On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome

Background:Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.Methods:Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.Results:This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.Conclusion:Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started. © 2013 Bittar et al.

Genomic Signatures Predict Poor Outcome in Undifferentiated Pleomorphic Sarcomas and Leiomyosarcomas

Undifferentiated high-grade pleomorphic sarcomas (UPSs) display aggressive clinical behavior and frequently develop local recurrence and distant metastasis. Because these sarcomas often share similar morphological patterns with other tumors, particularly leiomyosarcomas (LMSs), classification by exclusion is frequently used. In this study, array-based comparative genomic hybridization (array CGH) was used to analyze 20 UPS and 17 LMS samples from untreated patients. The LMS samples presented a lower frequency of genomic alterations compared with the UPS samples. The most frequently altered UPS regions involved gains at 20q13.33 and 7q22.1 and losses at 3p26.3. Gains at 8q24.3 and 19q13.12 and losses at 9p21.3 were frequently detected in the LMS samples. Of these regions, gains at 1q21.3, 11q12.2-q12.3, 16p11.2, and 19q13.12 were significantly associated with reduced overall survival times in LMS patients. A multivariate analysis revealed that gains at 1q21.3 were an independent prognostic marker of shorter survival times in LMS patients (HR = 13.76; P = 0.019). Although the copy number profiles of the UPS and LMS samples could not be distinguished using unsupervised hierarchical clustering analysis, one of the three clusters presented cases associated with poor prognostic outcome (P = 0.022). A relative copy number analysis for the ARNT, SLC27A3, and PBXIP1 genes was performed using quantitative real-time PCR in 11 LMS and 16 UPS samples. Gains at 1q21-q22 were observed in both tumor types, particularly in the UPS samples. These findings provide strong evidence for the existence of a genomic signature to predict poor outcome in a subset of UPS and LMS patients. © 2013 Silveira et al.

Diabetic rats exercised prior to and during pregnancy: Maternal reproductive outcome, biochemical profile, and frequency of fetal anomalies

The aim of this study was to evaluate the effects of exercise prior to or during pregnancy on maternal reproductive outcome, biochemical profile, and on fetal anomaly frequency in a rat pregnancy model utilizing chemically induced diabetes. Wistar rats (minimum n = 11 animals/group) were randomly assigned the following groups: group 1 (G1), sedentary, nondiabetic; G2, nondiabetic, exercised during pregnancy; G3, nondiabetic, exercised prior to and during pregnancy; G4, sedentary, diabetic; G5, diabetic, exercised during pregnancy; and G6, diabetic, exercised prior to and during pregnancy. A swimming program was utilized for moderate exercise. On day 21 of pregnancy, all rats were anesthetized to obtain blood for biochemical measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The nondiabetic rats exercised prior to pregnancy presented a reduced maternal weight gain. Besides, G2 and G3 groups showed decreased fetal weights at term pregnancy, indicating slight intrauterine growth restriction (IUGR). In the diabetic dams, the swimming program did not have antihyperglycemic effects. The exercise applied only during pregnancy caused severe IUGR, as confirmed by reduced fetal weight mean, fetal weight classification, and ossification sites. Nevertheless, exercise was not a teratogenic factor and improved the rats' lipid profiles, demonstrating that the exercise presented possible benefits, but there are also risks prior and during pregnancy, especially in diabetic pregnant women. © The Author(s) 2012.

Validation of the English version of the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats

Background: A scale validated in one language is not automatically valid in another language or culture. The purpose of this study was to validate the English version of the UNESP-Botucatu multidimensional composite pain scale (MCPS) to assess postoperative pain in cats. The English version was developed using translation, back-translation, and review by individuals with expertise in feline pain management. In sequence, validity and reliability tests were performed.Results: Of the three domains identified by factor analysis, the internal consistency was excellent for 'pain expression' and 'psychomotor change' (0.86 and 0.87) but not for 'physiological variables' (0.28). Relevant changes in pain scores at clinically distinct time points (e.g., post-surgery, post-analgesic therapy), confirmed the construct validity and responsiveness (Wilcoxon test, p < 0.001). Favorable correlation with the IVAS scores (p < 0.001) and moderate to very good agreement between blinded observers and 'gold standard' evaluations, supported criterion validity. The cut-off point for rescue analgesia was > 7 (range 0-30 points) with 96.5% sensitivity and 99.5% specificity.Conclusions: The English version of the UNESP-Botucatu-MCPS is a valid, reliable and responsive instrument for assessing acute pain in cats undergoing ovariohysterectomy, when used by anesthesiologists or anesthesia technicians. The cut-off point for rescue analgesia provides an additional tool for guiding analgesic therapy. © 2013 Brondani et al.; licensee BioMed Central Ltd.

The Caribbean and the outcome of the Uruguay Round in the context of NAFTA and FTAA

Includes bibliography

Comparison of intrarectal ozone, ozone administered in acupoints and meloxicam for postoperative analgesia in bitches undergoing ovariohysterectomy

Since all analgesics currently available for use in dogs have been associated with some adverse effects, the search for an effective analgesic that does not cause harm is important. This study investigated the postoperative analgesic effects of ozone administered either intrarectally or into acupoints in bitches undergoing ovariohysterectomy (OH). Twenty-four healthy adult bitches were randomly assigned to one of the three treatments 10min after sedation, as follows: 0.2mg/kg of intramuscular (IM) meloxicam (M); rectal insufflation of 10mL of 30μg/mL ozone (OI), or acupoint injection of 0.5mL ozone (30μg/mL; OA). Following sedation with acetylpromazine, anaesthesia was induced with propofol and fentanyl and maintained with isoflurane/O2. Pain was assessed using the modified Glasgow pain scale (MGPS) and the visual analogue scale (VAS) on the day before surgery, before anaesthesia, and at 1, 2, 4, 6, 8, 12 and 24h after surgery. Rescue analgesia was performed using 0.5mg/kg of morphine IM if MGPS was >3.33 points.No statistically significant differences in pain scales were found among the three analgesic protocols or the time points in each group ( P>. 0.05). Two dogs treated with OA required rescue analgesia. Meloxicam, rectal insufflation of ozone and ozone injected into acupoints provided satisfactory analgesia for 24. h in bitches undergoing elective OH. Ozone had no measurable adverse effects and is an alternative option to promote pain relief. © 2013 Elsevier Ltd.

Identificação das variáveis associadas à mortalidade de pacientes internados em unidade de terapia intensiva adulto

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evolução do peso e qualidade de vida de pacientes submetidos à derivação gástrica em Y-de-Roux

Pós-graduação em Alimentos e Nutrição - FCFAR

Autoenxerto de crista ilíaca como espaçador na técnica modificada de avanço da tuberosidade tibial na ruptura do ligamento cruzado cranial: estudo clínico em cães

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Desenvolvimento, aplicação e avaliação de nova técnica de avanço da tuberosidade tibial com uso de espaçador de polímero de mamona fixado com parafusos para correção da ruptura do ligamento cruzado cranial em cães

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Ten Years of Operation of the World Trade Organization Dispute Settlement Mechanism: Outcome for Latin America and the Caribbean

Dispute settlement mechanisms help to create a fairly predictable and accurate environment in which economic agents can pursue their activities in the international arena. The World Trade Organization (WTO) Dispute Settlement Body (DSB) has now been in operation for 10 years and it is fitting, at this point to assess the progress achieved by Latin America and the Caribbean, the region that made most use of this mechanism during the period, and whose countries have made significant gains against protectionism in key export sectors. These successes constitute important precedents which will influence upcoming multilateral negotiations and future trade disputes.This article reviews the work carried out by the DSB, the role of the leading stakeholders in the system (the United States and the European Union) and progress made by countries of the region in a global context marked by the complexity of trade issues and the legal framework that regulates them. The findings presented in this article are based on the study "Una década de funcionamiento del Sistema de Solución de Diferencias de la OMC: avances y desafíos".

Regional review and appraisal of implementation of the Beijing Declaration and Platform for Action and the outcome of the twenty-third special session of the General Assembly (2000) in Latin American and Caribbean countries

This report indicates the main advances of the past 20 years based on the information provided by the region’s countries on implementation of the Beijing Declaration and Platform for Action, in response to the recommendations made in the final document of the twenty-third special session of the General Assembly (2000) for the regional and global reviews that would take place in 2015, on the twentieth anniversary of the Beijing Conference (Beijing+20). The subregional report on the Caribbean (ECLAC, 2014c) has also been taken into account, which includes data from the country gender assessments prepared by the Caribbean Development Bank, the country poverty assessments and information provided by the Caribbean Community (CARICOM).

A contagem de plaquetas pré-operatória é fator de risco em pacientes cirróticos com hepatocarcinoma submetidos a hepatectomia?: revisão sistemática e metanálise de estudos coorte

Pós-graduação em Bases Gerais da Cirurgia - FMB

Clinical evaluation of postoperative sensitivity using self-etching adhesives containing glutaraldehyde

The present clinical study aimed to assess the postoperative sensitivity (POS) after 48 hours and seven days in occlusal restorations bonded with three different adhesive systems, two of them containing glutaraldehyde. The restorative procedures were performed using the three-step etch-and-rinse Adper SBMP-Plus adhesive (SBMP), the two-step etch-and-rinse Gluma Comfort One Bond + Desensitizer adhesive (GC+D) and the all-in-one self-etching/priming I Bond (IB) adhesive, which also has glutaraldehyde in its formula. All cavities were restored with Filtek Supreme nanoparticle composite resin. After 48 hours and seven days the patients were recalled and the postoperative sensitivity evaluated. The data analyzed by non-parametric Friedman test showed no significant differences in POS among the three tested groups after 48 hours and seven days.