High-Resolution Molecular Epidemiology and Evolutionary History of HIV-1 Subtypes in Albania

HIV-1 epidemic in Western Europe is largely due to subtype B. Little is known about the HIV-1 in Eastern Europe, but a few studies have shown that non-B subtypes are quite common. In Albania, where a recent study estimated a ten-fold increase of AIDS incidence during the last six years, subtype A and B account for 90% of the know infections.We investigated the demographic history of HIV-1 subtype A and B in Albania by using a statistical framework based on coalescent theory and phylogeography. High-resolution phylogenetic and molecular clock analysis showed a limited introduction to the Balkan country of subtype A during the late 1980s followed by an epidemic outburst in the early 1990 s. In contrast, subtype B was apparently introduced multiple times between the mid-1970s and mid-1980s. Both subtypes are growing exponentially, although the HIV-1A epidemic displays a faster growth rate, and a significantly higher basic reproductive number R(0). HIV-1A gene flow occurs primarily from the capital Tirane, in the center of the country, to the periphery, while HIV-1B flow is characterized by a balanced exchange between center and periphery. Finally, we calculated that the actual number of infections in Albania is at least two orders of magnitude higher than previously thought.Our analysis demonstrates the power of recently developed computational tools to investigate molecular epidemiology of pathogens, and emphasize the complex factors involved in the establishment of HIV-1 epidemics. We suggest that a significant correlation exists between HIV-1 exponential spread and the socio-political changes occurred during the Balkan wars. The fast growth of a relatively new non-B epidemic in the Balkans may have significant consequences for the evolution of HIV-1 epidemiology in neighboring countries in Eastern and Western Europe

Comparative biochemical analysis of recombinant reverse transcriptase enzymes of HIV-1 subtype B and subtype C

<p>Abstract</p> <p>Background</p> <p>HIV-1 subtype C infections account for over half of global HIV infections, yet the vast focus of HIV-1 research has been on subtype B viruses which represent less than 12% of the global pandemic. Since HIV-1 reverse transcriptase (RT) is a major target of antiviral therapy, and since differential drug resistance pathways have been observed among different HIV subtypes, it is important to study and compare the enzymatic activities of HIV-1 RT derived from each of subtypes B and C as well as to determine the susceptibilities of these enzymes to various RT inhibitors in biochemical assays.</p> <p>Methods</p> <p>Recombinant subtype B and C HIV-1 RTs in heterodimeric form were purified from <it>Escherichia coli </it>and enzyme activities were compared in cell-free assays. The efficiency of (-) ssDNA synthesis was measured using gel-based assays with HIV-1 PBS RNA template and tRNA₃^Lysas primer. Processivity was assayed under single-cycle conditions using both homopolymeric and heteropolymeric RNA templates. Intrinsic RNase H activity was compared using 5'-end labeled RNA template annealed to 3'-end recessed DNA primer in a time course study in the presence and absence of a heparin trap. A mis-incorporation assay was used to assess the fidelity of the two RT enzymes. Drug susceptibility assays were performed both in cell-free assays using recombinant enzymes and in cell culture phenotyping assays.</p> <p>Results</p> <p>The comparative biochemical analyses of recombinant subtype B and subtype C HIV-1 reverse transcriptase indicate that the two enzymes are very similar biochemically in efficiency of tRNA-primed (-) ssDNA synthesis, processivity, fidelity and RNase H activity, and that both enzymes show similar susceptibilities to commonly used NRTIs and NNRTIs. Cell culture phenotyping assays confirmed these results.</p> <p>Conclusions</p> <p>Overall enzyme activity and drug susceptibility of HIV-1 subtype C RT are comparable to those of subtype B RT. The use of RT inhibitors (RTIs) against these two HIV-1 enzymes should have comparable effects.</p

Da Rio+20 a Rio-2016:: caminhos da sustentabilidade nas olimpíadas

This article seeks to analyze the way the Olympic Games have incorporated the main sustainability commitments agreed upon during the Rio 92, Rio + 10 and Rio + 20 Conferences, both in their planning and their operational processes, thus influencing host cities in the construction of the Games’ legacy. Tourism is one of the mainstays of Rio’s economy, and the link between the Games and the city’s images will be lasting.The Olympic games will influence the quantity and the quality of the touristic demand during, but especially after the event. They will showcase the city’s innovative initiatives for sustainability. The IOC can play a vital role orienting those initiatives. The Games’sustainability legacy may constitute an opportunity for the city to change its image for ever. We still have three years ahead of us to advance, but the basis need to be settled now.Este artigo busca analisar a maneira como os Jogos Olímpicos têm incorporado os principais compromissos da sustentabilidade acordados nas Conferencias Rio 92, Rio+10 e Rio+20 nos seus processos de planejamento e operação, influenciando as cidades anfitriãs na construção do legado dos Jogos. O turismo é um dos carros-chefes da economia do Rio, e a ligação entre os Jogos e a imagem da cidade que vai ficar. Os Jogos irão refletir na quantidade e qualidade da demanda turística durante, mas principalmente depois das Olimpíadas. Eles podem ser uma vitrine para iniciativas inovadoras na área de sustentabilidade que a cidade introduzir. O papel do COI pode ser fundamental para direcionar as ações de sustentabilidade na cidade. O legado de sustentabilidade pode ter nos Jogos seu “ponto de inflexão” para mudar definitivamente a imagem da cidade. Ainda temos um pouco mais de três anos para avançar, mas as bases precisam ser criadas agora

Autoethnography as an Instrument for Professional (Trans) Formation in Pharmaceutical Care Practice

The recent inclusion of pharmacists in primary healthcare in Brazil through the Family Health Support Team has encouraged them to reflect on the need to change from a professional focused on medications to one focused on individuals. This autoethnography allowed a pharmacist to confront her perspectives on clinical practice between 2014 and 2016, a period when she decided to challenge her traditional training as a pharmacist centered on medications. Using pharmaceutical care practice as the theoretical framework that prompted the profession of pharmacy to change its focus to the patient, the authors collaborated to construct a monologue that engages readers in the meanings of becoming patient centered. The research findings also support the versatility of application of the reflective process provided by autoethnography. Through fieldwork, reflective writing and interviews, the pharmacist discovered a new way to relate to caring and patients in her daily routine

Efficacy of Neratinib Plus Capecitabine in the Subgroup of Patients with Central Nervous System Involvement from the NALA Trial

Capecitabina; Neoplàsies del sistema nerviós central; Neratinibcapecitabina; Neoplasias del sistema nervioso central; NeratinibCapecitabine; Central nervous system neoplasms; NeratinibBackground Neratinib has efficacy in central nervous system (CNS) metastases from HER2-positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C). Materials and Methods NALA was a randomized, active-controlled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m2 twice daily) orally. Independently adjudicated progression-free survival (PFS), overall survival (OS), and CNS endpoints were considered. Results Of 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n = 51; L + C, n = 50); 81 had received prior CNS-directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41–1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59–1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline (n = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed. Conclusion These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2-positive MBC.Funded by Puma Biotechnology, Inc. Medical writing support was also funded by Puma Biotechnology Inc. and provided by Miller Medical Communications

Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes

<p>Abstract</p> <p>Background</p> <p>Integrase inhibitors are currently being incorporated into highly active antiretroviral therapy (HAART). Due to high HIV variability, integrase inhibitor efficacy must be evaluated against a range of integrase enzymes from different subtypes.</p> <p>Methods</p> <p>This study compares the enzymatic activities of HIV-1 integrase from subtypes B and C as well as susceptibility to various integrase inhibitors <it>in vitro</it>. The catalytic activities of both enzymes were analyzed in regard to each of 3' processing and strand transfer activities both in the presence and absence of the integrase inhibitors raltegravir (RAL), elvitegravir (EVG), and MK-2048.</p> <p>Results</p> <p>Our results show that integrase function is similar with enzymes of either subtype and that the various integrase strand transfer inhibitors (INSTIs) that were employed possessed similar inhibitory activity against both enzymes.</p> <p>Conclusion</p> <p>This suggests that the use of integrase inhibitors against HIV-1 subtype C will result in comparable outcomes to those obtained against subtype B infections.</p

La Autoenografía como un instrumento de (trans)formación profesional en la práctica del Pharmaceutical Care

La inclusión reciente de farmacéuticos en atención primaria en Brasil a través del Equipo de Apoyo de Salud Familiar los ha alentado a reflexionar sobre la necesidad de dejar de ser un profesional enfocado en los medicamentos a un profesional enfocado en las personas. La autoetnografía le permitió a una farmacéutica confrontar sus perspectivas sobre la práctica clínica entre 2014 y 2016, período en el que ella decidió desafiar, como farmacéutica, su formación tradicional centrada en los medicamentos. Utilizando como marco teórico la práctica del Pharmaceutical Care que había impulsadoa la profesión farmacéutica a cambiar su enfoque hacia el paciente, los autores colaboraron en la construcción de un monólogo sobre lo que significa centrarse en el paciente,de manera que éste cautivara a los lectores. Los hallazgos de la investigación también respaldan la versatilidad de la aplicación del proceso reflexivo proporcionado por la autoetnografía. Durante el trabajo de campo, a través de una redacción reflexiva y la realización de entrevistas, la farmacéutica descubrió una nueva forma de relacionarse con el "cuidado" y los "pacientes" en su rutina diaria

La Autoenografía como un instrumento de (trans)formación profesional en la práctica del Pharmaceutical Care

La inclusión reciente de farmacéuticos en atención primaria en Brasil a través del Equipo de Apoyo de Salud Familiar los ha alentado a reflexionar sobre la necesidad de dejar de ser un profesional enfocado en los medicamentos a un profesional enfocado en las personas. La autoetnografía le permitió a una farmacéutica confrontar sus perspectivas sobre la práctica clínica entre 2014 y 2016, período en el que ella decidió desafiar, como farmacéutica, su formación tradicional centrada en los medicamentos. Utilizando como marco teórico la práctica del Pharmaceutical Care que había impulsadoa la profesión farmacéutica a cambiar su enfoque hacia el paciente, los autores colaboraron en la construcción de un monólogo sobre lo que significa centrarse en el paciente,de manera que éste cautivara a los lectores. Los hallazgos de la investigación también respaldan la versatilidad de la aplicación del proceso reflexivo proporcionado por la autoetnografía. Durante el trabajo de campo, a través de una redacción reflexiva y la realización de entrevistas, la farmacéutica descubrió una nueva forma de relacionarse con el "cuidado" y los "pacientes" en su rutina diaria

The effect of socio-demographic factors on mental health and addiction high-cost use : a retrospective, population-based study in Saskatchewan

Objective: A small proportion of the population accounts for the majority of healthcare costs. Mental health and addiction (MHA) patients are consistently high-cost. We aimed to delineate factors amenable to public health action that may reduce high-cost use among a cohort of MHA clients in Saskatoon, Saskatchewan. Methods: We conducted a population-based retrospective cohort study. Administrative health data from fiscal years (FY) 2009–2015, linked at the individual level, were analyzed (n = 129,932). The outcome of interest was ≥ 90th percentile of costs for each year under study (‘persistent high-cost use’). Descriptive analyses were followed by logistic regression modelling; the latter excluded long-term care residents. Results: The average healthcare cost among study cohort members in FY 2009 was ~ $2300; for high-cost users it was ~$19,000. Individuals with unstable housing and hospitalization(s) had increased risk of persistent high-cost use; both of these effects were more pronounced as comorbidities increased. Patients with schizophrenia, particularly those under 50 years old, had increased probability of persistent high-cost use. The probability of persistent high-cost use decreased with good connection to a primary care provider; this effect was more pronounced as the number of mental health conditions increased. Conclusion: Despite constituting only 5% of the study cohort, persistent high-cost MHA clients (n = 6455) accounted for ~ 35% of total costs. Efforts to reduce high-cost use should focus on reduction of multimorbidity, connection to a primary care provider (particularly for those with more than one MHA), young patients with schizophrenia, and adequately addressing housing stability