Patterns of alcohol use and associated physical and lifestyle characteristics according to new Australian guidelines

Objective: To describe the pattern of alcohol consumption and associated physical and lifestyle characteristics in a population-based sample of Australian men.
Method: A community-based age-stratifi ed random sample of 1420 men (median age 56 years, range 20 – 93) participating in the Geelong Osteoporosis Study, an epidemiological study set in south-eastern Australia. Daily alcohol intake was ascertained from a detailed food frequency questionnaire and categorized according to the Australian National Health and Medical Research Council 2009 guidelines (non-drinkers, greater than zero but ≤ 2 drinks per day, > 2 drinks per day), with a standard drink equivalent to 10 g of ethanol. Anthropometry was measured and lifestyle factors self-reported. Body composition was determined using dual energy absorptiometry. Socio-economic status was categorized according to the Australian Bureau of Statistics data. Results were age standardized to the Australian male population figures.
Results: The median daily ethanol consumption was 12 g (IQR 2 – 29) per day with a range of 0 – 117 g/day. The age-standardized proportion of non-drinkers was 8.7%, 51.5% consumed up to two drinks per day ( ≤ 20 g ethanol/day), and 39.9% exceeded 2 standard drinks per day ( > 20 g ethanol/day). Alcohol consumption was positively associated with cigarette smoking, weight, higher SES and inversely with age and physical activity.
Conclusions: Approximately, 40% of Australian men consume alcohol at levels in excess of current recommendations, which in combination with other risk factors may adversely impact upon health.

Chemotoxicity of doxorubicin and surface expression of P-glycoprotein (MDR1) is regulated by the Pseudomonas aeruginosa toxin Cif

P-glycoprotein (Pgp), a member of the adenosine triphosphate-binding cassette (ABC) transporter superfamily, is a major drug efflux pump expressed in normal tissues, and is overexpressed in many human cancers. Overexpression of Pgp results in reduced intracellular drug concentration and cytotoxicity of chemotherapeutic drugs and is thought to contribute to multidrug resistance of cancer cells. The involvement of Pgp in clinical drug resistance has led to a search for molecules that block Pgp transporter activity to improve the efficacy and pharmacokinetics of therapeutic agents. We have recently identified and characterized a secreted toxin from Pseudomonas aeruginosa, designated cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif). Cif reduces the apical membrane abundance of CFTR, also an ABC transporter, and inhibits the CFTR-mediated chloride ion secretion by human airway and kidney epithelial cells. We report presently that Cif also inhibits the apical membrane abundance of Pgp in kidney, airway, and intestinal epithelial cells but has no effect on plasma membrane abundance of multidrug resistance protein 1 or 2. Cif increased the drug sensitivity to doxorubicin in kidney cells expressing Pgp by 10-fold and increased the cellular accumulation of daunorubicin by 2-fold. Thus our studies show that Cif increases the sensitivity of Pgp-overexpressing cells to doxorubicin, consistent with the hypothesis that Cif affects Pgp functional expression. These results suggest that Cif may be useful to develop a new class of specific inhibitors of Pgp aimed at increasing the sensitivity of tumors to chemotherapeutic drugs, and at improving the bioavailability of Pgp transport substrates.

Innate immunity and intracellular trafficking : insights for novel anti-HIV-1 therapeutics

It is now evident that host cells have evolved a remarkable variety of antiretroviral activities to defend themselves against viral invaders and in return viruses have developed ingenious ways to circumvent these defences and, in some cases, actually hijack cellular proteins in order to facilitate their replication. Study of this cat and mouse interplay between viruses and their host cells throughout evolution has lead to the identification of some of the most sophisticated antiviral strategies that mammals have developed to prevent viral infection. Recently, a wave of publications has significantly enhanced our understanding of the relationship between human immunodeficiency virus type 1 (HIV-1) and its host, including: 1) the HIV-1 protein Vif and its interaction with host cell nucleic acid editing enzymes; 2) the host cell restrictive factors that provide protection against retroviral infection, such as TRIM5; and 3) the late domains of retroviruses and their relationship with the host cell vacuolar protein sorting pathway. The focus of this review is to provide an up-to-date account of these important areas of HIV-1 research and highlight how some of these new discoveries can potentially be exploited for the development of novel anti-retroviral therapeutics.

A review of the relationship between socioeconomic position and the early-life predictors of obesity

A range of important early-life predictors of later obesity have been identified. Children of lower socioeconomic position (SEP) have a steeper weight gain trajectory from birth with a strong socioeconomic gradient in child and adult obesity prevalence. An assessment of the association between SEP and the early-life predictors of obesity has been lacking. The review involved a two-stage process: Part 1, using previously published systematic reviews, we developed a list of the potentially modifiable determinants of obesity observable in the pre-natal, peri-natal or post-natal (pre-school) periods; and part 2, conducting a literature review of evidence for socioeconomic patterning in the determinants identified in part 1. Strong evidence was found for an inverse relationship between SEP and (1) pre-natal risk factors (pre-pregnancy maternal body mass index (BMI), diabetes and pre-pregnancy diet), (2) antenatal/peri natal risk factors (smoking during pregnancy and low birth weight) and (3) early-life nutrition (including breastfeeding initiation and duration, early introduction of solids, maternal and infant diet quality, and some aspects of the home food environment), and television viewing in young children. Less strong evidence (because of a lack of studies for some factors) was found for paternal BMI, maternal weight gain during pregnancy, child sleep duration, high birth weight and lack of physical activity in young children. A strong socioeconomic gradient exists for the majority of the early-life predictors of obesity suggesting that the die is cast very early in life (even pre-conception). Lifestyle interventions targeting disadvantaged women at or before child-bearing age may therefore be particularly important in reducing inequality. Given the likely challenges of reaching this target population, it may be that during pregnancy and their child's early years are more feasible windows for engagement.

Problem gambling patterns among Australian young adults: associations with prospective risk and protective factors and adult adjustment outcomes

There is instability in the developmental course of problem gambling [PG] over time; however, studies that examine PG at an aggregate level obscure these variations. The current study employed data from a longitudinal study of Australian young adults to investigate: 1) PG patterns (i.e., resistance, persistence, desistence, and new incidence); 2) prospective risk and protective factors for these patterns; and 3) behavioural outcomes associated with these patterns. A sample of 2261 young adults (55.73% female) from Victoria, Australia, who were part of the International Youth Development Study completed a survey in 2010 (T1, age 21) and 2012 (T2, age 23) measuring PG (two items based on established measures), risk and protective factors, and behavioural outcomes. The majority of the sample (91.69%) were resistors (no PG at T1 and T2), 3.62% were new incidence PG cases, 2.63% were desistors (PG at T1 but not T2), and 2.07% reported persistent PG at T1 and T2. Individual civic activism was protective of new incidence PG, while affiliation with antisocial peers and frequent alcohol use increased the risk of persistence. Persistent problem gamblers also experienced the greatest number of poor behavioural outcomes at T2. New incidence was associated with internalising symptoms at T2, while desistance was not associated with any behavioural outcomes. In conclusion, each PG pattern was associated with different predictors and outcomes, highlighting the need to consider variation in the course of young adult PG in order to provide efficacious prevention and intervention approaches, and to protect against relapse.

Migratory implications for coronary heart disease risk prevention in Asian Indians: Evidence from the leading health indicators.

OBJECTIVEctives of this descriptive comparative study were to (1) review data obtained from the World Health Organisation Statistical Information System (WHOSIS) database relating to the prevalence of risk factors for coronary heart disease (CHD) among Indians and Australians and (2) compare these data with published epidemiological studies of CHD riskfactors in adult migrant Asian Indians to provide a comprehensive and comparable assessment of risk factors relating to CHD and the mortality attributable to these risk factors. Design: ThDESIGNdy was undertaken using a database search and integrative review methodology. Data were obtained for comparison of CHD risk factors between Indians and Australians using the WHOSIS database. For the integrative review the MEDLINE, CINAHL, EMBASE, and Cochrane databases were searched using the keywords 'Migrants', 'Asian Indian', 'India', 'Migration', 'Immigration', 'Risk factors', and coronary heart disease. Two reviewers independently assessed the eligibility of the studies for inclusion in the review, the methodological quality and extracted details of eligible studies. Results from the integrative review on CHD risk factors in Asian Indians are presented in a narrative format, along with results from the WHOSIS database. Results: TRESULTSadjusted mortality for CHD was four times higher in migrant Asian Indians when compared to both the native population of the host country and migrants from other countries. Similarly when compared to migrants from other countries migrant Asian Indians had the highest prevalence of overweight individuals. Prevalence rates for hypercholesterolemia were up to 18.5 % among mgrant Asian Indians and migrant Asian Indian women had a higher prevalence of hypertriglyceridaemia compared to Caucasian females. Migrant Asian Indians also had a higher incidence of hypertension and upto 71 % of migrnt Asian Indian men did not meet current guidelines for participation in physical activity. Ethnic-specific prevalence of diabetes ranged from 6-7% among the normal weight to 19-33% among the obese migrant Asian Indians compared with non-Hispanic whites. ConclusionCONCLUSIONAsian Indians have an increased risk of CHD. Culturally sensitive strategies that recognise the effects of migration and extend beyond the health sector should be developed to target lifestyle changes in this high risk population.

Manufacturing techniques and surface engineering of polymer based nanoparticles for targeted drug delivery to cancer

The evolution of polymer based nanoparticles as a drug delivery carrier via pharmaceutical nano/microencapsulation has greatly promoted the development of nano- and micro-medicine in the past few decades. Poly(lactide-co-glycolide) (PLGA) and chitosan, which are biodegradable and biocompatible polymers, have been approved by both the Food & Drug Administration (FDA) and European Medicine Agency (EMA), making them ideal biomaterials that can be advanced from laboratory development to clinical oral and parental administrations. PLGA and chitosan encapsulated nanoparticles (NPs) have successfully been developed as new oral drug delivery systems with demonstrated high efficacy. This review aims to provide a comprehensive overview of the fabrication of PLGA and chitosan particulate systems using nano/microencapsulation methods, the current progress and the future outlooks of the nanoparticulate drug delivery systems. Especially, we focus on the formulations and nano/micro-encapsulation techniques using top-down techniques. It also addresses how the different phases including the organic and aqueous ones in the emulsion system interact with each other and subsequently influence the properties of the drug delivery system. Besides, surface modification strategies which can effectively engineer intrinsic physicochemical properties are summarised. Finally, future perspectives and potential directions of PLGA and chitosan nano/microencapsulated drug systems are outlined.

Risk of cardiovascular disease and diabetes in a working population with sedentary occupations

OBJECTIVE: To assess the prevalence of risk factors and risk for cardiovascular disease and Type 2 diabetes in employees with sedentary occupations enrolled in a workplace health-promotion program. METHODS: Participants (n = 762) were recruited from ten Melbourne workplaces, participating in a physical activity program. Demographic, behavioral, biomedical, and physical measurements were collected. RESULTS: The majority of employees were not meeting recommended guidelines for physical activity (62%), fruit intake (70%), vegetable intake (86%), body mass index (58%), or waist circumference (53%). Most had intermediate (53%) or high (7%) risk of developing Type 2 diabetes. CONCLUSIONS: The majority of Australian adults in sedentary occupations were not meeting guidelines for a number of chronic disease risk factors and a substantial proportion were unaware of their increased risk. This study supports the potential of chronic disease risk factor detection and intervention programs in the workplace.