Stable isotope metabolomics of pulmonary artery smooth muscle and endothelial cells in pulmonary hypertension and with TGF-beta treatment.

Altered metabolism in pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) contributes to the pathology of pulmonary hypertension (PH), but changes in substrate uptake and how substrates are utilized have not been fully characterized. We hypothesized stable isotope metabolomics would identify increased glucose, glutamine and fatty acid uptake and utilization in human PASMCs and PAECs from PH versus control specimens, and that TGF-β treatment would phenocopy these metabolic changes. We used 13C-labeled glucose, glutamine or a long-chain fatty acid mixture added to cell culture media, and mass spectrometry-based metabolomics to detect and quantify 13C-labeled metabolites. We found PH PASMCs had increased glucose uptake and utilization by glycolysis and the pentose shunt, but no changes in glutamine or fatty acid uptake or utilization. Diseased PAECs had increased proximate glycolysis pathway intermediates, less pentose shunt flux, increased anaplerosis from glutamine, and decreased fatty acid β-oxidation. TGF-β treatment increased glycolysis in PASMCs, but did not recapitulate the PAEC disease phenotype. In TGF-β-treated PASMCs, glucose, glutamine and fatty acids all contributed carbons to the TCA cycle. In conclusion, PASMCs and PAECs collected from PH subjects have significant changes in metabolite uptake and utilization, partially recapitulated by TGF-β treatment

Factors associated with prelacteal feeding practices in Debre Berhan district, North Shoa, Central Ethiopia: a cross-sectional, community-based study

Abstract Background Prelacteal feeding is one of the major harmful newborn feeding practices and is top on the list of global public health concerns. The practice deprives newborns of valuable nutrients and protection of colostrum and exposes them to preventable morbidity and mortality. Studying the prevalence and factors influencing the prelacteal feeding practice of mothers will help program managers and implementers to properly address broad major public health problems. Therefore, this study aims to investigate the prevalence of prelacteal feeding practices and its associated factors among mother-infant dyads in the Debre Berhan district of North Shoa administrative zone, central Ethiopia. Methods A community-based cross-sectional study design was conducted from January through to April 2014 among 634 mother-infant dyads. The data were entered into EPI Info version 3.5.1. (CDC, Atlanta, Georgia). All statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) research IBM version 20.0. The prevalence of prelacteal feeding was determined using the ‘recall since birth’ method. Multi-variable logistic regression analysis was employed to control confounders in determining the association between prelacteal feeding practices and selected independent variables. Adjusted Odds Ratio (AOR), with 95% Confidence Interval (CI) and P < 0.05 was used to claim statistical significance. Results The prevalence of prelacteal feeding practice was 14.2% (95% CI: 11.00–17.00%). Slightly greater than half, 48 (53.3%) of prelacteal fed newborns were given butter. Home delivery was a major risk factor for practicing prelacteal feeding. Mothers who delivered their indexed infant at home practiced prelacteal feeding over four folds more than mothers who delivered in a health institution (Adjusted Odds Ratio (AOR) 4.70; 95% CI: 2.56–8.60, p-value = 0.001). Mothers who did not initiate breastfeeding within an hour were six times more likely to practice prelacteal feeding (AOR 5.58; 3.21–9.46, p-value = 0.001). Similarly, with regards to the occupation of mothers, farmers practiced prelacteal feedings (AOR 4.33; 95% CI: 1.73–10.81, p-value = 0.002) up to four folds more than their counterpart housewives. Mothers who can read and write are 54% less likely to practice prelacteal feeding than their counterpart, illiterate mothers, with (AOR 0.46; 95% CI: 0.22–0.98, p-value = 0.044). Conclusions In the Debre Berhan town of North Shoa administrative zone, central Ethiopia, almost one-sixth of mothers practiced prelacteal feeding. Therefore, improving access to information about appropriate newborn feeding practices, encouraging mothers to deliver their babies in health institutions and inspiring them to initiate breastfeeding within an hour of birth is recommended

The major Ethiopian milksheds : an assessment of development potential

The development potential of 8 milksheds in Ethiopia was assessed and ranked for potential for value chain development, as part of the MIDD project. Major criteria for ranking were market potential, production potential, presence of services, and commercialization level of the value chain. Highest ranking milk sheds were Addis Abeba, Adama-Asella, and Bahir Dar–Gondar milksheds

In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Central Ethiopia

<p>Abstract</p> <p>Background</p> <p><it>In vivo </it>efficacy assessments of the first-line treatments for <it>Plasmodium falciparum </it>malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated <it>P. falciparum </it>malaria since 2004.</p> <p>Methods</p> <p>Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for <it>P. falciparum </it>in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented <it>P. falciparum </it>mono-infection were enrolled and followed according to the standard 2009 World Health Organization <it>in vivo </it>drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively.</p> <p>Results</p> <p>Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight <it>P. falciparum </it>patients (6.7%) presented with <it>Plasmodium vivax </it>infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events.</p> <p>Conclusions</p> <p>AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with <it>P. vivax </it>possibly from relapse or new infection was observed.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01052584">NCT01052584</a></p

Multiple post-domestication origins of kabuli chickpea through allelic variation in a diversification-associated transcription factor

Chickpea (Cicer arietinum) is among the founder crops domesticated in the Fertile Crescent. One of two major forms of chickpea, the so-called kabuli type, has white flowers and light-colored seed coats, properties not known to exist in the wild progenitor. The origin of the kabuli form has been enigmatic. We genotyped a collection of wild and cultivated chickpea genotypes with 538 single nucleotide polymorphisms (SNPs) and examined patterns of molecular diversity relative to geographical sources and market types. In addition, we examined sequence and expression variation in candidate anthocyanin biosynthetic pathway genes. A reduction in genetic diversity and extensive genetic admixture distinguish cultivated chickpea from its wild progenitor species. Among germplasm, the kabuli form is polyphyletic. We identified a basic helix-loop-helix (bHLH) transcription factor at chickpea\u27s B locus that conditions flower and seed colors, orthologous to Mendel\u27s A gene of garden pea, whose loss of function is associated invariantly with the kabuli type of chickpea. From the polyphyletic distribution of the kabuli form in germplasm, an absence of nested variation within the bHLH gene and invariant association of loss of function of bHLH among the kabuli type, we conclude that the kabuli form arose multiple times during the phase of phenotypic diversification after initial domestication of cultivated chickpea

Etiological spectrum and treatment outcome of Obstructive jaundice at a University teaching Hospital in northwestern Tanzania: A diagnostic and therapeutic challenges

Obstructive jaundice poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was undertaken to highlight the etiological spectrum, treatment outcome of obstructive jaundice in our setting and to identify prognostic factors for morbidity and mortality. This was a descriptive prospective study which was conducted at Bugando Medical Centre between July 2006 and June 2010. All patients with a clinical diagnosis of obstructive jaundice were, after informed consent for the study, consecutively enrolled into the study. Data were collected using a pre-tested structured questionnaire and analyzed using SPSS computer software version 11.5. A total of 116 patients were studied. Females outnumbered males by a ratio of 1.3:1. Patients with malignant obstructive jaundice were older than those of benign type. Ca head of pancreas was the commonest malignant cause of jaundice where as choledocholithiasis was the commonest benign cause. Abdominal ultrasound was the only diagnostic imaging done in all patients and revealed dilated intra and extra-hepatic ducts, common bile stones and abdominal masses in 56.2%, 78.9%, 58.1% and 72.4% of the cases respectively. A total of 110 (94.8%) patients underwent surgical treatment and the remaining 6 (5.2%) patients were unfit for surgery. The complication rate was 22.4% mainly surgical site infections. The mean hospital stay and mortality rate were 14.54 days and 15.5% respectively. A low haematocrit and presence of postoperative sepsis were the main predictors of the hospital stay (P < 0.001), whereas age > 60 years, prolonged duration of jaundice, malignant causes and presence of postoperative complications mainly sepsis significantly predicted mortality (P < 0.001). Obstructive jaundice in our setting is more prevalent in females and the cause is mostly malignant. The result of this study suggests that early diagnosis and treatment plays an important role in the prognosis of patients with obstructive jaundice