Improving the quality of diabetes care in general practice

Objective: The evidence treatment gap for patients with type 2 diabetes.
Design: A summary of convenience sample of seven general practices.
Setting: Metropolitan and rural Victoria, Australia.
Participants: 561 patients of general practices (75% from rural general practices).
Main outcome measures: Demographic data, duration of diabetes, diabetes complications, HbA1c and lipid levels, blood pressure and score on PHQ-9.
Results: Patients with depression show more severe, progressive and intensively treated diabetes. The prevalence of depression in diabetes is about twice that of the general population.
Conclusion: Australian guidelines for diabetes should recommend screening for depression.

Implementation of diabetes prevention programs in rural areas : Montana and south-eastern Australia compared

Objective: To identify the key elements that enabled the Greater Green Triangle Diabetes Prevention Project (GGT DPP) and the Montana Cardiovascular Disease and Diabetes Prevention (CDDP) programs successful establishment and implementation in rural areas, as well as identifying specific challenges or barriers for implementation in rural communities.
Methods: Focus groups were held with the facilitators who delivered the GGT DPP in Australia and the Montana CDDP programs in the USA. Interview questions covered the facilitators’ experiences with recruitment, establishing the program, the components and influence of rurality on the program, barriers and challenges to delivering the program, attributes of successful participants, and the influence of community resources and partnerships on the programs.
Results: Four main themes emerged from the focus groups: establishing and implementing the diabetes prevention program in the community; strategies for recruitment and retention of participants; what works in lifestyle intervention programs; and rural-centred issues.
Conclusions: The results from this study have assisted in determining the factors that contribute to developing, establishing and implementing successful diabetes prevention programs in two rural areas. Recommendations to increase the likelihood of success of programs in rural communities include: securing funding early for the program; establishing support from community leaders and developing positive relationships with health care providers; creating a professional team with passion for the program; encouraging participants to celebrate their small and big successes; and developing procedures for providing post-intervention support to help participants maintain their success.

Young mothers’ lived experiences prior to becoming pregnant in rural Victoria : a phenomenological study

Objective: To explore the lived experiences and social context prior to becoming pregnant, of women who became mothers during adolescence in rural Victoria.
Design: Qualitative interpretive phenomenological study using semistructured interviews.
Setting: Rural community in North East Victoria, Australia.
Participants: Four rural women who gave birth to a child between the ages of 15 and 19.
Results: Five themes emerged from the data as being essential to the participants’ experiences prior to pregnancy. These included feeling isolated; life change: transition into adulthood; support and understanding in sexual relationships; feeling dissatisfied; and overcoming adversity. Participants’ provided practical recommendations to improve life for young people in rural areas through reflecting on their own experiences.
Conclusion: These findings highlight the complex nature of rural young women’s experiences leading up to pregnancy and suggest that early motherhood might be largely reflective of the social environment in which one lives prior to pregnancy. Providing somewhere safe to go, organised and appropriate social activities and increasing access to health services were identified as being pertinent to improving experiences for rural young people prior to pregnancy. Health professionals should consider the importance of supporting young women through non-judgemental, approachable and accessible services.

Sequence requirements for the export of the Plasmodium falciparum Maurer's clefts protein REX2

A short motif termed Plasmodium export element (PEXEL) or vacuolar targeting signal (VTS) characterizes Plasmodium proteins exported into the host cell. These proteins mediate host cell modifications essential for parasite survival and virulence. However, several PEXEL-negative exported proteins indicate that the currently predicted malaria exportome is not complete and it is unknown whether and how these proteins relate to PEXEL-positive export. Here we show that the N-terminal 10 amino acids of the PEXEL-negative exported protein REX2 (ring-exported protein 2) are necessary for its targeting and that a single-point mutation in this region abolishes export. Furthermore we show that the REX2 transmembrane domain is also essential for export and that together with the N-terminal region it is sufficient to promote export of another protein. An N-terminal region and the transmembrane domain of the unrelated PEXEL-negative exported protein SBP1 (skeleton-binding protein 1) can functionally replace the corresponding regions in REX2, suggesting that these sequence features are also present in other PEXEL-negative exported proteins. Similar to PEXEL proteins we find that REX2 is processed, but in contrast, detect no evidence for N-terminal acetylation.

Functional analysis of the leading malaria vaccine candidate AMA-1 reveals an essential role for the cytoplasmic domain in the invasion process

A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies.

Transcriptional profiling of growth perturbations of the human malaria parasite Plasmodium falciparum

Functions have yet to be defined for the majority of genes of Plasmodium falciparum, the agent responsible for the most serious form of human malaria. Here we report changes in P. falciparum gene expression induced by 20 compounds that inhibit growth of the schizont stage of the intraerythrocytic development cycle. In contrast with previous studies, which reported only minimal changes in response to chemically induced perturbations of P. falciparum growth, we find that ~59% of its coding genes display over three-fold changes in expression in response to at least one of the chemicals we tested. We use this compendium for guilt-by-association prediction of protein function using an interaction network constructed from gene co-expression, sequence homology, domain-domain and yeast two-hybrid data. The subcellular localizations of 31 of 42 proteins linked with merozoite invasion is consistent with their role in this process, a key target for malaria control. Our network may facilitate identification of novel antimalarial drugs and vaccines.

Repulsive interaction between coplanar cracks in the double–cantilever geometry

Experiments on thin mica sheets are used to demonstrate that coplanar cracks in double-cantilever beam specimens do not universally attract each other, as conventionally portrayed, but, at long range, actually repel. An elasticity analysis explains the repulsion in terms of a compression zone, 0.35 times the beam half-thickness ahead of the crack tip, generated by bending moments from the cantilever arms on the remaining specimen section.

Potential of pharmacists to help reduce the burden of poorly managed cardiovascular risk

Introduction: Rural areas require better use of existing health professionals to ensure capacity to deliver improved cardiovascular outcomes. Community pharmacists (CPs) are accessible to most communities and can potentially undertake expanded roles in prevention of cardiovascular disease (CVD).

Objective: This study aims to establish frequency of contact with general practitioners (GPs) and CPs by patients at high risk of CVD or with inadequately controlled CVD risk factors.

Design, setting and participants: Population survey using randomly selected individuals from the Wimmera region electoral roll and incorporating a physical health check and self-administered health questionnaire. Overall, 1500 were invited to participate.

Results: The participation rate was 51% when ineligible individuals were excluded. Nine out of 10 participants visited one or both types of practitioner in the previous 12 months. Substantially more participants visited GPs compared with CPs (88.5% versus 66.8%). With the exception of excess alcohol intake, the median number of opportunities to intervene for every inadequately controlled CVD risk factor and among high risk patient groups at least doubled for the professions combined when compared with GP visits alone.

Conclusion: Opportunities exist to intervene more frequently with target groups by engaging CPs more effectively but would require a significant attitude shift towards CPs. Mechanisms for greater pharmacist integration into primary care teams should be investigated.

Cardiovascular risk factors and psychological distress in Australian farming communities

Objective:  To examine the prevalence of cardiovascular disease (CVD) risk factors, psychological distress and associations between physical and mental health parameters within a cohort of the Australian farming community.

Design:  Cross-sectional descriptive study.

Setting:  Farming communities across Australia.

Participants:  Data of men (n = 957) and women (n = 835) farmers from 97 locations across Australia were stratified into categories based on National Cholesterol Education Program guidelines.

Main outcome measure(s):  Prevalence of and interrelationship between overweight, obesity, dyslipidaemia, hypertension, diabetes risk and psychological distress.

Results:  There was a higher prevalence of overweight (42.5%, 95% confidence interval (CI), 34.2–50.8), obesity (21.8%, 95% CI, 18.3–25.3), abdominal adiposity (38.4% 95% CI, 24.5–52.5), hypertension (54.0%, 95% CI, 34.4–73.5) and diabetes risk (25.3%, 95% CI, 17.7–36.7) in the farming cohort compared with national data. There was also a positive significant association between the prevalence of psychological distress and obesity, abdominal adiposity, body fat percentage and metabolic syndrome in older (age ≥ 50 years) participants.

Conclusions:  This study group of farming men and women exhibited an increased prevalence of CVD risk factors and co-morbidities. The findings indicate a positive association between psychological distress and risk for developing CVD, particularly in the older farmers. If the younger cohort were to maintain elevated rates of psychological distress, then it is foreseeable that the next generation of farmers could experience poorer physical health than their predecessors.

1H-NMR and mass spectrometric characterization of the metabolic response of juvenile Atlantic salmon (Salmo salar) to long-term handling stress

Stressors of various kinds constantly affect fish both in the wild and in culture, examples being acute water temperature and quality changes, predation, handling, and confinement. Known physiological responses of fish to stress such as increases in plasma cortisol and glucose levels, are considered to be adaptive, allowing the animal to cope in the short term. Prolonged exposure to stressors however, has the potential to affect growth, immune function, and survival. Nonetheless, little is known about the mechanisms underlying the long-term stress response. We have investigated the metabolic response of juvenile Atlantic salmon (Salmo salar) to long-term handling stress by analyzing fish plasma via ¹H nuclear magnetic resonance spectroscopy and ultra high performance liquid chromatography–mass spectrometry (UPLC–MS), and comparing results with controls. Analysis of NMR data indicated a difference in the metabolic profiles of control and stressed fish after 1 week of stress with a maximum difference observed after 2 weeks. These differences were associated with stress-induced increases in phosphatidyl choline, lactate, carbohydrates, alanine, valine and trimethylamine-N-oxide, and decreases in low density lipoprotein, very low density lipoprotein, and lipid. UPLC-MS data showed differences at week 2, associated with another set of compounds, tentatively identified on the basis of their mass/charge. Overall the results provided a multi-faceted view of the response of fish to long-term handling stress, indicating that the metabolic disparity between the control and stress groups increased to week 2, but declined by weeks 3 and 4, and revealed several new molecular indicators of long-term stress.