In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates.

COVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies. The DMAbs were designed to enhance in vivo expression and delivered intramuscularly to cynomolgus and rhesus macaques with a modified in vivo delivery regimen. Serum levels were detected in macaques, along with specific binding to SARS-CoV-2 spike receptor binding domain protein and neutralization of multiple SARS-CoV-2 variants of concern in pseudovirus and authentic live virus assays. Prophylactic administration was protective in rhesus macaques against signs of SARS-CoV-2 (USA-WA1/2020) associated disease in the lungs. Overall, the data support further study of DNA-encoded antibodies as an additional delivery mode for prevention of COVID-19 severe disease. These data have implications for human translation of gene-encoded mAbs for emerging infectious diseases and low dose mAb delivery against COVID-19.

Longitudinal invariance of psychotic experiences in children and adolescents: What do the data tell us?

BACKGROUND: Psychotic experiences are common in adults, adolescents, and children. While usually self-limited, they can indicate psychosis proneness when persistent. The Community Assessment of Psychic Experiences (CAPE) measures lifetime psychotic experiences in three dimensions. The 20-item subscale addressing positive symptoms (CAPE-positive) is the most widely used. No study investigated its measurement invariance across timepoints during childhood and adolescence. This step is required to conduct reliable comparisons in longitudinal studies with different age groups. METHODS: We used data from the Brazilian High-Risk Cohort, which enrolled 2511 individuals aged 6-12 years from public schools for the baseline evaluation. A 3-year follow-up assessment evaluated 1880 participants. Subjects were rated with the CAPE-positive and we performed, at each wave, a Multigroup Confirmatory Factor Analysis testing Exploratory and Confirmatory Factor Analysis models identified in a previous systematic review, to assess longitudinal invariance. RESULTS: A three-factor solution was the best fitting model, comprising Persecutory Ideation, Bizarre Experiences and Perceptual Abnormalities. The longitudinal invariance analysis of the best-fit model was unsatisfactory, achieving only the metric level of invariance. CONCLUSIONS: Our findings suggest that the CAPE-positive scale has good model fit indices for each evaluated time point individually (children and adolescents), but it is not invariant over time. Identifying which factors affect CAPE latent structure at different time points can improve our understanding of psychosis proneness and how to measure it.

The enduring gap in educational attainment in schizophrenia according to the past 50 years of published research: a systematic review and meta-analysis.

BACKGROUND: Educational attainment is associated with wellbeing and health, but patients with schizophrenia achieve lower levels of education than people without. Several effective interventions can ameliorate this situation. However, the magnitude of the education gap in schizophrenia and its change over time are unclear. We aimed to reconstruct the trajectories of educational attainment in patients with schizophrenia and, if reported, their healthy comparator controls. METHODS: We did a systematic review and meta-analysis including all studies reporting on patients with schizophrenia (of mean age ≥18 years) and describing the number of years of education of the participants, with or without healthy controls. There were no other design constraints on studies. We excluded studies that included only patients with other schizophrenia spectrum disorders and studies that did not specify the number of years of education of the participants. 22 reviewers participated in retrieving data from a search in PubMed and PsycINFO (Jan 1, 1970, to Nov 24, 2020). We estimated the birth date of participants from their mean age and publication date, and meta-analysed these data using random-effects models, focusing on educational attainment, the education gap, and changes over time. The primary outcome was years of education. The protocol was registered on PROSPERO (CRD42020220546). FINDINGS: From 32 593 initial references, we included 3321 studies reporting on 318 632 patients alongside 138 675 healthy controls (170 941 women and 275 821 men from studies describing sex or gender; data on ethnicity were not collected). Patients' educational attainment increased over time, mirroring that of controls. However, patients with schizophrenia in high-income countries had 19 months less education than controls (-1·59 years, 95% CI -1·66 to -1·53; p<0·0001), which is equivalent to a Cohen's d of -0·56 (95% CI -0·58 to -0·54) and implies an odds ratio of 2·58 for not completing 12 years of education (ie, not completing secondary education) for patients compared with controls. This gap remained stable throughout the decades; the rate of change in number of total years of education in time was not significant (annual change: 0·0047 years, 95% CI -0·0005 to 0·0099; p=0·078). For patients in low-income and middle-income countries, the education gap was significantly smaller than in high-income countries (smaller by 0·72 years, 0·85 to 0·59; p<0·0001), yet there was evidence that this gap was widening over the years, approaching that of high-income countries (annual change: -0·024 years, -0·037 to -0·011; p=0·0002). INTERPRETATION: Patients with schizophrenia have faced persistent inequality in educational attainment in the last century, despite advances in psychosocial and pharmacological treatment. Reducing this gap should become a priority to improve their functional outcomes. FUNDING: Ciencia y Tecnología para el Desarrollo (CYTED) to the Latin American Network for the Study of Early Psychosis (ANDES).

Innovative vaccine approaches-a Keystone Symposia report.

The rapid development of COVID-19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically improve global health, low-and-middle-income countries around the world often experience reduced access to vaccines and reduced vaccine efficacy. Addressing these issues will require novel vaccine approaches and platforms, deeper insight how vaccines mediate protection, and innovative trial designs and models. On June 28-30, 2021, experts in vaccine research, development, manufacturing, and deployment met virtually for the Keystone eSymposium "Innovative Vaccine Approaches" to discuss advances in vaccine research and development.

Gender, age and geographical representation over the past 50 years of schizophrenia research.

Previous studies have suggested that subjects participating in schizophrenia research are not representative of the demographics of the global population of people with schizophrenia, particularly in terms of gender and geographical location. We here explored if this has evolved throughout the decades, examining changes in geographical location, gender and age of participants in studies of schizophrenia published in the last 50 years. We examined this using a meta-analytical approach on an existing database including over 3,000 studies collated for another project. We found that the proportion of studies and participants from low-and-middle income countries has significantly increased over time, with considerable input from studies from China. However, it is still low when compared to the global population they represent. Women have been historically under-represented in studies, and still are in high-income countries. However, a significantly higher proportion of female participants have been included in studies over time. The age of participants included has not changed significantly over time. Overall, there have been improvements in the geographical and gender representation of people with schizophrenia. However, there is still a long way to go so research can be representative of the global population of people with schizophrenia, particularly in geographical terms.

Pharyngeal Airway Modifications in Skeletal Class III Patients Undergoing Bimaxillary Advancement Surgery.

PURPOSE: The purposes were to study the pharyngeal airway in patients with skeletal Class III malocclusion submitted to surgical orthodontic treatment and to correlate the alterations with bone movements. MATERIALS AND METHODS: The sample consisted of multislice computed tomography images from 13 patients obtained before and 6 months after maxillomandibular advancement surgery. The following measurements were obtained using Dolphin Imaging software (Dolphin Imaging, Chatsworth, CA): volume and area of the oropharynx, nasopharynx, and total airway, as well as the most constricted area, anteroposterior and lateral dimensions of the narrowest axial cross-sectional area, and airway length. The paired t test was applied at a significance level of 5%. RESULTS: Sagittal displacement of the maxilla and mandible was correlated with airway alterations using the Pearson correlation test. Alterations in airway measurements were observed in all patients after surgery. We noted a significant increase (P < .05) in total airway area, oropharyngeal area, and anteroposterior dimension of the most constricted area, as well as a significant reduction (P < .05) in airway length. A significant correlation (P < .05) was observed between nasopharyngeal area and maxillary movement and between airway length and mandibular movement (P < .05). CONCLUSIONS: The results of this study suggest significant alterations in pharyngeal airway measurements when preoperative and postoperative periods of bimaxillary advancement surgery were compared.

Effect of early intervention in an interdisciplinary group of children with Down syndrome in a special integration center / Efeito da estimulação precoce em grupo interdisciplinar de crianças com síndrome de Down em um centro de integração especial

Objective: To verify the effects of early stimulation on the motor and cognitive development of children with Down syndrome taking part of an interdisciplinary early stimulation group at a Special Child Integration Center. Methods: Prospective Observational Study carried out at a Special Child Integration Center with children from 0 to less than 1 year of age, taking part of an early stimulation group and who were not participating in any other intervention. Children included were evaluated in the rehabilitation sector of the institution. The instrument used was the Child Behavior Development Scale and the data were presented descriptively with percentage based on the answers of individual behavior and on the group average pre- and post-intervention. Results: The group was homogeneous regarding the characteristics and possible factors associated to developmental delay. In the motor and cognitive performance, individually all children had an improvement on their performance equal or greater than 50% in comparison to the initial assessment, and the group had a 62.5% growth in comparison to the initial evaluation. Conclusion: In group early stimulation brings benefits on the motor and cognitive development of children with Down syndrome in interdisciplinary care. (AU)

Objetivo: Verificar os efeitos da estimulação precoce sobre o desenvolvimento motor e cognitivo de crianças com síndrome de Down que participam do grupo interdisciplinar de estimulação precoce oferecido em um Centro de Integração da Criança Especial. Métodos: Estudo observacional prospectivo. Foi realizado em um Centro de Integração da Criança Especial com crianças de zero a um ano incompleto, que estivessem participando do grupo de estimulação precoce e que não participassem anteriormente de outra intervenção. As crianças incluídas foram avaliadas no setor de reabilitação da instituição. O instrumento utilizado foi a Escala do Desenvolvimento do Comportamento da Criança e os dados foram apresentados de forma descritiva com percentual baseado nas respostas do comportamento individual e da média do grupo pré e pós-intervenção. Resultados: O grupo foi homogêneo em relação às características e possíveis fatores associados ao atraso do desenvolvimento. No desempenho motor e cognitivo, individualmente todas as crianças obtiveram um crescimento em seu desempenho igual ou superior a 50% comparado com a avaliação inicial e o grupo obteve crescimento de 62,5% comparado com a avaliação inicial. Conclusão: A estimulação precoce em grupo traz benefícios sobre o desenvolvimento motor e cognitivo de crianças com síndrome de Down em atendimento interdisciplinar. (AU)

Detection of the influenza A(H1N1)pdm09 virus carrying the K-15E, P83S and Q293H mutations in patients who have undergone bone marrow transplant.

The 2009 pandemic influenza A(H1N1)pdm09 virus emerged and caused considerable morbidity and mortality in the third world, especially in Brazil. Although circulating strains of A(H1N1)pdm09 are A/California/04/2009-like (CA-04-like) viruses, various studies have suggested that some mutations in the viral hemagglutinin (HA) may be associated with enhanced severity and fatality. This phenomenon is particularly challenging for immunocompromised individuals, such as those who have undergone bone marrow transplant (BMT), because they are more likely to display worse clinical outcomes to influenza infection than non-immunocompromised individuals. We studied the clinical and viral aspects of post-BMT patients with confirmed A(H1N1)pdm09 diagnosis in the largest cancer hospital in Brazil. We found a viral strain with K-15E, P83S and Q293H polymorphisms in the HA, which is presumably more virulent, in these individuals. Despite that, these patients showed only mild symptoms of infection. Our findings complement the discovery of mild cases of infection with the A(H1N1)pdm09 virus with the K-15E, P83S and Q293H mutations in Brazil and oppose other studies that have linked these changes with increased disease severity. These results could be important for a better comprehension of the impact of the pandemic influenza in the context of BMT.

Synthesis and anti-HSV-1 activity of new 1,2,3-triazole derivatives.

In this work, a new series of arysulfonylhydrazine-1H-1,2,3-triazole derivatives were synthesized, and their ability to inhibit the in vitro replication of HSV-1 was evaluated. Among the 1,2,3-triazole derivatives, 1-[(5″-methyl-1″-(4‴-fluorophenylamino)-1H-1,2,3-triazol-4″-yl)carbonyl]-2-(4'-methylphenylsulfonyl)hydrazine and 1-[(5'-methyl-1'-(2″,5″-dichlorophenylamino)-1H-1,2,3-triazol-4'-yl)carbonyl]-2-(phenylsulfonyl)hydrazine, with IC(50) values of 1.30 and 1.26 µM, respectively, displayed potent activity against HSV-1. Because these compounds have low cytotoxicity, their selectivity indices are high. Under the assay conditions, they have better performance than does the reference compound acyclovir. The structures of all of the compounds were confirmed by one- and two-dimensional NMR techniques ((1)H, (13)C-APT, COSY-(1)H×(1)H and HETCOR (1)J(CH)) and by elemental analysis.

A fisioterapia respiratória na prevenção de pneumonia em pacientes com leishmaniose visceral (CALAZAR) / Respiratory physiotherapy on pneumonia prevention in patients with visceral leishmaniasis (KALAZAR)

uso do tratamento fisioterapêutico respiratório como forma de prevenir o surgimento de pneumonia em pacientes com diagnóstico clínico de leishmaniose visceral (LV) e comparar incidência de pneumonia e tempo de internação. Método: estudo transversal comparativo entre 13crianças com Leishmaniose Visceral (LV) internadas no Hospital Universitário João de Barros Barreto (HUJBB), no período de julho a outubro de 2006, submetidas a tratamento fisioterapêuticorespiratório; com 40 casos da mesma doença analisados na Divisão de Arquivo Médico e Estatístico (DAME) do referido hospital, do ano de 2005, que não foram submetidos a tratamento fisioterapêutico respiratório. Resultados: observou-se que 47,2% dos pacientes que não foramsubmetidos a tratamento fisioterapêutico respiratório evoluíram com pneumonia e com média de permanência de 24.14 dias; enquanto que, 0% dos pacientes submetidos a tratamento fisioterapêutico respiratório evoluiu com pneumonia e com média de permanência de 16.31 dias. Conclusão: afisioterapia colaborou para a prevenção de pneumonia nos pacientes com LV, reduzindo a taxa de incidência de pneumonia e o tempo de internação hospitalar

This study aimed to apply respiratory physiotherapist treatment as a way to prevent pneumonia in patients with clinical diagnosis of Visceral Leishmaniasis (LV) and to compare pneumonia incidence and time of internment. Methods: a comparative transversal study was carriedtrough with 13 children with clinical diagnosis of LV, interned in HUJBB. They were submitted to respiratory physiotherapist treatment from July to October of 2006; 40 cases of statistic and medical archive division of the referred hospital in the year of 2005 that were not submitted to respiratoryphysiotherapist treatment. Results: it was observed that 47.2% of the patients that were not submitted to respiratory physiotherapist treatment developed pneumonia with time of permanence around 24.14days; mean while, 0% of the patients submitted to respiratory physiotherapist treatment developed pneumonia with time of permanence around 16.31 days. Conclusion: Therefore, this research provedstatistically that physiotherapy collaborated for pneumonia prevention in patients with LV, reducing the rate of pneumonia incidence and the time of hospital internment

Legislação básica de proteção à infância: uma abordagem para a prática de enfermagem / Basic legislation of protection to the childhood: an approach for the pediatric nursing practice / Legislación básica de protección a la infancia: un abordage para la práctica de la enfermeria pediatrica

O presente estudo tem como foco central a legislação de proteção à criança no sentido de proporcionar subsídios a prática de enfermagem e da enfermeira pediatrica em seu exercício profissional. Tivemos como objetivo destacar os aspectos legais, constantes em Leis e Resolução, que asseguram a proteção à infância e analisar a contribuição desta legislação para a prática da enfermagem. A pesquisa documental foi orientada pelas palavras-chave: Lei, Decreto, Resolução, criança, direito, dever e proteção. Foram destacados Leis e Resoluções pertencentes aos campos geral e profissional cujos dados qualitativos foram categorizados a saber: legislação de base, de prática assistencial e de prática da pesquisa.