Shelf-ocean exchange and hydrography west of the Antarctic Peninsula: A review

The West Antarctic Peninsula (WAP) is a highly productive marine ecosystem where extended periods of change have been observed in the form of glacier retreat, reduction of sea-ice cover and shifts in marine populations, among others. The physical environment on the shelf is known to be strongly influenced by the Antarctic Circumpolar Current flowing along the shelf slope and carrying warm, nutrient-rich water, by cold waters flooding into the northern Bransfield Strait from the Weddell Sea, by an extensive network of glaciers and ice shelves, and by strong seasonal to inter-annual variability in sea-ice formation and air–sea interactions, with significant modulation by climate modes like El Niño–Southern Oscillation and the Southern Annular Mode. However, significant gaps have remained in understanding the exchange processes between the open ocean and the shelf, the pathways and fate of oceanic water intrusions, the shelf heat and salt budgets, and the long-term evolution of the shelf properties and circulation. Here, we review how recent advances in long-term monitoring programmes, process studies and newly developed numerical models have helped bridge these gaps and set future research challenges for the WAP system

ELSID-Diabetes study-evaluation of a large scale implementation of disease management programmes for patients with type 2 diabetes. Rationale, design and conduct – a study protocol [ISRCTN08471887]

BACKGROUND: Diabetes model projects in different regions of Germany including interventions such as quality circles, patient education and documentation of medical findings have shown improvements of HbA1c levels, blood pressure and occurrence of hypoglycaemia in before-after studies (without control group). In 2002 the German Ministry of Health defined legal regulations for the introduction of nationwide disease management programs (DMP) to improve the quality of care in chronically ill patients. In April 2003 the first DMP for patients with type 2 diabetes was accredited. The evaluation of the DMP is essential and has been made obligatory in Germany by the Fifth Book of Social Code. The aim of the study is to assess the effectiveness of DMP by example of type 2 diabetes in the primary care setting of two German federal states (Rheinland-Pfalz and Sachsen-Anhalt). METHODS/DESIGN: The study is three-armed: a prospective cluster-randomized comparison of two interventions (DMP 1 and DMP 2) against routine care without DMP as control group. In the DMP group 1 the patients are treated according to the current situation within the German-Diabetes-DMP. The DMP group 2 represents diabetic care within ideally implemented DMP providing additional interventions (e.g. quality circles, outreach visits). According to a sample size calculation a sample size of 200 GPs (each GP including 20 patients) will be required for the comparison of DMP 1 and DMP 2 considering possible drop-outs. For the comparison with routine care 4000 patients identified by diabetic tracer medication and age (> 50 years) will be analyzed. DISCUSSION: This study will evaluate the effectiveness of the German Diabetes-DMP compared to a Diabetes-DMP providing additional interventions and routine care in the primary care setting of two different German federal states

Exercise training does not improve myocardial diastolic tissue velocities in Type 2 diabetes

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Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin

Animal health depends on the ability of immune cells to kill invading pathogens, and on the resilience of tissues to tolerate the presence of pathogens. Trueperella pyogenes causes tissue pathology in many mammals by secreting a cholesterol-dependent cytolysin, pyolysin (PLO), which targets stromal cells. Cellular cholesterol is derived from squalene, which is synthesized via the mevalonate pathway enzymes, including HMGCR, FDPS and FDFT1. The present study tested the hypothesis that inhibiting enzymes in the mevalonate pathway to reduce cellular cholesterol increases the resilience of stromal cells to PLO. We first verified that depleting cellular cholesterol with methyl-β-cyclodextrin increased the resilience of stromal cells to PLO. We then used siRNA to deplete mevalonate pathway enzyme gene expression, and used pharmaceutical inhibitors, atorvastatin, alendronate or zaragozic acid to inhibit the activity of HMGCR, FDPS and FDFT1, respectively. These approaches successfully reduced cellular cholesterol abundance, but mevalonate pathway enzymes did not affect cellular resilience equally. Inhibiting FDFT1 was most effective, with zaragozic acid reducing the impact of PLO on cell viability. The present study provides evidence that inhibiting FDFT1 increases stromal cell resilience to a cholesterol-dependent cytolysin

An Australian Aboriginal birth cohort: a unique resource for a life course study of an Indigenous population. A study protocol

BACKGROUND: The global rise of Type 2 diabetes and its complications has drawn attention to the burden of non-communicable diseases on populations undergoing epidemiological transition. The life course approach of a birth cohort has the potential to increase our understanding of the development of these chronic diseases. In 1987 we sought to establish an Australian Indigenous birth cohort to be used as a resource for descriptive and analytical studies with particular attention on non-communicable diseases. The focus of this report is the methodology of recruiting and following-up an Aboriginal birth cohort of mobile subjects belonging to diverse cultural and language groups living in a large sparsely populated area in the Top End of the Northern Territory of Australia. METHODS: A prospective longitudinal study of Aboriginal singletons born at the Royal Darwin Hospital 1987–1990, with second wave cross-sectional follow-up examination of subjects 1998–2001 in over 70 different locations. A multiphase protocol was used to locate and collect data on 686 subjects with different approaches for urban and rural children. Manual chart audits, faxes to remote communities, death registries and a full time subject locator with past experience of Aboriginal communities were all used. DISCUSSION: The successful recruitment of 686 Indigenous subjects followed up 14 years later with vital status determined for 95% of subjects and examination of 86% shows an Indigenous birth cohort can be established in an environment with geographic, cultural and climatic challenges. The high rates of recruitment and follow up indicate there were effective strategies of follow-up in a supportive population

Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disease, characterized by neonatal/early-onset non-autoimmune insulin-requiring diabetes associated with skeletal dysplasia and growth retardation. Fewer than 60 cases have been described in the literature, although WRS is now recognised as the most frequent cause of neonatal/early-onset diabetes in patients with consanguineous parents. Typically, diabetes occurs before six months of age, and skeletal dysplasia is diagnosed within the first year or two of life. Other manifestations vary between patients in their nature and severity and include frequent episodes of acute liver failure, renal dysfunction, exocrine pancreas insufficiency, intellectual deficit, hypothyroidism, neutropenia and recurrent infections. Bone fractures may be frequent. WRS is caused by mutations in the gene encoding eukaryotic translation initiation factor 2α kinase 3 (EIF2AK3), also known as PKR-like endoplasmic reticulum kinase (PERK). PERK is an endoplasmic reticulum (ER) transmembrane protein, which plays a key role in translation control during the unfolded protein response. ER dysfunction is central to the disease processes. The disease variability appears to be independent of the nature of the EIF2AK3 mutations, with the possible exception of an older age at onset; other factors may include other genes, exposure to environmental factors and disease management. WRS should be suspected in any infant who presents with permanent neonatal diabetes associated with skeletal dysplasia and/or episodes of acute liver failure. Molecular genetic testing confirms the diagnosis. Early diagnosis is recommended, in order to ensure rapid intervention for episodes of hepatic failure, which is the most life threatening complication. WRS should be differentiated from other forms of neonatal/early-onset insulin-dependent diabetes based on clinical presentation and genetic testing. Genetic counselling and antenatal diagnosis is recommended for parents of a WRS patient with confirmed EIF2AK3 mutation. Close therapeutic monitoring of diabetes and treatment with an insulin pump are recommended because of the risk of acute episodes of hypoglycaemia and ketoacidosis. Interventions under general anaesthesia increase the risk of acute aggravation, because of the toxicity of anaesthetics, and should be avoided. Prognosis is poor and most patients die at a young age. Intervention strategies targeting ER dysfunction provide hope for future therapy and prevention

The role of physical activity in the management of impaired glucose tolerance: a systematic review

Although physical activity is widely reported to reduce the risk of type 2 diabetes in individuals with prediabetes, few studies have examined this issue independently of other lifestyle modifications. The aim of this review is to conduct a systematic review of controlled trials to determine the independent effect of exercise on glucose levels and risk of type 2 diabetes in people with prediabetes (IGT and/or IFG). A detailed search of MEDLINE (1966–2006) and EMBASE (1980–2006) found 279 potentially relevant studies, eight of which met the inclusion criteria for this review. All eight studies were controlled trials in individuals with impaired glucose tolerance. Seven studies used a multi-component lifestyle intervention that included exercise, diet and weight loss goals and one used a structured exercise training intervention. Four studies used the incidence of diabetes over the course of the study as an outcome variable and four relied on 2-h plasma glucose as an outcome measure. In the four studies that measured the incidence of diabetes as an outcome, the risk of diabetes was reduced by approximately 50% (range 42–63%); as these studies reported only small changes in physical activity levels, the reduced risk of diabetes is likely to be attributable to factors other than physical activity. In the remaining four studies, only one reported significant improvements in 2-h plasma glucose even though all but one reported small to moderate increases in maximal oxygen uptake. These results indicate that the contribution of physical activity independent of dietary or weight loss changes to the prevention of type 2 diabetes in people with prediabetes is equivocal