Extracellular vesicle miR-206 improves chronic binge alcohol mediated decreased myoblast differentiation in SIV-infected female macaques.

Alcohol misuse in people with HIV (PWH) and chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected macaques are associated with increased physical frailty and impaired functional skeletal muscle mass, respectively. Previous studies by our group demonstrate that muscle-enriched microRNAs (myomiRs) are differentially expressed in skeletal muscle (SKM) from CBA-administered SIV-infected male macaques and their altered expression contributes to impaired differentiation of SKM stem cells, or myoblasts. MicroRNAs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular communication. The current study tested the hypothesis that EV-mediated delivery of miR-206 can ameliorate CBA-mediated decreased myoblast differentiation. Myoblasts were isolated from SKM of female SIV-infected, antiretroviral therapy-treated macaques that received either CBA (2.5g/kg/day, CBA/SIV) or water (VEH/SIV) for 14.5 months. Myotube and myotube derived EV myomiR expression, including miR-206, was lower in the CBA/SIV group. Overexpression of miR-206 decreased histone deacetylase 4 (HDAC4) and paired box 7 (PAX7) expression in myotubes and increased fusion index, a differentiation index, in CBA/SIV-derived myotubes. Similarly, EV-mediated delivery of miR-206 increased both fusion index and myotube density of CBA/SIV-derived myoblasts. These results support the potential therapeutic utility of EVs in delivering myomiRs to improve SKM stem cell differentiation.

Aligning front-of-pack labelling with dietary guidelines: including whole grains in the health star rating.

PURPOSE: Front-of-pack labelling systems, such as the Health Star Rating (HSR), aim to aid healthy consumer dietary choices and complement national dietary guidelines. Dietary guidelines aim to be holistic by extending beyond the individual nutrients of food, including other food components that indicate diet quality, including whole grains. We aimed to test the feasibility of including whole grains in the HSR algorithm, to better inform dietary guidance in Australia coherent with existing dietary guidelines. METHODS: We assigned whole-grain points as a favourable component of the HSR based on the whole-grain content of foods. We compared the original, and three modified HSR algorithms (including altered thresholds for star ratings) using independent-samples median tests. Finally, we used Spearman's correlation to measure the strength of association between an item's nutritional composition (all components of the HSR algorithm including all favourable and unfavourable components) and their HSR using each algorithm. RESULTS: Up to 10 points were added for products with ≥ 50% whole-grain content, with no points for products with < 25%. Adjusting the HSR score cut-off by 3 points for grain products created the greatest difference in median HSR between refined and whole-grain items (up to 2 stars difference), compared to the original algorithm (a maximum of 1 star). CONCLUSIONS: The addition of whole grains to the HSR algorithm improved the differentiation of refined and whole-grain items, and therefore better aligned with dietary guidelines. Holistic approaches to food guidance systems are required to provide consistent messaging and inform positive food choices.

Chronic binge alcohol mediated hepatic metabolic adaptations in SIV-infected female rhesus macaques.

AIMS: As the interactions of alcohol and HIV/SIV infection and their impact on liver metabolic homeostasis remain to be fully elucidated, this study aimed to determine alcohol-mediated hepatic adaptations of metabolic pathways in SIV/ART-treated female rhesus macaques fed a nutritionally balanced diet. METHODS: Macaques were administered chronic binge alcohol (CBA; 13-14 g ethanol/kg/week for 14.5 months; n = 7) or vehicle (VEH; n = 8) for 14.5 months. Livers were excised following an overnight fast. Gene and protein expression, enzymatic activity, and lipid content were determined using frozen tissue and histological staining was performed using paraffin-embedded tissue. RESULTS: CBA/SIV macaques showed increased hepatic protein expression of electron transport Complex III and increased gene expression of glycolytic (phosphofructokinase and aldolase) and gluconeogenic (pyruvate carboxylase) enzymes and of genes involved in lipid turnover homeostasis (perilipin 1, peroxisome proliferator-activated receptor gamma, carbohydrate responsive binding protein, and acetyl-CoA carboxylase B) as compared to that of livers from the VEH/SIV group. Plasma triglyceride concentration had a significant positive association with liver triglyceride content in the CBA/SIV group. CONCLUSIONS: These results reflect CBA-associated alterations in expression of proteins and genes involved in glucose and lipid metabolism homeostasis without significant evidence of steatosis or dysglycemia. Whether these changes predispose to greater liver pathology upon consumption of a high fat/high sugar diet that is more aligned with dietary intake of PWH and/or exposure to additional environmental factors warrants further investigation.

The social determinants of Aboriginal and Torres Strait Islander adults who do not smoke in regional Australia.

INTRODUCTION: Commercial tobacco use was systematically embedded as a valuable commodity through colonisation that continues to be exploited for profit by the Tobacco Industry. There have been significant declines in current smoking prevalence among Aboriginal and Torres Strait Islander peoples 18 years and over, from 55% in 1994 to 43% in 2018-2019. This paper seeks to better understand smoke-free behaviours, and to systematically quantify associations between a range of SDOH and non-smoking/never-smoking among Aboriginal and Torres Strait Islander adults (≥18) living in regional Australia. OBJECTIVE: To explore the social determinants of health (SDOH) related to non- and never-smoking among Aboriginal and Torres Strait Islander peoples in regional Australia. DESIGN: Cross-sectional analysis of the NATSIHS, weighted to the Aboriginal and Torres Strait Islander adult population living in regional Australia, was conducted. Participants were characterised as people who were current smokers, never-smokers and non-smokers (ex- and never-smokers). The social determinants of health exposures related to socioeconomic position, well-being and access to healthcare. SETTING: Regional Australia is distinct from urban and remote areas, based on the ASGS Remoteness Structure (ABS) 2018-2019. PARTICIPANTS: Aboriginal and Torres Strait Islander adults (≥18 years) who were selected, consented and asked questions about smoking in the National Aboriginal and Torres Strait Islander Health Survey (NATSIHS 2018/19). RESULTS: High income was associated with non-smoking (Prevalence Ratio [PR] = 2.07; 95% CI: 1.66-2.57) and never-smoking (PR = 2.02; 1.46-2.79), as was completing year 10 (non-smoking PR = 1.34; 1.12-1.61 and never-smoking PR = 1.56; 1.20-2.03). Better food security was associated with a higher prevalence of never-smoking (PR = 2.42; 1.48-3.98). Lower psychological distress scores were associated with non-smoking (PR = 1.30; 1.10-1.53) and never-smoking (PR = 1.56; 1.21-2.01). Never-smoking was more frequent in participants reporting no experiences of unfair treatment (PR = 1.59; 1.22-2.06). Having a usual healthcare provider was associated with non-smoking (PR = 1.38; 1.02-1.86). Positive exposure to the SDOH were associated with non- and never-smoking among Aboriginal and Torres Strait Islander adults in regional Australia. Structural and systemic changes to address the SDOH, including discrimination and racism, are expected to accelerate non-smoking behaviours and improve health outcomes for Aboriginal and Torres Strait Islander peoples.

Helical remodeling augments 5-lipoxygenase activity in the synthesis of proinflammatory mediators.

The synthesis of proinflammatory leukotrienes implicated in asthma, allergic rhinitis, and atherosclerosis is initiated by the enzyme 5-lipoxygenase (5-LOX). The crystal structure of human Stable-5-LOX revealed a conformation where the catalytic iron was inaccessible to bulk solvent as two aromatic residues on a conserved helix-α2 (Hα2) plugged the substrate access portal. Whether 5-LOX can also adopt a more open conformation has not been resolved. Here, we present a new conformation of 5-LOX where Hα2 adopts an elongated conformation equivalent to that described in other animal lipoxygenase structures. Our observation of the sigmoidal kinetic behavior of 5-LOX, which is indicative of positive cooperativity, is consistent with a substrate-induced conformational change that shifts the ensemble of enzyme populations to favor the catalytically competent state. Strategic point mutations along Hα2 designed to unlock the closed conformation and elongate Hα2 resulted in improved kinetic parameters, altered limited proteolysis data, and a drastic reduction in the length of the lag phase yielding the most active Stable-5-LOX to date. Structural predictions by AlphaFold2 of these variants statistically favor an elongated Hα2 and reinforce a model in which improved kinetic parameters correlate with a more readily adopted open conformation. Taken together, these data provide valuable insights into the synthesis of leukotrienes.

The Effect of Retail Food Environment Interventions on Dietary Behavior in Postsecondary Education Settings: A Systematic Review and Meta-analysis.

BACKGROUND: Postsecondary education institutions, where hundreds of millions of people work and study globally, are a key setting for retail food environment interventions. OBJECTIVE: We aimed to synthesize the evidence for the effectiveness of retail food environment interventions in improving the healthiness of dietary behavior of students and staff in postsecondary education settings. METHODS: Academic databases were searched for randomized controlled trials (RCTs) and quasi-experimental studies published until August 2023. Studies were eligible if they assessed the impact of a retail food environment intervention on healthiness of dietary behavior (purchases or consumption) in students or staff in postsecondary education settings and targeted one of the following food environment elements: placement, price, product, or promotion. Business-related outcomes (total sales, profit, or revenue) were included as secondary outcomes. Findings were synthesized in narrative form, organized by retail food environment element. Where comparable dietary outcome data were available from ≥10 interventions, findings were pooled using random effects meta-analysis. RESULTS: Of 10,126 studies initially identified, 55 (76% quasi-experimental) were included, describing 71 separate interventions (n = 49 single-element and n = 22 multi-element). Two-thirds (n = 47, 66%) of interventions (n = 32 single-element and n = 15 multi-element) demonstrated significant improvements in dietary behavior. Single-element interventions targeting placement (n = 1) and price (n = 3) improved dietary behavior. Most (n = 9/10, 90%) interventions targeting product availability or convenience (product element) improved dietary behavior, while n = 19/35 (54%) targeting promotion did. Pooled findings from 12 interventions reporting changes in energy content demonstrated a significant decrease in purchased or consumed energy (-7.9%; 95% confidence interval: -10.3%, -5.6%). Almost all interventions (n = 11/12, 92%) that evaluated the impact on business-related outcomes found either a significant increase or no change following the intervention. CONCLUSIONS: We established encouraging evidence supporting the role of retail food environment interventions in postsecondary education settings to support healthy dietary behaviors of students and staff. REGISTRY: PROSPERO (International Prospective Register of Systematic Reviews, URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=295836; registration number CRD42022295836).

Glucagon-Like Peptide 1 Receptor Agonists Have the Potential to Revolutionize the Attainment of Target A1C Levels in Type 2 Diabetes-So Why Is Their Uptake So Low?

A target A1C of <7% is the recommended goal for most people with type 2 diabetes. However, many are not achieving this target with their current treatment. Glucagon-like peptide 1 (GLP-1) receptor agonists are highly efficacious in achieving glycemic control and could aid primary care providers (PCPs) in getting patients to their A1C target. However, despite their potential, use of GLP-1 receptor agonists in the primary care setting is limited. This review provides guidance for PCPs on how to help patients achieve their glycemic target and overcome perceived barriers of GLP-1 receptor agonist use, with the overall goal of improving PCP confidence in prescribing these agents.

Estradiol Regulation of the Prelimbic Cortex and the Reinstatement of Cocaine Seeking in Female Rats.

Relapse susceptibility in women with substance use disorders (SUDs) has been linked to the estrogen, 17ß-estradiol (E2). Our previous findings in female rats suggest that the influence of E2 on cocaine seeking can be localized to the prelimbic prefrontal cortex (PrL-PFC). Here, we investigated the receptor mechanisms through which E2 regulates the reinstatement of extinguished cocaine seeking. Sexually mature female rats underwent intravenous cocaine self-administration (0.5 mg/inf; 14 × 2 h daily) and extinction, and then were ovariectomized before reinstatement testing. E2 (10 µg/kg, i.p.) alone did not reinstate cocaine seeking, but it potentiated reinstatement when combined with an otherwise subthreshold priming dose of cocaine. A similar effect was observed following intra-PrL-PFC microinfusions of E2 and by systemic or intra-PrL-PFC administration of the estrogen receptor (ER)ß agonist, DPN, but not agonists at ERα or the G-protein-coupled ER1 (GPER1). By contrast, E2-potentiated reinstatement was prevented by intra-PrL-PFC microinfusions of the ERß antagonist, MPP, or the GPER1 antagonist, G15, but not an ERα antagonist. Whole-cell recordings in PrL-PFC layer (L)5/6 pyramidal neurons revealed that E2 decreases the frequency, but not amplitude, of GABAA-dependent miniature IPSCs (mIPSC). As was the case with E2-potentiated reinstatement, E2 reductions in mIPSC frequency were prevented by ERß and GPER1, but not ERα, antagonists and mimicked by ERß, but not GPER1, agonists. Altogether, the findings suggest that E2 activates ERß and GPER1 in the PrL-PFC to attenuate the GABA-mediated constraint of key outputs that mediate cocaine seeking.

The relationship of socioeconomic factors to the use of preventative cardiovascular disease medications: A prospective Australian cohort study.

Cardiovascular disease (CVD) events are highly preventable through appropriate treatment and disproportionally affect socioeconomically disadvantaged individuals. This study quantified the relationship of socioeconomic factors to dispensing and persistent use of lipid- and blood pressure-lowering medication following hospital admission for a major CVD event (myocardial infarction, ischaemic stroke/transient ischaemic attack). Data from 8285 people with such events aged ≥45 years from the Australian 45 and Up Study with linked medication data were used to estimate relative risks (RRs) for combined lipid- and blood pressure-lowering dispensing at three-months following hospital discharge and for 12-month persistent use, in relation to education, income, and level of medication subsidisation. Overall, 56% were dispensed guideline-recommended medications at three months and 37% persistently used them across 12 months. After adjusting for demographic factors, type of CVD and history of CVD hospitalisation, RRs for lowest (no educational qualifications) compared to highest education level (university degree) were 1.14 (95% CI: 1.06, 1.22) for medication dispensing and 1.15 (1.02, 1.29) for persistent medication use; 1.14 (1.06, 1.22) and 1.17 (1.04, 1.32) respectively for lowest (<$20,000) versus highest (≥$70,000) household pre-tax income; and 1.25 (1.17, 1.33) and 1.28 (1.15, 1.43) respectively for those receiving highest versus lowest subsidisation. There was little to no evidence of a relationship of income and education to medication use after adjustment for medication subsidisation. While preventive medication use is sub-optimal, subsidisation is substantially associated with increased use and accounts for most of the relationship with socioeconomic position, suggesting subsidy schemes are working in the intended direction.

Clearing the air: underestimation of youth smoking prevalence associated with proxy-reporting compared to youth self-report.

BACKGROUND: Smoking remains a leading cause of disease burden globally. Declining youth smoking prevalence is an essential feature of effective tobacco control; however, accurate data are required to assess progress. This study investigates bias in youth smoking prevalence estimates by respondent type (proxy-reported, self-report with parent present, or self-report independently) for Aboriginal and Torres Strait Islander and total populations of Australia. METHODS: Repeated cross-sectional analysis of representative Aboriginal and Torres Strait Islander Health and National Health Surveys, 2007-2019. Data were restricted to participants aged 15-17 years. Prevalence ratios (PR) and 95% Confidence Intervals (CI) for ever-smoking by respondent type were calculated using Poisson regression with robust standard errors. National youth current-smoking prevalence was estimated if all data were collected by youth self-report; estimates and trends were compared to observed estimates. RESULTS: Over 75% of all smoking status data were reported by proxy or with parent present. Ever-smoking prevalence among youth self-reporting independently versus proxy-reported was 1.29 (95% CI:0.96-1.73) to 1.99 (95% CI:1.39-2.85) times as high for Aboriginal and Torres Strait Islander youth, and 1.83 (95% CI:0.92-3.63) to 2.72 (95% CI:1.68-4.41) times as high for total population youth. Across surveys, predicted national current-smoking prevalence if all youth self-reported independently was generally higher than observed estimate. CONCLUSIONS: Estimates of youth smoking prevalence are likely inaccurate and underestimated if data are collected by proxy or with parent present. Increased reliance on data reported by youth independently is crucial to improve data accuracy, including to enable accurate assessment of national prevalence.

Fortification of grain foods and NOVA: the potential for altered nutrient intakes while avoiding ultra-processed foods.

PURPOSE: NOVA is a food classification system describing a hierarchy from minimally processed to ultra-processed foods (UPF). Research has associated intake of UPF with chronic diseases. In Australia, the primary sources of grains, both refined and whole, are breads and breakfast cereals, which are typically fortified. Most are classified as UPF, yet are recommended core foods according to the Australian Dietary Guidelines (ADG). This research aimed to identify if avoidance of ultra-processed grain foods would alter nutrient intakes in an Australian population and whether sample diets using substitute (non-UPF) foods would be likely to meet nutrient requirements. METHODS: Quantitative analysis of usual nutrient intake from the National Nutrition and Physical Activity Survey 2011-12 (n = 12,153) for all foods including and excluding UPF. Dietary modelling examined the nutritional adequacy of sample diets aligned with the ADG and another containing replacements for UPF. We particularly focused on grain foods and meeting whole-grain intake targets. RESULTS: There was a significant decrease (all p < 0.05) in modelled intake of key nutrients when UPF were excluded, specifically, thiamin, folate and iodine, as substitutions are rarely fortified. Diets with no UPF, where substitutes are carefully chosen, have the potential to meet Nutrient Reference Values, but deviation from customary food choices may mean adoption of substitutes is unlikely. CONCLUSIONS: Exclusion of UPF may result in lowered intakes of key nutrients of particular concern for at risk groups (including women of child-bearing age), negating gains made by public health policy of fortification. Substitutions may not be realistic in these at-risk populations.

Acute Blockade of PACAP-Dependent Activity in the Ventromedial Nucleus of the Hypothalamus Disrupts Leptin-Induced Behavioral and Molecular Changes in Rats.

Leptin signaling pathways, stemming primarily from the hypothalamus, are necessary for maintaining normal energy homeostasis and body weight. In both rodents and humans, dysregulation of leptin signaling leads to morbid obesity and diabetes. Since leptin resistance is considered a primary factor underlying obesity, understanding the regulation of leptin signaling could lead to therapeutic tools and provide insights into the causality of obesity. While leptin actions in some hypothalamic regions such as the arcuate nuclei have been characterized, less is known about leptin activity in the hypothalamic ventromedial nuclei (VMN). Recently, pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to reduce feeding behavior and alter metabolism when administered into the VMN in a pattern similar to that of leptin. In the current study, we examined whether leptin and PACAP actions in the VMN share overlapping pathways in the regulation of energy balance. Interestingly, PACAP administration into the VMN increased STAT3 phosphorylation and SOCS3 mRNA expression, both of which are hallmarks of leptin receptor activation. In addition, BDNF mRNA expression in the VMN was increased by both leptin and PACAP administration. Moreover, antagonizing PACAP receptors fully reversed the behavioral and cellular effects of leptin injections into the VMN. Electrophysiological studies further illustrated that leptin-induced effects on VMN neurons were blocked by antagonizing PACAP receptors. We conclude that leptin dependency on PACAP signaling in the VMN suggests a potential common signaling cascade, allowing a tonically and systemically secreted neuropeptide to be more precisely regulated by central neuropeptides.

Whole grain and cereal fibre intake in the Australian Health Survey: associations to CVD risk factors.

OBJECTIVE: To explore associations of whole grain and cereal fibre intake to CVD risk factors in Australian adults. DESIGN: Cross-sectional analysis. Intakes of whole grain and cereal fibre were examined in association to BMI, waist circumference (WC), blood pressure (BP), serum lipid concentrations, C-reactive protein, systolic BP, fasting glucose and HbA1c. SETTING: Australian Health Survey 2011-2013. PARTICIPANTS: A population-representative sample of 7665 participants over 18 years old. RESULTS: Highest whole grain consumers (T3) had lower BMI (T0 26·8 kg/m2, T3 26·0 kg/m2, P < 0·0001) and WC (T0 92·2 cm, T3 90·0 cm, P = 0·0005) compared with non-consumers (T0), although only WC remained significant after adjusting for dietary and lifestyle factors, including cereal fibre intake (P = 0·03). Whole grain intake was marginally inversely associated with fasting glucose (P = 0·048) and HbA1c (P = 0·03) after adjusting for dietary and lifestyle factors, including cereal fibre intake. Cereal fibre intake was inversely associated with BMI (P < 0·0001) and WC (P < 0·0008) and tended to be inversely associated with total cholesterol, LDL-cholesterol and apo-B concentrations, although associations were attenuated after further adjusting for BMI and lipid-lowering medication use. CONCLUSIONS: The extent to which cereal fibre is responsible for the CVD-protective associations of whole grains may vary depending on the mediators involved. Longer-term intervention studies directly comparing whole grain and non-whole grain diets of similar cereal fibre contents (such as through the use of bran or added-fibre refined grain products) are needed to confirm independent effects.

Whole grain intake compared with cereal fibre intake in association to CVD risk factors: a cross-sectional analysis of the National Diet and Nutrition Survey (UK).

OBJECTIVE: To investigate how intakes of whole grains and cereal fibre were associated to risk factors for CVD in UK adults. DESIGN: Cross-sectional analyses examined associations between whole grain and cereal fibre intakes and adiposity measurements, serum lipid concentrations, C-reactive protein, systolic blood pressure, fasting glucose, HbA1c, homocysteine and a combined CVD relative risk score. SETTING: The National Diet and Nutrition Survey (NDNS) Rolling Programme 2008-2014. PARTICIPANTS: A nationally representative sample of 2689 adults. RESULTS: Participants in the highest quartile (Q4) of whole grain intake had lower waist-hip ratio (Q1 0·872; Q4 0·857; P = 0·04), HbA1c (Q1 5·66 %; Q4 5·47 %; P = 0·01) and homocysteine (Q1 9·95 µmol/l; Q4 8·76 µmol/l; P = 0·01) compared with participants in the lowest quartile (Q1), after adjusting for dietary and lifestyle factors, including cereal fibre intake. Whole grain intake was inversely associated with C-reactive protein using multivariate analysis (P = 0·02), but this was not significant after final adjustment for cereal fibre. Cereal fibre intake was also inversely associated with waist-hip ratio (P = 0·03) and homocysteine (P = 0·002) in multivariate analysis. CONCLUSIONS: Similar inverse associations between whole grain and cereal fibre intakes to CVD risk factors suggest the relevance of cereal fibre in the protective effects of whole grains. However, whole grain associations often remained significant after adjusting for cereal fibre intake, suggesting additional constituents may be relevant. Intervention studies are needed to compare cereal fibre intake from non-whole grain sources to whole grain intake.

Whole grain and high-fibre grain foods: How do knowledge, perceptions and attitudes affect food choice?

The health benefits of whole grains and dietary fibre are well established, however intakes of both remain low across the globe. Innovative added-fibre refined grain products may present a solution to increase fibre intakes given potential sensory barriers to whole grain intake. However, to consider the efficacy of such products, or potential alternative measures, an awareness of consumer knowledge, perceptions and attitudes towards both whole grain and added-fibre grain foods is needed. Focus groups (with adults with no formal nutrition education) were conducted to explore factors affecting consumer grain choice. Discussions were transcribed verbatim and analysed using inductive thematic analysis. Nine focus groups composed of 52 participants (23 men; 29 women) were conducted. Participants tended to report choosing 'grainy' bread but few other whole grain foods. Most participants were unaware of the long-term health benefits of whole grains, recommended whole grain intakes, or how to identify foods that were high in whole grains, thereby limiting motivation to increase intake. Additionally, scepticism surrounding the health value of carbohydrate-based foods appeared to hinder grain intakes in general. These findings suggest that further public education and promotion of whole grain benefits, with a focus on food-based targets and messaging, may be important in efforts to increase whole grain and subsequently fibre intakes. Added-fibre grain products may be a useful addition, specifically for avid whole grain-avoiders who are unlikely to accept whole grain sensory properties. However, as most participants were open to whole grain consumption, industry innovation should also focus efforts on increasing availability and variety of products high in whole grains.

Using Continuous Glucose Monitoring in Clinical Practice.

Continuous glucose monitoring is poised to radically change the treatment of diabetes and patient engagement of those afflicted with this disease. This article will provide an overview of CGM and equip health care providers to begin integrating this technology into their clinical practice.

Treatment Intensification With Insulin Pumps and Other Technologies in Patients With Type 2 Diabetes: Results of a Physician Survey in the United States.

An online survey was conducted to assess the perspectives and use of diabetes technologies by a sample of U.S. primary care physicians (PCPs) and endocrinologists to optimize intensive insulin therapy in patients with type 2 diabetes. Overall, endocrinologists reported using diabetes technologies more frequently than PCPs for patients with type 2 diabetes requiring basal-bolus insulin therapy. PCPs and endocrinologists who were highly focused on diabetes management with insulin therapy reported using insulin delivery devices (insulin pumps and wearable tube-free patches) when patients are not achieving their A1C target while taking basal plus three or more prandial injections of insulin daily.

Whole grain, bran and cereal fibre consumption and CVD: a systematic review.

Whole grain intake is associated with lower CVD risk in epidemiological studies. It is unclear to what extent cereal fibre, located primarily within the bran, is responsible. This review aimed to evaluate association between intake of whole grain, cereal fibre and bran and CVD risk. Academic databases were searched for human studies published before March 2018. Observational studies reporting whole grain and cereal fibre or bran intake in association with any CVD-related outcome were included. Studies were separated into those defining whole grain using a recognised definition (containing the bran, germ and endosperm in their natural proportions) (three studies, seven publications) and those using an alternative definition, such as including added bran as a whole grain source (eight additional studies, thirteen publications). Intake of whole grain, cereal fibre and bran were similarly associated with lower risk of CVD-related outcomes. Within the initial analysis, where studies used the recognised whole grain definition, results were less likely to show attenuation after adjustment for cereal fibre content. The fibre component of grain foods appears to play an important role in protective effects of whole grains. Adjusting for fibre content, associations remained, suggesting that additional components within the whole grain, and the bran component, may contribute to cardio-protective association. The limited studies and considerable discrepancy in defining and calculating whole grain intake limit conclusions. Future research should utilise a consistent definition and methodical approach of calculating whole grain intake to contribute to a greater body of consistent evidence surrounding whole grains.

Cereal fibre intake in Australia: a cross-sectional analysis of the 2011-12 National Nutrition and Physical Activity Survey.

Extensive evidence supports health benefits of cereal fibre, however globally no national intake data exists. This study aimed to determine estimates of intake and food sources of cereal fibre, and relationships to dietary fibre intake in an Australian sample population. A cereal fibre database was applied to dietary intake data from the 2011-12 National Nutrition and Physical Activity Survey (n = 12,153). Usual intake based on 2-day intake data was weighted to infer population results. Median daily cereal fibre intake was 6.4 g/d (9.7 g/10 MJ/d) for adults (19-85 years) and 6.2 g/d (10.2 g/10 MJ/d) for children/adolescents (2-18 years). Individuals with the highest cereal fibre intake were more likely to meet dietary fibre recommendations than those with the lowest intake (males Q4: 17.1% Q1: 3.9%; females Q4: 20.3% Q1: 6.6%). Breakfast cereals, bread and bread rolls provided the most cereal fibre. This study provides first quantification of cereal fibre from all sources in an Australian national sample.

Tuning and Predicting Mesh Size and Protein Release from Step Growth Hydrogels.

Hydrogel-based depots are of growing interest for release of biopharmaceuticals; however, a priori selection of hydrogel compositions that will retain proteins of interest and provide desired release profiles remains elusive. Toward addressing this, in this work, we have established a new tool for the facile assessment of protein release from hydrogels and applied it to evaluate the effectiveness of mesh size estimations on predicting protein retention or release. Poly(ethylene glycol) (PEG)-based hydrogel depots were formed by photoinitiated step growth polymerization of four-arm PEG functionalized with norbornene (PEG-norbornene, 4% w/w to 20% w/w, Mn ∼ 5 to 20 kDa) and different dithiol cross-linkers (PEG Mn ∼ 1.5 kDa or enzymatically degradable peptide), creating well-defined, robust materials with a range of mesh sizes estimated with Flory-Rehner or rubber elasticity theory (∼5 to 15 nm). A cocktail of different model proteins was released from compositions of interest, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to facilely and quantitatively analyze temporal release profiles. Mesh size was predictive of retention of relatively large proteins and release of relatively small proteins. Proteins with diameters comparable to the mesh size, which is often the case for growth factors, were released by hindered diffusion and required experimental assessment of retention and release. With this knowledge, hydrogels were designed for the controlled release of a therapeutically relevant growth factor, PDGF-BB.