Long-term assessment of didanosine, lamivudine, and efavirenz in antiretroviral-naive patients: 3-year follow-up.

The aim of this study was to evaluate the long-term efficacy and safety of didadosine (ddI), lamivudine (3TC), and efavirenz (EFV). This was a follow-up to the VESD study, a 12-month open-label, observational, multicenter study of adult patients with HIV infection who started antiretroviral treatment with the ddI-3TC-EFV once-daily regimen. Of the 167 patients originally included, 106 patients remained on the same triple therapy at the end of the study (1 year), and they were offered an extra 24 months of follow-up; 96 were enrolled in this study (VESD-2). Seventy patients out of the initial cohort were still on the same regimen at month 36, with 97% of them with plasma viral load <50 copies /ml. An intention-to-treat analysis showed that the percentage of patients with plasma viral load <50 copies/ml was 73% at 36 months. CD4 cell counts increased 344 cells/microl over the 36 months. Safety and tolerance were good with no unexpected long-term toxicity. After 3 years of treatment with ddI-3TC-EFV, more than 40% of the patients were still receiving the initial antiretroviral therapy with sustained, durable immunovirological benefit and good acceptance. Long-term toxicity and virological failure were low.

A study of multidrug-resistant tuberculosis in risk groups in the city of Santos, São Paulo, Brazil

Monitoring the extent of and trends in multidrug-resistant tuberculosis (MDR-TB) is a priority of the Brazilian National Tuberculosis Control Programme. The current study aimed to estimate the incidence of MDR-TB, describe the profile of TB drug resistance in risk groups and examine whether screening for MDR-TB adhered to the recommended guidelines. A descriptive study that examined diagnosed cases of pulmonary TB was conducted in the city of Santos, Brazil, between 2000-2004. Of the 2,176 pulmonary TB cases studied, 671 (30.8%) met the criteria for drug sensitivity testing and, of these cases, 31.7% (213/671) were tested. Among the tested cases, 9.4% were resistant to one anti-TB drug and 15% were MDR. MDR was observed in 11.6% of 86 new TB cases and 17.3% of 127 previously treated cases. The average annual incidence of MDR-TB was 1.9 per 100,000 inhabitants-years. The extent of known MDR-TB in the city of Santos is high, though likely to be underestimated. Our study therefore indicates an inadequate adherence to the guidelines for MDR-TB screening and suggests the necessity of alternative strategies of MDR-TB surveillance.

Computational and Biological Evaluation of N-octadecyl-N'-propylsulfamide, a Selective PPARα Agonist Structurally Related to N-acylethanolamines.

To further understand the pharmacological properties of N-oleoylethanolamine (OEA), a naturally occurring lipid that activates peroxisome proliferator-activated receptor alpha (PPARα), we designed sulfamoyl analogs based on its structure. Among the compounds tested, N-octadecyl-N'-propylsulfamide (CC7) was selected for functional comparison with OEA. The performed studies include the following computational and biological approaches: 1) molecular docking analyses; 2) molecular biology studies with PPARα; 3) pharmacological studies on feeding behavior and visceral analgesia. For the docking studies, we compared OEA and CC7 data with crystallization data obtained with the reference PPARα agonist GW409544. OEA and CC7 interacted with the ligand-binding domain of PPARα in a similar manner to GW409544. Both compounds produced similar transcriptional activation by in vitro assays, including the GST pull-down assay and reporter gene analysis. In addition, CC7 and OEA induced the mRNA expression of CPT1a in HpeG2 cells through PPARα and the induction was avoided with PPARα-specific siRNA. In vivo studies in rats showed that OEA and CC7 had anorectic and antiobesity activity and induced both lipopenia and decreases in hepatic fat content. However, different effects were observed when measuring visceral pain; OEA produced visceral analgesia whereas CC7 showed no effects. These results suggest that OEA activity on the PPARα receptor (e.g., lipid metabolism and feeding behavior) may be dissociated from other actions at alternative targets (e.g., pain) because other non cannabimimetic ligands that interact with PPARα, such as CC7, do not reproduce the full spectrum of the pharmacological activity of OEA. These results provide new opportunities for the development of specific PPARα-activating drugs focused on sulfamide derivatives with a long alkyl chain for the treatment of metabolic dysfunction.

Characterisation of divergent flavivirus NS3 and NS5 protein sequences detected in Rhipicephalus microplus ticks from Brazil

Transcripts similar to those that encode the nonstructural (NS) proteins NS3 and NS5 from flaviviruses were found in a salivary gland (SG) complementary DNA (cDNA) library from the cattle tick Rhipicephalus microplus.Tick extracts were cultured with cells to enable the isolation of viruses capable of replicating in cultured invertebrate and vertebrate cells. Deep sequencing of the viral RNA isolated from culture supernatants provided the complete coding sequences for the NS3 and NS5 proteins and their molecular characterisation confirmed similarity with the NS3 and NS5 sequences from other flaviviruses. Despite this similarity, phylogenetic analyses revealed that this potentially novel virus may be a highly divergent member of the genus Flavivirus. Interestingly, we detected the divergent NS3 and NS5 sequences in ticks collected from several dairy farms widely distributed throughout three regions of Brazil. This is the first report of flavivirus-like transcripts inR. microplus ticks. This novel virus is a potential arbovirus because it replicated in arthropod and mammalian cells; furthermore, it was detected in a cDNA library from tick SGs and therefore may be present in tick saliva. It is important to determine whether and by what means this potential virus is transmissible and to monitor the virus as a potential emerging tick-borne zoonotic pathogen.

Detection of Wuchereria bancrofti DNA in paired serum and urine samples using polymerase chain reaction-based systems

The Global Program for the Elimination of Lymphatic Filariasis (GPELF) aims to eliminate this disease by the year 2020. However, the development of more specific and sensitive tests is important for the success of the GPELF. The present study aimed to standardise polymerase chain reaction (PCR)-based systems for the diagnosis of filariasis in serum and urine. Twenty paired biological urine and serum samples from individuals already known to be positive for Wuchereria bancrofti were collected during the day. Conventional PCR and semi-nested PCR assays were optimised. The detection limit of the technique for purified W. bancrofti DNA extracted from adult worms was 10 fg for the internal systems (WbF/Wb2) and 0.1 fg by using semi-nested PCR. The specificity of the primers was confirmed experimentally by amplification of 1 ng of purified genomic DNA from other species of parasites. Evaluation of the paired urine and serum samples by the semi-nested PCR technique indicated only two of the 20 tested individuals were positive, whereas the simple internal PCR system (WbF/Wb2), which has highly promising performance, revealed that all the patients were positive using both samples. This study successfully demonstrated the possibility of using the PCR technique on urine for the diagnosis of W. bancrofti infection.

Atención al paciente quirúrgico : proceso asistencial integrado

Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Salud / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

Interleukin-10 rs1800896 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock

Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α,interlelukin (IL)-1β, IL-10,IL-8, Toll-like receptor 4, CXCR1and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock.

Lipid changes in HIV-patients switching to the coformulated single tablet FTC/RPV/TDF (Eviplera®). Efficacy and safety analysis. GeSida Study 8114.

INTRODUCTION Rilpivirine (RPV) has a better lipid profile than efavirenz (EFV) in naïve patients (1). Switching to RPV may be convenient for many patients, while maintaining a good immunovirological control (2). The aim of this study was to analyze lipid changes in HIV-patients at 24 weeks after switching to Eviplera® (emtricitabine/RPV/tenofovir disoproxil fumarate [FTC/RPV/TDF]). MATERIALS AND METHODS Retrospective, multicentre study of a cohort of asymptomatic HIV-patients who switched from a regimen based on 2 nucleoside reverse transcriptase inhibitors (NRTI)+protease inhibitor (PI)/non nucleoside reverse transcriptase inhibitor (NNRTI) or ritonavir boosted PI monotherapy to Eviplera® during February-December, 2013; all had undetectable HIV viral load for ≥3 months prior to switching. Patients with previous failures on antiretroviral therapy (ART) including TDF and/or FTC/3TC, with genotype tests showing resistance to components of Eviplera®, or who had changed the third drug of the ART during the study period were excluded. Changes in lipid profile and cardiovascular risk (CVR), and efficacy and safety at 24 weeks were analyzed. RESULTS Among 305 patients included in the study, 298 were analyzed (7 cases were excluded due to lack of data). Men 81.2%, mean age 44.5 years, 75.8% of HIV sexually transmitted. 233 (78.2%) patients switched from a regimen based on 2 NRTI+NNRTI (90.5% EFV/FTC/TDF). The most frequent reasons for switching were central nervous system (CNS) adverse events (31.0%), convenience (27.6%) and metabolic disorders (23.2%). At this time, 293 patients have reached 24 weeks: 281 (95.9%) have continued Eviplera®, 6 stopped it (3 adverse events, 2 virologic failures, 1 discontinuation) and 6 have been lost to follow up. Lipid profiles of 283 cases were available at 24 weeks and mean (mg/dL) baseline vs 24 weeks are: total cholesterol (193 vs 169; p=0.0001), HDL-c (49 vs 45; p=0.0001), LDL-c (114 vs 103; p=0.001), tryglycerides (158 vs 115; p=0.0001), total cholesterol to HDL-c ratio (4.2 vs 4.1; p=0.3). CVR decreased (8.7 vs 7.5%; p= 0.0001). CD4 counts were similar to baseline (653 vs 674 cells/µL; p=0.08), and 274 (96.8%) patients maintained viral suppression. CONCLUSIONS At 24 weeks after switching to Eviplera®, lipid profile and CVR improved while maintaining a good immunovirological control. Most subjects switched to Eviplera® from a regimen based on NNRTI, mainly EFV/FTC/TDF. CNS adverse events, convenience and metabolic disorders were the most frequent reasons for switching.

Accesibilidad en los espacios públicos urbanizados

El libro, coordinado por el Director de ACCEPLAN, Fernando Alonso López, viene a ser un reflejo de los avances entorno a la búsqueda de accessibilidad universal en los espacios públicos urbanizados. Para aproximarse a la realidad normativa y técnica de la Orden Ministerial el libro se estructura en artículos referentes al contexto normativo, a los contenidos de la Orden, y a reflexiones y criterios en torno a la accesibilidad en la ciudad. Del conjunto de artículos, por su variedad y por su carácter multidiciplinar, se extrae un libro de referencia que ofrece la variedad de enfoques del tema y que ayuda a interpretar mejor la Orden Ministerial, su contribución a los objetivos de la Ley 51/2003 de Igualdad de Oportunidades No Discriminación y Accesibilidad Universal, LIONDAU, y su utilidad en la comformación de unas ciudades cada vez más abiertas a la diversidad funcional y a la convivencia.

Decisão de escolha de carreira no Brasil: uma abordagem por opções reais

RESUMOA escolha da carreira é uma decisão importante e em geral é feita em um ambiente repleto de incertezas por pessoas relativamente jovens e inexperientes. Neste estudo, buscou-se analisar a decisão de escolha entre uma carreira em uma empresa privada e outra em um órgão público, considerando que existe flexibilidade para migrar do setor privado para o público por meio de concurso. Para tanto, utilizou-se a metodologia das opções reais para modelar essa opção de troca, assumindo-se que os ganhos futuros no setor privado são incertos. Os resultados sugerem que a opção de ingressar na carreira pública pode ter valor significativo em relação à privada.

La automatización de la programación diaria de tareas en el C.A.I. Fernando de Dios Buñuel (Cuba)

Desenvolupar una eina de software que pugui automatitzar i resoldre un model matemàtic, amb l'objectiu de minimitzar les despeses de transport des del camp a una central del sucre, i a la vegada garantir l'abastament diàri d'aquesta, per tal de minimitzar les despeses i situar adequadament els recursos disponibles.

Propagandas de remédio na imprensa ilustrada e a imagem da enfermeira brasileira (1920-1925)

Estudo histórico-social sobre efeito simbólico das propagandas de remédios protagonizadas por mulheres com representações objetais utilizadas por enfermeiras, veiculadas na Revista Fon-Fon, que descreve as propagandas de remédios veiculadas neste meio de comunicação; analisa as representações objetais da imagem da enfermeira presente nessas propagandas e discute o efeito simbólico dessas representações para o consumo do remédio pela sociedade brasileira. As fontes documentais foram escritas, iconográficas e literatura referentes à História do Brasil, da Imprensa, da Propaganda e da Enfermagem. As propagandas de remédios analisadas, mediante uma matriz de análise baseada em conceitos da semiótica, derivam da Revista Fon-Fon. O estudo evidenciou que as propagandas analisadas investiram em representações objetais utilizadas pelas enfermeiras, de modo a obterem credibilidade em relação ao medicamento anunciado.

Revisão integrativa da literatura sobre gestão do regime terapêutico em pacientes com doença pulmonar obstrutiva crônica

Com este estudo pretende-se identificar qual a melhor estratégia de intervenção de enfermagem na promoção da gestão do regime terapêutico em pacientes com Doença Pulmonar Obstrutiva Crônica no ambiente hospitalar. Realizamos uma revisão integrativa da literatura dos anos 2006 a 2009. A partir da análise dos dados, constatamos que os estudos utilizam diferentes elementos e diferentes indicadores de efetividade para avaliarem as estratégias de intervenção utilizadas. Baseando-se nas evidências disponíveis, não é possível identificar qual a melhor estratégia. Desta revisão emerge a definição dos indicadores de resultado mais consensuais na avaliação da efetividade das estratégias de intervenção. Torna-se agora necessário desenvolver, implementar e avaliar a efetividade das estratégias de intervenção de enfermagem, recorrendo a estes indicadores, para definir qual a melhor estratégia de intervenção, baseada na evidência.

QuesTInSitu mobile: aplicació per a rutes de preguntes geolocalitzades

En plena era de la informació, les noves tecnologies s’han posat també al servei del’ensenyament. Per tal de proveir a l’estudiant dels mètodes més útils i eficients per donar suport al seu aprenentatge, han sorgit eines cada cop més acurades amb la intenció de proveird’una manera robusta tot allò que fins fa poc només es podia fer a les aules. Així va néixer el concepte d’e-learning.QuesTInSitu és una eina concebuda dins d’aquesta àrea que permet crear preguntesgeolocalitzades sobre mapes de GoogleMaps i organitzar-les com a rutes (qüestionaris), sobre el mapa que es desitgi del món. Aquest projecte ofereix la possibilitat de poder realitzar físicament l’activitat creada per QuesTInSitu mitjançant terminals mòbils amb connexió 3G i GPS. Per això, s’ha dissenyat un portal web adaptat, QuesTInSitu mobile, que permet realitzar les gimcanes geolocalitzades dissenyades prèviament. Malgrat aquest projecte està contingut enl’àrea del e-learning, ofereix un llarg ventall de possibilitats d’ús; publicitat o turisme en són alguns exemples.