining whole cell patch clamp recordings with k-means clustering of a range of electrophysiological parameters. Additional morphologic analysis separated these neuronal classes into parasympathetic preganglionic populations (PGN) and a fast-firing interneuronal population. Kv3 channels are voltage-gated potassium channels (Kv) that allow fast and precise firing of neurons. We found that blockade of Kv3 channels by tetraethylammonium (TEA) reduced neuronal firing frequency and isolated high-voltage-activated Kv currents in the fast-firing population but had no effect in PGN populations. Furthermore, Kv3 blockade potentiated the local and descending inhibitory inputs to PGN indicating that Kv3-expressing inhibitory neurons are synaptically connected to PGN. Taken together, our data reveal that Kv3 channels are crucial for fast and regulated neuronal output of a defined population that may be involved in intrinsic spinal bladder circuits that underpin recurrent inhibition of PGN.The action of acetylcholine in the cortex is critical for cognitive functions and cholinergic drugs can improve functions such as attention and working memory. An alternative means of enhancing cholinergic neuromodulation in primates is the intermittent electrical stimulation of the cortical source of acetylcholine, the nucleus basalis (NB) of Meynert. NB stimulation generally increases firing rate of neurons in the prefrontal cortex, however its effects on single neurons are diverse and complex. We sought to understand how NB stimulation affects global measures of neural activity by recording and analyzing local field potentials (LFPs) in monkeys as they performed working memory tasks. NB stimulation primarily decreased power in the alpha frequency range during the delay interval of working memory tasks. The effect was consistent across variants of the task. No consistent modulation in the delay interval of the task was observed in the gamma frequency range, which has previously been implicated in the maintenance of working memory. Our results reveal global effects of cholinergic neuromodulation via deep brain stimulation, an emerging intervention for the improvement of cognitive function.Our previous studies have shown that ethanol intoxication combined with burn injury increases intestinal bacterial growth, disrupts the intestinal barrier, and enhances bacterial translocation. Additionally, studies show that Th17 effector cytokines IL-17 and IL-22, which are dependent on IL-23, play important roles in maintaining intestine mucosal barrier integrity. Recent findings suggest neutrophils are a significant source of IL-17 and IL-22. We determined the effect of ethanol and burn injury on neutrophil IL-17 and IL-22 production, as well as their ability to phagocytose and in bacterial clearance, and whether these effects are modulated by IL-23. Mice were given ethanol 4 h prior to receiving ∼12.5% total body surface area burn and were euthanized day 1 after injury. We observed that intoxication combined with burn injury significantly decreases blood neutrophil phagocytosis and bacteria killing, as well as their ability to produce IL-17 and IL-22, compared with sham vehicle mice. The treatment of neutrophils with rIL-23 significantly increases IL-22 and IL-17 release and promotes expression of IL-23R, retinoic acid-related orphan receptor γt, Lipocalin2, and Nod-like receptor 2 following ethanol and burn injury. Furthermore, IL-22- and IL-17-producing neutrophils have enhanced neutrophil extracellular trap formation and bacterial killing ability, which are dependent on IL-23. Finally, although we observed that peritoneal neutrophils harvested after casein treatment are functionally different from blood neutrophils, both blood and peritoneal neutrophils exhibited the same response to rIL-23 treatment. Together these findings suggest that IL-23 promotes neutrophil IL-22 and IL-17 production and their ability to kill bacteria following ethanol and burn injury.<br /><br /> To assess how and to what extent adherence to medication is reported in pivotal clinical trials of oral cancer drugs.<br /><br /> All drugs authorised by the European Medicines Agency from 1 January 2014 to 31 December 2019 were considered for analysis. For each pivotal trial we extracted the journal of publication, phase of the study, posology, mention of adherence within the main text of the published article or additional material and the terms in which the adherence was reported.<br /><br /> Thirty drugs were included in the analysis from 56 clinical trials. Eleven articles (19.6%) contained a mention of medication adherence in the main document, 26 (46.4%) in the supplementary material and 19 (33.9%) did not contain any reference to adherence. Seven studies reported medication adherence between the results, expressed as number of patients discontinuing treatment for non-compliance and mean or median percentage.<br /><br /> Medication adherence in pivotal clinical trials of oral oncological drugs is poorly represented. There should be a greater level of reporting in the results and it should be included among the minimum set of recommendations in reporting health research.<br /><br />Medication adherence in pivotal clinical trials of oral oncological drugs is poorly represented. There should be a greater level of reporting in the results and it should be included among the minimum set of recommendations in reporting health research.<br /><br /> Traffic injury is a leading and preventable cause of child death and disability, with child pedestrians and cyclists particularly vulnerable. Examining built environment correlates of child pedestrian and cyclist motor vehicle collisions (PCMVC) in different settings is needed to promote an evidence-based approach to road safety.<br /><br /> We conducted a cross-sectional study across multiple urban/suburban environments in Canada (Calgary, Toronto, Montreal, Laval, Peel Region). All public elementary schools were included (n=1030). We examined the role of land use/social environments, road environments and traffic safety interventions on the rates of child PCMVC within 1000 m of schools. Multivariable negative binomial regression was conducted for all cities and by individual city. In a subset of schools (n=389), we examined associations when controlling for active school transportation (AST).<br /><br /> Mean PCMVC rate per school ranged from 0.13 collisions/year in Peel to 0.35 in Montreal. Child PCMVC were correlated with land use, social and road environments and traffic safety interventions. In fully adjusted models, social and land use features remained the most important correlates. New immigrant population had the largest positive association with child PCMVC (incidence rate ratio (IRR) 1.26, 95% CI 1.06 to 1.50), while old housing (pre-1960) density was most protective (IRR 0.83, 95% CI 0.77 to 0.90). AST was associated with PCMVC, but it had no effect on the relationships between PCMVC and other social/environmental correlates.<br /><br /> The built environment and social factors influence rates of child PCMVC. Opportunities to reduce child PCMVC exist through modifications to city design and road environments and implementing traffic safety interventions.<br /><br />The built environment and social factors influence rates of child PCMVC. Opportunities to reduce child PCMVC exist through modifications to city design and road environments and implementing traffic safety interventions.<br /><br /> Awareness-raising campaigns play a central role in efforts to combat drug resistance. These campaigns assume that knowledge deficits drive poor practices that increase resistance. Therefore, increasing awareness will promote prudent practices and reduce resistance. However, most awareness campaigns have been developed and evaluated in high-income and public health settings. Consequently, it is not clear whether these campaigns are effective in low-income and middle-income countries and/or within animal health settings.<br /><br /> Focus group discussions and in-depth interviews were used to collect narratives of veterinary drug use among Maasai pastoralists (n=70), animal health professionals (n=10) and veterinary drug sellers (n=5). Thematic analysis was used to identify recurring themes across narratives and groups.<br /><br /> Narratives of Maasai and animal health professionals indicated that Maasai treated their livestock with limited input from the professional sector and that non-prudent treatment practices were observeng efforts. In contrast, Maasai narratives highlight how animal health practices are patterned by cultural norms interacting with factors largely outside of Maasai control, including a constrained professional veterinary sector. If these cultural and structural contexts remain unconsidered in awareness-raising strategies, current campaigns are unlikely to motivate practices necessary to limit drug resistance, especially within low-income and middle-income settings.