Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission.

After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cART, but aviremia persisting to 36 or more months was observed in only 32%. We observed that male infants have lower baseline plasma viral loads (P = 0.01). Unexpectedly, a subset (n = 5) of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3-10 months (n = 4) or intermittent cART adherence during 17-month loss to follow-up (n = 1). We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) (P < 0.0001) that was markedly stronger for males than for females (r = -0.51 versus r = -0.07 for IFN-α). Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort (P < 0.0001 and P = 0.0003, respectively), the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity (P < 0.0001). These data suggest that viremic control can occur in some infants with in utero-acquired HIV infection after early cART initiation and may be associated with innate immune sex differences.

Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study.

BACKGROUND: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. METHODS: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); Ctau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. INTERPRETATION: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. FUNDING: Gilead Sciences.

Factors associated with the lifestyle of state basic education teachers of state during the pandemic.

OBJECTIVE: To analyze the prevalence and factors associated with the lifestyle profile of public basic education teachers in Minas Gerais during the COVID-19 pandemic. METHOD: Epidemiological websurvey carried out with public basic education teachers in Minas Gerais. Data collection took place from August to September2020 via digital form. Anthropometric, sociodemographic, work, and lifestyle characteristics were evaluated. Poisson Regression was used. RESULTS: 15,641 teachers participated and 31.1% had inadequate health habits. There was a higher prevalence among men (PR=1.38; 95%CI:1.31;1.45), older age (PR=1.20; 95%CI: 1.07;1.34), greater weekly workload (RP=1.10; 95%CI:1.03;1.17) and those dissatisfied with work (RP=1.21; 95%CI:1.15;1.27). As a protective factor, professors with longer teaching experience (RP=0.92; 95%CI:0.87;0.98) and those hired or appointed (PR=0.89; 95%CI:0.85) ;0.94). CONCLUSION: Lifestyle inadequacy was found among older male teachers, with longer working hours and job dissatisfaction.

Human mobility and socioeconomic datasets of the Rio de Janeiro metropolitan area.

This data descriptor presents two main datasets and a set of auxiliary files. The mobility dataset presents a long-term study of human mobility in the Rio de Janeiro Metropolitan Area (RJMA) performed in the entire year of 2014 based on mobile phone data. The socioeconomic dataset presents selected socioeconomic variables of the Brazilian 2010 census. A set of auxiliary files is included to present georeferenced information and geographic features (shapefiles) and data used to validate the mobility estimates. The human mobility estimation was carried out using a methodology that allows direct integration with census data, based on an approximation of the geographic boundaries of census units by an aggregation of Voronoi polygons of the mobile phone antennas. The study area is the Brazilian local area 21, which includes the entire RJMA and four other municipalities. The mobility dataset is divided into two files: one is an estimation of the origin-destination (OD) matrix per day, and the other is a visitors' dataset where the number of visitors of each location is estimated in four shifts each day. The socioeconomic dataset presents information of 55 variables for each location, which have been used in different studies and present the longest human mobility dataset available for public use.

Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype.

HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ART-naive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1+CD8+ T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4+ T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8+ T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment.

Rock n' Seeds: A database of seed functional traits and germination experiments from Brazilian rock outcrop vegetation.

Advancing functional ecology depends fundamentally on the availability of data on reproductive traits, including those from tropical plants, which have been historically underrepresented in global trait databases. Although some valuable databases have been created recently, they are mainly restricted to temperate areas and vegetative traits such as leaf and wood traits. Here, we present Rock n' Seeds, a database of seed functional traits and germination experiments from Brazilian rock outcrop vegetation, recognized as outstanding centers of diversity and endemism. Data were compiled through a systematic literature search, resulting in 103 publications from which seed functional traits were extracted. The database includes information on 16 functional traits for 383 taxa from 148 genera, 50 families, and 25 orders. These 16 traits include two dispersal, six production, four morphological, two biophysical, and two germination traits-the major axes of the seed ecological spectrum. The database also provides raw data for 48 germination experiments, for a total of 10,187 records for 281 taxa. Germination experiments in the database assessed the effect of a wide range of abiotic and biotic factors on germination and different dormancy-breaking treatments. Notably, 8255 of these records include daily germination counts. This input will facilitate synthesizing germination data and using this database for a myriad of ecological questions. Given the variety of seed traits and the extensive germination information made available by this database, we expect it to be a valuable resource advancing comparative functional ecology and guiding seed-based restoration and biodiversity conservation in tropical megadiverse ecosystems. There are no copyright restrictions on the data; please cite this paper when using the current data in publications; also the authors would appreciate notification of how the data are used in publications.

O avanço da ecologia funcional depende fundamentalmente da disponibilidade de dados sobre traços reprodutivos, incluindo dados de plantas tropicais, que têm sido historicamente subrepresentados em bancos de dados de traços funcionais globais. Embora alguns bancos de dados valiosos tenham sido criados recentemente, eles são restritos principalmente a áreas temperadas e a traços vegetativos, como traços de folhas e madeira. Neste artigo apresentamos Rock n' Seeds, um banco de dados de traços funcionais de sementes e experimentos de germinação de vegetações associadas a afloramentos rochosos do Brasil, os quais são reconhecidos como centros notáveis de diversidade e endemismo. Os dados foram compilados através de uma revisão sistemática na literatura, resultando em 103 publicações das quais foram extraídos os traços funcionais das sementes. O banco de dados inclui informações de 16 traços funcionais para 383 taxa de 148 gêneros, 50 famílias e 25 ordens. Estes dezesseis traços incluem dois traços de dispersão, seis de produção, quatro morfológicos, dois biofísicos e dois germinativos; os eixos principais do espectro ecológico da semente. O banco de dados também fornece os dados brutos para 48 experimentos de germinação para um total de 10.187 registros para 281 taxa. Os experimentos de germinação no banco de dados avaliaram o efeito de uma ampla gama de fatores abióticos e bióticos sobre a germinação e diferentes tratamentos de quebra de dormência. Particularmente, 8.255 desses registros incluem a contagem diária da germinação. Estas informações facilitarão a síntese de dados de germinação e a utilização deste banco de dados para uma grande variedade de questões ecológicas. Dada a variedade de traços das sementes e as amplas informações sobre germinação disponibilizadas por este banco de dados, esperamos que ele seja um recurso valioso para o avanço da ecologia funcional comparativa e para orientar a restauração baseada em sementes e a conservação da biodiversidade em ecossistemas tropicais megadiversos. Não há restrições de direitos autorais sobre os dados; favor citar este artigo ao utilizar os dados nas publicações e os autores agradeceriam uma notificação de como os dados são utilizados nas publicações.

El avance de la ecología funcional depende fundamentalmente de la disponibilidad de datos sobre rasgos reproductivos-incluyendo los de las plantas tropicales-los cuales han estado poco representados en las bases de datos globales de rasgos. Aunque recientemente se han creado algunas bases de datos valiosas, estas se encuentran restringidas principalmente a las zonas templadas y a los rasgos vegetativos, como los de las hojas y la madera. En este artículo presentamos Rock n' Seeds, una base de datos de rasgos funcionales de semillas y experimentos de germinación de la vegetación asociada a afloramientos rocosos de Brasil, los cuales son destacados centros de diversidad y endemismo. Los datos se recopilaron mediante una búsqueda bibliográfica sistemática, que dio como resultado 103 publicaciones de las que se extrajeron los rasgos funcionales de las semillas. La base de datos incluye información de dieciséis rasgos funcionales para 383 taxones de 148 géneros, 50 familias y 25 órdenes. Estos rasgos incluyen dos rasgos de dispersión, seis de producción, cuatro morfológicos, dos biofísicos y dos de germinación; siendo estos los principales ejes del espectro ecológico de las semillas. La base de datos también proporciona los datos brutos de 48 experimentos de germinación, para un total de 10.187 registros de 281 taxones. Dichos experimentos de germinación evaluaron el efecto de una amplia gama de factores abióticos y bióticos sobre la germinación y de diferentes tratamientos para romper la dormancia. En particular, 8.255 de estos registros cuentan con conteos diarios de germinación. Esto facilitará la síntesis de los datos de germinación y el uso de esta base de datos para una gran diversidad de preguntas ecológicas. Dada la variedad de rasgos de las semillas y la amplia información sobre germinación que ofrece esta base de datos, esperamos que sea un recurso valioso para el avance de la ecología funcional comparativa y para orientar la restauración basada en semillas y la conservación de la biodiversidad en ecosistemas tropicales megadiversos. No hay restricciones de derechos de autor sobre los datos; se solicita citar este documento cuando se utilicen los datos en publicaciones y los autores agradecerán ser notificados sobre cómo se utilizan los datos en las publicaciones.

O clube de leitura "por uma prescrição segura" como ensino e aprendizagem de estudantes de medicina: um relato de experiência / The journal club "for a sefety prescription" as teaching and learning for medical students: an experience report / Club de lectura "por prescripción segura" como enseñanza y aprendizaje de estudiantes de medicina: informe de experiencia

Objetivo: O presente estudo busca descrever o relato de experiência do clube de leitura "Por uma Prescrição Segura" de estudantes de medicina como estratégia para desenvolver habilidades de pesquisa na literatura científica e estudo crítico de evidências, focando em uma prescrição segura. Método: Desenvolveu-se o clube de leitura com nove estudantes de medicina, os quais participaram de reuniões dirigidas por líder estudantil e uma professora. As reuniões ocorreram quinzenalmente, ao vivo, via Google Meet. Os estudantes desenvolveram questões sobre diferentes temas, pesquisaram a literatura, localizaram e estudaram criticamente os artigos. Resultados: os dados revelaram a participação dos estudantes no Clube de Leitura nas reuniões planejadas coletivamente e com os temas: "Medicina Baseada em Evidências"; "Revisão Integrativa"; "Segurança da prescrição, paciente e medicamento"; "Polifarmácia"; "Resistência aos antimicrobianos"; "Prescrição de psicofármacos"; "Incorporação de tecnologias"; "Práticas integrativas e complementares, Cuidados paliativos". Conclusão: O clube de leitura proporcionou o desenvolvimento do trabalho acadêmico de pesquisa e estudo da literatura científica sobre prescrição segura. Além disso, trouxe compreensão dos conceitos e modelos de práticas de medicina baseada em evidência no estágio pré-clínico. Foi uma estratégia-modelo liderada por estudante e orientada pela professora com resultado favorável para integrar as atividades curriculares.

Objective: The present study seeks to describe the experience report of the medical students' jornal club "For a Sefety Prescription" as strategy to develop skills on searching in cientific literature and critically study of the evidences, focusing on safe prescription. Method: The journal club was developed with nine medical students, who participated in meetings led by a student leader and a teacher. The meetings ocorred biweekly, live, via Google Meet. The students developed questions on different topics, searched the literature, located and critically studied the articles. Results: the data revealed the participation of students in the jornal club in meetings planned collectively and with the themes: "Evidence-Based Medicine"; "Integrative Review"; "Prescription, patient and medication safety"; "Polypharmacy"; "Antimicrobial resistance"; "Prescription of psychotropic drugs"; "Incorporation of technologies"; "Integrative and complementary practices, Palliative care". Conclusion: The article-centered journal club provided the development of academic work on research and study of the scientific literature on safe prescribing. In addition, broght understanding of the concepts and models of evidence-based medicine practices in the preclinical stage. It is a student-led and teacher-led model strategy with favorable outcome for integrating curricular activities.

Objetivo: El presente estudio describe el relato de experiencia del club de lectura de estudiantes de medicina como una estrategia para desarrollar habilidades de investigacion en la literatura cientifica y estudio critico de la evidencia, con enfoque en la prescripción segura. Método: se desarrolló un club de lectura con nueve estudiantes de medicina que participaron en reuniones dirigidas por un líder estudiantil y un maestro. Las reuniones se realizaron quincenalmente, en vivo, a través de Google Meet. Los estudiantes desarrollaron preguntas sobre diferentes temas, investigaron la literatura, localizaron y estudiaron críticamente los artículos. Resultados: los datos revelaron la participación de los estudiantes del club de lectura en encuentros planificados colectivamente y con los temas: "Medicina Basada en la Evidencia"; "Revisión Integrativa"; "Seguridad de la prescripción, del paciente y de los medicamentos"; "Polifarmacia"; "Resistencia antimicrobiana"; "Prescripción de psicofármacos"; "Incorporación de tecnologías"; "Prácticas integradoras y complementarias, cuidados paliativos". Conclusión: El club de lectura centrado en el artículo proporcionó el trabajo académico de investigar y estudiar la literatura científica sobre la prescripción segura. Además, comprensión de los conceptos y modelos de las prácticas de la medicina basada en la evidencia en la etapa preclínica. Es una estrategia modelo dirigida por el estudiante y el docente con resultados favorables para la integración de actividades curriculares.

Factors associated with the lifestyle of state basic education teachers of state during the pandemic / Factores asociados al estilo de vida de los docentes de educación básica estatal durante la pandemia / Fatores associados ao estilo de vida dos professores da educação básica estadual na pandemia

ABSTRACT Objective: To analyze the prevalence and factors associated with the lifestyle profile of public basic education teachers in Minas Gerais during the COVID-19 pandemic. Method: Epidemiological websurvey carried out with public basic education teachers in Minas Gerais. Data collection took place from August to September2020 via digital form. Anthropometric, sociodemographic, work, and lifestyle characteristics were evaluated. Poisson Regression was used. Results: 15,641 teachers participated and 31.1% had inadequate health habits. There was a higher prevalence among men (PR=1.38; 95%CI:1.31;1.45), older age (PR=1.20; 95%CI: 1.07;1.34), greater weekly workload (RP=1.10; 95%CI:1.03;1.17) and those dissatisfied with work (RP=1.21; 95%CI:1.15;1.27). As a protective factor, professors with longer teaching experience (RP=0.92; 95%CI:0.87;0.98) and those hired or appointed (PR=0.89; 95%CI:0.85) ;0.94). Conclusion: Lifestyle inadequacy was found among older male teachers, with longer working hours and job dissatisfaction.

RESUMEN Objetivo: Analizar la prevalencia y los factores asociados al perfil de estilo de vida de los docentes de educación básica pública de Minas Gerais durante la pandemia de COVID-19. Método: Encuesta epidemiológica de tipo websurvey realizada con profesores de educación básica pública en Minas Gerais. La recolección de datos ocurrió de agosto a septiembre2020 a través de formulario digital. Se evaluaron características antropométricas, sociodemográficas, laborales y de estilo de vida. Se utilizó la Regresión de Poisson. Resultados: Participaron 15.641 docentes y el 31,1% presentaba hábitos de salud inadecuados. Hubo mayor prevalencia en hombres (RP=1,38; IC 95%: 1,31; 1,45), mayor edad (RP=1,20; IC 95%: 1,07; 1,34), mayor carga de trabajo semanal (RP=1,10; IC 95%: 1,03). ;1,17) y los insatisfechos con el trabajo (RP=1,21; IC95%:1,15;1,27). Como factor protector, profesores con mayor experiencia docente (RP=0,92; IC95%:0,87;0,98) y contratados o nombrados (RP=0,89; IC95%:0,85;0,94). Conclusión: Se encontró inadecuación en el estilo de vida entre los maestros hombres y mayores, con jornadas laborales más largas e insatisfacción laboral.

RESUMO Objetivo: Analisar a prevalência e fatores associados ao perfil do estilo de vida dos professores da educação básica pública de Minas Gerais na pandemia da COVID-19. Método: Inquérito epidemiológico websurvey realizado com professores da educação básica pública de Minas Gerais. A coleta de dados ocorreu de agosto a setembro/2020 via formulário digital. Foram avaliadas as características antropométricas, sociodemográficas, laborais e estilo de vida. Utilizou-se a Regressão de Poisson. Resultados: Participaram 15.641 professores e 31,1% apresentaram hábitos inadequados de saúde. Houve maior prevalência entre homens (RP=1,38; IC95%:1,31;1,45), maior idade (RP=1,20; IC95%: 1,07;1,34), maior carga semanal de trabalho (RP=1,10; IC95%:1,03;1,17) e os insatisfeitos com o trabalho (RP=1,21; IC95%:1,15;1,27). Como fator de proteção encontraram-se os professores com mais tempo de trabalho docente (RP=0,92; IC95%:0,87;0,98) e contratados ou designados (RP=0,89; IC95%:0,85;0,94). Conclusão: Verificou-se inadequação do estilo de vida entre os professores homens mais velhos, com maior jornada laboral e insatisfação com o trabalho.

Complexidade e transdisciplinaridade no currículo médico comprometido com bioéticas latino-americanas / Complexity and transdisciplinary in medical curricula committed to Latin American bioethics / Complejidad y transdisciplinariedad en el currículo médico comprometido con las bioéticas latinoamericanas

Resumo Este ensaio aborda, à luz da bioética, a transformação do currículo médico no Brasil de um modelo multidisciplinar para um inter ou transdisciplinar. Em revisão narrativa, discutem-se a teoria da complexidade e a transdisciplinaridade, estabelecendo analogia entre a maneira como bioéticas latino-americanas usufruem dessa teoria para a compreensão da realidade, formulando bases conceituais de um currículo médico que supere a fragmentação na formação. Para as bioéticas do sul global, o pensamento complexo e a transdisciplinaridade são fundamentais para compreender uma realidade não reducionista, aberta à construção de conhecimentos que não se isolem na explicação biomédica do mundo. De maneira semelhante, para a formação de médicos com visão de saúde ampliada, que valorizem os determinantes sociais e subjetivos do processo saúde-doença, o currículo deve proporcionar a religação dos saberes. A introdução do pensamento complexo no currículo médico pode estimular o ensino não reducionista.

Abstract Adopting bioethics as the framework, this essay discusses the transformation of medical curricula in Brazil from a multidisciplinary model to an inter- or transciplinary one. The narrative review method is used to discuss the theory of complexity and transdiciplinarity, establishing an analogous understanding between how Latin American bioethics views use this theory to understand reality, creating conceptual framework of a medical curricula that goes beyond fragmentation in training. Complex thought and transdiciplinarity are fundamental for the bioethics views of the global south to understand a non-reductionist reality, one that is open to constructing knowledge that is not isolated in a biomedical understanding of the world. Likewise, to train physicians with a broader view of health and who value the social and subjective determinant aspects in the health-disease process, the curriculum must provide a rekindling of pieces of knowledge. The introduction of complex though in medical curricula can stimulate non-reductionist teaching.

Resumen Este ensayo muestra, basándose en la bioética, la transformación del currículo de medicina en Brasil del modelo multidisciplinar al modelo inter- o transdisciplinar. Desde una revisión narrativa se discute la teoría de la complejidad y la transdisciplinariedad bajo una analogía de cómo las bioéticas latinoamericanas utilizan esa teoría para comprender la realidad, sentando bases conceptuales para un currículo de medicina que supere una formación fragmentaria. Para las bioéticas del sur global, el pensamiento complejo y la transdisciplinariedad son claves para comprender una realidad no reduccionista, abierta a la construcción de saberes que no se restringen a la explicación biomédica de mundo. Asimismo, para una formación médica con visión amplia de la salud y que valora los determinantes sociales y subjetivos del proceso salud-enfermedad, el currículo debe propiciar la reconexión de saberes. La introducción del pensamiento complejo en el currículo de medicina puede fomentar una enseñanza no reduccionista.

Characterisation of Omicron Variant during COVID-19 Pandemic and the Impact of Vaccination, Transmission Rate, Mortality, and Reinfection in South Africa, Germany, and Brazil.

Several variants of SARS-CoV-2 have been identified in different parts of the world, including Gamma, detected in Brazil, Delta, detected in India, and the recent Omicron variant, detected in South Africa. The emergence of a new variant is a cause of great concern. This work considers an extended version of an SIRD model capable of incorporating the effects of vaccination, time-dependent transmissibility rates, mortality, and even potential reinfections during the pandemic. We use this model to characterise the Omicron wave in Brazil, South Africa, and Germany. During Omicron, the transmissibility increased by five for Brazil and Germany and eight for South Africa, whereas the estimated mortality was reduced by three-fold. We estimated that the reported cases accounted for less than 25% of the actual cases during Omicron. The mortality among the nonvaccinated population in these countries is, on average, three to four times higher than the mortality among the fully vaccinated. Finally, we could only reproduce the observed dynamics after introducing a new parameter that accounts for the percentage of the population that can be reinfected. Reinfection was as high as 40% in South Africa, which has only 29% of its population fully vaccinated and as low as 13% in Brazil, which has over 70% and 80% of its population fully vaccinated and with at least one dose, respectively. The calibrated models were able to estimate essential features of the complex virus and vaccination dynamics and stand as valuable tools for quantifying the impact of protocols and decisions in different populations.

Role of Early Life Cytotoxic T Lymphocyte and Natural Killer Cell Immunity in Paediatric HIV Cure/Remission in the Anti-Retroviral Therapy Era.

Only three well-characterised cases of functional cure have been described in paediatric HIV infection over the past decade. This underlines the fact that early initiation of combination antiretroviral therapy (cART), whilst minimising the size of the viral reservoir, is insufficient to achieve cure, unless other factors contribute. In this review, we consider these additional factors that may facilitate functional cure in paediatric infection. Among the early life immune activity, these include HIV-specific cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell responses. The former have less potent antiviral efficacy in paediatric compared with adult infection, and indeed, in early life, NK responses have greater impact in suppressing viral replication than CTL. This fact may contribute to a greater potential for functional cure to be achieved in paediatric versus adult infection, since post-treatment control in adults is associated less with highly potent CTL activity, and more with effective antiviral NK cell responses. Nonetheless, antiviral CTL responses can play an increasingly effective role through childhood, especially in individuals expressing then 'protective' HLA-I molecules HLA-B*27/57/58:01/8101. The role of the innate system on preventing infection, in shaping the particular viruses transmitted, and influencing outcome is discussed. The susceptibility of female fetuses to in utero mother-to-child transmission, especially in the setting of recent maternal infection, is a curiosity that also provides clues to mechanisms by which cure may be achieved, since initial findings are that viral rebound is less frequent among males who interrupt cART. The potential of broadly neutralising antibody therapy to facilitate cure in children who have received early cART is discussed. Finally, we draw attention to the impact of the changing face of the paediatric HIV epidemic on cure potential. The effect of cART is not limited to preventing AIDS and reducing the risk of transmission. cART also affects which mothers transmit. No longer are mothers who transmit those who carry genes associated with poor immune control of HIV. In the cART era, a high proportion (>70% in our South African study) of transmitting mothers are those who seroconvert in pregnancy or who for social reasons are diagnosed late in pregnancy. As a result, now, genes associated with poor immune control of HIV are not enriched in mothers who transmit HIV to their child. These changes will likely influence the effectiveness of HLA-associated immune responses and therefore cure potential among children.

Timing the race of vaccination, new variants, and relaxing restrictions during COVID-19 pandemic.

Late in 2019, China identified a new type of coronavirus, SARS-CoV-2, and due to its fast spread, the World Health Organisation (WHO) declared a pandemic named COVID-19. Some variants of this virus were detected, including the Delta, which caused new waves of infections. This work uses an extended version of a SIRD model that includes vaccination effects to measure the impact of the Delta variant in three countries: Germany, Israel and Brazil. The calibrated models were able to reproduce the dynamics of the above countries. In addition, hypothetical scenarios were simulated to quantify the impact of vaccination and mitigation policies during the Delta wave. The results showed that the model could reproduce the complex dynamics observed in the different countries. The estimated increase of transmission rate due to the Delta variant was highest in Israel (7.9), followed by Germany (2.7) and Brazil (1.5). These values may support the hypothesis that people immunised against COVID-19 may lose their defensive antibodies with time since Israel, Germany, and Brazil fully vaccinated half of the population in March, July, and October. The scenario to study the impact of vaccination revealed relative reductions in the total number of deaths between 30% and 250%; an absolute reduction of 300 thousand deaths in Brazil due to vaccination during the Delta wave. The second hypothetical scenario revealed that mitigation policies saved up to 300 thousand Brazilians; relative reductions in the total number of deaths between 24% and 120% in the three analysed countries. Therefore, the results suggest that both vaccination and mitigation policies were crucial in decreasing the spread and the number of deaths during the Delta wave.

Divergent trajectories of antiviral memory after SARS-CoV-2 infection.

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.

A simple, robust flow cytometry-based whole blood assay for investigating sex differential interferon alpha production by plasmacytoid dendritic cells.

Central to sex differences observed in outcome from infection and vaccination is the innate immune response, and specifically production of type I interferons by plasmacytoid dendtiric cells (pDCs), the main producers of IFN-α. Evaluation of IFN-α production by pDCs is therefore critical for studies of innate immune function. However, reliable measurement of pDC IFN-α is hampered by reduced cell yields and cytokine production after cryopreservation or after even short delays in stimulating freshly isolated cells. We here describe a simple yet robust method for measuring IFN-α production in pDCs that preserves cell activation and cytokine production through immediate stimulation of whole blood and subsequent maintenance at 37 °C.

Accuracy of Acoustic Voice Quality Index and Its Isolated Acoustic Measures to Discriminate the Severity of Voice Disorders.

OBJECTIVE: To evaluate the Acoustic Voice Quality Index (AVQI) and its isolated acoustic measures accuracy in discriminating voices with different degrees of deviation. METHODS: Two hundred and fifty-eight voice samples (160 dysphonic; 98 vocally healthy). Information regarding acoustic analysis and overall degree of deviation (G) were considered. The acoustic analysis consisted of the AVQI total score and its isolated acoustic measures: smoothed cepstral peak prominence (CPPs); harmonic-to-noise ratio (HNR); shimmer local and dB (Shim, ShdB); the general slope of the spectrum (Slope) and tilt of the regression line through the spectrum (Tilt). The auditory-perceptual judgment was the median G score of five voice specialists (Cohen's = 0.605-0.773; Fleiss = 0.370). Quadratic discriminant analysis and accuracy, sensitivity, and specificity of performance measures were used to investigate the discriminatory power of these measures. RESULTS: AVQI presented acceptable accuracy to differentiate voices with no vocal deviation and with vocal deviation (73.9%) and among the degrees of deviation (mild vs. moderate = 70.49%; mild vs. moderate = 71.39%; moderate vs. severe = 87.5%). No isolated acoustic measurement was consistent with differentiating voice quality among all degrees of deviation. A combination of five acoustic measures (CPPs, HNR, ShdB, Slope, Tilt) had the highest accuracy to differentiate between healthy and deviated voice (75.55%). Shimmer was more accurate to discriminate between voices with mild, moderate, and severe deviation; almost all isolated acoustic measurements were accurate to discriminate voices with moderate and severe deviation. The combination of acoustic measures presented higher accuracy (mild vs. moderate = 70.21%-74.29%; mild vs. moderate = 71.53%-76.11%; moderate vs. severe = 86%-95.50%). CONCLUSION: AVQI is an accepted tool to discriminate among different degrees of vocal deviation, and more accurate between voices with moderate and severe deviations. Isolated acoustic measures perform better when discriminating voices with a higher degree of deviation. A combination of acoustic parameters, with the same weight, is more accurate to discriminate different degrees of deviation, however, not consistent.

Does the Combination of Glottal and Supraglottic Acoustic Measures Improve Discrimination Between Women With and Without Voice Disorders?

AIM: To analyze the accuracy of traditional acoustic measurements (F0, perturbation, and noise) and formant measurements in discriminating between women with and without voice disorders, and with different laryngeal disorders. STUDY DESIGN: A descriptive, cross-sectional, and retrospective. METHOD: Two hundred and sixty women participated. All participants recorded the spoken vowel /Ɛ/ and underwent laryngeal visual examination. Acoustic measures of the mean and standard deviation of the fundamental frequency (F0), jitter, shimmer, glottal-to-noise excitation ratio, and the values of the first three formants (F1, F2, and F3) were obtained. RESULTS: Individual acoustic measurements did not demonstrate adequate (<70%) performance when discriminating between women with and without voice disorders. The combination of the standard deviation of the F0, shimmer, glottal-to-noise excitation ratio, F1, F2, and F3 showed acceptable (>70%) performance in classifying women with and without voice disorders. Individual measures of jitter as well as F1 and F3 demonstrated acceptable (>70%) performance when distinguishing women with different laryngeal diagnoses, including without voice disorders (healthy larynges), Reinke's edema, unilateral vocal fold paralysis, and sulcus vocalis. The combination of acoustic measurements showed excellent (>80%) performance when discriminating women without voice disorder from those with Reinke's edema (mean of F0, F1, and F3) and with sulcus vocalis (mean of F0, F1, and F2). CONCLUSIONS: Individual formant and traditional acoustic measurements do not demonstrate adequate performance when discriminating between women with and without voice disorders. However, the combination of traditional and formant measurements improves the discrimination between the presence and absence of voice disorders and differentiates several laryngeal diagnoses.

Performance of Different Acoustic Measures to Discriminate Individuals With and Without Voice Disorders.

The goal of this study is to compare and combine different acoustic features in discriminating subjects with and without voice disorders. A database of 484 adult patients participated in the research. All subjects recorded a sustained vowel /Ɛ/ and underwent a laryngoscopic examination of the larynx. From the results of the laryngeal examination performed by a physician and the auditory-perceptual judgment performed by a Speech-Language Pathologist, the subjects were allocated to the group with (n = 52) and without (n = 432) voice disorder. Four types of acoustic features were used: traditional measures, cepstral measures, nonlinear measures, and recurrence quantification measures. Recordings comprised the emission of the vowel /ε/. Quadratic discriminant analysis was used as classifier. Individual features in the context of traditional, cepstral, and recurrence quantification measures achieved an acceptable performance of ≥70%. Combination of measures improved the classifier performance. The best classification result (86.43% accuracy) was obtained by combining traditional linear and recurrence quantification measures. Results shown that Traditional, Cepstral, and recurrence quantification measures are promising features that capture meaningful information about voice production, which provides good classification performances. The findings of this study can be used to develop a computational tool for voice disorders diagnosis and monitoring.

Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors.

BACKGROUND: Elite controllers are therapy-naive individuals living with HIV capable of spontaneous control of plasma viraemia for at least a year. Although viremic nonprogressors are more common in vertical HIV-infection than in adults' infection, elite control has been rarely characterized in the pediatric population. DESIGN: We analyzed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four pediatric elite controllers (PECs) compared with age-matched nonprogressors (PNPs), progressors and HIV-exposed uninfected (HEUs) adolescents. RESULTS: PECs T-cell populations had lower immune activation and exhaustion levels when compared with progressors, reflected by a more sustained and preserved effector function. The HIV-specific T-cell responses among PECs were characterized by high-frequency Gag-specific CD4+ T-cell activity, and markedly more polyfunctional Gag-specific CD8+ activity, compared with PNPs and progressors. These findings were consistently observed even in the absence of protective HLA-I molecules such as HLA-B∗27/57/81. CONCLUSION: Pediatric elite control is normally achieved after years of infection, and low immune activation in PNPs precedes the increasing ability of CD8+ T-cell responses to achieve immune control of viraemia over the course of childhood, whereas in adults, high immune activation in acute infection predicts subsequent CD8+ T-cell mediated immune control of viremia, and in adult elite controllers, low immune activation is therefore the consequence of the rapid CD8+ T-cell mediated immune control generated after acute infection. This distinct strategy adopted by PECs may help identify pathways that facilitate remission in posttreatment controllers, in whom protective HLA-I molecules are not the main factor.

Two Distinct Mechanisms Leading to Loss of Virological Control in the Rare Group of Antiretroviral Therapy-Naive, Transiently Aviremic Children Living with HIV.

HIV-specific CD8+ T cells play a central role in immune control of adult HIV, but their contribution in pediatric infection is less well characterized. Previously, we identified a group of ART-naive children with persistently undetectable plasma viremia, termed "elite controllers," and a second group who achieved aviremia only transiently. To investigate the mechanisms of failure to maintain aviremia, we characterized in three transient aviremic individuals (TAs), each of whom expressed the disease-protective HLA-B*81:01, longitudinal HIV-specific T-cell activity, and viral sequences. In two TAs, a CD8+ T-cell response targeting the immunodominant epitope TPQDLNTML (Gag-TL9) was associated with viral control, followed by viral rebound and the emergence of escape variants with lower replicative capacity. Both TAs mounted variant-specific responses, but only at low functional avidity, resulting in immunological progression. In contrast, in TA-3, intermittent viremic episodes followed aviremia without virus escape or a diminished CD4+ T-cell count. High quality and magnitude of the CD8+ T-cell response were associated with aviremia. We therefore identify two distinct mechanisms of loss of viral control. In one scenario, CD8+ T-cell responses initially cornered low-replicative-capacity escape variants, but with insufficient avidity to prevent viremia and disease progression. In the other, loss of viral control was associated with neither virus escape nor progression but with a decrease in the quality of the CD8+ T-cell response, followed by recovery of viral control in association with improved antiviral response. These data suggest the potential for a consistently strong and polyfunctional antiviral response to achieve long-term viral control without escape. IMPORTANCE Very early initiation of antiretroviral therapy (ART) in pediatric HIV infection offers a unique opportunity to limit the size and diversity of the viral reservoir. However, only rarely is ART alone sufficient to achieve remission. Additional interventions that likely include contributions from host immunity are therefore required. The HIV-specific T-cell response plays a central role in immune control of adult HIV, often mediated through protective alleles such as HLA-B*57/58:01/81:01. However, due to the tolerogenic and type 2 biased immune response in early life, HLA-I-mediated immune suppression of viremia is seldom observed in children. We assessed a rare group of HLA-B*81:01-positive, ART-naive children who achieved aviremia, albeit only transiently, and investigated the role of the CD8+ T-cell response in the establishment and loss of viral control. We identified a mechanism by which the HIV-specific response can achieve viremic control without viral escape that can be explored in strategies to achieve remission.

An HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+ T-cell-mediated immune control in adults.

Natural Killer (NK) cells contribute to HIV control in adults, but HLA-B-mediated T-cell activity has a more substantial impact on disease outcome. However, the HLA-B molecules influencing immune control in adults have less impact on paediatric infection. To investigate the contribution NK cells make to immune control, we studied >300 children living with HIV followed over two decades in South Africa. In children, HLA-B alleles associated with adult protection or disease-susceptibility did not have significant effects, whereas Bw4 (p = 0.003) and low HLA-A expression (p = 0.002) alleles were strongly associated with immunological and viral control. In a comparator adult cohort, Bw4 and HLA-A expression contributions to HIV disease outcome were dwarfed by those of protective and disease-susceptible HLA-B molecules. We next investigated the immunophenotype and effector functions of NK cells in a subset of these children using flow cytometry. Slow progression and better plasma viraemic control were also associated with high frequencies of less terminally differentiated NKG2A+NKp46+CD56dim NK cells strongly responsive to cytokine stimulation and linked with the immunogenetic signature identified. Future studies are indicated to determine whether this signature associated with immune control in early life directly facilitates functional cure in children.