Biological and clinical abnormalities leading to cardiovascular disease during antiretroviral treatment in a university hospital in Abidjan

Antiretroviral drugs are involved in the occurrence of adverse effects. In Côte d'Ivoire, HIV1 treatment protocols are non-nucleoside reverse transcriptase inhibitors based. No study has been undertaken in the country about cardiovascular risk. Thus, the objective of our study was to assess the prevalence of biological abnormalities and clinical markers of cardiovascular risk during antiretroviral therapy. We conducted a prospective cross-sectional study with 238 patients who were on antiretroviral treatment including nonnucleoside reverse transcriptase inhibitors for at least 6 months in the Pneumophtisiology department of the university hospital of Cocody (Abidjan). Metabolic syndrome was determined according to NCEP-ATP III criteria. Biological parameters investigated were: triglyceride, HDL cholesterol and LDL, glucose and clinical parameters: blood pressure and waist circumference. Eleven patients (4.62%) have a metabolic syndrome, 17.6% had hypertriglyceridemia. An increase in LDL cholesterol and lower HDL-cholesterol were found in both cases in 13.9% of patients and an atherogenic index greater than 4.5 in 5% of patients. Hyperglycemia occurred during antiretroviral therapy in 28% of the study population. Patients who developed hypertension and increased waist circumference during antiretroviral therapy were 9.75% and 15.5% respectively. Our results testify to the potential existence of a cardiovascular risk during the non-nucleoside inhibitor used.© 2015 International Formulae Group. All rights reserved.Keywords: Antiretrovirals, biological, clinical abnormalities, cardiovascular risk

Characterization and Analysis of Anthocyanin-Related Genes in Wild-Type Blueberry and the Pink-Fruited Mutant Cultivar ‘Pink Lemonade’: New Insights into Anthocyanin Biosynthesis

Blueberries are one of the richest sources of antioxidants, such as anthocyanins, among fruits and vegetables. Anthocyanin mutants, like the pink-fruited cultivar ‘Pink Lemonade’, are valuable resources for investigating anthocyanin biosynthesis in blueberries. In this study, we examined expression of flavonoid pathway genes during fruit development in wild-type, blue-fruited blueberries using quantitative real-time PCR. Expression was also compared between wild-type and the pink-fruited ‘Pink Lemonade’. This revealed significantly lower expression in ‘Pink Lemonade’ than in wild-type of nearly all the structural genes examined suggesting that a transcriptional regulator of the pathway was affected. Hence, we compared expression of three known regulatory genes and found that the gene encoding the transcription factor MYB1 was expressed at a significantly lower level in ‘Pink Lemonade’ than in the wild-type. To validate the capacity of this MYB1 to regulate the transcription of anthocyanin genes in blueberries, a transient expression assay was conducted. Results indicated MYB1 overexpression enhanced anthocyanin production. Comparative sequence analysis between wild-type and mutant MYB1 variants found differences in highly conserved features suggesting a mechanistic explanation for the mutant phenotype. Collectively, the results presented here contribute to a better understanding of mechanisms regulating anthocyanin biosynthesis in Vaccinium

RNA-seq combined with a bulked-segregant analysis identifies candidate genes for the waxy coating on blueberry fruit

The most significant difference between blueberries with a light blue fruit color and black fruit color is the visible layer of an epicuticular waxy coating. This layer functions in disease defense and prevention of water loss. In this study, we constructed a northern-adapted rabbiteye hybrid breeding population, ‘Nocturne’ x T 300, which segregated for fruit color (light blue versus black). We screened this population and selected plants of each extreme phenotype, waxy- coated plants with light blue colored fruit versus non-waxy plants with black colored fruit, then isolated RNA from fruit tissue of each bulk, respectively. We sequenced the transcriptome of each bulk using RNA-seq, which resulted in a total of 167,093,354 reads for both libraries combined. We de novo assembled this data set into 171,678 contigs and used the assembled transcriptome as a reference for differential expression analysis using EdgeR. A total of 515 differentially expressed genes were identified with at least a four-fold difference in expression, and efforts were made to functionally annotate them using publicly available databases. From these, one excellent candidate ‘waxy’ gene has emerged, which we are investigating further

Reply to Oliver W Quarrell et al.:"Letter in response to Tibben et al., Risk Assessment for Huntington's Disease for (Future) Offspring Requires Offering Preconceptional CAG Analysis to Both Partners"

Genetics of disease, diagnosis and treatmen

Risk Assessment for Huntington's Disease for (Future) Offspring Requires Offering Preconceptional CAG Analysis to Both Partners

Amongst the main reasons people at risk for Huntington's disease (HD) have for undergoing predictive genetic testing are planning a family and prevention of passing on an expanded CAG-repeat to future offspring. After having received an unfavourable test result, a couple may consider prenatal testing in the foetus or preimplantation genetic diagnostic testing (PGD) in embryos. Testing of the foetus or embryos is possible by means of direct testing of the expanded repeat. Optimal reliability in testing the foetus or embryos requires the establishment of the origin of the repeats of both parents in the foetus. For PGD the analysis is combined with or sometimes solely based on identification of the at-risk haplotype in the embryo. This policy implies that in the context of direct testing, the healthy partner's CAG repeat lengths in the HD gene are also tested, but with the expectation that the repeat lengths of the partner are within the normal range, with the proviso that the partner's pedigree is free of clinically confirmed HD. However, recent studies have shown that the expanded repeat has been observed more often in the general population than previously estimated. Moreover, we have unexpectedly observed an expanded repeat in the non-HD partner in four cases which had far-reaching consequences. Hence, we propose that in the context of reproductive genetic counselling, prior to a planned pregnancy, and irrespective of the outcome of the predictive test in the HD-partner, the non-HD partner should also be given the option of being tested on the expanded allele. International recommendations for predictive testing for HD should be adjusted.Genetics of disease, diagnosis and treatmen

Pulmonary Sarcoidosis

Background: A 34-year-old male teacher was referred to the hospital with a persisting dry cough and dyspnea on exercise since eight weeks. He had no fever, neither complaints of ear, nose or throat. There were no complaints during the night. He had been a smoker until four months before presentation (12 pack years). At work a student was diagnosed with pulmonary tuberculosis, but the Mantoux and Quantiferon tests were negative. Physical examination was normal, without fever, lymphadenopathy or auscultation abnormalities. Laboratory investigation revealed a C-reactive protein of 2 mg/L. Pulmonary function testing showed a slight restriction. Immunological bronchial alveolar lavage (BAL) was rich of cells, especially T-lymphocytes of the CD4 type. CD4+/CD8+ ratio of the BAL was raised to 4.2, compared to a ratio of 2.4 in blood. There were no eosinophils found in the BAL. Conventional chest radiographs were performed, and showed multiple areas of consolidation in the bilateral lung fields, predominantly on the right side

Changes in drug sensitivity and anti-malarial drug resistance mutations over time among Plasmodium falciparum parasites in Senegal

Background: Malaria treatment efforts are hindered by the rapid emergence and spread of drug resistant parasites. Simple assays to monitor parasite drug response in direct patient samples (ex vivo) can detect drug resistance before it becomes clinically apparent, and can inform changes in treatment policy to prevent the spread of resistance. Methods: Parasite drug responses to amodiaquine, artemisinin, chloroquine and mefloquine were tested in approximately 400 Plasmodium falciparum malaria infections in Thiès, Senegal between 2008 and 2011 using a DAPI-based ex vivo drug resistance assay. Drug resistance-associated mutations were also genotyped in pfcrt and pfmdr1. Results: Parasite drug responses changed between 2008 and 2011, as parasites became less sensitive to amodiaquine, artemisinin and chloroquine over time. The prevalence of known resistance-associated mutations also changed over time. Decreased amodiaquine sensitivity was associated with sustained, highly prevalent mutations in pfcrt, and one mutation in pfmdr1 – Y184F – was associated with decreased parasite sensitivity to artemisinin. Conclusions: Directly measuring ex vivo parasite drug response and resistance mutation genotyping over time are useful tools for monitoring parasite drug responses in field samples. Furthermore, these data suggest that the use of amodiaquine and artemisinin derivatives in combination therapies is selecting for increased drug tolerance within this population

Fiskalische Kosten einer steuerlichen Förderung von Forschung und Entwicklung in Deutschland - Eine empirische Analyse verschiedener Gestaltungsoptionen

Der Beitrag berechnet die Aufkommensausfälle verschiedener Gestaltungsmodelle für eine steuerliche Forschungsförderung in Deutschland auf Basis eines Mikrosimulationsmodells. Die fiskalischen Kosten betragen zwischen 464 Mio. € und 5.701 Mio. €. Eine Erstattungsoption der Steuergutschrift über die Gewerbe- und Körperschaftsteuerschuld hinaus ist unerlässlich, da sonst etwa ein Drittel der Unternehmen nicht oder nur teilweise in den Genuss der Förderung kommen würde und sich dadurch starke Verzerrungen zwischen ertragsstarken und ertragsschwachen Unternehmen ergeben. Eine Differenzierung der Fördersätze für KMU und große Unternehmen kann die Aufkommensausfälle wirksam begrenzen. Eine Kappungsgrenze in Höhe eines absoluten Betrages ist wegen der Verzerrungen innerhalb der Gruppe großer Unternehmen ungünstig. Als besonders pragmatisch erscheint eine Verrechnung der Steuergutschrift mit der abzuführenden Lohnsteuer

The Center for Independent Experts: The National External Peer Review Program of NOAA's National Marine Fisheries Service

Requirements are growing for peer review of the science used for governmental management decisions. This is particularly true for fisheries science, where management decisions are often controversial. The National Oceanic and Atmospheric Administration's National Marine Fisheries Service instituted the Center for Independent Experts (CIE) in 1998 as a national peer-review program. Operations of the CIE, run under a contract with the University of Miami, maintain the independence of reviewers from the agency, and follow strict conflict of interest guidelines. Reviews by the CIE fulfill the requirements of the Information Quality Act and the Office of Management and Budget's Peer Review Bulletin. The CIE completed 101 reviews between 1999 and September 2006. Ninety-eight reviewers have participated in CIE reviews, with 72% of them coming from overseas. Case studies involving groundfish data and stock assessments, and marine-mammal abundance, are described, including the scientific issues, CIE operations, requirements for the reviews, conclusions of the reviewers, and the agency's responses. Impacts of the CIE on the agency's science include improvements to regional stock assessment processes and to stock-assessment and field-survey methods, and reductions in contentious challenges to the agency's science.Keywords: Experts, Peer Review, Fishery Managemen