Disruption of the Unique ABCG-Family NBD:NBD Interface Impacts Both Drug Transport and ATP Hydrolysis

ABCG2 is one of a triumvirate of human multidrug ATP binding cassette (ABC) transporters that are implicated in defense of cells and tissues against cytotoxic chemicals, but which can confer chemotherapy resistance states in oncology. Understanding the mechanism of ABCG2 is thus imperative if we are to be able to counter its deleterious activity. The structure of ABCG2 and related family members (ABCG5/G8) demonstrated that there were two interfaces between the nucleotide binding domains. In addition to the canonical ATP “sandwich-dimer” interface, there was a second contact region between residues at the C-terminus of the NBD. We mutated this second interface by making mutations to a series of residues which are in close interaction with the opposite NBD. Mutated ABCG2 isoforms were expressed in HEK293T cells and analyzed for targeting to the membrane, drug transport and ATPase activity. Mutations to this second interface had a number of effects on ABCG2 including altered drug specificity, altered drug transport and, in two mutants, a loss of ATPase activity. The results demonstrate that this region is particularly sensitive to mutation and can impact upon both direct, local NBD events (i.e. ATP hydrolysis) but also on the allosteric communication to the transmembrane domains and drug transport

Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia

A white paper resulting from the outcomes of the Osteoporosis Australia Summit, 20 October 2011 Abstract Osteoporosis imposes a tremendous burden on Australia: 1.2 million Australians have osteoporosis and 6.3 million have osteopenia. In the 2007–08 financial year, 82 000 Australians suffered fragility fractures, of which > 17 000 were hip fractures. In the 2000–01 financial year, direct costs were estimated at $1.9 billion per year and an additional$5.6 billion on indirect costs. Osteoporosis was designated a National Health Priority Area in 2002; however, implementation of national plans has not yet matched the rhetoric in terms of urgency. Building healthy bones throughout life, the Osteoporosis Australia strategy to prevent osteoporosis throughout the life cycle, presents an evidence-informed set of recommendations for consumers, health care professionals and policymakers. The strategy was adopted by consensus at the Osteoporosis Australia Summit in Sydney, 20 October 2011. Primary objectives throughout the life cycle are: to maximise peak bone mass during childhood and adolescence to prevent premature bone loss and improve or maintain muscle mass, strength and functional capacity in healthy adults to prevent and treat osteoporosis in order to minimise the risk of suffering fragility fractures, and reduce falls risk, in older people. The recommendations focus on three affordable and important interventions — to ensure people have adequate calcium intake, vitamin D levels and appropriate physical activity throughout their lives. Recommendations relevant to all stages of life include: daily dietary calcium intakes should be consistent with Australian and New Zealand guidelines serum levels of vitamin D in the general population should be above 50nmol/L in winter or early spring for optimal bone health regular weight-bearing physical activity, muscle strengthening exercises and challenging balance/mobility activities should be conducted in a safe environment

Technology-assisted dietary assessment

Dietary intake provides valuable insights for mounting intervention programs for prevention of disease. With growing concern for adolescent obesity, the need to accurately measure diet becomes imperative. Assessment among adolescents is problematic as this group has irregular eating patterns and have less enthusiasm for recording food intake. Preliminary studies among adolescents suggest that innovative use of technology may improve the accuracy of diet information from young people. In this paper, we propose a novel food record method using a mobile device that will provide an accurate account of daily food and nutrient intake among adolescents. Our approach includes the use of image analysis tools for identification and quantification of food consumption. Images obtained before and after food is consumed can be used to estimate the diet of an individual. In this paper we describe our initial results and indicate the potential of the proposed system

Application of fluorescence correlation spectroscopy to study substrate binding in styrene maleic acid lipid copolymer encapsulated ABCG2

© 2020 The Authors ABCG2 is one of a trio of human ATP binding cassette transporters that have the ability to bind and transport a diverse array of chemical substrates out of cells. This so-called “multidrug” transport has numerous physiological consequences including effects on how drugs are absorbed into and eliminated from the body. Understanding how ABCG2 is able to interact with multiple drug substrates remains an important goal in transporter biology. Most drugs are believed to interact with ABCG2 through the hydrophobic lipid bilayer and experimental systems for ABCG2 study need to incorporate this. We have exploited styrene maleic acid to solubilise ABCG2 from HEK293T cells overexpressing the transporter, and confirmed by dynamic light scattering and fluorescence correlation spectroscopy (FCS) that this results in the extraction of SMA lipid copolymer (SMALP) particles that are uniform in size and contain a dimer of ABCG2, which is the predominant physiological state. FCS was further employed to measure the diffusion of a fluorescent ABCG2 substrate (BODIPY-prazosin) in the presence and absence of SMALP particles of purified ABCG2. Autocorrelation analysis of FCS traces enabled the mathematical separation of free BODIPY-prazosin from drug bound to ABCG2 and allowed us to show that combining SMALP extraction with FCS can be used to study specific drug: transporter interactions

Differences in satiety effects of alginate- and whey protein-based foods

Satiety is important in regulating food intake and has important public health significance in the control of obesity. Food containing protein and non-starch polysaccharides provides a satiety effect through various mechanisms but a comparison of the satiety effect on each has not previously been investigated. This study compared the satiety effect or reduction of hunger after consumption of (i) a whey proteinbased drink versus an alginate-based drink of the same viscosity where only the protein content differed, (ii) two alginate-based drinks differing in alginate type and viscosity, and (iii) a whey protein-based drink versus an alginate-based drink differing in protein content and viscosity. Fasted subjects assessed the effect of a drink on hunger that was one of three variants: a low viscosity whey protein drink (LVHP); a high viscosity low protein alginate-based drink (HVLP); or a low viscosity low protein alginate-based drink (LVLP) over the 240 min postprandial period using a Visual Analogue Scale (VAS). When protein differed and viscosity was the same, results showed subjects felt significantly less hungry after consuming the LVHP drink compared to the LVLP drink, so protein reduced hunger. Subjects reported reduced hunger from the HVLP drink compared to the LVLP drink where viscosity of drinks differed, suggesting viscosity and/or gelation reduced hunger. Subjects reported reduced hunger from the HVLP drink compared to LVHP drink where both protein and viscosity differed, suggesting that viscosity reduced hunger more than the protein effect. Results suggest the physical characteristics such as viscosity and/or gel strength and protein content reduce hunger. Further studies should investigate which of these parameters is more important

How willing are adolescents to record their dietary intake? The mobile food record

Background: Accurately assessing the diets of children and adolescents can be problematic. Use of technologies, such as mobile apps designed to capture food and beverages consumed at eating occasions with images taken using device-embedded cameras, may address many of the barriers to gathering accurate dietary intake data from adolescents. Objective: The objectives of this study were to assess the willingness of adolescents to take images of food and beverages at their eating occasions using a novel mobile food record (mFR) and to evaluate the usability of the user confirmation component of the mFR app, referred to as the “review process.” Methods: Mixed methods combining quantitative and qualitative protocols were used in this study. Adolescents (11-15-year olds) attending a summer camp were recruited to participate in the study. First, the participants were asked to take images of foods and beverages consumed as meals and snacks for 2 consecutive days using the mFR app running on an iPhone and the number of images taken was noted. This was followed by focus group sessions to evaluate usability, which was analyzed by content and themes. After using the mFR, a think-aloud method was used to evaluate the usability of the mFR method for reviewing system-identified foods (ie, the review process). A usability questionnaire was administered at the end of all activities.Results: The mFR was accepted by the majority of the 24 boys and 17 girls (n=41) but varied according to gender and eating occasion. Girls were significantly more likely than boys to capture images of their eating occasions (Fisher exact test, P=.03). Participants were more likely to take images of their breakfasts (90%, 36/40) and lunches (90%, 72/80) and least likely to capture afternoon and evening snacks, 54% (43/80) and 40% (32/80), respectively. The major themes from the focus groups with regard to using the mFR were games, rewards, and the need to know more about why they were using the app. Results of the usability questionnaire indicated that including a game component would be important to increase willingness to use the mFR, and a high majority of the participants indicated a willingness to use the mFR for 7 days or more. The image review process was found to be easy to use except for some confusion with overlapping markers on the screen. Conclusions: The adolescents’ experiences with and feedback about the mFR highlighted the importance of increased training, reminders, entertainment (eg, games), and training with practice in using the device to capture complete dietary intake as part of their active lifestyles

Food Insecurity, Food Assistance, and Psychological Distress among University Students: Cross-Sectional Survey Western Australia, 2020

University students have been identified as a population sub-group vulnerable to food insecurity. This vulnerability increased in 2020 due to the COVID-19 pandemic. This study aimed to assess factors associated with food insecurity among university students and the differences between students with and without children. A cross-sectional survey of (n = 213) students attending one university in Western Australia measured food insecurity, psychological distress, and socio-demographic characteristics. Logistic regression analyses were conducted to identify factors associated with food insecurity. Forty-eight percent of students who responded to the survey had experienced food insecurity in 2020. International students who were studying in Australia were nine times more likely to experience food insecurity than domestic students (AOR = 9.13; 95% CI = 2.32–35.97). International students with children were more likely to experience food insecurity than international students without children (p < 0.001) and domestic students with (p < 0.001) or without children (p < 0.001). For each unit increase in depression level, the likelihood of experiencing food insecurity increased (AOR = 1.62; 95% CI = 1.12–2.33). Findings show a higher prevalence of food insecurity among international university students and students with children during the COVID-19 pandemic and that food insecurity was associated with higher levels of psychological distress. These findings highlight the need for targeted interventions to mitigate the risk of food insecurity among Australian university students, particularly among international students, students with children, and those experiencing psychological distress

Multiple uncontrolled conditions and blood pressure medication intensification: an observational study

Abstract Background Multiple uncontrolled medical conditions may act as competing demands for clinical decision making. We hypothesized that multiple uncontrolled cardiovascular risk factors would decrease blood pressure (BP) medication intensification among uncontrolled hypertensive patients. Methods We observed 946 encounters at two VA primary care clinics from May through August 2006. After each encounter, clinicians recorded BP medication intensification (BP medication was added or titrated). Demographic, clinical, and laboratory information were collected from the medical record. We examined BP medication intensification by presence and control of diabetes and/or hyperlipidemia. 'Uncontrolled' was defined as hemoglobin A1c &#8805; for diabetes, BP &#8805; 140/90 mmHg (&#8805; 130/80 mmHg if diabetes present) for hypertension, and low density lipoprotein cholesterol (LDL-c) &#8805; 130 mg/dl (&#8805; 100 mg/dl if diabetes present) for hyperlipidemia. Hierarchical regression models accounted for patient clustering and adjusted medication intensification for age, systolic BP, and number of medications. Results Among 387 patients with uncontrolled hypertension, 51.4% had diabetes (25.3% were uncontrolled) and 73.4% had hyperlipidemia (22.7% were uncontrolled). The BP medication intensification rate was 34.9% overall, but higher in individuals with uncontrolled diabetes and uncontrolled hyperlipidemia: 52.8% overall and 70.6% if systolic BP &#8805; 10 mmHg above goal. Intensification rates were lowest if diabetes or hyperlipidemia were controlled, lower than if diabetes or hyperlipidemia were not present. Multivariable adjustment yielded similar results. Conclusions The presence of uncontrolled diabetes and hyperlipidemia was associated with more guideline-concordant hypertension care, particularly if BP was far from goal. Efforts to understand and improve BP medication intensification in patients with controlled diabetes and/or hyperlipidemia are warranted.http://deepblue.lib.umich.edu/bitstream/2027.42/78266/1/1748-5908-5-55.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78266/2/1748-5908-5-55.pdfPeer Reviewe