Epigenomes in Cardiovascular Disease.

If unifying principles could be revealed for how the same genome encodes different eukaryotic cells and for how genetic variability and environmental input are integrated to impact cardiovascular health, grand challenges in basic cell biology and translational medicine may succumb to experimental dissection. A rich body of work in model systems has implicated chromatin-modifying enzymes, DNA methylation, noncoding RNAs, and other transcriptome-shaping factors in adult health and in the development, progression, and mitigation of cardiovascular disease. Meanwhile, deployment of epigenomic tools, powered by next-generation sequencing technologies in cardiovascular models and human populations, has enabled description of epigenomic landscapes underpinning cellular function in the cardiovascular system. This essay aims to unpack the conceptual framework in which epigenomes are studied and to stimulate discussion on how principles of chromatin function may inform investigations of cardiovascular disease and the development of new therapies

Effects of Credit Utilization on Youth Farmers’ Rice Output in Patigi Local Government Area of Kwara State, Nigeria

The study examined the effects of credit utilization on the output of the youth rice farmers in Nigeria. It also examined the sources of information on credit available to the farmers; the use of the credit and the problems encountered by the farmers in having access to credit. Primary data was used for the study. Descriptive statistics was used to analyze the data collected for the study. Results of the findings showed that “past experience" is the major source of information on credit used by the farmers, though the farmers prefer cooperative societies to every other source of credit information. Banks, cooperative societies and Esusu/saving groups are the major sources of credit to the farmers. The mean amount of credit obtained by the farmers is N132, 301. The most of the farmers spent their credits on fertilizers, seeds and farmland expansion. The major problems faced by the farmers in accessing credit are: insufficient amount, lack of collateral and high interest rates. However, the general effect of credit utilization by the farmers is increased output. It is therefore recommended that banks are situated in the study area and they should disburse sufficient loans to the farmers at affordable interest rates. The farmers should also form cooperative and savings groups in order to enjoy economies of scale in accessing credit facilities

A hybrid intelligent agent for notification of users distracted by mobile phones in an urban environment

Mobile devices are now ubiquitous in daily life and the number of activities that can be performed using them is continually growing. This implies increased attention being placed on the device and diverted away from events taking place in the surrounding environment. The impact of using a smartphone on pedestrians in the vicinity of urban traffic has been investigated in a multimodal, fully immersive, virtual reality environment. Based on experimental data collected, an agent to improve the attention of users in such situations has been developed. The proposed agent uses explicit, contextual data from experimental conditions to feed a statistical learning model. The agent’s decision process is aimed at notifying users when they become unaware of critical events in their surroundings

Disability in multiple sclerosis is related to thalamic connectivity and cortical network atrophy.

BACKGROUND: Thalamic atrophy is proposed to be a major predictor of disability progression in multiple sclerosis (MS), while thalamic function remains understudied. OBJECTIVES: To study how thalamic functional connectivity (FC) is related to disability and thalamic or cortical network atrophy in two large MS cohorts. METHODS: Structural and resting-state functional magnetic resonance imaging (fMRI) was obtained in 673 subjects from Amsterdam (MS: N = 332, healthy controls (HC): N = 96) and Graz (MS: N = 180, HC: N = 65) with comparable protocols, including disability measurements in MS (Expanded Disability Status Scale, EDSS). Atrophy was measured for the thalamus and seven well-recognized resting-state networks. Static and dynamic thalamic FC with these networks was correlated with disability. Significant correlates were included in a backward multivariate regression model. RESULTS: Disability was most strongly related (adjusted R2 = 0.57, p < 0.001) to higher age, a progressive phenotype, thalamic atrophy and increased static thalamic FC with the sensorimotor network (SMN). Static thalamus-SMN FC was significantly higher in patients with high disability (EDSS ⩾ 4) and related to network atrophy but not thalamic atrophy or lesion volumes. CONCLUSION: The severity of disability in MS was related to increased static thalamic FC with the SMN. Thalamic FC changes were only related to cortical network atrophy, but not to thalamic atrophy

Spondarthritis in the Triassic

Background: The evidence of several forms of arthritis has been well documented in the fossil record. However, for pre-Cenozoic vertebrates, especially regarding reptiles, this record is rather scarce. In this work we present a case report of spondarthritis found in a vertebral series that belonged to a carnivorous archosaurian reptile from the Lower Triassic (,245 million years old) of the South African Karoo. Methodology/Principal Findings: Neutron tomography confirmed macroscopic data, revealing the ossification of the entire intervertebral disc space (both annulus fibrosus and nucleus pulposus), which supports the diagnosis of spondarthritis. Conclusions/Significance: The presence of spondarthritis in the new specimen represents by far the earliest evidence of any form of arthritis in the fossil record. The present find is nearly 100 million years older than the previous oldest report of this pathology, based on a Late Jurassic dinosaur. Spondarthritis may have indirectly contributed to the death of the anima

Error, reproducibility and sensitivity : a pipeline for data processing of Agilent oligonucleotide expression arrays

Background Expression microarrays are increasingly used to obtain large scale transcriptomic information on a wide range of biological samples. Nevertheless, there is still much debate on the best ways to process data, to design experiments and analyse the output. Furthermore, many of the more sophisticated mathematical approaches to data analysis in the literature remain inaccessible to much of the biological research community. In this study we examine ways of extracting and analysing a large data set obtained using the Agilent long oligonucleotide transcriptomics platform, applied to a set of human macrophage and dendritic cell samples. Results We describe and validate a series of data extraction, transformation and normalisation steps which are implemented via a new R function. Analysis of replicate normalised reference data demonstrate that intrarray variability is small (only around 2% of the mean log signal), while interarray variability from replicate array measurements has a standard deviation (SD) of around 0.5 log2 units ( 6% of mean). The common practise of working with ratios of Cy5/Cy3 signal offers little further improvement in terms of reducing error. Comparison to expression data obtained using Arabidopsis samples demonstrates that the large number of genes in each sample showing a low level of transcription reflect the real complexity of the cellular transcriptome. Multidimensional scaling is used to show that the processed data identifies an underlying structure which reflect some of the key biological variables which define the data set. This structure is robust, allowing reliable comparison of samples collected over a number of years and collected by a variety of operators. Conclusions This study outlines a robust and easily implemented pipeline for extracting, transforming normalising and visualising transcriptomic array data from Agilent expression platform. The analysis is used to obtain quantitative estimates of the SD arising from experimental (non biological) intra- and interarray variability, and for a lower threshold for determining whether an individual gene is expressed. The study provides a reliable basis for further more extensive studies of the systems biology of eukaryotic cells

The quality of maternity care services as experienced by women in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Maternity care is all care in relation to pregnancy, childbirth and the postpartum period. In the Netherlands maternity care is provided by midwives and general practitioners (GPs) in primary care and midwives and gynecologists in secondary care. To be able to interpret women's experience with the quality of maternity care, it is necessary to take into account their 'care path', that is: their route through the care system.</p> <p>In the Netherlands a new tool is being developed to evaluate the quality of care from the perspective of clients. The tool is called: 'Consumer Quality Index' or CQI and is, within a standardized and systematic framework, tailored to specific health care issues.</p> <p>Within the framework of developing a CQI Maternity Care, data were gathered about the care women in the Netherlands received during pregnancy, childbirth, and the postpartum period. In this paper the quality of maternity care in the Netherlands is presented, as experienced by women at different stages of their care path.</p> <p>Methods</p> <p>A sample of 1,248 pregnant clients of four insurance companies, with their due date in early April 2007, received a postal survey in the third trimester of pregnancy (response 793). Responders to the first questionnaire received a second questionnaire twelve weeks later, on average four weeks after delivery (response 632). Based on care provider and place of birth the 'care path' of the women is described. With factor analysis and reliability analysis five composite measures indicating the quality of treatment by the care provider at different stages of the care path have been constructed. Overall ratings relate to eight different aspects of care, varying from antenatal care by a midwife or GP to care related to neonatal screening.</p> <p>Results</p> <p>41.5 percent of respondents remained in primary care throughout pregnancy, labor, birth and the postpartum period, receiving care from a midwife or general practitioner, 31.3% of respondents gave birth at home. The majority of women (58.5%) experienced referral from one care provider to another, i.e. from primary to secondary care or reverse, at least once. All but two percent of women had one or more ultrasound scans during pregnancy. The composite measures for the quality of treatment in different settings and by different care providers showed that women, regardless of parity, were very positive about the quality of the maternity care they received. Quality-of-treatment scores were high: on average 3.75 on a scale ranging from 1 to 4. Overall ratings on a 0 – 10 scale for quality of care during the antenatal period and during labor, birth and the postpartum period were high as well, on average 8.36.</p> <p>Conclusion</p> <p>The care path of women in maternity care was seldom straight forward. The majority of pregnant women switched from primary to secondary care and back at least once, during pregnancy or during labor and birth or both.</p> <p>The results of the quality measures indicate that the quality of care as experienced by women is high throughout the care system. But with regard to the care during labor and birth the quality of care scores are higher when women know their care provider, when they give birth at home, when they give birth in primary care and when they are assisted by their own midwife.</p

HIV Infection Is Associated with a Lower Incidence of Constriction in Presumed Tuberculous Pericarditis: A Prospective Observational Study

The original publication is available at http:/www.plosone.orgBackground: Pericardial constriction is a serious complication of tuberculous pericardial effusion that occurs in up to a quarter of patients despite anti-tuberculosis chemotheraphy. The impact of human immunodeficiency virus (HIV) infection on the incidence of constrictive pericarditis following tuberculous pericardial effusion is unknown. Methods and Results: We conducted a prospective observational study to determine the association between HIV infection and the incidence of constrictive pericarditis among 185 patients (median age 33 years) with suspected tuberculous pericardial effusion. These patients were recruited consecutively between March and October 2004 on commencement of anti-tuberculosis treatment, from 15 hospitals in Cameroon, Nigeria and South Africa. Surviving patients (N = 119) were assessed for clinical evidence of constrictive pericarditis at 3 and 6 months of follow-up. Clinical features of HIV infection were present in 42 (35.2%) of the 119 patients at enrolment into the study.66 of the 119 (56.9%) patients consented to HIV testing at enrolment. During the 6 months of follow-up, a clinical diagnosis of constrictive pericarditis was made in 13 of the 119 patients (10.9%, 95% confidence interval [CI] 5.9-18%). Patients with clinical features of HIV infection appear less likely to develop constriction than those without (4.8% versus 14.3%; P = 0.08). None of the 33 HIV seropositive patients developed constriction, but 8 (24.2%, 95%CI 11.1-42.3%)of the 33 HIV seronegative patients did (P = 0.005). In a multivariate logistic regression model adjusting simultaneously for several baseline characteristics, only clinical signs of HIV infection were significantly associated with a lower risk of constriction (odd ratio 0.14, 95% CI 0.02-0.87, P = 0.035). Conclusions: These data suggest that HIV infection is associated with a lower incidence of pericardial constriction in patients with presumed tuberculous pericarditis. © 2008 Ntsekhe et al.This study was funded, in part, through research grants from the University of Cape Town, the Medical Scholarships for South African Blacks (MESAB), the Medical Research Council of South Africa, the National Research Foundation of South Africa.Publishers' versio

Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes.

Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n = 12) and healthy individuals (n = 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p < 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.Peer reviewedFinal Published versio