Modeling the impact of prevention policies on future diabetes prevalence in the United States: 2010-2030

Background Although diabetes is one of the most costly and rapidly increasing serious chronic diseases worldwide, the optimal mix of strategies to reduce diabetes prevalence has not been determined. Methods Using a dynamic model that incorporates national data on diabetes prevalence and incidence, migration, mortality rates, and intervention effectiveness, we project the effect of five hypothetical prevention policies on future US diabetes rates through 2030: 1) no diabetes prevention strategy; 2) a “high-risk” strategy, wherein adults with both impaired fasting glucose (IFG) (fasting plasma glucose of 100–124 mg/dl) and impaired glucose tolerance (IGT) (2-hour post-load glucose of 141–199 mg/dl) receive structured lifestyle intervention; 3) a “moderate-risk” strategy, wherein only adults with IFG are offered structured lifestyle intervention; 4) a “population-wide” strategy, in which the entire population is exposed to broad risk reduction policies; and 5) a “combined” strategy, involving both the moderate-risk and population-wide strategies. We assumed that the moderate- and high-risk strategies reduce the annual diabetes incidence rate in the targeted subpopulations by 12.5% through 2030 and that the population-wide approach would reduce the projected annual diabetes incidence rate by 2% in the entire US population. Results We project that by the year 2030, the combined strategy would prevent 4.6 million incident cases and 3.6 million prevalent cases, attenuating the increase in diabetes prevalence by 14%. The moderate-risk approach is projected to prevent 4.0 million incident cases, 3.1 million prevalent cases, attenuating the increase in prevalence by 12%. The high-risk and population approaches attenuate the projected prevalence increases by 5% and 3%, respectively. Even if the most effective strategy is implemented (the combined strategy), our projections indicate that the diabetes prevalence rate would increase by about 65% over the 23 years (i.e., from 12.9% in 2010 to 21.3% in 2030). Conclusions While implementation of appropriate diabetes prevention strategies may slow the rate of increase of the prevalence of diabetes among US adults through 2030, the US diabetes prevalence rate is likely to increase dramatically over the next 20 years. Demand for health care services for people with diabetes complications and diabetes-related disability will continue to grow, and these services will need to be strengthened along with primary diabetes prevention efforts

Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence

<p>Abstract</p> <p>Background</p> <p>People with diabetes can suffer from diverse complications that seriously erode quality of life. Diabetes, costing the United States more than $174 billion per year in 2007, is expected to take an increasingly large financial toll in subsequent years. Accurate projections of diabetes burden are essential to policymakers planning for future health care needs and costs.</p> <p>Methods</p> <p>Using data on prediabetes and diabetes prevalence in the United States, forecasted incidence, and current US Census projections of mortality and migration, the authors constructed a series of dynamic models employing systems of difference equations to project the future burden of diabetes among US adults. A three-state model partitions the US population into no diabetes, undiagnosed diabetes, and diagnosed diabetes. A four-state model divides the state of "no diabetes" into high-risk (prediabetes) and low-risk (normal glucose) states. A five-state model incorporates an intervention designed to prevent or delay diabetes in adults at high risk.</p> <p>Results</p> <p>The authors project that annual diagnosed diabetes incidence (new cases) will increase from about 8 cases per 1,000 in 2008 to about 15 in 2050. Assuming low incidence and relatively high diabetes mortality, total diabetes prevalence (diagnosed and undiagnosed cases) is projected to increase from 14% in 2010 to 21% of the US adult population by 2050. However, if recent increases in diabetes incidence continue and diabetes mortality is relatively low, prevalence will increase to 33% by 2050. A middle-ground scenario projects a prevalence of 25% to 28% by 2050. Intervention can reduce, but not eliminate, increases in diabetes prevalence.</p> <p>Conclusions</p> <p>These projected increases are largely attributable to the aging of the US population, increasing numbers of members of higher-risk minority groups in the population, and people with diabetes living longer. Effective strategies will need to be undertaken to moderate the impact of these factors on national diabetes burden. Our analysis suggests that widespread implementation of reasonably effective preventive interventions focused on high-risk subgroups of the population can considerably reduce, but not eliminate, future increases in diabetes prevalence.</p

mspecLINE: bridging knowledge of human disease with the proteome

<p>Abstract</p> <p>Background</p> <p>Public proteomics databases such as PeptideAtlas contain peptides and proteins identified in mass spectrometry experiments. However, these databases lack information about human disease for researchers studying disease-related proteins. We have developed mspecLINE, a tool that combines knowledge about human disease in MEDLINE with empirical data about the detectable human proteome in PeptideAtlas. mspecLINE associates diseases with proteins by calculating the semantic distance between annotated terms from a controlled biomedical vocabulary. We used an established semantic distance measure that is based on the co-occurrence of disease and protein terms in the MEDLINE bibliographic database.</p> <p>Results</p> <p>The mspecLINE web application allows researchers to explore relationships between human diseases and parts of the proteome that are detectable using a mass spectrometer. Given a disease, the tool will display proteins and peptides from PeptideAtlas that may be associated with the disease. It will also display relevant literature from MEDLINE. Furthermore, mspecLINE allows researchers to select proteotypic peptides for specific protein targets in a mass spectrometry assay.</p> <p>Conclusions</p> <p>Although mspecLINE applies an information retrieval technique to the MEDLINE database, it is distinct from previous MEDLINE query tools in that it combines the knowledge expressed in scientific literature with empirical proteomics data. The tool provides valuable information about candidate protein targets to researchers studying human disease and is freely available on a public web server.</p

Long-term consequences of an intensive care unit stay in older critically ill patients: design of a longitudinal study

<p>Abstract</p> <p>Background</p> <p>Modern methods in intensive care medicine often enable the survival of older critically ill patients. The short-term outcomes for patients treated in intensive care units (ICUs), such as survival to hospital discharge, are well documented. However, relatively little is known about subsequent long-term outcomes. Pain, anxiety and agitation are important stress factors for many critically ill patients. There are very few studies concerned with pain, anxiety and agitation and the consequences in older critically ill patients. The overall aim of this study is to identify how an ICU stay influences an older person's experiences later in life. More specific, this study has the following objectives: (1) to explore the relationship between pain, anxiety and agitation during ICU stays and experiences of the same symptoms in later life; and (2) to explore the associations between pain, anxiety and agitation experienced during ICU stays and their effect on subsequent health-related quality of life, use of the health care system (readmissions, doctor visits, rehabilitation, medication use), living situation, and survival after discharge and at 6 and 12 months of follow-up.</p> <p>Methods/Design</p> <p>A prospective, longitudinal study will be used for this study. A total of 150 older critically ill patients in the ICU will participate (ICU group). Pain, anxiety, agitation, morbidity, mortality, use of the health care system, and health-related quality of life will be measured at 3 intervals after a baseline assessment. Baseline measurements will be taken 48 hours after ICU admission and one week thereafter. Follow-up measurements will take place 6 months and 12 months after discharge from the ICU. To be able to interpret trends in scores on outcome variables in the ICU group, a comparison group of 150 participants, matched by age and gender, recruited from the Swiss population, will be interviewed at the same intervals as the ICU group.</p> <p>Discussion</p> <p>Little research has focused on long term consequences after ICU admission in older critically ill patients. The present study is specifically focussing on long term consequences of stress factors experienced during ICU admission.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN52754370">ISRCTN52754370</a></p

Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas

BACKGROUND: Colorectal cancer remains a major cause of cancer mortality in the Western world. A limited number of studies has been conducted in respect of Her-3 and Her-4 expression and their correlation with clinical parameters and prognosis in colorectal carcinomas . In this study we sought to determine the pattern and the prognostic significance of HER-3 and HER-4 in colorectal adenocarcinoma. METHODS: We studied HER-3 and HER-4 protein expression in106 paraffin embedded specimens of primary colorectal tumors using immunohistochemistry. The pattern and protein expression levels of HER-3 and HER-4 were correlated with several clinical and pathological parameters. RESULTS: HER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p = 0,032) and older median age (p = 0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymphnodes (p = 0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome. CONCLUSION: HER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential

Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study)

10.1186/1471-2407-12-529BMC Cancer12-BCMA

ProteinHistorian: Tools for the Comparative Analysis of Eukaryote Protein Origin

The evolutionary history of a protein reflects the functional history of its ancestors. Recent phylogenetic studies identified distinct evolutionary signatures that characterize proteins involved in cancer, Mendelian disease, and different ontogenic stages. Despite the potential to yield insight into the cellular functions and interactions of proteins, such comparative phylogenetic analyses are rarely performed, because they require custom algorithms. We developed ProteinHistorian to make tools for performing analyses of protein origins widely available. Given a list of proteins of interest, ProteinHistorian estimates the phylogenetic age of each protein, quantifies enrichment for proteins of specific ages, and compares variation in protein age with other protein attributes. ProteinHistorian allows flexibility in the definition of protein age by including several algorithms for estimating ages from different databases of evolutionary relationships. We illustrate the use of ProteinHistorian with three example analyses. First, we demonstrate that proteins with high expression in human, compared to chimpanzee and rhesus macaque, are significantly younger than those with human-specific low expression. Next, we show that human proteins with annotated regulatory functions are significantly younger than proteins with catalytic functions. Finally, we compare protein length and age in many eukaryotic species and, as expected from previous studies, find a positive, though often weak, correlation between protein age and length. ProteinHistorian is available through a web server with an intuitive interface and as a set of command line tools; this allows biologists and bioinformaticians alike to integrate these approaches into their analysis pipelines. ProteinHistorian's modular, extensible design facilitates the integration of new datasets and algorithms. The ProteinHistorian web server, source code, and pre-computed ages for 32 eukaryotic genomes are freely available under the GNU public license at http://lighthouse.ucsf.edu/ProteinHistorian/

Overfeeding Reduces Insulin Sensitivity and Increases Oxidative Stress, without Altering Markers of Mitochondrial Content and Function in Humans

BACKGROUND: Mitochondrial dysfunction and increased oxidative stress are associated with obesity and type 2 diabetes. High fat feeding induces insulin resistance and increases skeletal muscle oxidative stress in rodents, but there is controversy as to whether skeletal muscle mitochondrial biogenesis and function is altered. METHODOLOGY AND PRINCIPAL FINDINGS: Forty (37±2 y) non-obese (25.6±0.6 kg/m2) sedentary men (n = 20) and women (n = 20) were overfed (+1040±100 kcal/day, 46±1% of energy from fat) for 28 days. Hyperinsulinemic-euglycemic clamps were performed at baseline and day 28 of overfeeding and skeletal muscle biopsies taken at baseline, day 3 and day 28 of overfeeding in a sub cohort of 26 individuals (13 men and 13 women) that consented to having all 3 biopsies performed. Weight increased on average in the whole cohort by 0.6±0.1 and 2.7±0.3 kg at days 3 and 28, respectively (P<0.0001, without a significant difference in the response between men and women (P = 0.4). Glucose infusion rate during the hyperinsulinemic-euglycemic clamp decreased from 54.8±2.8 at baseline to 50.3±2.5 mmol/min/kg FFM at day 28 of overfeeding (P = 0.03) without a significant difference between men and women (P = 0.4). Skeletal muscle protein carbonyls and urinary F2-isoprostanes increased with overfeeding (P,<.05). Protein levels of muscle peroxisome proliferator-activated receptor gamma coactivator-1a (PGC1a) and subunits from complex I, II and V of the electron transport chain were increased at day 3 (all P<0.05) and returned to basal levels at day 28. No changes were detected in muscle citrate synthase activity or ex vivo CO2 production at either time point. CONCLUSIONS: Peripheral insulin resistance was induced by overfeeding, without reducing any of the markers of mitochondrial content that were examined. Oxidative stress was however increased, and may have contributed to the reduction in insulin sensitivity observed.Dorit Samocha-Bonet, Lesley V. Campbell, Trevor A. Mori, Kevin D. Croft, Jerry R. Greenfield, Nigel Turner and Leonie K. Heilbron

The association between exposure to social media alcohol marketing and youth alcohol use behaviors in India and Australia

© 2018 The Author(s). Background: Alcohol marketing on social networking sites (SNS) is associated with alcohol use among young people. Alcohol companies adapt their online marketing content to specific national contexts and responses to such content differ by national settings. However, there exists very little academic work comparing the association between alcohol marketing on SNS and alcohol use among young people in different national settings and across different SNS. Therefore, we aimed to extend the limited existing work by investigating and comparing the association between self-reported exposure to alcohol marketing on three leading SNS (Facebook, YouTube, and Twitter) and alcohol use among young people in diverse national contexts (India and Australia). Methods: Cross-sectional, self-report data were obtained from a convenience sample of 631 respondents (330 in India; 301 in Australia) aged 13-25 years via online surveys. Respondents answered questions on their drinking behaviors and involvement with alcohol marketing on SNS. Results: Many respondents from both countries reported interacting with alcohol content online, predominantly on Facebook, followed by YouTube and then Twitter. The interaction was primarily in the forms of posting/liking/sharing/commenting on items posted on alcohol companies' social media accounts, viewing the event page/attending the event advertised by an alcohol company via social media, and/or accessing an alcohol website. Multivariate analyses demonstrated significant associations between respondents' interaction with alcohol content and drinking levels, with effects differing by SNS, demographic group, and country. For example, having friends who shared alcohol-related content was an important predictor of usual alcohol consumption for Indian respondents (p &lt;.001), whereas posting alcohol-related information themselves was a stronger predictor among Australians (p &lt;.001). Conclusions: The results suggest that interaction with alcohol-related content on SNS is associated with young people's alcohol use behaviors and that these behaviors vary by national settings. This study extends previous work by demonstrating this connection across varying social media platforms and national contexts. The results highlight the need to formulate and implement strategies to effectively regulate the SNS alcohol marketing, especially among younger SNS users

Cutaneous Bacteria of the Redback Salamander Prevent Morbidity Associated with a Lethal Disease

Chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), is an infectious disease that causes population declines of many amphibians. Cutaneous bacteria isolated from redback salamanders, Plethodon cinereus, and mountain yellow-legged frogs, Rana muscosa, inhibit the growth of Bd in vitro. In this study, the bacterial community present on the skin of P. cinereus individuals was investigated to determine if it provides protection to salamanders from the lethal and sub-lethal effects of chytridiomycosis. When the cutaneous bacterial community was reduced prior to Bd exposure, salamanders experienced a significantly greater decrease in body mass, which is a symptom of the disease, when compared to infected individuals with a normal bacterial community. In addition, a greater proportion of infected individuals with a reduced bacterial community experienced limb-lifting, a behavior seen only in infected individuals. Overall, these results demonstrate that the cutaneous bacterial community of P. cinereus provides protection to the salamander from Bd and that alteration of this community can change disease resistance. Therefore, symbiotic microbes associated with this species appear to be an important component of its innate skin defenses