Yearly evolution of organ damage markers in diabetes or metabolic syndrome: data from the LOD-DIABETES study

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease morbidity-mortality is greater in people with type 2 diabetes mellitus or metabolic syndrome. The purpose of this study was to evaluate the yearly evolution of organ damage markers in diabetes or metabolic syndrome, and to analyze the associated factors.</p> <p>Methods</p> <p>An observational prospective study was carried out in the primary care setting, involving 112 patients: 68 diabetics and 44 subjects with metabolic syndrome, subjected to 12 months of follow-up. Measurements: traditional cardiovascular risk factors (blood pressure, blood glucose, lipids, smoking, body mass index (BMI) and) and non-traditional risk factors (waist circumference, hsC Reactive Protein and fibrinogen); subclinical vascular (carotid intima-media thickness, pulse wave velocity and ankle/brachial index), cardiac (Cornell voltage-duration product), renal organ damage (creatinine, glomerular filtration and albumin/creatinine index), and antihypertensive and lipid-lowering drugs.</p> <p>Results</p> <p>At baseline, the diabetics presented a mean age of 59.9 years, versus 55.2 years in the subjects with metabolic syndrome (p = 0.03). Diastolic blood pressure, total cholesterol and HDL-cholesterol were lower among the patients with diabetes, while blood glucose and HbA1c, as well as antihypertensive and lipid-lowering drug use, were greater. At evaluation after one year, the diabetics showed a decrease in BMI (-0.39), diastolic blood pressure (-3.59), and an increase in fibrinogen (30.23 mg/dL), ankle/brachial index (0.07) and the number of patients with ankle/brachial index pathologic decreased in 6. In turn, the patients with metabolic syndrome showed an increase in HDL-cholesterol (1-91 mg/dL), fibrinogen (25.54 mg/dL), Cornell voltage-duration product (184.22 mm/ms), ankle/brachial index (0.05) and the use of antihypertensive and lipid-lowering drugs, and a reduction in serum glucose (3.74 mg/dL), HOMA, systolic (-6.76 mmHg), diastolic blood pressure (-3.29 mmHg), and pulse wave velocity (-0.72 m/s). The variable that best predicted a decrease in pulse wave velocity in subjects with metabolic syndrome was seen to be an increase in antihypertensive drug use.</p> <p>Conclusions</p> <p>The annual assessment of cardiovascular risk factors and the decrease in pulse wave velocity was more favorable in the patients with metabolic syndrome, probably influenced by the increased percentage of subjects treated with antihypertensive and lipid lowering drugs in this group.</p

Adverse Birth Outcomes and Maternal Exposure to Trichloroethylene and Tetrachloroethylene through Soil Vapor Intrusion in New York State

Background: Industrial spills of volatile organic compounds (VOCs) in Endicott, New York (USA), have led to contamination of groundwater, soil, and soil gas. Previous studies have reported an increase in adverse birth outcomes among women exposed to VOCs in drinking water

Synergy-COPD: a systems approach for understanding and managing chronic diseases.

Chronic diseases (CD) are generating a dramatic societal burden worldwide that is expected to persist over the next decades. The challenges posed by the epidemics of CD have triggered a novel health paradigm with major consequences on the traditional concept of disease and with a profound impact on key aspects of healthcare systems. We hypothesized that the development of a systems approach to understand CD together with the generation of an ecosystem to transfer the acquired knowledge into the novel healthcare scenario may contribute to a cost-effective enhancement of health outcomes. To this end, we designed the Synergy-COPD project wherein the heterogeneity of chronic obstructive pulmonary disease (COPD) was addressed as a use case representative of CD. The current manuscript describes main features of the project design and the strategies put in place for its development, as well the expected outcomes during the project life-span. Moreover, the manuscript serves as introductory and unifying chapter of the different papers associated to the Supplement describing the characteristics, tools and the objectives of Synergy-COP

Predictive medicine: outcomes, challenges and opportunities in the Synergy-COPD project

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a major challenge for healthcare. Heterogeneities in clinical manifestations and in disease progression are relevant traits in COPD with impact on patient management and prognosis. It is hypothesized that COPD heterogeneity results from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering. OBJECTIVES: To assess the potential of systems medicine to better understand non-pulmonary determinants of COPD heterogeneity. To transfer acquired knowledge to healthcare enhancing subject-specific health risk assessment and stratification to improve management of chronic patients. METHOD: Underlying mechanisms of skeletal muscle dysfunction and of co-morbidity clustering in COPD patients were explored with strategies combining deterministic modelling and network medicine analyses using the Biobridge dataset. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was done (ICD9-CM data from Medicare, 13 million people). A targeted network analysis using the two studies: skeletal muscle dysfunction and co-morbidity clustering explored shared pathways between them. RESULTS: (1) Evidence of abnormal regulation of pivotal skeletal muscle biological pathways and increased risk for co-morbidity clustering was observed in COPD; (2) shared abnormal pathway regulation between skeletal muscle dysfunction and co-morbidity clustering; and, (3) technological achievements of the projects were: (i) COPD Knowledge Base; (ii) novel modelling approaches; (iii) Simulation Environment; and, (iv) three layers of Clinical Decision Support Systems. CONCLUSIONS: The project demonstrated the high potential of a systems medicine approach to address COPD heterogeneity. Limiting factors for the project development were identified. They were relevant to shape strategies fostering 4P Medicine for chronic patients. The concept of Digital Health Framework and the proposed roadmap for its deployment constituted relevant project outcomes

Oxygen pathway modeling estimates high Reactive oxygen species production above the highest permanent human habitation.

The production of reactive oxygen species (ROS) from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po2 (). Because depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering

ChainRank, a chain prioritisation method for contextualisation of biological networks

Advances in high throughput technologies and growth of biomedical knowledge have contributed to an exponential increase in associative data. These data can be represented in the form of complex networks of biological associations, which are suitable for systems analyses. However, these networks usually lack both, context specificity in time and space as well as the distinctive borders, which are usually assigned in the classical pathway view of molecular events (e.g. signal transduction). This complexity and high interconnectedness call for automated techniques that can identify smaller targeted subnetworks specific to a given research context (e.g. a disease scenario)

Effect of the anisotropy on the glory structure of molecule-molecule scattering cross sections

Total (elastic + rotationally inelastic) integral cross sections are computed for O$_2(^3\Sigma_g^-)$-O$_2(^3\Sigma_g^-)$ using a recent ab initio potential energy surface. The sampled velocity range allows us a thorough comparison of the glory interference pattern observed in molecular beam experiments. The computed cross sections are about 10% smaller than the measured ones, however, a remarkable agreement in the velocity positions of the glory extrema is achieved. By comparing with models where the anisotropy of the interaction is reduced or removed, it is found that the glory pattern is very sensitive to the anisotropy, especially the positions of the glory extrema.Comment: 13 pages, 3 figure

The COPD Knowledge Base: enabling data analysis and computational simulation in translational COPD research

Background Previously we generated a chronic obstructive pulmonary disease (COPD) specific knowledge base (http://www.copdknowledgebase.eu) from clinical and experimental data, text-mining results and public databases. This knowledge base allowed the retrieval of specific molecular networks together with integrated clinical and experimental data. Results The COPDKB has now been extended to integrate over 40 public data sources on functional interaction (e.g. signal transduction, transcriptional regulation, protein-protein interaction, gene-disease association). In addition we integrated COPD-specific expression and co-morbidity networks connecting over 6 000 genes/proteins with physiological parameters and disease states. Three mathematical models describing different aspects of systemic effects of COPD were connected to clinical and experimental data. We have completely redesigned the technical architecture of the user interface and now provide html and web browser-based access and form-based searches. A network search enables the use of interconnecting information and the generation of disease-specific sub-networks from general knowledge. Integration with the Synergy-COPD Simulation Environment enables multi-scale integrated simulation of individual computational models while integration with a Clinical Decision Support System allows delivery into clinical practice. Conclusions The COPD Knowledge Base is the only publicly available knowledge resource dedicated to COPD and combining genetic information with molecular, physiological and clinical data as well as mathematical modelling. Its integrated analysis functions provide overviews about clinical trends and connections while its semantically mapped content enables complex analysis approaches. We plan to further extend the COPDKB by offering it as a repository to publish and semantically integrate data from relevant clinical trials. The COPDKB is freely available after registration at http://www.copdknowledgebase.eu

Biomedical research in a digital health framework

This article describes a Digital Health Framework (DHF), benefitting from the lessons learnt during the three-year life span of the FP7 Synergy-COPD project. The DHF aims to embrace the emerging requirements--data and tools--of applying systems medicine into healthcare with a three-tier strategy articulating formal healthcare, informal care and biomedical research. Accordingly, it has been constructed based on three key building blocks, namely, novel integrated care services with the support of information and communication technologies, a personal health folder (PHF) and a biomedical research environment (DHF-research). Details on the functional requirements and necessary components of the DHF-research are extensively presented. Finally, the specifics of the building blocks strategy for deployment of the DHF, as well as the steps toward adoption are analyzed. The proposed architectural solutions and implementation steps constitute a pivotal strategy to foster and enable 4P medicine (Predictive, Preventive, Personalized and Participatory) in practice and should provide a head start to any community and institution currently considering to implement a biomedical research platform

Duration of untreated illness and bipolar disorder: time for a new definition? Results from a cross-sectional study

Background: We primarily aimed to explore the associations between duration of untreated illness (DUI), treatment response, and functioning in a cohort of patients with bipolar disorder (BD). Methods: 261 participants with BD were recruited. DUI was defined as months from the first affective episode to the start of a mood-stabilizer. The functioning assessment short test (FAST) scores and treatment response scores for lithium, valproate, or lamotrigine according to the Alda Scale Total Score (TS) were compared between patients with short (<24 months) or long DUI. Differences in FAST scores among good (GR; TS≥7), poor (PR; TS=2-6), or non-responders (NR; TS<2) to each mood-stabilizer were analyzed. Linear regression was computed using the FAST global score as the dependent variable. Results: DUI and FAST scores showed no statistically significant correlation. Patients with a longer DUI showed poorer response to lithium (Z=-3.196; p<0.001), but not to valproate or lamotrigine. Response to lithium (β=-1.814; p<0.001), number of hospitalizations (β=0.237; p<0.001), and illness duration (β=0.160; p=0.028) were associated with FAST total scores. GR to lithium was associated with better global functioning compared to PR or NR [H=27.631; p<0.001]. Limitations: The retrospective design could expose our data to a recall bias. Also, only few patients were on valproate or lamotrigine treatment. Conclusions: Poor functioning in BD could be the result of multiple affective relapses, rather than a direct effect of DUI. A timely diagnosis with subsequent effective prophylactic treatment, such as lithium, may prevent poor functional outcomes in real-world patients with BD