Primer reporte de la mutación F1534C asociada con resistencia cruzada a DDT y piretroides en Aedes aegypti en Colombia

Introduction: The main strategy for the control of Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is based on the use of insecticides to reduce its populations. However, their use has led to insect resistance to these chemicals. Objective: To determine the presence of the F1534C mutation associated with cross-resistance to DDT and pyrethroids in A. aegypti in Sincelejo, Colombia. Materials and methods: We studied nine specimens of A. aegypti that showed resistance to lambdacyhalothrin in bioassays developed by the Secretaría de Salud de Sucre. We used a semi-nested PCR as previously described by Harris, et al., to amplify exon 31 of the para gene of the voltage-dependent sodium channel of A. aegypti. We sequenced, edited, and analyzed PCR products with the MEGA 5 software. Results: We detected the wild and mutant alleles of exon 31 in all of the nine mosquitoes tested, and observed the substitution of thymine for guanine in the nucleotide sequence of the mutant allele, producing a change to UGC in the UUC codon, which led to the replacement of phenylalanine by cysteine in residue 1534 of the protein. Conclusion: The nine mosquitoes analyzed presented a heterozygote genotype for the F1534C mutation, whose phenotypic effect is knockdown resistance (kdr) to DDT and pyrethroids.Introducción. La principal estrategia para el control de Aedes aegypti, vector de los virus del dengue, del chikungunya y del zika, se basa en la utilización de insecticidas con el fin de disminuir su población. Sin embargo, su uso ha implicado que el insecto desarrolle resistencia a estos agentes químicos. Objetivo. Determinar la presencia de la mutación F1534C asociada con resistencia cruzada al DDT y los piretroides en mosquitos de la especie A. aegypti en Sincelejo, Colombia. Materiales y métodos. El estudio se desarrolló con nueve ejemplares de A. aegypti que mostraron resistencia a lambdacialotrina en bioensayos desarrollados por la Secretaría de Salud de Sucre. Se utilizó una reacción en cadena de la polimerasa (PCR) semianidada siguiendo la metodología descrita por Harris, et al., para amplificar el exón 31 del gen para del canal de sodio dependiente de voltaje de A. aegypti. Los productos de la PCR se secuenciaron, editaron y analizaron con el programa MEGA 5. Resultados. En todos los mosquitos evaluados se detectó la presencia del alelo silvestre y mutante del exón 31. En la secuencia de nucleótidos del alelo mutante, se observó la sustitución de timina por guanina, la cual produce el cambio del codón UUC por UGC y conlleva el reemplazo del aminoácido fenilalanina por cisteína en el residuo 1534 de la proteína. Conclusión. Los nueve mosquitos analizados presentaron un genotipo heterocigoto para la mutación F1534C, cuyo efecto fenotípico es la resistencia al “derribo” (knock-down resistance, kdr) con DDT y piretroides

Increase of Transmitted Drug Resistance among HIV-Infected Sub-Saharan Africans Residing in Spain in Contrast to the Native Population

BACKGROUND: The prevalence of transmitted HIV drug resistance (TDR) is stabilizing or decreasing in developed countries. However, this trend is not specifically evaluated among immigrants from regions without well-implemented antiretroviral strategies. METHODS: TDR trends during 1996-2010 were analyzed among naïve HIV-infected patients in Spain, considering their origin and other factors. TDR mutations were defined according to the World Health Organization list. RESULTS: Pol sequence was available for 732 HIV-infected patients: 292 native Spanish, 226 sub-Saharan Africans (SSA), 114 Central-South Americans (CSA) and 100 from other regions. Global TDR prevalence was 9.7% (10.6% for Spanish, 8.4% for SSA and 7.9% for CSA). The highest prevalences were found for protease inhibitors (PI) in Spanish (3.1%), for non-nucleoside reverse transcriptase inhibitors (NNRTI) in SSA (6.5%) and for nucleoside reverse transcriptase inhibitors (NRTI) in both Spanish and SSA (6.5%). The global TDR rate decreased from 11.3% in 2004-2006 to 8.4% in 2007-2010. Characteristics related to a decreasing TDR trend in 2007-10 were Spanish and CSA origin, NRTI- and NNRTI-resistance, HIV-1 subtype B, male sex and infection through injection drug use. TDR remained stable for PI-resistance, in patients infected through sexual intercourse and in those carrying non-B variants. However, TDR increased among SSA and females. K103N was the predominant mutation in all groups and periods. CONCLUSION: TDR prevalence tended to decrease among HIV-infected native Spanish and Central-South Americans, but it increased up to 13% in sub-Saharan immigrants in 2007-2010. These results highlight the importance of a specific TDR surveillance among immigrants to prevent future therapeutic failures, especially when administering NNRTIs

Plasticity in oligomerization, operator architecture, and DNA binding in the mode of action of a bacterial B12-based photoreceptor.

Newly discovered bacterial photoreceptors called CarH sense light by using 5′-deoxyadenosylcobalamin (AdoCbl). They repress their own expression and that of genes for carotenoid synthesis by binding in the dark to operator DNA as AdoCbl-bound tetramers, whose light-induced disassembly relieves repression. High-resolution structures of Thermus thermophilus CarHTt have provided snapshots of the dark and light states and have revealed a unique DNA-binding mode whereby only three of four DNA-binding domains contact an operator comprising three tandem direct repeats. To gain further insights into CarH photoreceptors and employing biochemical, spectroscopic, mutational, and computational analyses, here we investigated CarHBm from Bacillus megaterium. We found that apoCarHBm, unlike monomeric apoCarHTt, is an oligomeric molten globule that forms DNA-binding tetramers in the dark only upon AdoCbl binding, which requires a conserved W-X9-EH motif. Light relieved DNA binding by disrupting CarHBm tetramers to dimers, rather than to monomers as with CarHTt. CarHBm operators resembled that of CarHTt, but were larger by one repeat and overlapped with the −35 or −10 promoter elements. This design persisted in a six-repeat, multipartite operator we discovered upstream of a gene encoding an Spx global redox-response regulator whose photoregulated expression links photooxidative and general redox responses in B. megaterium. Interestingly, CarHBm recognized the smaller CarHTt operator, revealing an adaptability possibly related to the linker bridging the DNA- and AdoCbl-binding domains. Our findings highlight a remarkable plasticity in the mode of action of B12-based CarH photoreceptors, important for their biological functions and development as optogenetic tools

Development and validation of an HIV risk exposure and indicator conditions questionnaire to support targeted HIV screening

The aim of our study was to develop a Spanish-structured HIV risk of exposure and indicator conditions (RE&IC) questionnaire. People attending to an emergency room or to a primary clinical care center were offered to participate in a prospective, 1 arm, open label study, in which all enrolled patients filled out our developed questionnaire and were HIV tested. Questionnaire accuracy, feasibility, and reliability were evaluated. Valid paired 5329 HIV RE&IC questionnaire and rapid HIV tests were performed, 69.3% in the primary clinical care center, 49.6% women, median age 37 years old, 74.9% Spaniards, 20.1% Latin-Americans. Confirmed hidden HIV infection was detected in 4.1%, while HIV RE&IC questionnaire was positive in 51.2%. HIV RE&IC questionnaire sensitivity was 100% to predict HIV infection, with a 100% negative predictive value. When considered separately, RE or IC items sensitivity decreases to 86.4% or 91%, and similarly their negative predictive value to 99.9% for both of them. The majority of people studied, 90.8% self-completed HIV RE&IC questionnaire. Median time to complete was 3 minutes. Overall HIV RE&IC questionnaire test-retest Kappa agreement was 0.82 (almost perfect), likewise for IC items 0.89, while for RE items was lower 0.78 (substantial). A feasible and reliable Spanish HIV RE&IC self questionnaire accurately discriminated all non–HIV-infected people without missing any HIV diagnoses, in a low prevalence HIV infection area. The best accuracy and reliability were obtained when combining HIV RE&IC items

Explorando saberes: la etnobotánica a través del registro audiovisual como instrumento de innovación docente para el aprendizaje significativo y la acción social del desarrollo sostenible

Memoria ID-170. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2019-2020

Immigrant women living with HIV in Spain: a qualitative approach to encourage medical follow-up

Abstract Background: Immigrant women living with HIV generally have worse adherence to medical treatment and follow-up when compared to native women and immigrant or native men. The general aim of this study was to improve healthcare services for HIV-positive women and to better understand why some of them discontinue treatment. The specific objectives were: (1) to explore the barriers and facilitators to medical follow-up among women and (2) to use the findings to create a guide for healthcare professionals with strategies and tools to encourage the immigrant women to continue with their healthcare treatment. Methods: We conducted a qualitative, patient-centred research based on semi-structured interviews in order to understand the drivers and barriers for HIV positive immigrant women to adhere to medical follow-up. A total of 26 women in active or discontinued treatment (from sub-Saharan Africa (10), Latin America (8) and Spain (8)) were interviewed in 2012 using a purposive sampling methodology. The semi-structured interviews were transcribed and analysed based on the grounded theory approach and the framework method. Three researchers took part in the triangulation of results. The study was approved by the Ethical Committee of the Hospital Universitario Ramón y Cajal

Creación de un índice de citas de revistas españolas de Humanidades para el estudio de la actividad investigadora de los científicos de estas disciplinas

Los estudios bibliométricos basados en el análisis de citaciones han demostrado tener un gran interés, puesto que permiten evaluar la actividadcientífica desde distintas perspectivas. Sin embargo, su utilización entraña el problema del acceso a fuentes que proporcionen los datos necesarios sobre la bibliografía referenciada por los autores en sus trabajos, pues rara vezlos incluyen las bases de datos. El Institute for Scientific Information (ISI) es la única institución que produce bases de datos con las referencias bibliográficas de los documentos que indizan (Science Citation Index, SocialSciences Citation Index y Arts & Humanities Citation Index). Sin embargo,estas bases de datos tienen una escasa cobertura de las publicaciones editadas por países no anglosajones, especialmente en las áreas de humanidades.Por ello, un equipo multidisciplinar de la Universidad Carlos III de Madrid emprendió un proyecto piloto dirigido a crear un índice de citas de revistas españolas de humanidades, concretamente en el área de Historia, con el fin de analizar distintos aspectos vinculados con la actividad científica en esta disciplina, como autores y fuentes más citadas, la tipología documental utilizada por este colectivo, la obsolescencia de la información, o su capacidad idiomática. Estos aspectos se analizaron a partir de la información obtenida de las casi 25.000 referencias bibliográficas de revistas de españolas de Historia seleccionadas, durante los años 1997 y 1998.Bibliometric studies based on the analysis of citations have proved interesting in the evaluation of scientific activity from different perspectives. Their use, however, depends on access to data on the bibliography referenced by authors in their papers, information that is rarely included in databases. In fact, the Institute for Scientific Information (ISI) is the only institution whose databases contain the bibliographic references cited in the papers indexed (Science Citation Index, Social Sciences Citation Index and Arts & Humanities Citation Index) and their coverage of scientific literature published outside Anglo-Saxon countries is limited, particularly in the area of humanities. For this reason, a multidisciplinary group at Madrid’s Carlos III University undertook a pilot project designed to create a citation index of Spanish humanities journals, specifically in the area of History, to analyse a number of aspects relating to scientific activity in this discipline, such as the authors and sources most often cited, typology of the documentation used, obsolescence of the information or their knowledge of languages. These issues were analysed based on nearly 25.000 bibliographic references cited in papers published by selected Spanish history journals in 1997 and 1998

How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort

Background: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women.This work was supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I + D + I and cofinanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) and Accion Estrategica en Salud Intramural (PI15CIII/00027).S

Use of maraviroc in patients with undetectable viral load: efficacy, tolerance and predictors of viral response in MARAVIROC-cohort study

Introduction: No controlled clinical trials had studied the role of maraviroc (MRV) in fully suppressed patients [1]. Methods and Materials: MRV-cohort is an observational, retrospective, multicentric (27 sites) large cohort study of patients starting MRV in clinical practice under different circumstances, with at least 48 weeks of follow-up. For the present analysis we selected all those patients starting with an HIV-RNAB50 copies/mL. Demographics, baseline CD4 cell count, past history of antiretroviral treatment (ART), tropism, reasons for MRV use, MRV based therapy and change/end of MRV use were assessed. Paired analysis of lipid, hepatic and kidney profile changes and univariate and multivariate analyses of HIV-RNAB50 copies/mL at 48 weeks were explored. Results: We included 247 out of 667 subjects from the entire cohort. At study entry, their median age was 47 years, 23% were women, 31% MSM, 49% had CDC category C, median CD4 counts were 468 cells/mm3 , 46% were HCV and 4.5% AgHBs. Tropism information was available in 197 (94% R5). Median length of prior ARTV was 10.7 years, with exposure to a median of three drug families. Main reasons for prescribing MRV were: toxicity 38%, inmunodiscordance 23%, simplification 19% and admission in a clinical trial 10.4%. MRV based therapies used were MRV2NRTIs 9%, MRVPI 46%, MRVPIother 40% and MRVother 5%. At 48 weeks, 23% of patients had changed or finished MRV therapy due to toxicity 2.4%, virological failure 2%, immunological failure 1.2%, simplification 3,2%, trial requirement 9.7%, medical decision 2.8%, treatment suspension 1.2% and unknown 0.4%. At 48 weeks, no significant changes were observed in lipid, hepatic or kidney profiles, and 85% of patients remained with HIV-RNAB50 copies/mL. Focusing on viral response univariate and multivariate models did not show any significant baseline variable explaining viral failure. Conclusions: In clinical practice MRV was used, mostly in R5 positive patients, with adequate efficacy and tolerance, but important number of patients changed due to non-clinical reasons. In this scenario neither reason for use of MRV nor MRVbased therapy explained viral failure