Environmental epigenomics: Current approaches to assess epigenetic effects of endocrine disrupting compounds (EDC's) on human health

Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis

Role of PTPN22 and CSK gene polymorphisms as predictors of susceptibility and clinical heterogeneity in patients with Henoch-Schönlein purpura (IgA vasculitis)

INTRODUCTION: To determine whether the PTPN22 (protein tyrosine phosphatase nonreceptor 22)/CSK (c-src tyrosine kinase) pathway is implicated in the susceptibility and clinical heterogeneity of Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies. METHODS: A set of 329 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria and 515 sex and ethnically matched controls were recruited in this study. Two well-known CSK (CSK rs34933034 and CSK rs1378942) and two functional PTPN22 (PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q)) polymorphisms, previously associated with autoimmunity, were genotyped with TaqMan single nucleotide polymorphism (SNP) genotyping assays. RESULTS: No significant differences in the genotype and allele frequencies between HSP patients and controls were observed when the CSK rs34933034, CSK rs1378942, PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q) polymorphisms were analyzed independently. In keeping with this observation, no significant differences were found when we assessed these polymorphisms combined conforming haplotypes. In addition, there were no differences in the allele or genotype frequencies when HSP patients were stratified according the age at disease onset, sex, presence of arthralgia/arthritis, nephritis or gastrointestinal manifestations. CONCLUSIONS: Our results do not support association between PTPN22/CSK and HSP

Maximal respiratory static pressures in patients with different stages of COPD severity

<p>Abstract</p> <p>Background</p> <p>In this study, we analyzed maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values in a stable COPD population compared with normal subjects. We evaluated the possible correlation between functional maximal respiratory static pressures and functional and anthropometric parameters at different stages of COPD. Furthermore, we considered the possible correlation between airway obstruction and MIP and MEP values.</p> <p>Subject and methods</p> <p>110 patients with stable COPD and 21 age-matched healthy subjects were enrolled in this study. Patients were subdivided according to GOLD guidelines: 31 mild, 39 moderate and 28 severe.</p> <p>Results</p> <p>Both MIP and MEP were lower in patients with severe airway impairment than in normal subjects. Moreover, we found a correlation between respiratory muscle function and some functional and anthropometric parameters: FEV₁(forced expiratory volume in one second), FVC (forced vital capacity), PEF (peak expiratory flow), TLC (total lung capacity) and height. MIP and MEP values were lower in patients with severe impairment than in patients with a slight reduction of FEV₁.</p> <p>Conclusion</p> <p>The measurement of MIP and MEP indicates the state of respiratory muscles, thus providing clinicians with a further and helpful tool in monitoring the evolution of COPD.</p

Cost-Effectiveness Analysis of Insulin Detemir Compared to Neutral Protamine Hagedorn (NPH) in Patients with Type 1 and Type 2 Diabetes Mellitus in Spain

Introduction: An Excel® (Microsoft Corporation) model was adapted to estimate the short-term (1-year) cost effectiveness of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) insulin in patients initiating insulin treatment with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in Spain. Methods: Clinical benefits included the non-severe hypoglycemia rate for T1DM and T2DM, and weight change for T2DM. Three scenarios were included with different hypoglycemia rates estimated on the basis of clinical trials and observational studies. Costs, estimated from perspective of the Spanish Public Healthcare System (Euros 2014), included insulin treatment and non-severe hypoglycemia management costs. Non-severe hypoglycemia, defined as a self-managed event, implied the use of extra glucose testing strips and a general practitioner visit during the week following the event for 25% of patients. An average disutility value was associated to non-severe hypoglycemia events and, for T2DM, to one body mass index unit gain to calculate quality-adjusted life years (QALYs). Results: For the three scenarios a range of 0.025–0.076 QALYs for T1DM and 0.014–0.051 QALYs for T2DM were gained for IDet versus NPH due to non-severe hypoglycemia and weight gain avoidance, in return of an incremental cost of €145–192 for T1DM and €128–206 for T2DM. This resulted in the IDet versus NPH incremental cost-effectiveness ratio (ICER) ranging between €1910/QALY and €7682/QALY for T1DM and €2522/QALY and €15,009/QALY for T2DM. Conclusion: IDet was a cost-effective alternative to NPH insulin in the first year of treatment of patients with T1DM and patients with T2DM in Spain, with ICERs under the threshold value commonly accepted in Spain (€30,000/QALY)

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Monitoring of water quality in a shrimp farm using a FANET

This paper develops an architecture for flying ad-hoc networks (FANETs) to enable monitoring of water quality in a shrimp farm. Firstly, the key monitoring parameters for the characterization of water quality are highlighted and their desired operational ranges are summarized. These parameters directly influence shrimp survival and healthy growth. Based on the considered sensing modality, a reference architecture for implementing a cost-effective FANET based mobile sensing platform is developed. The controlled mobility of the platform is harnessed to increase the spatial monitoring resolution without the need for extensive infrastructure deployment. The proposed solution will be offered to shrimp farmers in the Mexican state of Colima once the laboratory trials are concluded

Maternal protein and folic acid intake during gestation does not program leptin transcription or serum concentration in rat progeny

Maternal nutrition during gestation influences the development of the fetus, thereby determining its phenotype, including nutrient metabolism, appetite, and feeding behavior. The control of appetite is a very complex process and can be modulated by orexigenic and anorexigenic mediators such as leptin, which is involved in the regulation of energy homeostasis by controlling food intake and energy expenditure. Leptin transcription and secretion are regulated by numerous factors, nutrition being one of them. The present study was designed to test whether maternal nutrition can permanently affect leptin gene transcription and leptin serum concentration in rat progeny. Moreover, we analyzed whether leptin expression and secretion in response to high-fat postweaning feeding depends on the maternal diet during gestation. Pregnant rats were fed either a normal protein, normal folic acid diet (the AIN-93 diet); a protein-restricted, normal folic acid diet; a protein-restricted, folic acid-supplemented diet; or a normal protein, folic acid-supplemented diet. After weaning, the progeny was fed either the AIN-93 diet or a high-fat diet. Neither maternal nutrition nor the postweaning diet significantly affected Lep transcription. High-fat feeding after weaning was associated with higher serum leptin concentration, but the reaction of an organism to the fat content of the diet was not determined by maternal nutrition during gestation. There was no correlation between Lep mRNA level and serum leptin concentration. Global DNA methylation in adipose tissue was about 30% higher in rats fed postnatally the high-fat diet (P < 0.01). Our study showed that the protein and folic acid content in the maternal diet had no significant programming effect on Lep transcription and serum leptin concentration in the rats

Vegetation fire smoke, indigenous status and cardio-respiratory hospital admissions in Darwin, Australia, 1996–2005: a time-series study

<p>Abstract</p> <p>Background</p> <p>Air pollution in Darwin, Northern Australia, is dominated by smoke from seasonal fires in the surrounding savanna that burn during the dry season from April to November. Our aim was to study the association between particulate matter less than or equal to 10 microns diameter (PM₁₀) and daily emergency hospital admissions for cardio-respiratory diseases for each fire season from 1996 to 2005. We also investigated whether the relationship differed in indigenous Australians; a disadvantaged population sub-group.</p> <p>Methods</p> <p>Daily PM₁₀exposure levels were estimated for the population of the city from visibility data using a previously validated model. We used over-dispersed Poisson generalized linear models with parametric smoothing functions for time and meteorology to examine the association between admissions and PM₁₀up to three days prior. An interaction between indigenous status and PM₁₀was included to examine differences in the impact on indigenous people.</p> <p>Results</p> <p>We found both positive and negative associations and our estimates had wide confidence intervals. There were generally positive associations between respiratory disease and PM₁₀but not with cardiovascular disease. An increase of 10 μg/m³in same-day estimated ambient PM₁₀was associated with a 4.81% (95%CI: -1.04%, 11.01%) increase in total respiratory admissions. When the interaction between indigenous status and PM₁₀was assessed a statistically different association was found between PM₁₀and admissions three days later for respiratory infections of indigenous people (15.02%; 95%CI: 3.73%, 27.54%) than for non-indigenous people (0.67%; 95%CI: -7.55%, 9.61%). There were generally negative estimates for cardiovascular conditions. For non-indigenous admissions the estimated association with total cardiovascular admissions for same day ambient PM₁₀and admissions was -3.43% (95%CI: -9.00%, 2.49%) and the estimate for indigenous admissions was -3.78% (95%CI: -13.4%, 6.91%), although ambient PM₁₀did have positive (non-significant) associations with cardiovascular admissions of indigenous people two and three days later.</p> <p>Conclusion</p> <p>We observed positive associations between vegetation fire smoke and daily hospital admissions for respiratory diseases that were stronger in indigenous people. While this study was limited by the use of estimated rather than measured exposure data, the results are consistent with the currently small evidence base concerning this source of air pollution.</p

The Use of Preoperative Epoetin-α in Revision Hip Arthroplasty

PURPOSE: To evaluate the efficacy of preoperative epoetin-α on the revision hip arthroplasty patient. We hypothesized that epoetin-α will reduce blood transfusion. A pertinent review of the literature is provided. METHODS: Forty-six patients were retrospectively reviewed. Sixteen patients received epoetin-α. Patients were case matched by age, preoperative hemoglobin, surgery, gender, and BMI. The clinical triggers for blood transfusion during or after the procedure were determined based on peri- and postoperative hemoglobin levels, ASA score, and/or clinical symptoms consistent with anemia. Blood salvage was not used. RESULTS: Blood transfusion and length of stay were decreased in the epoetin-α group. Hemoglobin in the intervention group increased from 12.0 to 14.5, preoperatively. Patients who received epoetin-α were 0.78 (RR=0.225) times as likely to receive a transfusion. Number Needed to Treat (NNT) to avoid one allogeneic transfusion was 1.84. Age, Gender, BMI, ASA, total and hidden blood loss, preoperative Iron supplements, preop Hct, preop PLT, PT, PTT, and INR were similar. One (6.0%) patient developed an uncomplicated deep venous thrombosis in the intervention group. CONCLUSIONS: The mildly anemic revision hip arthroplasty patient is at increased risk for transfusion. Epoetin-α increased preoperative hemoglobin counts and reduced transfusions in this study; it also decreased patient length of hospital stay likely allowing for an earlier readiness to resume normal activities and/or meet short-term milestones. A randomized study to evaluate the direct and indirect costs of such a treatment methodology in the mildly anemic revision patient may be warranted

Sending money home: a mixed-Methods study of remittances by migrant nurses in Ireland

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