Increasing HbA1c is associated with reduced CD8+ T cell functionality in response to influenza virus in a TCR-dependent manner in individuals with diabetes mellitus.

Diabetes mellitus is on the rise globally and is a known susceptibility factor for severe influenza virus infections. However, the mechanisms by which diabetes increases the severity of an influenza virus infection are yet to be fully defined. Diabetes mellitus is hallmarked by high glucose concentrations in the blood. We hypothesized that these high glucose concentrations affect the functionality of CD8+ T cells, which play a key role eliminating virus-infected cells and have been shown to decrease influenza disease severity. To study the effect of hyperglycemia on CD8+ T cell function, we stimulated peripheral blood mononuclear cells (PBMCs) from donors with and without diabetes with influenza A virus, anti-CD3/anti-CD28-coated beads, PMA and ionomycin (PMA/I), or an influenza viral peptide pool. After stimulation, cells were assessed for functionality [as defined by expression of IFN-γ, TNF-α, macrophage inflammatory protein (MIP)-1ß, and lysosomal-associated membrane protein-1 (CD107a)] using flow cytometry. Our results showed that increasing HbA1c correlated with a reduction in TNF-α production by CD8+ T cells in response to influenza stimulation in a TCR-specific manner. This was not associated with any changes to CD8+ T cell subsets. We conclude that hyperglycemia impairs CD8+ T cell function to influenza virus infection, which may be linked with the increased risk of severe influenza in patients with diabetes.

Dietary supplements, guideline alignment and biochemical nutrient status in pregnancy: Findings from the Queensland Family Cohort pilot study.

In high-income nations, multiple micronutrient (MMN) supplementation during pregnancy is a common practice. We aimed to describe maternal characteristics associated with supplement use and daily dose of supplemental nutrients consumed in pregnancy, and whether guideline alignment and nutrient status are related to supplement use. The Queensland Family Cohort is a prospective, Australian observational longitudinal study. Maternal characteristics, nutrient intake from food and supplements, and biochemical nutrient status were assessed in the second trimester (n = 127). Supplement use was reported by 89% of participants, of whom 91% reported taking an MMN supplement. Participants who received private obstetric care, had private health insurance and had greater alignment to meat/vegetarian alternatives recommendations were more likely to report MMN supplement use. Private obstetric care and general practitioner shared care were associated with higher daily dose of supplemental nutrients consumed compared with midwifery group practice. There was high reliance on supplements to meet nutrient reference values for folate, iodine and iron, but only plasma folate concentrations were higher in MMN supplement versus nonsupplement users. Exceeding the upper level of intake for folic acid and iron was more likely among combined MMN and individual supplement/s users, and associated with higher plasma concentrations of the respective nutrients. Given the low alignment with food group recommendations and potential risks associated with high MMN supplement use, whole food diets should be emphasized. This study confirms the need to define effective strategies for optimizing nutrient intake in pregnancy, especially among those most vulnerable where MMN supplement use may be appropriate.

Elevated BMI reduces the humoral response to SARS-CoV-2 infection.

Objective: Class III obesity (body mass index [BMI] ≥ 40 kg m-2) significantly impairs the immune response to SARS-CoV-2 vaccination. However, the effect of an elevated BMI (≥ 25 kg m-2) on humoral immunity to SARS-CoV-2 infection and COVID-19 vaccination remains unclear. Methods: We collected blood samples from people who recovered from SARS-CoV-2 infection approximately 3 and 13 months of post-infection (noting that these individuals were not exposed to SARS-CoV-2 or vaccinated in the interim). We also collected blood samples from people approximately 5 months of post-second dose COVID-19 vaccination (the majority of whom did not have a prior SARS-CoV-2 infection). We measured their humoral responses to SARS-CoV-2, grouping individuals based on a BMI greater or less than 25 kg m-2. Results: Here, we show that an increased BMI (≥ 25 kg m-2), when accounting for age and sex differences, is associated with reduced antibody responses after SARS-CoV-2 infection. At 3 months of post-infection, an elevated BMI was associated with reduced antibody titres. At 13 months of post-infection, an elevated BMI was associated with reduced antibody avidity and a reduced percentage of spike-positive B cells. In contrast, no significant association was noted between a BMI ≥ 25 kg m-2 and humoral immunity to SARS-CoV-2 at 5 months of post-secondary vaccination. Conclusions: Taken together, these data showed that elevated BMI is associated with an impaired humoral immune response to SARS-CoV-2 infection. The impairment of infection-induced immunity in individuals with a BMI ≥ 25 kg m-2 suggests an added impetus for vaccination rather than relying on infection-induced immunity.

Transdermal Measurement of Glomerular Filtration Rate in Preclinical Research.

The measurement of glomerular filtration rate (GFR) is essential to understanding renal physiology, including the monitoring of disease progression and treatment effectiveness. Transdermal measurement of glomerular filtration rate (tGFR) using a miniaturized fluorescence monitor in combination with a fluorescent exogenous GFR tracer has become a common technique to measure GFR in the preclinical setting, especially in rodent models. It allows for close to real-time measurement of GFR in conscious unrestrained animals and overcomes several limitations of other GFR measures. Its widespread use is reflected by published research articles and conference abstracts from different research fields, including in the assessment of new and existing kidney therapeutics, evaluation of nephrotoxicity, screening of novel chemical or medical agents, and fundamental understanding of kidney function.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

Prevalence and Patterns of Prenatal Alcohol Exposure in Australian Cohort and Cross-Sectional Studies: A Systematic Review of Data Collection Approaches.

This study sought to determine data collection approaches in Australian cohort studies and explore the potential impact on reported prenatal alcohol exposure (PAE) prevalence and patterns. Inclusion criteria were that studies related to a general Australian antenatal population where PAE was assessed and reported. Studies were excluded if they were not peer reviewed, examined the prevalence of PAE in pregnancies complicated by alcohol-use disorders, or were published in a language other than English. A systematic search of five electronic databases (PubMed, Embase, CINAHL, Web of Science, and Scopus) was conducted. Risk of bias was assessed using the Effective Public Health Practice Project quality assessment tool. Results were synthesised using MetaXL. Data from 16 separate birth cohorts (n = 78 articles) were included. Included cohorts were either general cohorts that included alcohol as a variable or alcohol-focused cohorts that were designed with a primary focus on PAE. PAE prevalence was estimated as 48% (95% CI: 38 to 57%). When subgroup analysis was performed, estimates of PAE prevalence when self-administered surveys and interviews were used for data collection were 53% (95% CI: 41% to 64%) and 43% (95% CI: 28% to 59%), respectively. Use of trained assessors was an influencing factor of the prevalence estimates when data were collected via interview. Alcohol-focused studies reported higher prevalence of PAE, regardless of method of survey administration. Where interviewer training is not possible, self-administered questionnaires will likely provide the most reliable PAE estimates. No funding sources are relevant to mention. Review was registered with PROSPERO (CRD42020204853).

Altered bone and body composition in children and adolescents with confirmed prenatal alcohol exposure.

Prenatal alcohol exposure can contribute to long term adverse health outcomes. Development of the skeletal system begins at the early embryonic stage and continues into early adulthood but the effect of prenatal alcohol exposure on skeletal growth is relatively unexplored in a clinical population. Here, we performed dual X-ray absorptiometry to examine bone, fat, and muscle accrual in children and adolescents diagnosed with, or at risk of, fetal alcohol spectrum disorders (FASDs). Children (aged 4-9 years) with FASD or at risk of FASD (n = 10) had similar growth to age matched controls (n = 27). By adolescence (aged ≥10 years), those with FASDs (n = 13) were shorter and had lower areal bone mineral density and lean tissue mass than typically developing peers (n = 29). Overall, adolescents diagnosed with FASDs had greater odds of impairments to bone and body composition. These findings highlight the importance of early FASD diagnosis and appropriate post-diagnostic medical follow-up to enable timely, effective interventions to optimize bone and body composition during paediatric growth.

Advanced Glycation End Products (AGEs) and Chronic Kidney Disease: Does the Modern Diet AGE the Kidney?

Since the 1980s, chronic kidney disease (CKD) affecting all ages has increased by almost 25%. This increase may be partially attributable to lifestyle changes and increased global consumption of a "western" diet, which is typically energy dense, low in fruits and vegetables, and high in animal protein and ultra-processed foods. These modern food trends have led to an increase in the consumption of advanced glycation end products (AGEs) in conjunction with increased metabolic dysfunction, obesity and diabetes, which facilitates production of endogenous AGEs within the body. When in excess, AGEs can be pathological via both receptor-mediated and non-receptor-mediated pathways. The kidney, as a major site for AGE clearance, is particularly vulnerable to AGE-mediated damage and increases in circulating AGEs align with risk of CKD and all-cause mortality. Furthermore, individuals with significant loss of renal function show increased AGE burden, particularly with uraemia, and there is some evidence that AGE lowering via diet or pharmacological inhibition may be beneficial for CKD. This review discusses the pathways that drive AGE formation and regulation within the body. This includes AGE receptor interactions and pathways of AGE-mediated pathology with a focus on the contribution of diet on endogenous AGE production and dietary AGE consumption to these processes. We then analyse the contribution of AGEs to kidney disease, the evidence for dietary AGEs and endogenously produced AGEs in driving pathogenesis in diabetic and non-diabetic kidney disease and the potential for AGE targeted therapies in kidney disease.

A decline in planned, but not spontaneous, preterm birth rates in a large Australian tertiary maternity centre during COVID-19 mitigation measures.

BACKGROUND: Reports from around the world suggest that rates of preterm birth decreased during COVID-19 lockdown measures. AIMS: To compare the prevalence of preterm birth and stillbirth rates during COVID-19 restriction measures with infants born at the same maternity centre during the same weeks in 2013-2019. MATERIALS AND METHODS: Deidentified data were extracted from the Mater Mothers' healthcare records database. This is a supra-regional tertiary perinatal centre. Logistic regressions were used to examine singleton live preterm birth rates during the beginning of COVID-19 restrictions (16 March-17 April; 'early'; 6955 births) and during the strictest part of COVID-19 restrictions (30 March-1 May; 'late'; 6953 births), according to gestational age subgroups and birth onset (planned or spontaneous). We adjusted for multiple covariates, including maternal age, body mass index, ethnicity, parity, socioeconomic status, maternal asthma, diabetes mellitus and/or hypertensive disorder. Singleton stillbirth rates were also examined between 16 March-1 May. RESULTS: Planned moderate/late preterm births declined by more than half during early COVID-19 restrictions compared with the previous seven years (29 vs an average of 64 per 1000 births; adjusted odds ratio 0.39, 95% CI 0.22-0.71). There was no effect on extremely or very preterm infants, spontaneous preterm births, or stillbirth rates. Rolling averages from January to June revealed a two-week non-significant spike in spontaneous preterm births from late April to early May, 2020. CONCLUSIONS: Together with evidence from other nations, the pandemic provides a unique opportunity to identify causal and preventative factors for preterm birth.

Adherence to Dietary and Physical Activity Guidelines in Australian Undergraduate Biomedical Students and Associations with Body Composition and Metabolic Health: A Cross-Sectional Study.

There is a paucity of data on whether Australian university students are meeting specific nutrient guidelines, and the relationship between diet and physical activity patterns with body composition and metabolic health. In this study, biomedical students from The University of Queensland were recruited (150 males and 211 females, 19-25 years), and nutritional intake (ASA24-Australia) and physical activity levels (Active Australia Survey) quantified. Body composition (height, waist circumference, body mass, BMI, and percentage body fat; BOD POD) and metabolic health (oral glucose tolerance test) were also measured. Median daily energy intake was 6760 kJ in females and 10,338 kJ in males, with more than 30% of total energy coming from energy-dense, nutrient-poor foods. Only 1 in 10 students met fruit or vegetable recommendations, with less than one third meeting recommendations for fibre, calcium, and potassium. Intakes of calcium and iron were particularly low among female students, with only 16% and 6% of students meeting the recommended dietary intake (RDI), respectively. The majority of males and almost half of all females exceeded the suggested dietary target (SDT) for sodium. Sufficient physical activity (≥150 min over ≥5 sessions per week) was met by more than 80% of students. Body composition and blood glucose concentrations were largely normal but an early sign of insulin resistance (HOMA-IR > 2.0), measured in a subset of students, was present in 21% of males and 17% of females. Modest reductions in blood glucose levels and percentage body fat were associated with increasing vigorous activity. Low intakes of fibre, calcium, and potassium could be corrected by increasing fruit, vegetable, and dairy intake, and, among females, health promotion messages focusing on iron-rich foods should be prioritised. While these nutrient deficiencies did not translate into immediate metabolic heath concerns, dietary behaviours can track into adulthood and have lasting effects on overall health.

Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection.

People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected control mice, infected diabetic mice had increased serum cardiac troponin I and creatine-kinase MB, left ventricular structural changes and right ventricular functional alterations, providing the first experimental evidence of type I diabetes increasing risks of influenza-induced cardiovascular complications.

Sotagliflozin, a Dual SGLT1/2 Inhibitor, Improves Cardiac Outcomes in a Normoglycemic Mouse Model of Cardiac Pressure Overload.

Selective SGLT2 inhibition reduces the risk of worsening heart failure and cardiovascular death in patients with existing heart failure, irrespective of diabetic status. We aimed to investigate the effects of dual SGLT1/2 inhibition, using sotagliflozin, on cardiac outcomes in normal diet (ND) and high fat diet (HFD) mice with cardiac pressure overload. Five-week-old male C57BL/6J mice were randomized to receive a HFD (60% of calories from fat) or remain on ND for 12 weeks. One week later, transverse aortic constriction (TAC) was employed to induce cardiac pressure-overload (50% increase in right:left carotid pressure versus sham surgery), resulting in left ventricular hypertrophic remodeling and cardiac fibrosis, albeit preserved ejection fraction. At 4 weeks post-TAC, mice were treated for 7 weeks by oral gavage once daily with sotagliflozin (10 mg/kg body weight) or vehicle (0.1% tween 80). In ND mice, treatment with sotagliflozin attenuated cardiac hypertrophy and histological markers of cardiac fibrosis induced by TAC. These benefits were associated with profound diuresis and glucosuria, without shifts toward whole-body fatty acid utilization, increased circulating ketones, nor increased cardiac ketolysis. In HFD mice, sotagliflozin reduced the mildly elevated glucose and insulin levels but did not attenuate cardiac injury induced by TAC. HFD mice had vacuolation of proximal tubular cells, associated with less profound sotagliflozin-induced diuresis and glucosuria, which suggests dampened drug action. We demonstrate the utility of dual SGLT1/2 inhibition in treating cardiac injury induced by pressure overload in normoglycemic mice. Its efficacy in high fat-fed mice with mild hyperglycemia and compromised renal morphology requires further study.

The role of T-cell immunity in COVID-19 severity amongst people living with type II diabetes.

The COVID-19 pandemic has highlighted the vulnerability of people with diabetes mellitus (DM) to respiratory viral infections. Despite the short history of COVID-19, various studies have shown that patients with DM are more likely to have increased hospitalisation and mortality rates as compared to patients without. At present, the mechanisms underlying this susceptibility are unclear. However, prior studies show that the course of COVID-19 disease is linked to the efficacy of the host's T-cell responses. Healthy individuals who can elicit a robust T-cell response are more likely to limit the severity of COVID-19. Here, we investigate the hypothesis that an impaired T-cell response in patients with type 2 diabetes mellitus (T2DM) drives the severity of COVID-19 in this patient population. While there is currently a limited amount of information that specifically addresses T-cell responses in COVID-19 patients with T2DM, there is a wealth of evidence from other infectious diseases that T-cell immunity is impaired in patients with T2DM. The reasons for this are likely multifactorial, including the presence of hyperglycaemia, glycaemic variability and metformin use. This review emphasises the need for further research into T-cell responses of COVID-19 patients with T2DM in order to better inform our response to COVID-19 and future disease outbreaks.

Prenatal alcohol consumption and placental outcomes: a systematic review and meta-analysis of clinical studies.

OBJECTIVE: A systematic review was conducted to determine placental outcomes following prenatal alcohol exposure in women. DATA SOURCES: The search terms "maternal OR prenatal OR pregnant OR periconception" AND "placenta" AND "alcohol OR ethanol" were used across 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and CINAHL) from inception until November 2020. STUDY ELIGIBILITY CRITERIA: Articles were included if they reported placental outcomes in an alcohol exposure group compared with a control group. Studies were excluded if placentas were from elective termination before 20 weeks' gestation, animal studies, in vitro studies, case studies, or coexposure studies. METHODS: Study quality was assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment Scale. Title and abstract screening was conducted by 2 reviewers to remove duplicates and irrelevant studies. Remaining full text articles were screened by 2 reviewers against inclusion and exclusion criteria. Placental outcome data were extracted and tabulated separately for studies of placentation, placental weight, placental morphology, and placental molecular studies. Meta-analyses were conducted for outcomes reported by >3 studies. RESULTS: Database searching retrieved 640 unique records. Screening against inclusion and exclusion criteria resulted in 33 included studies. The quality assessment identified that 61% of studies were high quality, 30% were average quality, and 9% were low quality. Meta-analyses indicated that prenatal alcohol exposure increased the likelihood of placental abruption (odds ratio, 1.48; 95% confidence interval, 1.37-1.60) but not placenta previa (odds ratio, 1.14; 95% confidence interval, 0.84-1.34) and resulted in a reduction in placental weight of 51 g (95% confidence interval, -82.8 to -19.3). Reports of altered placental vasculature, placental DNA methylation, and gene expression following prenatal alcohol exposure were identified. A single study examined placentas from male and female infants separately and found sex-specific placental outcomes. CONCLUSION: Prenatal alcohol exposure increases the likelihood of placental abruption and is associated with decreased placental weight, altered placental vasculature, DNA methylation, and molecular pathways. Given the critical role of the placenta in determining pregnancy outcomes, further studies investigating the molecular mechanisms underlying alcohol-induced placental dysfunction are required. Sex-specific placental adaptations to adverse conditions in utero have been well documented; thus, future studies should examine prenatal alcohol exposure-associated placental outcomes separately by sex.

Maternal gut microbiota displays minor changes in overweight and obese women with GDM.

BACKGROUND AND AIMS: Previous literature have shown a diversity of findings regarding the relationship between the maternal gut microbiota and gestational diabetes mellitus (GDM). We investigated the gut microbiota of overweight and obese women with gestational diabetes mellitus (GDM) against matched euglycaemic women at 16 and 28-weeks' gestation. METHODS AND RESULTS: This study included women from the SPRING (Study of PRobiotics IN Gestational diabetes) cohort. Overweight and obese women with no impaired glucose tolerance or impaired fasted glucose were enrolled prior to gestational age <16 weeks. Participants with a diagnosis of GDM (n = 29) were matched with euglycaemic (n = 29) women for body mass index, probiotic or placebo intervention, maternal age, parity and ethnicity. Anthropometric, clinical and fecal microbiota (16S rRNA amplicon-based sequencing of V6-V8 region) data was assessed at 16 and 28-weeks' gestation. The relative abundances of key bacterial genera were not significantly altered between euglycaemic women and women with GDM. Occurrence of bacterial taxa was similar between groups at both timepoints. GDM was associated with decreased Shannon diversity (p = 0.02) without differentiated clustering measured by beta diversity at 28-weeks' gestation. CONCLUSIONS: Overweight and obese women with GDM demonstrate minor variation in the gut microbiota at 16 and 28-weeks' gestation compared with matched euglycaemic women. This study expands on previous literature concluding the microbiota does not likely have a disease-specific characterisation in GDM.

Advanced glycation end products as predictors of renal function in youth with type 1 diabetes.

To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes (N = 100; 20.0 ± 2.8 years; M:F 54:46; FBG-11.6 ± 4.9 mmol/mol; diabetes duration 10.7 ± 5.2 years; BMI 24.5(5.3) kg/m2) and healthy controls (N = 299; 20.3 ± 1.8 years; M:F-83:116; FBG 5.2 ± 0.8 mmol/L; BMI 22.5(3.3) kg/m2) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFRCKD-EPI CysC and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI (Pmodel = 1.5 × 10-12). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk (Pmodel = 2.2 × 10-9), which increased with diabetes duration (51%; Pmodel < 2.2 × 10-16) and random blood glucose concentrations (56%; Pmodel < 2.2 × 10-16). HbA1C and circulating fructosamine albumin were higher in individuals with type 1 diabetes at high versus low DKD risk. eGFR was independently associated with DKD risk in all models. Higher eGFR and longer diabetes duration are associated with DKD risk in youth with type 1 diabetes. sAF, circulating AGEs, and urinary AGEs were not independent predictors of DKD risk. Changes in eGFR should be monitored early, in addition to uACR, for determining DKD risk in type 1 diabetes.

A meta-analysis on the role of pre-existing chronic disease in the cardiac complications of SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with multiple direct and indirect cardiovascular complications. We sought to analyze the association of host co-morbidities (chronic respiratory illnesses, cardiovascular disease [CVD], hypertension or diabetes mellitus [DM]) with the acute cardiovascular complications associated with SARS-CoV-2 infection. Individual analyses of the majority of studies found median age was higher by ~10 years in patients with cardiovascular complications. Pooled analyses showed development of SARS-CoV-2 cardiovascular complications was significantly increased in patients with chronic respiratory illness (odds ratio (OR): 1.67 [1.48, 1.88]), CVD (OR: 3.37 [2.57, 4.43]), hypertension (OR: 2.68 [2.11, 3.41]), DM (OR: 1.60 [1.31, 1.95]) and male sex (OR: 1.31 [1.21, 1.42]), findings that were mostly conserved during sub-analysis of studies stratified into global geographic regions. Age, chronic respiratory illness, CVD, hypertension, DM, and male sex may represent prognostic factors for the development of cardiovascular complications in COVID-19 disease, highlighting the need for a multidisciplinary approach to chronic disease patient management.

High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier.

Diabetes mellitus is a known susceptibility factor for severe influenza virus infections. However, the mechanisms that underlie this susceptibility remain incompletely understood. Here, the effects of high glucose levels on influenza severity were investigated using an in vitro model of the pulmonary epithelial-endothelial barrier as well as an in vivo murine model of type II diabetes. In vitro we show that high glucose conditions prior to IAV infection increased virus-induced barrier damage. This was associated with an increased pro-inflammatory response in endothelial cells and the subsequent damage of the epithelial junctional complex. These results were subsequently validated in vivo. This study provides the first evidence that hyperglycaemia may increase influenza severity by damaging the pulmonary epithelial-endothelial barrier and increasing pulmonary oedema. These data suggest that maintaining long-term glucose control in individuals with diabetes is paramount in reducing the morbidity and mortality associated with influenza virus infections.

The Impact of Isolation Measures Due to COVID-19 on Energy Intake and Physical Activity Levels in Australian University Students.

The coronavirus disease 2019 (COVID-19) pandemic resulted in physical isolation measures in many parts of the world. In Australia, nationwide restrictions included staying at home, unless seeking medical care, providing care, purchasing food, undertaking exercise, or attending work in an essential service. All undergraduate university classes transitioned to online, mostly home-based learning. We, therefore, examined the effect of isolation measures during the early phase of the COVID-19 pandemic in Australia (March/April) on diet (24-h recall) and physical activity (Active Australia Survey) patterns in third-year biomedical students. Findings were compared with students enrolled in the same course in the previous two years. In females, but not males, energy intake was ~20% greater during the pandemic, and snacking frequency and energy density of consumed snacks also increased compared with 2018 and 2019. Physical activity was impacted for both sexes during the pandemic with ~30% fewer students achieving "sufficient" levels of activity, defined by at least 150 min over at least five sessions, compared with the previous two years. In a follow-up study six to eight weeks later (14-18% response rate), during gradual easing of nationwide restrictions albeit continued gym closures and online learning, higher energy intake in females and reduced physical activity levels in both sexes persisted. These data demonstrate the health impacts of isolation measures, with the potential to affect long-term diet and activity behaviours.

Glycemic Variability in Diabetes Increases the Severity of Influenza.

People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus.IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.