Elevated Hypothalamic Glucocorticoid Levels Are Associated With Obesity and Hyperphagia in Male Mice.

Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However, the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone (Cort)-induced obesity and analyzed Cort levels in the hypothalamus and expression of genes relevant to Gc action. Mice were administered Cort (75 μg/mL) or ethanol (1%, vehicle) in drinking water for 4 weeks. Cort-treated mice had increased body weight, food intake, and adiposity. As expected, Cort increased plasma Cort levels at both zeitgeber time 1 and zeitgeber time 13, ablating the diurnal rhythm. Liquid chromatography dual tandem mass spectrometry revealed a 4-fold increase in hypothalamic Cort, which correlated with circulating levels and concentrations of Cort in other brain regions. This occurred despite decreased 11β-hydroxysteroid dehydrogenase (Hsd11b1) expression, the gene encoding the enzyme that regenerates active Gcs, whereas efflux transporter Abcb1 mRNA was unaltered. In addition, although Cort decreased hypothalamic GR (Nr3c1) expression 2-fold, the Gc-induced leucine zipper (Tsc22d3) mRNA increased, which indicated elevated GR activation. In keeping with the development of hyperphagia and obesity, Cort increased Agrp, but there were no changes in Pomc, Npy, or Cart mRNA in the hypothalamus. In summary, chronic Cort treatment causes chronic increases in hypothalamic Cort levels and a persistent elevation in Agrp, a mediator in the development of metabolic disturbances

Students as co-creators of teaching approaches, course design and curricula: implications for academic developers

Within higher education, students’ voices are frequently overlooked in the design of teaching approaches, courses and curricula. In this paper we outline the theoretical background to arguments for including students as partners in pedagogical planning processes. We present examples where students have worked collaboratively in design processes along with the beneficial outcomes of these examples. Finally we focus on some of the implications and opportunities for academic developers of proposing collaborative approaches to pedagogical planning

Improving vitamin D content in pork meat by UVB biofortification

Publication history: Accepted - 11 January 2023; Published online - 14 January 2023Vitamin D deficiency is prevalent worldwide and identification of alternative food-based strategies are urgently warranted. In two studies, 12-week old crossbred pigs (Duroc x (Large White x Landrace)) were exposed daily to narrowband UVB radiation for ∼10 weeks or control (no UVB exposure) until slaughter. In Study 1 (n = 48), pigs were exposed to UVB for 2 min and in Study 2 (n = 20), this duration was tripled to 6 min. All pigs were fed the maximum permitted 2000 IU vitamin D3/kg feed. Loin meat was cooked prior to vitamin D LC-MS/MS analysis. In Study 1, pork loin vitamin D3 did not differ between groups. Study 2 provided longer UVB exposure time and resulted in significantly higher loin vitamin D3 (11.97 vs. 6.03 μg/kg), 25(OH)D3 (2.09 vs. 1.65 μg/kg) and total vitamin D activity (22.88 vs. 14.50 μg/kg) concentrations, compared to control (P < 0.05). Pigs remained healthy during both studies and developed no signs of erythema. Biofortification by UVB radiation provides an effective strategy to further safely increase the naturally occurring vitamin D content of pork loin, alongside feed supplementationThis work was funded as part of a Department for the Economy (DfE) Co-operative Awards in Science and Technology (CAST) PhD studentship, supported by Devenish Nutrition Limited and Agri-Food Quest Competence Centre (AFQCC)

Annual Incidence of Snake Bite in Rural Bangladesh

Snake bite is one of the major causes of morbidity and mortality in many rural tropical areas. As a neglected public health problem, estimate of the risk is largely unknown. However, the associated personal and economic impact of snake bite is substantial across developing countries. This national survey investigated the risk and consequences of snake bite among the rural Bangladeshi population. We surveyed 18857 individuals from 24 out of 64 districts in Bangladesh where 98 snake bites including one death were reported. The estimated incidence density of snake bite is 623.4/ 100,000 person years (95% CI: 513.4–789.2/100,000 person years). Biting occurs mostly when individuals are at work. The majority of the victims (71%) received snake bites to their lower extremities. Eighty-six percent of the victims received some form of management within two hours of snake bite, although only three percent of them went directly to either a medical doctor or a hospital. The observed rate of snake bite in rural Bangladesh is substantially higher than anticipated. This coupled with poor access to health services led to an increase in related morbidity and mortality. An improvement in public health actions is therefore warranted

Clinical impact of genomic testing in patients with suspected monogenic kidney disease

Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design

Zinc status alters Alzheimer’s disease progression through NLRP3-dependent inflammation

Alzheimer’s disease is a devastating neurodegenerative disease with a dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing Alzheimer’s disease. Zinc deficiency is the most prevalent malnutrition in the world and may be a risk factor for Alzheimer’s disease potentially through enhanced inflammation, although evidence for this is limited. Here we provide epidemiological evidence suggesting that zinc supplementation was associated with reduced risk and slower cognitive decline, in people with Alzheimer’s disease and mild cognitive impairment. Using the APP/PS1 mouse model of Alzheimer’s disease fed a control (35mg/kg zinc) or diet deficient in zinc (3mg/kg zinc), we determined that zinc deficiency accelerated Alzheimer’s-like memory deficits without modifying amyloid beta (β) plaque burden in the brains of male mice. The NLRP3-inflammasome complex is one of the most important regulators of inflammation and we show here that zinc deficiency in immune cells, including microglia, potentiated NLRP3 responses to inflammatory stimuli in vitro including amyloid oligomers, while zinc supplementation inhibited NLRP3 activation. APP/PS1 mice deficient in NLRP3 were protected against the accelerated cognitive decline with zinc deficiency. Collectively, this research suggests that zinc status is linked to inflammatory reactivity and may be modified in people to reduce the risk and slow the progression of Alzheimer’s disease

THISTLE:trial of hands-on Interprofessional simulation training for local emergencies: a research protocol for a stepped-wedge clustered randomised controlled trial

Peer reviewedPublisher PD

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy