Hepatitis C virus molecular evolution: Transmission, disease progression and antiviral therapy

Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era.Fil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valva, Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Escobar Gutierrez, Alejandro. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Rahal, Paula. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Ruiz Tovar, Karina. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Yamasaki, Lilian. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Vazquez Chacon, Carlos. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Martinez Guarneros, Armando. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Carpio Pedroza, Juan Carlos. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Fonseca Coronado, Salvador. Universidad Nacional Autónoma de México; MéxicoFil: Cruz Rivera, Mayra. Universidad Nacional Autónoma de México; Méxic

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia, departamento de Boyacá

Nota. En esta tabla se relacionan las preguntas asociadas a la narrativa del caso de Amparo, Nota. Se relacionan en la tabla las estrategias aplicadas para generar un cambio de la población de El salado.El conflicto armado ha dejado una marca oscura en sus víctimas, en donde la afectación psicosocial es grande está acompañada de miedo y aquellas heridas que siguen abiertas, en donde es importante promover el perdón, de la reconciliación y la aceptación como un camino en búsqueda de la justicia y la reparación. Tomando el Capítulo 3 de la narrativa de la historia y las vivencias de amparo desde su experiencia del secuestro y desaparición de su esposo, además del exilio vivido por ella y su familia la cual es una realidad que afrontan muchas familias en Colombia debido al conflicto armado. Teniendo en cuenta el caso se desarrolla una entrevista integrando preguntas de forma reflexivas, circulares y estratégicas con el fin de realizar una aproximación psicosocial proactivo y ético, identificando la manera en que supero sus condiciones de victimización. por otro lado, se aborda el caso de la masacre del salado la cual se identifica hechos victimizantes y traumáticos que han afectado psicológica y emocionalmente a las poblaciones. Se plantean tres estrategias que brindan unas herramientas hacia un proceso de afrontamiento en pro de su bienestar físico y emocional. Desde el estudio de la herramienta foto voz, se identificaron las diferentes problemáticas encontradas desde los diversos contextos asociados desde la violencia (inseguridad, consumo de sustancias, intolerancia, etc.) a partir de lo anterior se determina que la violencia ha afectado considerablemente la parte psicológica, física y emocional de las personas desde sus diferentes contextos y tipos de violencia a los cuales están expuestos.The armed conflict has left a dark mark on its victims, where the psychosocial impact is great, accompanied by fear and those wounds that remain open, where it is important to promote forgiveness, reconciliation, and acceptance as a path in search of justice and reparation. Taking Chapter 3 of the narrative of the story and the experiences of protection from her experience of the kidnapping and disappearance of her husband, in addition to the exile experienced by her and her family which is a reality that many families face in Colombia due to the armed conflict. Considering the case, an interview is developed integrating reflective, circular and strategic questions in order to carry out a proactive and ethical psychosocial approach, identifying the way in which they overcome their conditions of victimization. On the other hand, the case of the Salado massacre is addressed, which identifies victimizing and traumatic events that have psychologically and emotionally affected the populations. Three strategies are proposed that provide tools towards a coping process for your physical and emotional well-being. From the study of the photo voice tool, the different problems found from the various contexts associated with violence (insecurity, substance consumption, intolerance, etc.) were identified. From the above it is determined that violence has considerably affected the psychological, physical, and emotional of people from their different contexts and types of violence to which they are exposed

Travelling with Dengue: From the Skin to the Nodes

Dengue virus (DENV) infects humans through the skin. The early infection and encounters between DENV and cutaneous immune and non‐immune cells only recently are under investigation. We have reported DENV‐infected cutaneous dendritic cells (DCs), also keratinocytes and dermal fibroblasts permissive to DENV infection. Now, upon cutaneously inoculating fluorescently labeled DENV into immune‐competent mice, we found DENV mostly in dermis from 1 h post‐inoculation. Afterwards, DENV rapidly localized in the subcapsular sinus of draining lymph nodes (DLNs) associated with CD169+ macrophages, suggesting virus travelling through lymph flow. However, DENV association with CD11c+ DCs in the paracortex and T:B border suggests DENV being ferried from the skin to DLNs by DCs too. DENV was not associated with F4/80+ macrophages nor with DEC205+ DCs, but it was inside B cell follicles early after cutaneous inoculation. DENV inside B follicles likely affects the development of humoral responses. Antibody responses deserve very careful scrutiny as neutralizing memory antibodies are crucial to counteract homotypic reinfections whereas non‐neutralizing ones might facilitate heterotypic DENV infection or even Zika infection, another flavivirus. Unravelling the DENV journey from skin to lymph into regional nodes and the cellular compartments will aid to understand the disease, its pathology and how to counteract it

Is ultra-violet radiation the main force shaping molecular evolution of varicella-zoster virus?

<p>Abstract</p> <p>Background</p> <p>Varicella (chickenpox) exhibits a characteristic epidemiological pattern which is associated with climate. In general, primary infections in tropical regions are comparatively less frequent among children than in temperate regions. This peculiarity regarding varicella-zoster virus (VZV) infection among certain age groups in tropical regions results in increased susceptibility during adulthood in these regions. Moreover, this disease shows a cyclic behavior in which the number of cases increases significantly during winter and spring. This observation further supports the participation of environmental factors in global epidemiology of chickenpox. However, the underlying mechanisms responsible for this distinctive disease behavior are not understood completely. In a recent publication, Philip S. Rice has put forward an interesting hypothesis suggesting that ultra-violet (UV) radiation is the major environmental factor driving the molecular evolution of VZV.</p> <p>Discussion</p> <p>While we welcomed the attempt to explain the mechanisms controlling VZV transmission and distribution, we argue that Rice's hypothesis takes lightly the circulation of the so called "temperate VZV genotypes" in tropical regions and, to certain degree, overlooks the predominance of such lineages in certain non-temperate areas. Here, we further discuss and present new information about the overwhelming dominance of temperate VZV genotypes in Mexico regardless of geographical location and climate.</p> <p>Summary</p> <p>UV radiation does not satisfactorily explain the distribution of VZV genotypes in different tropical and temperate regions of Mexico. Additionally, the cyclic behavior of varicella does not shown significant differences between regions with different climates in the country. More studies should be conducted to identify the factors directly involved in viral spreading. A better understanding of the modes of transmissions exploited by VZV and their effect on viral fitness is likely to facilitate the implementation of preventive measures for disease control.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Taenia solium: Immune response against oral or systemic immunization with purified recombinant calreticulin in mice

Recombinant functional Taenia solium calreticulin (rTsCRT) confers different degrees of protection in the experimental model of intestinal taeniosis in hamsters. The aim of this study was to evaluate the immune response induced after oral or systemic immunization with an electroeluted rTsCRT in BALB/c mice. Oral immunization elicited high fecal IgA and the production of IL-4 and IL-5 by mesenteric lymph node cells after in vitro stimulation with rTSCRT, indicating a Th2 response. Mice subcutaneously immunized produced high amounts of serum IgG, being IgG1 (Th2-related) the predominant isotype, while in vitro stimulated spleen cells synthesized IL-4, IL-5 and also IFN-gamma, indicating a mixed Th1/Th2 cellular response after systemic immunization. Our data show that purified rTsCRT induces polarized Th2 responses after oral immunization of mice, a common characteristic of protective immunity against helminths and, consequently, a desirable hallmark in the search for a vaccine. (C) 2010 Elsevier Inc. All rights reserved

Efeitos do tratamento fisioterapêutico com o Wii Balance Board nas alterações posturais de duas crianças com paralisia cerebral. Caso clinico

Introducción: Este estudio pretendió determinar los efectos del tratamiento fisioterapéutico con el accesorio Wii Balance Board y el juego Wii Fit Plus —ambos de la consola Wii, de la empresa Nintendo Company Limited— en las alteraciones posturales de niños con hemiparesia espástica. Materiales y métodos: Estudio de caso de cohorte longitudinal, realizado con la participación de dos niños con parálisis cerebral, tipo hemiparesia espástica del municipio de Popayán, Cauca, a quienes se les realizó una evaluación de la postura estática con el software APIC v. 2.0. Posteriormente, se ejecutó un programa de ejercicios utilizando el juego Wii Fit Plus con el Wii Balance Board durante 20 sesiones. Resultados: Los dos pacientes presentaron cambios importantes en la lateralización del centro de gravedad, lo que, a largo plazo, puede favorecer la corrección de las alteraciones posturales. Conclusiones: Laaplicación del juego con Wii Fit Plus con el Wii Balance Board en fisioterapia es una alternativa útil en la rehabilitación de estos pacientes con hemiparesia, relacionado con una mejor distribución del centro de gravedad. Se debe evitar la sobrecarga de peso y las compensaciones.Introduction: This study tried to determine the effects on the treatments in physical therapy with the Wii Balance Board and Wii Fit Plus __both of Wii, Nintendo Company Limited__ concerning the postural changes on children suffering spastics hemiparesis. Material and methods: Longitudinalcohort case studies done with two children, from the municipality of Popayán, suffering cerebral palsy type spastic hemiparesis. This children had a test on static posture with the software APIC v. 2.0, previously, It was executed an exercises program using Wii Fit plus Balance Board for 20 sessions. Results: Both of the patients had remarkable changes on lateralization of the center of gravity. This change can subserve the postural changes later. Conclusions: Theapplication of the game with Wii Fit Plus with Wii Balance Board in physical therapy is a useful alternative in rehabilitation of hemi paretic patients related to a better distribution of the center of gravity. It is advisable to avoid weight overload and compensations.Introdução: Este estudo pretende determinar os efeitos do tratamento fisioterapéutico com o Balance Board Wii e Wii Fit Plus -tanto o Wii, Nintendo Company Limited- nas alterações posturais de crianças com hemiparesea espástica. Materiais e métodos: Estudos de caso longitudinais feitos com a participação de duas crianças com paralisia cerebral de tipo hemiparesia espástica, de cidade de Popayán, Cauca; avaliou-se a postura estática deles com o software APIC v. 2.0. Depois se executou um programa de exercícios usando o Wii Fit Plus Balance Board por vinte sessões. Resultados: Nenhum dos dois pacientes apresentaram efeitos favoráveis na correção das alteraçõesposturais; embora mostraram-se mudanças importantes na distribuição do centro da gravidade. Conclusões: A aplicação do jogo com o Wii Fit Plus com o Wii Balance Board não tem benéficos nas alterações posturais, po isso poderia recomendar-se fazer estudos com um número maior de participantes e com mais tempo para a intervenção