Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets.

AIMS/HYPOTHESIS: Ageing is a major risk factor for development of metabolic diseases such as type 2 diabetes. Identification of the mechanisms underlying this association could help to elucidate the relationship between age-associated progressive loss of metabolic health and development of type 2 diabetes. We aimed to determine molecular signatures during ageing in the endocrine pancreas. METHODS: Global gene transcription was measured in pancreatic islets isolated from young and old rats by Ilumina BeadChip arrays. Promoter DNA methylation was measured by Sequenom MassArray in 46 genes that showed differential expression with age, and correlations with expression were established. Alterations in morphological and cellular processes with age were determined by immunohistochemical methods. RESULTS: Age-related changes in gene expression were found at 623 loci (>1.5-fold, false discovery rate [FDR] <5%), with a significant (FDR < 0.05) enrichment in genes previously implicated in islet-cell function (Enpp1, Abcc8), type 2 diabetes (Tspan8, Kcnq1), inflammatory processes (Cxcl9, Il33) and extracellular matrix organisation (Col3a1, Dpt). Age-associated transcriptional differences negatively correlated with promoter DNA methylation at several loci related to inflammation, glucose homeostasis, cell proliferation and cell-matrix interactions (Il33, Cxcl9, Gpr119, Fbp2, Col3a1, Dpt, Spp1). CONCLUSIONS/INTERPRETATION: Our findings suggest that a significant proportion of pancreatic islets develop a low-grade 'chronic' inflammatory status with ageing and this may trigger altered functional plasticity. Furthermore, we identified changes in expression of genes previously linked to type 2 diabetes and associated changes in DNA methylation that could explain their age-associated dysregulation. These findings provide new insights into key (epi)genetic signatures of the ageing process in islets.Biotechnology and Biological Sciences Research Council (Grant ID: BB/H003312/1), British Heart Foundation, FP6 Epigenome Network of Excellence programme, GlaxoSmithKline, Nuffield Foundation, Royal Society, Medical Research Council (Grant ID: MRC_MC_UU_12012/4)This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00125-015-3837-

An investigation into the prevalence of dog bites to primary school children in Trinidad

<p>Abstract</p> <p>Background</p> <p>To estimate the prevalence of dog bites to primary school children between the ages of 8–12 years using a semi-structured interview process. With the increase in the pet population and popularity of dangerous breeds of dog and a high stray dog population combined with a dearth of information on the risk of dog attacks to children in Trinidad, a semi-structured interview process was used to determine risk factors associated with dog attacks.</p> <p>Methods</p> <p>A questionnaire survey of 1109 primary school children between the ages of 8–12 years was conducted in Trinidad from November 2002 to September 2003. The survey was conducted to determine the risk factors such as age, gender, size of dog and relationship of dog and victim, in dog bite incidents. The chi-square statistic and odds ratios were used to estimate risk factors for a bite incident.</p> <p>Results</p> <p>Twenty-eight percent of children were bitten at least once by a dog. Gender (male) and owning a dog were statistically significant risk factors (p = 0.003 and 0.008 respectively, χ²<it>df</it>, 95% confidence). Most attacks occurred outside of the home (58.0%) followed by the victims' home (42.0%) and were by a dog known but not owned (54.6%) by the victim. Many victims (33.0%) were bitten without having any interaction with the dog and the majority (61.9%) of victims did not receive professional medical assistance. Overall, the lower leg or foot was most often injured (39.3%).</p> <p>Conclusion</p> <p>A public educational campaign is needed on responsible pet ownership. In addition, children must be taught effective ways of avoiding attacks or reducing injury in the event of a dog attack. The Dangerous dogs Act 2000 must be proclaimed in parliament by the Government of Trinidad and Tobago to exert more pressure on pet owners to safeguard the public from the menace of dog attacks.</p

Potential and Actual Terrestrial Rabies Exposures in People and Domestic Animals, Upstate South Carolina, 1994–2004: A Surveillance Study

<p>Abstract</p> <p>Background</p> <p>Although there has been a reduction of rabies in pets and domestic animals during recent decades in the United States, rabies remains enzootic among bats and several species of terrestrial wildlife. Spillover transmission of wildlife rabies to domestic animals therefore remains a public health threat</p> <p>Methods</p> <p>Retrospective analysis of surveillance data of reported animal incidents (bites, scratches, mucous membrane contacts) from South Carolina, 1995 to 2003, was performed to assess risk factors of potential rabies exposures among human and animal victims.</p> <p>Results</p> <p>Dogs and cats contributed the majority (66.7% and 26.4%, respectively) of all reported incidents, with stray dogs and cats contributing 9.0% and 15.1 respectively. Current rabies vaccination status of dogs and cats (40.2% and 13.8%, respectively) were below World Health Organization recommended levels. Owned cats were half as likely to be vaccinated for rabies as dogs (OR 0.53, 95% CI 0.48, 0.58). Animal victims were primarily exposed to wildlife (83.0%), of which 27.5% were rabid. Almost 90% of confirmed rabies exposures were due to wildlife. Skunks had the highest prevalence of rabies among species of exposure animals (63.2%). Among rabid domestic animals, stray cats were the most commonly reported (47.4%).</p> <p>Conclusion</p> <p>While the majority of reported potential rabies exposures are associated with dog and cat incidents, most rabies exposures derive from rabid wildlife. Stray cats were most frequently rabid among domestic animals. Our results underscore the need for improvement of wildlife rabies control and the reduction of interactions of domestic animals, including cats, with wildlife.</p

Intergenerational Transmission of Glucose Intolerance and Obesity by In Utero Undernutrition in Mice

OBJECTIVE—Low birth weight (LBW) is associated with increased risk of obesity, diabetes, and cardiovascular disease during adult life. Moreover, this programmed disease risk can progress to subsequent generations. We previously described a mouse model of LBW, produced by maternal caloric undernutrition (UN) during late gestation. LBW offspring (F1-UN generation) develop progressive obesity and impaired glucose tolerance (IGT) with aging. We aimed to determine whether such metabolic phenotypes can be transmitted to subsequent generations in an experimental model, even in the absence of altered nutrition during the second pregnancy

Bio-psychosocial determinants of time lost from work following non life threatening acute orthopaedic trauma

<p>Abstract</p> <p>Background</p> <p>To determine factors predicting the duration of time away from work following acute orthopaedic non life threatening trauma</p> <p>Methods</p> <p>Prospective cohort study conducted at four hospitals in Victoria, Australia. The cohort comprised 168 patients aged 18-64 years who were working prior to the injury and sustained a range of acute unintentional orthopaedic injuries resulting in hospitalization. Baseline data was obtained by survey and medical record review. Multivariate Cox proportional hazards regression analysis was used to examine the association between potential predictors and the duration of time away from work during the six month study. The study achieved 89% follow-up.</p> <p>Results</p> <p>Of the 168 participants recruited to the study, 68% returned to work during the six month study. Multivariate Cox proportional hazards regression analysis identified that blue collar work, negative pain attitudes with respect to work, high initial pain intensity, injury severity, older age, initial need for surgery, the presence of co-morbid health conditions at study entry and an orthopaedic injury to more than one region were associated with extended duration away from work following the injury. Participants in receipt of compensation who reported high social functioning at two weeks were 2.58 times more likely to have returned to work than similar participants reporting low social functioning. When only those who had returned to work were considered, the participant reported reason for return to work " to fill the day" was a significant predictor of earlier RTW [RR 2.41 (95% C.I 1.35-4.30)] whereas "financial security" and "because they felt able to" did not achieve significance.</p> <p>Conclusions</p> <p>Many injury-related and psycho social factors affect the duration of time away from work following orthopaedic injury. Some of these are potentially modifiable and may be amenable to intervention. Further consideration of the reasons provided by participants for returning to work may provide important opportunities for social marketing approaches designed to alleviate the financial and social burden associated with work disability.</p

Who uses firearms as a means of suicide? A population study exploring firearm accessibility and method choice

<p>Abstract</p> <p>Background</p> <p>The 1996 Australian National Firearms Agreement introduced strict access limitations. However, reports on the effectiveness of the new legislation are conflicting. This study, accessing all cases of suicide 1997-2004, explores factors which may impact on the choice of firearms as a suicide method, including current licence possession and previous history of legal access.</p> <p>Methods</p> <p>Detailed information on all Queensland suicides (1997-2004) was obtained from the Queensland Suicide Register, with additional details of firearm licence history accessed from the Firearm Registry (Queensland Police Service). Cases were compared against licence history and method choice (firearms or other method). Odds ratios (OR) assessed the risk of firearms suicide and suicide by any method against licence history. A logistic regression was undertaken identifying factors significant in those most likely to use firearms in suicide.</p> <p>Results</p> <p>The rate of suicide using firearms in those with a current license (10.92 per 100,000) far exceeded the rate in those with no license history (1.03 per 100,000). Those with a license history had a far higher rate of suicide (30.41 per 100,000) compared to that of all suicides (15.39 per 100,000). Additionally, a history of firearms licence (current or present) was found to more than double the risk of suicide by any means (OR = 2.09, <it>P </it>< 0.001). The group with the highest risk of selecting firearms to suicide were older males from rural locations.</p> <p>Conclusion</p> <p>Accessibility and familiarity with firearms represent critical elements in determining the choice of method. Further licensing restrictions and the implementation of more stringent secure storage requirements are likely to reduce the overall familiarity with firearms in the community and contribute to reductions in rates of suicide.</p

Restructuring of Pancreatic Islets and Insulin Secretion in a Postnatal Critical Window

Function and structure of adult pancreatic islets are determined by early postnatal development, which in rats corresponds to the first month of life. We analyzed changes in blood glucose and hormones during this stage and their association with morphological and functional changes of alpha and beta cell populations during this period. At day 20 (d20), insulin and glucose plasma levels were two- and six-fold higher, respectively, as compared to d6. Interestingly, this period is characterized by physiological hyperglycemia and hyperinsulinemia, where peripheral insulin resistance and a high plasmatic concentration of glucagon are also observed. These functional changes were paralleled by reorganization of islet structure, cell mass and aggregate size of alpha and beta cells. Cultured beta cells from d20 secreted the same amount of insulin in 15.6 mM than in 5.6 mM glucose (basal conditions), and were characterized by a high basal insulin secretion. However, beta cells from d28 were already glucose sensitive. Understanding and establishing morphophysiological relationships in the developing endocrine pancreas may explain how events in early life are important in determining adult islet physiology and metabolism

Dog Bites in Humans and Estimating Human Rabies Mortality in Rabies Endemic Areas of Bhutan

Dog bites in humans are a public health problem worldwide. We conducted a hospital based questionnaire survey and described the incidence and risk factors for human dog bites in Bhutan. We also estimated the human death rate attributable to rabies in two rabies endemic areas of south Bhutan. Our study shows that dog bites incidents in humans are common in the survey areas. There were significant gender and age differences in bite incidents; males and the children are affected the most. The majority of the victims were bitten by stray dogs, increasing the risk of rabies infection if not treated in time. Our decision tree model predicted 2.23 (95% CI: 1.20–3.59) human deaths from rabies/year, equivalent to an annual incidence of 4.67 (95% CI: 2.53–7.53) deaths/100,000 in the two rabies endemic areas of south Bhutan. In the absence of post exposure prophylaxis, the model predicted 19.24 (95% CI: 13.69–25.14) deaths/year in these two areas. The public should be encouraged to visit hospitals for post exposure prophylaxis following dog bite injury in south Bhutan