Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder.

The hepatitis E virus (HEV) hypervariable region (HVR) presents the highest divergence of the entire HEV genome. It is characteristically rich in proline, and so is also known as the "polyproline region" (PPR). HEV genotype 3 (HEV-3) exhibits different PPR lengths due to insertions, PPR and/or RNA-dependent RNA polymerase (RdRp) duplications and deletions. A total of 723 PPR-HEV sequences were analyzed, of which 137 HEV-3 sequences were obtained from clinical specimens (from acute and chronic infection) by Sanger sequencing. Eight swine stool/liver samples were also analyzed. N- and C-terminal fragments were confirmed as being conserved, but they harbored differences between genotypes and were not proline-plentiful regions. The genuine PPR is the intermediate region between them. HEV-3 PPR contains a higher percentage (30.4%) of prolines than other genotypes. IDRWe describe for the first time: (1) the specific placement of HEV-3 PPR rearrangements in sites 1 to 14 of the PPR, noting that duplications are more frequently attached to sites 11 and 12 (AAs 74-79 and 113-118, respectively); (2) the cadence of repetitions follows a circular-like pattern of blocks A to J, with F, G, H, and I being the most frequent; (3) a previously unreported insertion homologous to apolipoprotein C1; and (4) the increase in frequency of potential N-glycosylation sites and differences in AAs composition related to duplications.This research was funded by ISCIII 2019, grant number MPY 501-19.S

Clinical and Virological Efficacy of Etravirine Plus Two Active Nucleos(t)ide Analogs in an Heterogeneous HIV-Infected Population.

Journal Article; ClinicalTrials.gov NCT01437241.Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to 200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. TRIAL REGISTRATION ClinicalTrials.gov NCT01437241.Ye

Estrategias de Redacción - HE59 - 202102

Descripción: Estrategias de Redacción es un curso de Humanidades, que brinda al participante un conjunto de herramientas lingüísticas para la redacción en el entorno laboral, tales como el uso apropiado de la normativa del español y la aplicación de la estrategia de redacción enumerativa. Esta última se emplea en la elaboración de un tipo de documento: el informe de recomendación. Propósito: El curso desarrolla la competencia de comunicación escrita en el primer nivel de logro. La asignatura 1se orienta a la redacción de un tipo de texto propio del entorno laboral que ayude a optimizar el desempeño profesional del participante

Proportion of patients with increased aminotransferases levels at any time-point throughout the follow-up.

<p>Proportion of patients with increased aminotransferases levels at any time-point throughout the follow-up.</p

Change in lipid plasma levels (mg/dL) throughout the follow-up.

<p>A: patients with normal baseline values. B: patients with abnormal baseline values on previous NNRTIs- or PI/rtv-based regimens. CT: total cholesterol. HDL-C: high-density lipoprotein cholesterol. LDL-C: low-density lipoprotein cholesterol. TG: triglycerides.</p

Genotypic resistance tests at virological failure.

<p>RT, reverse transcriptase. wt: wild-type. VL, viral load. VF, virogical failure.</p><p>*Mutation scoring according to reference 22.</p

Comprensión y Producción de Lenguaje I - HU543 - 202101

Descripción: Comprensión y Producción de Lenguaje 1 es un curso de primer ciclo, que busca desarrollar las habilidades vinculadas con la comprensión lectora y la redacción de textos escritos formales y adecuados a una situación comunicativa determinada. Por ello, durante el curso, las actividades posibilitarán que el estudiante reflexione sobre cómo el lenguaje es una herramienta que nos permite entender la realidad (comprensión) y comunicar adecuadamente nuestras ideas sobre ella (producción). Esta reflexión se realizará con énfasis en el uso del lenguaje en las redes sociales, espacio que se ha constituido como un nuevo lugar para la divulgación de asuntos diversos: desde temas de ocio o entretenimiento hasta temas académicos, científicos y políticos. En ese sentido, este curso propone que el alumno asuma el rol de un ciudadano crítico, es decir, aquella persona que no solo consume información, sino que produce contenido a partir de una investigación en fuentes confiables. Considerando lo explicado, nuestros alumnos no solo serán capaces de redactar un texto escrito formal de acuerdo con las necesidades comunicativas del ámbito universitario y de la sociedad actual, sino que podrán transformarlo en un texto multimodal (el cual involucra diferentes medios de comunicación: visual, auditivo, imagen, texto, entre otros) que tenga sentido en las redes sociales, lugar de interacción real con sus lectores. Estos productos comunicativos deberán presentar una organización conveniente, un desarrollo sólido y suficiente (lo que implica una lectura crítica de las fuentes de información), y una escritura acorde con la normativa vigente. 3 Propósito: El curso desarrolla la competencia de comunicación escrita, en el nivel 1; es decir, el estudiante es capaz de construir mensajes coherentes y sólidos que se adecúan a la situación y propósito comunicativo. Este desarrollo le permite la generación y construcción de nuevas ideas, lo cual es relevante para su vida académica y profesional. La actual sociedad de la información y el conocimiento, caracterizada por la disrupción, la innovación y la complejidad en las formas de comunicación mediadas por la tecnología, enfrenta al estudiante y al profesional a nuevos retos en las maneras de comunicar aquello que conoce y que construye. En este escenario, la competencia comunicativa escrita adquiere protagonismo como herramienta para transmitir el conocimiento creado. El curso se alinea con esta exigencia, pues contribuye a que el estudiante responda exitosamente a las demandas comunicativas del contexto académico, y a que el egresado pueda desenvolverse idóneamente en el campo profesional y laboral

Head and neck cancer surgery during the COVID-19 pandemic: An international, multicenter, observational cohort study

Background: The aims of this study were to provide data on the safety of head and neck cancer surgery currently being undertaken during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This international, observational cohort study comprised 1137 consecutive patients with head and neck cancer undergoing primary surgery with curative intent in 26 countries. Factors associated with severe pulmonary complications in COVID-19–positive patients and infections in the surgical team were determined by univariate analysis. Results: Among the 1137 patients, the commonest sites were the oral cavity (38%) and the thyroid (21%). For oropharynx and larynx tumors, nonsurgical therapy was favored in most cases. There was evidence of surgical de-escalation of neck management and reconstruction. Overall 30-day mortality was 1.2%. Twenty-nine patients (3%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 30 days of surgery; 13 of these patients (44.8%) developed severe respiratory complications, and 3.51 (10.3%) died. There were significant correlations with an advanced tumor stage and admission to critical care. Members of the surgical team tested positive within 30 days of surgery in 40 cases (3%). There were significant associations with operations in which the patients also tested positive for SARS-CoV-2 within 30 days, with a high community incidence of SARS-CoV-2, with screened patients, with oral tumor sites, and with tracheostomy. Conclusions: Head and neck cancer surgery in the COVID-19 era appears safe even when surgery is prolonged and complex. The overlap in COVID-19 between patients and members of the surgical team raises the suspicion of failures in cross-infection measures or the use of personal protective equipment. Lay Summary: Head and neck surgery is safe for patients during the coronavirus disease 2019 pandemic even when it is lengthy and complex. This is significant because concerns over patient safety raised in many guidelines appear not to be reflected by outcomes, even for those who have other serious illnesses or require complex reconstructions. Patients subjected to suboptimal or nonstandard treatments should be carefully followed up to optimize their cancer outcomes. The overlap between patients and surgeons testing positive for severe acute respiratory syndrome coronavirus 2 is notable and emphasizes the need for fastidious cross-infection controls and effective personal protective equipment

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AimThe SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery.MethodsThis was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin.ResultsOverall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P ConclusionOne in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease