Increased dolutegravir peak concentrations in people living with HIV aged 60 and over and analysis of sleep quality and cognition

Background Demographic data show an increasingly aging HIV population worldwide. Recent concerns over dolutegravir-related neuropsychiatric toxicity have emerged, particularly amongst older HIV patients. We describe the pharmacokinetics (PK) of dolutegravir (DTG) 50mg once daily in people living with HIV (PLWH) aged 60 and older. Additionally, to address the call for prospective neuropsychiatric toxicodynamic data, we evaluate changes in sleep quality and cognitive function after switching to abacavir (ABC)/lamivudine (3TC)/DTG, over 6 months in this population. Methods PLWH aged≥60years with HIV-RNA<50copies/mL on any non-DTG based antiretroviral combination were switched to ABC/3TC/DTG. On day 28, 24-hour PK sampling was undertaken. Steady-state PK parameters were compared to a published historical control population aged≤50years. Six validated sleep questionnaires and neurocognitive (Cogstate®) testing were administered pre-switch and over 180 days (NCT02509195). Results Forty-three participants were enrolled; 40 completed the PK phase. Overall, five discontinued (two due adverse events, both sleep related, 4.6%). DTG maximum concentration (Cmax) was significantly higher in patients≥60 versus controls (GM 4246ng/mL versus 3402ng/mL, p=0.005). In those who completed day 180 (n=38), sleep impairment was higher at day 28 (PSQI median global score 5.0 versus 6.0 p=0.02) but not at day 90 or 180. Insomnia, daytime function, fatigue test scores did not change statistically over time. Conclusion DTG Cmax was significantly higher in older PLWH. Our data provides clinicians with key information on the safety of prescribing DTG in older PLWH

Analycity and smoothing effect for the coupled system of equations of Korteweg - de Vries type with a single point singularity

We study that a solution of the initial value problem associated for the coupled system of equations of Korteweg - de Vries type which appears as a model to describe the strong interaction of weakly nonlinear long waves, has analyticity in time and smoothing effect up to real analyticity if the initial data only has a single point singularity at $x=0.

CARGO: a web portal to integrate customized biological information

There is a huge quantity of information generated in Life Sciences, and it is dispersed in many databases and repositories. Despite the broad availability of the information, there is a great demand for methods that are able to look for, gather and display distributed data in a standardized and friendly way. CARGO (Cancer And Related Genes Online) is a configurable biological web portal designed as a tool to facilitate, integrate and visualize results from Internet resources, independently of their native format or access method. Through the use of small agents, called widgets, supported by a Rich Internet Application (RIA) paradigm based on AJAX, CARGO provides pieces of minimal, relevant and descriptive biological information. The tool is designed to be used by experimental biologists with no training in bioinformatics. In the current state, the system presents a list of human cancer genes. Available at http://cargo.bioinfo.cnio.e

Detección de los herpesvirus equinos 1 y 4 y su relación con transcriptos asociados a la latencia en caballos infectados naturalmente en Colombia

Objetivo. El objetivo de este estudio fue determinar presencia de anticuerpos y genoma viral de EHV-1 y EHV-4, como también detectar la presencia de transcriptos asociados a latencia (LATs) en una población seleccionada de caballos colombianos. Materiales y métodos. Muestras de suero, nódulos linfáticos submandibulares y ganglio trigémino se obtuvieron de 50 caballos y fueron analizadas. Los sueros se evaluaron para la presencia de anticuerpos contra EHV-1 y EHV-4 mientras que los tejidos se evaluaron inicialmente para la presencia de genoma viral por nPCR. Finalmente, las muestras se emplearon para la detección de LATs a través de RT-PCR. Resultados. En general, 6/50 muestras mostraron anticuerpos para EHV-1 y 44/50 fueron positivos para EHV-4. En cuanto a la detección del genoma viral, 10/50 muestras fueron positivas para EHV-1 y 30/50 fueron positivas para EHV-4; además, 22/35 caballos positivos para DNA de EHV fueron positivos para LATs. El empleo de estas pruebas llevó a ocho posibles combinaciones de resultados. Conclusiones. Se confirma la presencia de estos virus en la población equina colombiana. Las pruebas empleadas demuestran que los caballos pueden tener infección viral simple, co-infecciones con ambos virus, estado de latencia debido a la presencia de los LATs y presencia simultánea de LATs y de replicación de genoma viral en un momento dado. Se aporta al entendimiento del comportamiento de la enfermedad en Colombia y se llama la atención sobre la importancia de implementar diagnósticos complementarios a la serología para el control de estos virus

The respiratory research agenda in primary care in Portugal: a Delphi study

Background: A research agenda can help to stimulate and guide research. The International Primary Care Respiratory Group (IPCRG) published a Research Needs Statement (RNS) in 2010 in which 145 research questions were identified. In 2012, priorities for respiratory research were established, based on these questions. To date, there has been no statement on primary care respiratory research needs in Portugal. The aim of the study was to develop a national consensus on research priorities in respiratory diseases in primary care in Portugal and to assess the applicability of the priorities for respiratory research set by the IPCRG. Method: We conducted a Delphi study by electronic mail with a panel of experts on respiratory disease from primary and secondary care in Portugal. In the first round, the research needs in respiratory disease in Portugal were identified. In the second round, 196 research questions in six disease areas, derived from the first round and from the IPCRG Respiratory needs statement, were prioritised on a five-point Likert-type scale. In the third round, the questions were prioritized again with feed-back provided on the median scores for each item in the second round. Consensus was considered to have been reached when 80 % of the participants gave a score of 4 or 5 out of five on a given item. Results: The 40 experts identified 121 respiratory research questions in Round 1 and expressed their views on 196 questions in Rounds 2 and 3. Twelve research questions (6 %) reached consensus. There were five questions in the asthma domain on early diagnosis, pulmonary function tests, the use of inhalers, and adherence to treatment. There were four questions in the chronic obstructive pulmonary disease domain on vaccinations, on routine monitoring and evaluation of treatment, on diagnosis, and on adherence to treatments. There was one question in the smoking domain on the effects of brief counselling. There were two questions on respiratory tract infections on the treatment of children and on the prescription of antibiotics. An additional 23 research questions (12 %) achieved consensus between 75 and 79 %. Conclusion: The results reflect the Portuguese reality in response the international agenda for research on respiratory diseases published by the IPCRG. They can support the development of future respiratory disease research in Portugal.Financial support for this work was provided by FEDER funds through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT - Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). PMT is partially supported by a grant from the International Primary Care Respiratory Group

A sweetpotato gene index established by de novo assembly of pyrosequencing and Sanger sequences and mining for gene-based microsatellite markers

<p>Abstract</p> <p>Background</p> <p>Sweetpotato (<it>Ipomoea batatas </it>(L.) Lam.), a hexaploid outcrossing crop, is an important staple and food security crop in developing countries in Africa and Asia. The availability of genomic resources for sweetpotato is in striking contrast to its importance for human nutrition. Previously existing sequence data were restricted to around 22,000 expressed sequence tag (EST) sequences and ~ 1,500 GenBank sequences. We have used 454 pyrosequencing to augment the available gene sequence information to enhance functional genomics and marker design for this plant species.</p> <p>Results</p> <p>Two quarter 454 pyrosequencing runs used two normalized cDNA collections from stems and leaves from drought-stressed sweetpotato clone <it>Tanzania </it>and yielded 524,209 reads, which were assembled together with 22,094 publically available expressed sequence tags into 31,685 sets of overlapping DNA segments and 34,733 unassembled sequences. Blastx comparisons with the UniRef100 database allowed annotation of 23,957 contigs and 15,342 singletons resulting in 24,657 putatively unique genes. Further, 27,119 sequences had no match to protein sequences of UniRef100database. On the basis of this gene index, we have identified 1,661 gene-based microsatellite sequences, of which 223 were selected for testing and 195 were successfully amplified in a test panel of 6 hexaploid (<it>I. batatas</it>) and 2 diploid (<it>I. trifida</it>) accessions.</p> <p>Conclusions</p> <p>The sweetpotato gene index is a useful source for functionally annotated sweetpotato gene sequences that contains three times more gene sequence information for sweetpotato than previous EST assemblies. A searchable version of the gene index, including a blastn function, is available at <url>http://www.cipotato.org/sweetpotato_gene_index</url>.</p

Natural Distribution of Parasitoids of Larvae of the Fall Armyworm, Spodoptera frugiperda, in Argentina

To develop a better understanding of the natural distribution of the fall armyworm, Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae), and to update the knowledge of the incidence of its complex of parasitoids. S. frugiperda, samplings in whorl-stage corn were carried out in provinces of Argentina from 1999 to 2003. S. frugiperda larvae were collected from corn in localities of the provinces of Tucumán, Salta, Jujuy, Santiago del Estero, La Rioja, Córdoba, San Luis, Chaco and Misiones. In each locality 30 corn plants were sampled and only larvae located in those plants were collected. The parasitoids that emerged from S. frugiperda larvae were identified and counted. The abundance of the parasitoids and the parasitism rate were estimated. The S. frugiperda parasitoids collected were Campoletis grioti (Blanchard) (Hymenoptera: Ichneumonidae), Chelonus insularis (Cresson) (Hymenoptera: Braconidae), Archytas marmoratus (Townsend) (Diptera Tachinidae) and/or A. incertus (Macquart), Ophion sp. (Hymenoptera: Ichneumonidae), Euplectrus platyhypenae Howard (Hymenoptera: Eulophidae), and Incamyia chilensis (Aldrich) (Diptera Tachinidae). C. grioti was the most abundant and frequent during the five-year survey. Similar diversity of parasitoids was obtained in all the provinces, with the exception of I. chilensis and E. platyhypenae that were recovered only in the province of Salta. In the Northwestern region, in Tucumán, C. grioti and species of Archytas were the most abundant and frequent parasitoids. On the contrary, in Salta and Jujuy Ch. insularis was the parasitoid most abundant and frequently recovered. The parasitism rate obtained in Tucumán, Salta and Jujuy provinces were 21.96%, 17.87% and 6.63% respectively with an average of 18.93%. These results demonstrate that hymenopteran and dipteran parasitoids of S. frugiperda occurred differentially throughout the Argentinian provinces and played an important role on the natural control of the S. frugiperda larval population

A prospective cohort study to assess seroprevalence, incidence, knowledge, attitudes and practices, willingness to pay for vaccine and related risk factors in dengue in a high incidence setting

Abstract Background Dengue is one of the most important vector-borne diseases in the world, causing significant morbidity and economic impact. In Colombia, dengue is a major public health problem. Departments of La Guajira, Cesar and Magdalena are dengue endemic areas. The objective of this research is to determine the seroprevalence and the incidence of dengue virus infection in the participating municipalities from these Departments, and also establish the association between individual and housing factors and vector indices with seroprevalence and incidence. We will also assess knowledge, attitudes and practices, and willingness-to-pay for dengue vaccine. Methods A cohort study will be assembled with a clustered multistage sampling in 11 endemic municipalities. Approximately 1000 homes will be visited to enroll people older than one year who living in these areas, who will be followed for 1 year. Dengue virus infections will be evaluated using IgG indirect ELISA and IgM and IgG capture ELISA. Additionally, vector indices will be measured, and adult mosquitoes will be captured with aspirators. Ovitraps will be used for continuous estimation of vector density. Discussion This research will generate necessary knowledge to design and implement strategies with a multidimensional approach that reduce dengue morbidity and mortality in La Guajira and other departments from Colombian Caribbean