Adult and pediatric physiologically-based biopharmaceutics modeling to explain lamotrigine immediate release absorption process.

Physiologically-based biopharmaceutics modeling (PBBM) has potential to accelerate the development of new drug and formulations. An important application of PBBM is for special populations such as pediatrics that have pharmacokinetics dependent on the maturation process. Lamotrigine (LTG) is a Biopharmaceutics Classification System (BCS) II drug and is widely prescribed. Therefore, the goal of this study was to assess the biopharmaceutics risk of the low-soluble drug LTG when the ontogeny on gastrointestinal tract (GIT) physiological parameters are considered. An oral physiologically-based pharmacokinetic model and a PBBM were developed and verified using GastroPlus™ software for both adults and children (2-12 years old, 12-52 kg). The biopharmaceutics properties and GIT physiological parameters were evaluated by sensitivity analysis. High doses were simulated assuming a worst case scenario, that is, the dose of 200 mg for adults and 5 mg/kg (up to the maximum of 200 mg) for 2-year-old children. Although several authors have suggested that ontogeny may have an effect on gastrointestinal fluid volume, our study found no evidence of interference between fluid and dose volumes with in vivo dissolution of LTG. The most impactful parameter was found to be the gastric transit time. Therefore, the hypothesis is developed to examine whether LTG exhibits characteristics of a BCS II classification in vitro while showing BCS I-like behavior in vivo. This hypothesis could act as a base for conducting novel studies on model-informed precision dosing, tailored to specific populations and clinical conditions. In addition, it could be instrumental in assessing the influence of various release profiles on in vivo performance for both adult and pediatric populations.

Development of an in vivo murine model of perineural invasion and spread of cutaneous squamous cell carcinoma of the head and neck.

Introduction: Cutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An in vivo sciatic nerve mouse model is used for cSCCHN PNI/PNS. Here we describe a complementary whisker pad model which allows for molecular studies investigating drivers of PNI/PNS in the head and neck environment. Methods: A431 cells were injected into the whisker pads of BALB/c Foxn1nu and NSG-A2 mice. Tumor progression was monitored by bioluminescence imaging and primary tumor resection was performed. PNI was detected by H&E and IHC. Tumor growth and PNI were assessed with inducible ablation of LOXL2. Results: The rate of PNI development in mice was 10%-28.6%. Tumors exhibited PNI/PNS reminiscent of the morphology seen in the human disease. Our model's utility was demonstrated with inducible ablation of LOXL2 reducing primary tumor growth and PNI. Discussion: This model consists in a feasible way to test molecular characteristics and potential therapies, offers to close a gap in the described in vivo methods for PNI/PNS of cSCCHN and has uses in concert with the established sciatic nerve model.

Environmental assessment of on-site source-separated wastewater treatment and reuse systems for resource recovery in a sustainable sanitation view.

Sustainable sanitation solutions are necessary for promoting public health and environmental security. In this study, on-site domestic wastewater treatment (WWT) systems used for households in rural and peri-urban areas of Brazil were compared in different scenarios from a life cycle assessment (LCA) perspective. The evaluated scenarios represented different practices in wastewater management, such as direct discharge into the soil, rudimentary treatment, septic tank, public sewerage system, and source separation of wastewater streams for water, nutrient, and organic matter recovery. The WWT technologies considered in the proposed scenarios of source-separated wastewater streams were as follows: an evapotranspiration tank (TEvap) and composting toilet for blackwater, a modified constructed wetland (EvaTAC) for greywater, and a storage tank for urine. LCA was performed in this study according to the ISO standards to assess the environmental impacts at both midpoint and endpoint levels. The results show that on-site source-separated wastewater treatment systems with resource recovery result in significant reductions in environmental impacts compared to scenarios with precarious conditions or 'end-of-pipe' solutions. For example, regarding the human health damage category, the scenarios involving resource recovery, including systems such as EvaTAC, TEvap, composting toilet, and urine storage tank, demonstrate significantly lower values (-0.0117 to -0.0115 DALY) compared to scenarios with rudimentary cesspits and septic tanks (0.0003 to 0.001 DALY). We conclude that the focus should be beyond mere pollution aspects and instead concentrate on the benefits of the co-products, which are: avoiding the extraction and consumption of valuable and increasingly scarce raw materials, such as potable water, and production of synthetic fertilizer. Furthermore, it is highly recommended that an LCA of sanitation systems synergistically integrates the WWT process, the constructive aspects, and the resource recovery potential.

Interplay between liver and blood stages of Plasmodium infection dictates malaria severity via γδ T cells and IL-17-promoted stress erythropoiesis.

Plasmodium replicates within the liver prior to reaching the bloodstream and infecting red blood cells. Because clinical manifestations of malaria only arise during the blood stage of infection, a perception exists that liver infection does not impact disease pathology. By developing a murine model where the liver and blood stages of infection are uncoupled, we showed that the integration of signals from both stages dictated mortality outcomes. This dichotomy relied on liver stage-dependent activation of Vγ4+ γδ T cells. Subsequent blood stage parasite loads dictated their cytokine profiles, where low parasite loads preferentially expanded IL-17-producing γδ T cells. IL-17 drove extra-medullary erythropoiesis and concomitant reticulocytosis, which protected mice from lethal experimental cerebral malaria (ECM). Adoptive transfer of erythroid precursors could rescue mice from ECM. Modeling of γδ T cell dynamics suggests that this protective mechanism may be key for the establishment of naturally acquired malaria immunity among frequently exposed individuals.

Perfuração coronária durante intervenção coronária percutânea: descrição de uma técnica de salvamento / Coronary perforation during percutaneous coronary intervention: description of a salvage technique

A perfuração de artéria coronária durante intervenção coronária percutânea é um evento incomum (0,43%), porém potencialmente grave e com elevado risco de tamponamento cardíaco e morte. Perfurações graves exigem implante de stent recoberto, muitas vezes indisponível. Descrevemos uma técnica alternativa e simples de tratamento, que pode ser realizada com uso de politetrafluoretileno de um balão amarrado sobre um stent coronário.

A coronary artery perforation during percutaneous coronary intervention is an uncommon (0.43%) but potentially severe event, with high risk of cardiac tamponade and death. Severe perforations require placing a covered stent, which is often unavailable. We describe an alternative and simple treatment technique, which can be performed using polytetrafluoroethylene from a balloon tied over a coronary stent.

Inflammation as a Prognostic Marker in Heart Failure.

BACKGROUND: Heart failure (HF) is a chronic cardiac disease of great importance worldwide and responsible for one-fifth of hospitalizations for cardiovascular disease in Brazil. Pro-inflammatory mediators are involved in the pathophysiology of HF. However, the impact of inflammatory markers on the prognosis of the disease remains uncertain. OBJECTIVE: We aimed to evaluate inflammation as a prognostic marker in chronic HF. METHODS: In this prospective, single-center, observational cohort study conducted from June 2018 through December 2019, we included outpatients with HF from a specialized service of a teaching hospital. Patients with decompensated HF requiring hospitalization in the last 30 days were excluded. At the time of inclusion, serum C-reactive protein (CRP) and albumin were collected and the presence of inflammation was defined as CRP/albumin ≥1.2. Patients with CRP/albumin ratio <1.2 (group A) and CRP/albumin ratio ≥1.2 (group B) were compared. The primary outcome was all-cause mortality. The secondary outcomes were hospitalization for decompensated HF, number of hospitalizations, and number of days of hospitalization in the 12-month follow-up. RESULTS: We included 77 patients, 49 (63.3%) in group A and 28 (3.4%) in group B. Six patients in group A (12.2%) and 10 patients in group B (35.7%) required at least one hospitalization during follow-up (p=0.01). The rate of hospitalizations for decompensated HF for every 100 patients was 16.3 in group A vs 50.0 in group B (p=0.0001) and the average in-hospital length of stay was 12.2 vs 14.2 days per hospitalized patient (p=0.36) in groups A and B, respectively. The mortality rate was 6.1% in group A vs 7.1% in group B (p=0.86). CONCLUSION: In HF outpatients with inflammation evidentiated by the CRP/albumin ratio ≥1.2, the risk of death was similar to patients without inflammation criteria. However, the presence of inflammation led to a three-fold higher risk of hospitalization for HF decompensation.

Involvement of the cannabinoid system in chronic inflammatory intestinal diseases: opportunities for new therapies.

The components of the endogenous cannabinoid system are widely expressed in the gastrointestinal tract contributing to local homeostasis. In general, cannabinoids exert inhibitory actions in the gastrointestinal tract, inducing anti-inflammatory, antiemetic, antisecretory, and antiproliferative effects. Therefore, cannabinoids are interesting pharmacological compounds for the treatment of several acute intestinal disorders, such as dysmotility, emesis, and abdominal pain. Likewise, the role of cannabinoids in the treatment of chronic intestinal diseases, such as irritable bowel syndrome and inflammatory bowel disease, is also under investigation. Patients with chronic intestinal inflammatory diseases present impaired quality of life, and mental health issues are commonly associated with long-term chronic diseases. The complex pathophysiology of these diseases contributes to difficulties in diagnosis and, therefore, in the choice of a satisfactory treatment. Thus, this article reviews the involvement of the cannabinoid system in chronic inflammatory diseases that affect the gastrointestinal tract and highlights possible therapeutic approaches related to the use of cannabinoids.

Resource-oriented sanitation: Identifying appropriate technologies and environmental gains by coupling Santiago software and life cycle assessment in a Brazilian case study.

Implementation of resource recovery technologies is becoming increasingly important, as humans are exhausting the world's natural resources. Recovering nutrients and water from wastewater treatment systems will play an important role in changing the current trends towards a circular economy. However, guidance is still needed to determine the most appropriate way to do this. In this study two decision-support tools, sanitation planning software (Santiago) and life cycle assessment (LCA), were applied to identify appropriate technologies and their environmental impacts. As a case study, current and alternative scenarios for a wastewater treatment plant (WWTP) in Campo Grande, west-central Brazil, were used. Among 12 scenarios provided by Santiago for efficient nutrient recovery, eight were selected for further assessment. The current WWTP system (UASB reactors) resulted in the highest negative impacts in two of nine assessment categories (freshwater and marine eutrophication), due to nutrient discharge to water. A source separation scenario with urine stored in a urine bank and co-composting of feces showed best overall performance. Electricity consumption played a crucial role for impacts in several categories, while water consumption was not significantly affected by choice of toilet. One Santiago scenario matched the most appropriate scenario with the best environmental performance, but the other seven scenarios were not as beneficial, indicating a need for some adjustments in the software. These results highlight the importance of performing LCA to compare alternative scenarios, even when using a tool designed to identify locally appropriate technologies. The results also indicate that the current wastewater treatment system has reasonable environmental performance, but could be improved if measures were taken to recover energy and reuse water.

Interchangeability among carbamazepine formulations: the impact over epilepsy patients

Abstract The treatment of epilepsy is complex and a matter of concern is the interchangeability among different formulations available for antiepileptic drugs. To evaluate the effects of interchangeability among carbamazepine formulations on patients with epilepsy. This is a prospective cohort study that included adult outpatients diagnosed with epilepsy and under pharmacological treatment with carbamazepine. Before switching the brand/manufacturer, the "Interchangeable Pharmaceutical Product in the Treatment of Epilepsies" questionnaire was applied. The questionnaires "Adverse Events Profile" and Quality of Life in Epilepsy-31, so as the plasma carbamazepine concentrations, were evaluated before and after the brand/ manufacturer switch. Physical-chemical tests aiming to assess tablets quality were performed in accordance with the Brazilian Pharmacopoeia 5th edition. The study population was composed by 14 patients (mean age: 44.6 years), with 10 of females. From those interviewed, 10 had no knowledge about the three antiepileptic drugs formulations available. The frequency of adverse event "problems with skin" incresead (p=0.023) and "upset stomach" decreased (p=0.041) after the changeover. The adverse events profile was associated with only two quality of life domains: "energy/fatigue" (p=0.048) and "total score" (p=0.018). Divergent results between generic and reference formulations were observed in purity-water test (reference: 1.96%, generic: 4.84%) and dissolution test, in which the generic formulation presented 66.27 to 85.77% of carbamazepine dissolved after the third level. Conclusions: Objective differences before and after the brand/manufacturer switch were not observed, in spite of patients' perceptions. Despite that, more studies in the field are necessary, especially on the interchangeability among generic antiepileptics, in order to better elucidate switching consequences on patients' life.

Reabilitação estética com facetas semidiretas: relato de caso / Aestethic rehabilitation with semidirect facets: case report / Rehabilitación estética con facetas semidirectas: reporte de caso

Introdução: É crescente a busca por tratamentos estéticos nas clínicas odontológicas, dentre esta demanda, encontra-se soluções reabilitadoras para casos de diastemas e incisivos laterais superiores com morfologia conoide, pois são tidos como fatores antiestéticos. Objetivo: Apresentar uma abordagem interdisciplinar no tratamento de diastemas e unidades dentárias com morfologia conoide. Relato de caso: O paciente procurou atendimento odontológico especializado para reabilitação provisória da estética e função das unidades anterossuperiores durante finalização do tratamento ortodôntico e posteriormente, após conclusão da ortodontia, a reabilitação final. Durante o exame clínico foram observados incisivos laterais superiores com morfologia conoides, ângulo incisal amplo entre os incisivos centrais, ausência de guia canina e diastemas. Após registro fotográfico, foram realizadas as restaurações provisórias. Finalizado o tratamento ortodôntico, o plano de tratamento consistiu na reabilitação através das facetas semidiretas em resina composta. Após moldagem anatômica, enceramento e clareamento dentário, foram realizados os preparos dentários e moldagem funcional, sendo a seguir realizado o ensaio restaurador. Sobre o modelo, foram confeccionadas as facetas em resina composta e realizado o acabamento inicial. Para a fase de cimentação priorizou-se a utilização de condicionamento ácido seletivo para esmalte, cimento fotopolimerizado e uso de polimerizador de alta potência. Após a cimentação foram realizados os ajustes oclusais e acabamento final, com texturização da superfície, seguido pelo polimento. Conclusão: O tratamento realizado evidenciou a importância do tratamento ortodôntico associado a Odontologia Restauradora para o restabelecimento da estética e função, obtendo resultados que melhoraram as relações entre dentes, posicionamento dos lábios, harmonia e equilíbrio dental e facial(AU)

Introduction: There is a growing demand for aesthetic treatments in dental clinics, among this demand, there are rehabilitation solutions for cases of diastemas and upper lateral incisors with conoidmorphology, as they are considered as anti-aesthetic factors. Objective: Present an interdisciplinary approach in the treatment of diastemas and dental units with conoid morphology. Case report: The patient sought specialized dental care for provisional rehabilitation of the aesthetics and function of the anterosuperior units during the finalisation of the orthodontic treatment and later, after completion of orthodontics, the final rehabilitation. During the clinical examination, upper lateral incisors with conoid morphology, wide incisal angle between the central incisors, absence of canine guide and diastemas were observed. After photographic register, provisional restorations were performed. After orthodontic treatment was completed, the treatment plan consisted of rehabilitation through semi-direct facets in composite resin. After anatomical moulding, waxing and tooth whitening, dental preparations and functional mouldingwere performed, hereinafter the restorative test was performed. In this connection,facets were made in composite resin and the initial finishing was carried out. For the cementation phase, priority was given to the use of selective acid conditioning for dental enamel, photopolymerized cement and the use of high-power polymerizer. After cementation, occlusal adjustments and finishing touch were performed with surface texturing, followed by polishing. Conclusion: The treatment performed showed the importance of orthodontic treatment associated with restorative dentistry for the restorationof aesthetics and function, obtaining results that improved the relationship between teeth, positioning of the lips, harmony and dental and facial balance(AU)

Introducción: Crece la búsqueda de tratamientos estéticos en las clínicas dentales, entre esta demanda se encuentran las soluciones rehabilitadoras para casos de diastema e incisivos laterales superiores con morfología conoide, por considerarse factores antiestéticos. Objetivo: Presentar un abordaje interdisciplinario en el tratamiento del diastema y unidades dentales con morfología conoide. Caso clínico: El paciente buscó atención odontológica especializada para la rehabilitación temporal de laestética y función de las unidades anterosuperiores durante la finalización del tratamiento de ortodoncia y posteriormente, trasla finalización de la ortodoncia, la rehabilitación final. Durante el examen clínico se observaron incisivos laterales superiores con morfología conoide, amplio ángulo incisal entre los incisivos centrales, ausencia de guía canina y diastema. Después del registro fotográfico, se realizaron restauraciones provisionales. Una vez finalizado el tratamiento de ortodoncia, el plan detratamiento consistió en la rehabilitación mediante carillas de resina compuesta semidirectas. Después del moldeado anatómico, encerado y blanqueamiento dental, se realizaron las preparaciones dentales y el moldeado funcional, seguido de la prueba restauradora.Sobre el modelo, las carillas se realizaron en resina compuesta y se realizó el acabado inicial. Para la fase de cementación se priorizó el uso de grabado ácido selectivo para esmalte, cemento fotopolimerizable y el uso de un polimerizador de alta potencia. Después de la cementación, se realizaron ajustes oclusales y acabado final, con texturizado de la superficie, seguido de pulido. Conclusión: El tratamiento realizado mostró la importancia del tratamiento de ortodoncia asociado a la odontología restauradora para la restauración de la estética y función, obteniendo resultados que mejoraron la relación entre los dientes, la posición de los labios, la armonía y el equilibrio dental y facial(AU)

Conhecimento teórico-prático da equipe de enfermagem referente à reanimação cardiopulmonar no âmbito intra-hospitalar / Conocimientos teórico-prácticos del equipo de enfermería sobre reanimación cardiopulmonar en el ámbito hospitalario / Theoretical-practical knowledge of the nursing team regarding cardiopulmonary resuscitation in the hospital environment

Objetivo: descrever o conhecimento teórico-prático da equipe de enfermagem referente a reanimação cardiopulmonar no âmbito intra-hospitalar. Método: revisão integrativa, realizada em Literatura Latino-Americana e do Caribe em Ciências da Saúde, Medical Literature Analysis and Retrieval System Online e Base de Dados em Enfermagem. Foram incluídos artigos originais, disponíveis na íntegra, publicados de 2010 a 2020, em qualquer idioma Resultados: como potencialidade, os profissionais sabem como detectar os sinais de parada cardiorrespiratória e realizar a sequência da reanimação cardiopulmonar do suporte básico de vida. Já como fragilidades, a maioria dos profissionais não sabe como realizar a relação compressão/ventilação do suporte avançado de vida, nem como identificar ritmos cardíacos ou fármacos utilizados. Conclusão: o conhecimento da equipe de enfermagem, referente a temática, encontra-se fragilizado e está relacionado à importância das capacitações nas instituições de saúde.(AU)

Objective: to describe the theoretical-practical knowledge of the nursing team regarding cardiopulmonary resuscitation in the hospital environment. Method: integrative review, performed in Latin American and Caribbean Literature in Health Sciences, Medical Literature Analysis and Retrieval System Online and Nursing Database. Original articles, available in full, published from 2010 to 2020, in any language, were included. Results: as a potentiality, professionals know how to detect signs of cardiorespiratory arrest and perform the sequence of cardiopulmonary resuscitation from basic life support. As for weaknesses, most professionals do not know how to perform the compression/ventilation ratio of advanced life support, nor how to identify cardiac rhythms or drugs used. Conclusion: the nursing team's knowledge regarding the theme is fragile and is related to the importance of training in health institutions.(AU)

Objetivo: describir los conocimientos teórico-prácticos del equipo de enfermería sobre la reanimación cardiopulmonar en el ámbito hospitalario. Método: revisión integradora, realizada en Literatura Latinoamericana y del Caribe en Ciencias de la Salud, Medical Literature Analysis and Retrieval System Online y Base de Datos de Enfermería. Se incluyeron artículos originales, disponibles íntegramente, publicados de 2010 a 2020, en cualquier idioma. Resultados: como potencialidad, los profesionales saben detectar signos de parada cardiorrespiratoria y realizar la secuencia de reanimación cardiopulmonar desde suporte vital básico. En cuanto a las debilidades, la mayoría de los profesionales no saben cómo realizar la relación compresión/ventilación del soporte vital avanzado, ni cómo identificar los ritmos cardíacos o los fármacos utilizados. Conclusión: el conocimiento del equipo de enfermería sobre el tema está debilitado y se relaciona con la importancia de la formación en las instituciones de salud.(AU)

Human papillomavirus infection and oral squamous cell carcinoma - a systematic review / Infecção por papilomavírus humano e carcinoma espinocelular oral - Uma revisão sistemática

Abstract Introduction The association between uterine cervix and anogenital carcinomas and human papillomavirus, HPV, is well established, however the involvement of this virus in the development of oral squamous cell carcinomas remains controversial. Objectives To evaluate the relationship between HPV infection and oral squamous cell carcinomas, and to estimate the incidence of this infection in these patients. Methods Four electronic databases were searched to find studies that met the following inclusion criteria: i) performed in humans; ii) were cohort, case-control or cross-sectional; iii) assessed the HPV oncogenic activity by the E6 and E7 mRNA; iv) included primary oral squamous cell carcinomas which; v) diagnosis had been confirmed by biopsy. Information about the country; study period; sample obtainment; sites of oral squamous cell carcinomas; number, gender and age range of the population; the prevalence of HPV infection and subtypes detected; use of tobacco or alcohol and oral sex practice were extracted. The methodological quality of included articles was assessed using 14 criteria. Results The search strategy retrieved 2129 articles. Assessment of the full text was done for 626 articles, but five were included. The total of participants included was 383, most of them male with mean age between 51.0 and 63.5 years old. Seventeen patients were HPV/mRNA-positive, being the subtypes 16 and 18 detected more frequently. Nine of the HPV/mRNA-positive oral squamous cell carcinomas occurred on the tongue. The quality score average of included articles was five points. Conclusions Among the 383 oral squamous cell carcinoma patients included, 17 (4.4%) were HPV/mRNA-positive, nevertheless it was not possible to assess if HPV infection was associated with oral squamous cell carcinomas because none of the studies included was longitudinal and cross-sectional investigations do not have control group.

Resumo Introdução A associação entre os carcinomas de colo uterino e anogenitais e o papilomavírus humano (HPV) está bem estabelecida; entretanto, o envolvimento desse vírus no desenvolvimento de carcinomas espinocelulares orais permanece controverso. Objetivos Avaliar a relação entre a infecção pelo HPV e os carcinomas espinocelulares orais e estimar a proporção dessa infecção nesses pacientes. Método Quatro bases de dados eletrônicas foram pesquisadas para encontrar estudos que atendessem aos seguintes critérios de inclusão: i) feitos em humanos; ii) estudos do tipo coorte, caso-controle ou transversal; iii) avaliaram a atividade oncogênica do HPV pelo mRNA E6 e E7; iv) incluíram CECOs primários, cujo diagnóstico foi confirmado por biópsia; v) o diagnóstico foi confirmado por biópsia. Informações sobre o país; período do estudos; obtenção da amostra; locais dos carcinomas espinocelulares orais; número, sexo e faixa etária da população; prevalência de infecção por HPV e subtipos detectados; informações sobre o uso de tabaco ou álcool e a prática de sexo oral foram obtidas. A qualidade metodológica dos artigos incluídos foi avaliada através de 14 critérios. Resultados A estratégia de busca recuperou 2.129 artigos. A avaliação de texto completo foi feita em 626 artigos, mas apenas cinco foram incluídos. O total de participantes incluídos foi de 383, a maioria do sexo masculino e com média de idade entre 51,0 e 63,5 anos. Dezessete pacientes eram HPV/mRNA-positivos, os subtipos 16 e 18 foram detectados com maior frequência. Nove dos carcinomas espinocelulares orais HPV/mRNA-positivos ocorreram na língua. A média do escore de qualidade dos artigos incluídos foi de cinco pontos. Conclusões Entre os 383 pacientes incluídos com carcinomas espinocelulares orais, 17 (4,4%) eram HPV/mRNA-positivos; entretanto, não foi possível avaliar se a infecção por HPV estava associada com carcinomas espinocelulares orais porque nenhum dos estudos incluídos era longitudinal e as investigações transversais não têm grupo controle.

Immunogenicity, duration of protection, effectiveness and safety of rubella containing vaccines: A systematic literature review and meta-analysis.

BACKGROUND: Rubella containing vaccines (RCV) prevent rubella virus infection and subsequent congenital rubella syndrome (CRS). To update the evidence on immunogenicity, duration of protection, effectiveness and safety of RCV, we conducted a systematic literature review. METHODS: We searched EMBASE and SCOPUS, using keywords for rubella vaccine in combination with immunogenicity (seroconversion and seropositivity), duration of protection, efficacy/effectiveness, and safety. Original research papers involving at least one dose of RCV (at any age), published between 1-1-2010 and 17-5-2019 were included. Where appropriate, meta-analyses were performed. Quality of included studies was assessed using GRADE methodology. RESULTS: We included 36 papers (32 randomized controlled trials (RCTs) and 4 observational studies) on immunogenicity (RA27/3 strain) in children and adolescent girls, 14 papers (5 RCTs and 9 observational studies) on duration of protection, one paper on vaccine effectiveness (VE) (BRDII strain), and 74 studies on safety, including three on safety in pregnancy. Meta-analysis of immunogenicity data showed 99% seroconversion (95% CI: 98-99%) after a single dose of RCV in children, independent of co-administration with other vaccines. Seroconversion after RCV1 below 9 months of age (BRDII strain, at 8 months) was 93% (95% CI: 92-95%). For duration of protection, the included studies showed a seropositivity of 88%-100% measured 1-20 years after one or two RCV doses. The single study on VE of BRDII strain, reported 100% VE after one and two doses. Among 34,332 individuals participating in the RCTs, 140 severe adverse events (SAEs) were reported as possibly related to RCV. Among the case reports on SAEs, the association with RCV was confirmed in one report (on fulminant encephalitis). Among 3,000 pregnant women who were inadvertently vaccinated, no SAEs were reported. CONCLUSIONS: One and two doses of RCV are highly immunogenic for a long period of time, effective in preventing rubella and CRS, and safe.

Human papillomavirus infection and oral squamous cell carcinoma - a systematic review.

INTRODUCTION: The association between uterine cervix and anogenital carcinomas and human papillomavirus, HPV, is well established, however the involvement of this virus in the development of oral squamous cell carcinomas remains controversial. OBJECTIVES: To evaluate the relationship between HPV infection and oral squamous cell carcinomas, and to estimate the incidence of this infection in these patients. METHODS: Four electronic databases were searched to find studies that met the following inclusion criteria: i) performed in humans; ii) were cohort, case-control or cross-sectional; iii) assessed the HPV oncogenic activity by the E6 and E7 mRNA; iv) included primary oral squamous cell carcinomas which; v) diagnosis had been confirmed by biopsy. Information about the country; study period; sample obtainment; sites of oral squamous cell carcinomas; number, gender and age range of the population; the prevalence of HPV infection and subtypes detected; use of tobacco or alcohol and oral sex practice were extracted. The methodological quality of included articles was assessed using 14 criteria. RESULTS: The search strategy retrieved 2129 articles. Assessment of the full text was done for 626 articles, but five were included. The total of participants included was 383, most of them male with mean age between 51.0 and 63.5 years old. Seventeen patients were HPV/mRNA-positive, being the subtypes 16 and 18 detected more frequently. Nine of the HPV/mRNA-positive oral squamous cell carcinomas occurred on the tongue. The quality score average of included articles was five points. CONCLUSIONS: Among the 383 oral squamous cell carcinoma patients included, 17 (4.4%) were HPV/mRNA-positive, nevertheless it was not possible to assess if HPV infection was associated with oral squamous cell carcinomas because none of the studies included was longitudinal and cross-sectional investigations do not have control group.

Primeiros socorros como objeto de educação em saúde para profissionais de escolas municipais / Primeros auxilios como objeto de educación en salud para profesionales de escuelas municipales / First aid as an object of health education for municipal school professionals

Objetivo: analisar o conhecimento dos profissionais de escolas municipais após a prática educativa de atendimento de primeiros socorros na infância. Método: estudo quase­experimental, quantitativo. Para a coleta de dados, utilizou-se um questionário sobre primeiros socorros na infância, aplicado antes e após uma prática educativa com 88 profissionais. Na análise dos dados, adotou-se o percentual de acertos para cada questão e a média percentual de acertos total. Aplicaram-se os testes McNemar e Wilcoxon. Resultados: após a prática educativa, houve aumento significativo no percentual de acertos em seis questões, redução do acerto em uma questão; e não alteração em duas questões, totalizando em 30% o acréscimo da retenção de conhecimento. Conclusão: o nível de conhecimento prévio dos profissionais sobre primeiros socorros foi relativamente baixo, entretanto observou-se uma apreensão de conhecimento significativo após a prática educativa, que poderá contribuir para o atendimento inicial de qualidade à vítima.

Objective: to analyze the knowledge of municipal school professionals after the educational practice of first aid service in childhood. Method: quasi-experimental, quantitative study. For data collection, a questionnaire on first aid in childhood was employed, applied before and after an educational practice with 88 professionals. In the data analysis, the percentage of correct answers for each question and the average percentage of full correct answers were adopted. McNemar and Wilcoxon tests were adopted. Results: after the educational practice, there was a significant increase in the percentage of correct answers in six questions, a reduction in correct answers in one question, and no change in two questions, numbering 30% the increase in knowledge acquisition. Conclusion: the level of professionals previous knowledge about first aid was relatively low, however there was a significant knowledge acquisition after the educational practice, which may contribute to the primary care for the victim with quality.

Objetivo: analizar el conocimiento de los profesionales de las escuelas municipales después de la práctica educativa de primeros auxilios en la infancia. Método: estudio cuasi experimental, cuantitativo. Para la recolección de datos se utilizó un cuestionario sobre primeros auxilios en la infancia, aplicado antes y después de una práctica educativa con 88 profesionales. En el análisis de datos se adoptó el porcentaje de aciertos de cada pregunta y la media porcentaje de aciertos total. Se aplicaron las pruebas de McNemar y de Wilcoxon. Resultados: después de la práctica educativa, hubo un aumento significativo en el porcentaje de respuestas correctas en seis preguntas, una reducción en las respuestas correctas en una pregunta y ningún cambio en dos preguntas, totalizando en 30% el aumento en la retención de conocimiento. Conclusión: el nivel de conocimiento previo de los profesionales sobre primeros auxilios fue relativamente bajo, sin embargo, hubo una retención de conocimiento significativa después de la práctica educativa, lo que puede contribuir para una atención inicial de calidad a la víctima.

Occupation- and age-associated risk of SARS-CoV-2 test positivity, the Netherlands, June to October 2020.

High coronavirus incidence has prompted the Netherlands to implement a second lockdown. To elucidate the epidemic's development preceding this second wave, we analysed weekly test positivity in public test locations by population subgroup between 1 June and 17 October 2020. Hospitality and public transport workers, driving instructors, hairdressers and aestheticians had higher test positivity compared with a reference group of individuals without a close-contact occupation. Workers in childcare, education and healthcare showed lower test positivity.

Expression of circulating microRNAs as predictors of diagnosis and surgical outcome in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

MicroRNAs have been progressively investigated as post-transcriptional regulators playing important roles in epilepsy pathophysiology. Here we investigate three promising microRNAs (miR-27a-3p, miR-328-3p and miR-654-3p) previously described in the literature as possible peripheral biomarkers for epilepsy diagnose and surgical prognosis. Serum samples from 28 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) were analyzed, 14 with good surgical prognosis (Engel I) and 14 with unfavorable surgical prognosis (Engel III-IV). Serum samples from 11 healthy volunteers were the control group. The microRNAs expression analysis was performed using real-time PCR. The present results did not endorse the role of miR-27a-3p as a peripheral biomarker for epilepsy diagnosis or surgical prognosis. MiR-328-3p, however, presented significant area under the curve (AUC) values when comparing controls to Engel I (90.3%), controls to Engel III-IV (96.8%) and controls to Engel I + Engel III-IV (i.e., epilepsy patients, AUC = 93.5%). Additionally, miR-654-3p displayed AUC = 74.7% when comparing controls to Engel I patients (p = 0.004), and AUC = 73.6% (p = 0.04) in the attempt to discriminate unfavorable from favorable surgical prognosis. In conclusion, the ANOVA and ROC analyzes with the respective AUC, specificity and sensitivity values allows us to conclude that miR-328-3p is the most important peripheral biomarker for the diagnosis of MTLE-HS. In terms of predicting the surgical prognosis of MTLE-HS patients, miR-654-3p proved to be the only microRNA evaluated to present statistical power to differentiate, as a peripheral biomarker, Engel I from Engel III-IV patients.

MenACWY vaccination campaign for adolescents in the Netherlands: Uptake and its determinants.

BACKGROUND: Between 2015 and 2018 the incidence of meningococcal disease serogroup W increased tenfold in the Netherlands with the highest case fatality among adolescents and young adults. In 2018-2019 a national mass vaccination campaign, with recall after non-attendance, was implemented targeting 14-18-years old adolescents. This study estimated the MenACWY-vaccine uptake and investigated its determinants. METHODS: The uptake before the start of the vaccination campaign was estimated from the number of vaccines administered by Municipal Health Services and dispensed by public pharmacies, and within the campaign from the national vaccination register. Possible determinants of uptake after the first invitation and recall were investigated among the first group invited for vaccination (born in May-December 2004) using random forest classification analysis. RESULTS: The uptake was 86% (of which 1.9% before the campaign) among all eligible adolescents and 88% among the first group invited, including 5% uptake achieved after the recall. The most important predictor of vaccination after the first invitation was parents' country of birth (lower uptake when parents were born abroad, range: 52%-Morocco to 88%-Netherlands). The most important predictors among those recalled were, respectively, distance to vaccination location (lower uptake with larger distance, range: 4-6%), percentage of votes for the conservative Christian (reformed) party in the municipality (lower uptake with higher percentage, range: 4-5%) and parents' country of birth (higher uptake when parents were born abroad, range: 4%-Netherlands to 11%-Syria). CONCLUSIONS: The MenACWY vaccination campaign for adolescents achieved a high uptake, with little vaccine use before the campaign. Parents' country of birth, votes for the conservative reformed political party and distance to the vaccination location were the most important predictors of vaccination. The recall strategy enhanced the uptake and was valuable to diminish immunization disparities. Future vaccination campaigns should put more effort into reaching adolescents with immigrant parents.

Psicanálise crítica: a escuta do sofrimento psíquico e suas implicações sociopolíticas / Critical psychoanalysis: psychic suffering listening and its socio-political implications / Psicoanálisis crítico: la escucha del sufrimiento psíquico y sus implicaciones sociopolíticas

O processo de constituição psíquica é perpassado por discursos identificantes que modelam a imagem de si. Esse psiquismo é formado dentro de uma família pertencente a determinado grupo social. A partir da análise do conceito freudiano de mal-estar e do contrato narcísico de Aulagnier, investigamos as lógicas estabelecidas entre o sujeito e a conjuntura social. O reinvestimento narcísico pós-Édipo se pauta no Ideal-de-Eu construído a partir das interdições e dos ideais parentais e socioculturais. Discursos identificatórios hegemônicos, que ressaltam a normatividade nas identidades sexuais, de gênero, étnicas e etárias, constroem identificações marcadas pela exclusão. Pensar nos modos de identificação na contemporaneidade implica assumir que os elementos formadores dessa identidade provêm da história de vida e dos processos histórico-sociais. Neste artigo, analisamos o sofrimento sociopsíquico a partir da narrativa de uma participante de um projeto de pesquisa realizado em centro de atendimento psicológico de uma universidade pública. Foram realizadas entrevistas individuais, cuja escuta clínica nos propiciou compreender as implicações sociais e políticas do sofrimento psíquico do sujeito em desamparo social. Para tanto, nos apoiamos em conceitos da psicanálise e da análise do discurso crítica para a análise das entrevistas. Observamos que o processo de exclusão social escancara o engodo do pacto social no qual o sujeito é desinvestido e lançado no desamparo. Nesse contexto, a experiência narrada e a escuta analítica crítica podem se estabelecer como estratégias de resistência ante a exclusão social...(AU)

The psyche constitution is permeated by identifying discourses that shape the image of itself. This psyche is constituted within a family belonging to a specific social group. By analyzing the Freudian concept of malaise and Aulagnier's 'narcissistic contract', we investigate the logic between the subject and the social context. The narcissistic reinvestment after Oedipus happens according to the Ideal-of-Ego constructed from the parental and social interdictions, but also following ideational cultural and parental introjection. Hegemonic identificatory discourses that emphasize normativity in sexual, gender, ethnic and age identities construct identities marked by exclusion. Thinking about the modes of identification in contemporaneity implies assuming that the elements that form this identity come from the history of life and social-historical processes. We analyzed the socio-psychic suffering from listening to the narrative of a participant in a research project carried out in a psychological care center of a public university. Individual interviews were conducted whose clinical listening enabled us to understand the social and political implications that constitute the psychic suffering of the subject in social neglect. We rely on concepts of Psychoanalysis and Critical Discourse Analysis that provided us with subsidies for the analysis of interviews. We observe that the process of social exclusion has eluded the deception of the social pact in which the subject is disinvested and cast into helplessness. In this context, narrative experience and critical analytical listening can be established as strategies of resistance to social exclusion...(AU)

La constitución psíquica es atravesada por discursos identificadores que modelan la imagen de sí. Este psiquismo se constituye dentro de una familia perteneciente a cierto grupo social. A partir del análisis del concepto freudiano del malestar y del "contrato narcisista" de Aulagnier, analizamos las lógicas establecidas entre el sujeto y la coyuntura social. La reinversión narcisista después del Edipo se basa en el Ideal-de-Yo construido a partir de prohibiciones y ideales parentales y socioculturales. Los discursos identificatorios hegemónicos que resaltan la normatividad en las identidades sexuales, de género, étnicas y de edad construyen identificaciones marcadas por la exclusión. Pensar en los modos de identificación en la contemporaneidad implica asumir que los elementos formadores de esa identidad provienen de la historia de vida y de los procesos histórico-sociales. En este artículo, analizamos el sufrimiento sociopsíquico desde la escucha de la narrativa de una participante de un proyecto de investigación realizado en centro de atención psicológica de una universidad pública. Se realizaron entrevistas cuya escucha clínica nos propició comprender las implicaciones sociales y políticas que constituyen el sufrimiento psíquico del sujeto en desamparo social. Apoyamos en conceptos del Psicoanálisis y del Análisis del Discurso Critico para analizar las entrevistas. Observamos que el proceso de exclusión social desvela el engaño del pacto social en el cual el sujeto es desinvestido y lanzado en el desamparo. En ese contexto, la experiencia narrada y la escucha analítica crítica pueden establecerse como estrategias de resistencia ante la exclusión social...(AU)