In silico analysis of non-structural protein 12 sequences from SARS-COV-2 found in Manaus, Amazonas, Brazil, reveals mutations linked to higher transmissibility.

The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs.

Polysacharide of Agaricus blazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling.

To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.

Exploring hematological alterations and genetics linked to SNV rs10974944 in myeloproliferative neoplasms among Amazon patients.

BCR::ABL1-negative myeloproliferative neoplasms are hematopoietic disorders characterized by panmyelosis. JAK2 V617F is a frequent variant in these diseases and often occurs in the 46/1 haplotype. The G allele of rs10974944 has been shown to be associated with this variant, specifically its acquisition, correlations with familial cases, and laboratory alterations. This study evaluated the association between the 46/1 haplotype and JAK2 V617F in patients with myeloproliferative neoplasms in a population from the Brazilian Amazon. Clinical, laboratory and molecular sequencing analyses were considered. Carriers of the G allele of rs10974944 with polycythemia vera showed an increase in mean corpuscular volume and mean corpuscular hemoglobin, while in those with essential thrombocythemia, there was an elevation in red blood cells, hematocrit, and hemoglobin. Associations were observed between rs10974944 and the JAK2 V617F, in which the G allele (OR 3.4; p < 0.0001) and GG genotype (OR 4.9; p = 0.0016) were associated with JAK2 V617F + and an increase in variant allele frequency (GG: OR 15.8; p = < 0.0001; G: OR 6.0; p = 0.0002). These results suggest an association between rs10974944 (G) and a status for JAK2 V617F, JAK2 V617F + _VAF ≥ 50%, and laboratory alterations in the erythroid lineage.

[Trend in breast cancer mortality rate among women aged 20 years or older in Brazil, 2005-2019]. / Tendência da taxa de mortalidade por câncer de mama em mulheres com 20 anos ou mais no Brasil, 2005-2019.

The aim is to analyze the trend in breast cancer mortality rates and its correlation with the socioeconomic development status in Brazil. It involved an ecological time series study carried out in the 26 units of the federation, Federal District and regions of Brazil. Data sources included the Mortality Information System (number of deaths), the Brazilian Institute of Geography and Statistics (resident population) and the study of the Global Burden of Disease (Socio-demographic Index - SDI). Data from 2005 to 2019 were used. The trend was analyzed using Prais-Winsten regression models. The relationship between the mortality rate and the SDI was analyzed using Spearman's correlation coefficient. During the study period, 207,683 deaths from breast cancer occurred. The average standardized mortality rate was 19.95 deaths per 100,000 women in Brazil. All the regions of Brazil showed an increasing trend in mortality. Of the total federative units, 22 showed an increasing trend. There was a positive relationship between the mortality rate and the SDI. The standardized mortality rate for breast cancer showed an increasing trend in Brazil, in all regions and in most states. There was a direct association between mortality and SDI, indicating a greater magnitude in more developed regions.

O objetivo é analisar a tendência da taxa de mortalidade por câncer de mama e sua correlação com o status de desenvolvimento socioeconômico no Brasil. Estudo ecológico de séries temporais realizado nos 26 estados, Distrito Federal e regiões do Brasil. As fontes de dados foram o Sistema de Informação sobre Mortalidade (número de óbitos), o Instituto Brasileiro de Geografia e Estatística (população residente) e o estudo da Carga Global de Doenças (socio-demographic index - SDI). Foram usados dados de 2005 a 2019. A tendência foi analisada pelos modelos de regressão de Prais-Winsten. A relação entre a taxa de mortalidade e o SDI foi analisada pelo coeficiente de correlação de Spearman. No período do estudo ocorrerem 207.683 óbitos por câncer de mama. A taxa padronizada de mortalidade média foi de 19,95 óbitos por 100.000 mulheres no Brasil. O Brasil e todas as regiões apresentaram tendência crescente da mortalidade. Do total de estados, 22 apresentaram tendência crescente. Verificou-se relação positiva entre a taxa de mortalidade e o SDI. A taxa de mortalidade padronizada por câncer de mama apresentou tendência crescente no Brasil, em todas as regiões e na maioria das unidades da federação. Verificou-se associação direta entre mortalidade e SDI, indicando maior magnitude em regiões mais desenvolvidas.

Episodic disability questionnaire (EDQ) measurement properties among adults living with HIV in Canada, Ireland, United Kingdom, and United States.

BACKGROUND: The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of the Episodic Disability Questionnaire (EDQ) with adults living with HIV. METHODS: We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; > 0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; > 0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity). RESULTS: Three hundred fifty nine participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed. CONCLUSIONS: The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV.

Is Unplanned Excision of Soft Tissue Sarcomas Associated with Worse Oncological Outcomes?-A Systematic Review and Meta-Analysis.

BACKGROUND: Soft tissue sarcomas are a group of rare neoplasms which can be mistaken for benign masses and be excised in a non-oncologic fashion (unplanned excision). Whether unplanned excision (UE) is associated with worse outcomes is highly debated due to conflicting evidence. METHODS: We performed a systematic review and meta-analysis following PRISMA guidelines. Main outcomes analyzed were five-year overall survival (OS), five-year local recurrence-free survival (LRFS), amputation rate and plastic reconstruction surgery rate. Risk ratios were used to compare outcomes between patients treated with planned and unplanned excision. RESULTS: We included 16,946 patients with STS, 6017 (35.5%) with UE. UE was associated with worse five-year LRFS (RR 1.35, p = 0.019). Residual tumor on the tumor bed was associated with lower five-year LRFS (RR = 2.59, p < 0.001). Local recurrence was associated with worse five-year OS (RR = 1.82, p < 0.001). UE was not associated with a worse five-year OS (RR = 0.90, p = 0.16), higher amputation rate (RR = 0.77, p = 0.134), or a worse plastic reconstruction surgery rate (RR = 1.25, p = 0.244). CONCLUSIONS: Unplanned excision of Soft Tissue Sarcomas and the presence of disease in tumor bed after one were associated with worse five-year LRFS. Tumor bed excision should remain the standard approach, with special consideration to the presence of residual disease.

Sweat induction using Pilocarpine microneedle patches for sweat testing in healthy adults.

BACKGROUND: The sweat test using pilocarpine iontophoresis remains the gold standard for diagnosing cystic fibrosis, but access and reliability are limited by specialized equipment and insufficient sweat volume collected from infants and young children. These shortcomings lead to delayed diagnosis, limited point-of-care applications, and inadequate monitoring capabilities. METHODS: We created a skin patch with dissolvable microneedles (MNs) containing pilocarpine that eliminates the equipment and complexity of iontophoresis. Upon pressing the patch to skin, the MNs dissolve in skin to release pilocarpine for sweat induction. We conducted a non-randomized pilot trial among healthy adults (clinicaltrials.gov, NCT04732195) with pilocarpine and placebo MN patches on one forearm and iontophoresis on the other forearm, followed by sweat collection using Macroduct collectors. Sweat output and sweat chloride concentration were measured. Subjects were monitored for discomfort and skin erythema. RESULTS: Fifty paired sweat tests were conducted in 16 male and 34 female healthy adults. MN patches delivered similar amounts of pilocarpine into skin (1.1 ± 0.4 mg) and induced equivalent sweat output (41.2 ± 25.0 mg) compared to iontophoresis (1.2 ± 0.7 mg and 43.8 ± 32.3 mg respectively). Subjects tolerated the procedure well, with little or no pain, and only mild transient erythema. Sweat chloride concentration measurements in sweat induced by MN patches (31.2 ± 13.4 mmol/L) were higher compared to iontophoresis (24.0 ± 13.2 mmol/L). Possible physiological, methodological, and artifactual causes of this difference are discussed. CONCLUSIONS: Pilocarpine MN patches present a promising alternative to iontophoresis to enable increased access to sweat testing for in-clinic and point-of-care applications.

Exploring uterine inflammation in postpartum primiparous precocious and conventional and multiparous Bos indicus beef cows.

This study aimed to compare the postpartum uterine dynamics of primiparous precocious (PP), primiparous conventional (PC) and multiparous conventional (MC) Bos indicus beef cows. For this purpose, PP (n = 8), PC (n = 18) and MC (n = 12) cows were enrolled in this study. These cows were evaluated at 20 and 10 days prepartum and weekly from parturition to 42 days postpartum (DPP). During this period, body weight (BW), subcutaneous fat thickness (SFT) and serum concentrations of glucose, ß-hydroxybutyrate, albumin and haptoglobin were measured. Proportion of polymorphonuclear (PMN) cells, and abundance of mRNA transcripts of genes involved in uterine inflammation and uterine health were evaluated. The PP cows had lower (p < .05) BW and SFT than that for PC and MC cows during the study period. The serum concentration of albumin after 35 DPP was lower (p < .05) in PP cows. The PP cows had the highest proportion of PMN on 28 and 35 DPP compared to PC and MC cows. The relative mRNA abundance of IL-1ß and IL-8 increased after 21 DPP in PP cows compared to the other groups. The PC had the highest, MC had an intermediate, and PP cows had the lowest relative abundance of IL10 mRNA. Overall, these findings indicated that uterine inflammation was more pronounced in PP cows. Moreover, based on the proportion of PMN and abundance of transcripts associated with inflammation in the uterus, PP cows may require a longer period to recover their uterine health after calving.

Tendência da taxa de mortalidade por câncer de mama em mulheres com 20 anos ou mais no Brasil, 2005-2019 / Trend in breast cancer mortality rate among women aged 20 years or older in Brazil, 2005-2019

Resumo O objetivo é analisar a tendência da taxa de mortalidade por câncer de mama e sua correlação com o status de desenvolvimento socioeconômico no Brasil. Estudo ecológico de séries temporais realizado nos 26 estados, Distrito Federal e regiões do Brasil. As fontes de dados foram o Sistema de Informação sobre Mortalidade (número de óbitos), o Instituto Brasileiro de Geografia e Estatística (população residente) e o estudo da Carga Global de Doenças (socio-demographic index - SDI). Foram usados dados de 2005 a 2019. A tendência foi analisada pelos modelos de regressão de Prais-Winsten. A relação entre a taxa de mortalidade e o SDI foi analisada pelo coeficiente de correlação de Spearman. No período do estudo ocorrerem 207.683 óbitos por câncer de mama. A taxa padronizada de mortalidade média foi de 19,95 óbitos por 100.000 mulheres no Brasil. O Brasil e todas as regiões apresentaram tendência crescente da mortalidade. Do total de estados, 22 apresentaram tendência crescente. Verificou-se relação positiva entre a taxa de mortalidade e o SDI. A taxa de mortalidade padronizada por câncer de mama apresentou tendência crescente no Brasil, em todas as regiões e na maioria das unidades da federação. Verificou-se associação direta entre mortalidade e SDI, indicando maior magnitude em regiões mais desenvolvidas.

Abstract The aim is to analyze the trend in breast cancer mortality rates and its correlation with the socioeconomic development status in Brazil. It involved an ecological time series study carried out in the 26 units of the federation, Federal District and regions of Brazil. Data sources included the Mortality Information System (number of deaths), the Brazilian Institute of Geography and Statistics (resident population) and the study of the Global Burden of Disease (Socio-demographic Index - SDI). Data from 2005 to 2019 were used. The trend was analyzed using Prais-Winsten regression models. The relationship between the mortality rate and the SDI was analyzed using Spearman's correlation coefficient. During the study period, 207,683 deaths from breast cancer occurred. The average standardized mortality rate was 19.95 deaths per 100,000 women in Brazil. All the regions of Brazil showed an increasing trend in mortality. Of the total federative units, 22 showed an increasing trend. There was a positive relationship between the mortality rate and the SDI. The standardized mortality rate for breast cancer showed an increasing trend in Brazil, in all regions and in most states. There was a direct association between mortality and SDI, indicating a greater magnitude in more developed regions.

Treatment and Outcomes of Radiation-Induced Soft Tissue Sarcomas of the Extremities and Trunk-A Systematic Review of the Literature.

INTRODUCTION: Radiation-induced soft tissue sarcomas (RISs) are rare secondary malignancies with a dire prognosis. The literature on the management of these tumors remains scarce due to their low incidence. Our systematic review sought to assess the treatment alternatives and outcomes of patients with RIS. METHODS: A systematic review was conducted following the PRISMA guidelines. Our study was registered in PROSPERO (ID: CRD42023438415). Quality assessment was performed using the STROBE checklist. Weighted means for both continuous and categorical values were calculated. RESULTS: Twenty-one studies comprising 1371 patients with RIS were included. The mean latency period from radiation to RIS diagnosis was 14 years, and the mean radiation dose delivered to the primary malignancy was 29.2 Gy. The most common histological type was undifferentiated pleomorphic sarcoma (42.2%), and 64% of all tumors were high-grade. The trunk was the most common location (59%), followed by extremities (21%) and pelvis (11%). Surgery was performed in 68% of patients and, among those with an appendicular tumor, the majority (74%) underwent limb-salvage surgery. Negative margins were attained in 58% of patients. Chemotherapy and radiotherapy were administered in 29% and 15% of patients, respectively. The mean 5-year overall survival was 45%, and the local recurrence and metastasis rates were 39% and 27%, respectively. CONCLUSIONS: In our study, the most common treatment was surgical resection, with RT and chemotherapy being administered in less than one third of patients. Patients with RIS exhibited poor oncologic outcomes. Future studies should compare RIS with de novo STS while controlling for confounders.

Nurseped: educational technology for safety in the management of intravenous antibiotics in pediatrics. / Nurseped: tecnología educativa para la seguridad en el manejo de antibióticos intravenosos en pediatría.

OBJECTIVE: to develop and validate the content of a serious game on the safe management of intravenous medications in pediatrics. METHOD: methodological study for the development and content validation of an educational technology. The cases and challenges of the serious game were developed based on a literature review and validated by 11 nurses with training and experience in the area. Content validity and agreement indices were adopted to analyze agreement and internal consistency (minimum of 0.8). RESULTS: the content is based on the main antibiotics used in the clinical management of infections in hospitalized children and patient safety. Absolute agreement was obtained in 60 of the 61 items evaluated, and the minimum obtained was 0.82 in the content validation index and 0.80 in agreement. Adjustments were suggested by experts in the response statement for a specific case and implemented to improve the quality of the technology content. CONCLUSION: the content of the serious game Nurseped was validated by nurse experts in child health regarding clinical cases, question statements and multiple-choice answers, in addition to feedback that presents the user with an evidence-based answer after getting the challenge right or wrong.

Nurseped: tecnología educativa para la seguridad en el manejo de antibióticos intravenosos en pediatría / Nurseped: educational technology for safety in the management of intravenous antibiotics in pediatrics / Nurseped: tecnologia educacional para a segurança no manejo de antibióticos endovenosos em pediatria

Objetivo: desarrollar y validar el contenido de un serious game sobre el manejo seguro de medicamentos intravenosos en pediatría. Método: estudio metodológico para el desarrollo y validación de contenido de una tecnología educativa. Los casos y desafíos del serious game se basaron en una revisión de la literatura y fueron validados por 11 enfermeros con formación y experiencia en el área. Se adoptaron índices de validez de contenido y concordancia para el análisis de concordancia y consistencia interna (mínimo de 0,8). Resultados: el contenido se basa en los principales antibióticos utilizados en el manejo clínico de infecciones en niños hospitalizados y en la seguridad del paciente. Se obtuvo una concordancia absoluta en 60 de los 61 ítems evaluados, y el mínimo obtenido fue de 0,82 en el índice de validación de contenido y 0,80 en concordancia. Los expertos sugirieron ajustes en la formulación de respuestas de un caso específico y se implementaron para mejorar la calidad del contenido de la tecnología. Conclusión: el contenido del serious game Nurseped fue validado por enfermeros expertos en salud infantil en cuanto a casos clínicos, enunciados de preguntas y respuestas de opción múltiple, además del feedback que presenta al usuario una respuesta basada en evidencia tras acertar o fallar en el desafío.

Objective: to develop and validate the content of a serious game on the safe management of intravenous medications in pediatrics. Method: methodological study for the development and content validation of an educational technology. The cases and challenges of the serious game were developed based on a literature review and validated by 11 nurses with training and experience in the area. Content validity and agreement indices were adopted to analyze agreement and internal consistency (minimum of 0.8). Results: the content is based on the main antibiotics used in the clinical management of infections in hospitalized children and patient safety. Absolute agreement was obtained in 60 of the 61 items evaluated, and the minimum obtained was 0.82 in the content validation index and 0.80 in agreement. Adjustments were suggested by experts in the response statement for a specific case and implemented to improve the quality of the technology content. Conclusion: the content of the serious game Nurseped was validated by nurse experts in child health regarding clinical cases, question statements and multiple-choice answers, in addition to feedback that presents the user with an evidence-based answer after getting the challenge right or wrong.

Objetivo: desenvolver e validar o conteúdo de um serious game sobre o manejo seguro de medicamentos endovenosos em pediatria. Método: estudo metodológico para o desenvolvimento e validação de conteúdo de uma tecnologia educacional. Os casos e desafios do serious game foram desenvolvidos com base em revisão da literatura e validados por 11 enfermeiros com formação e atuação na área. Adotou-se os índices de validade de conteúdo e concordância, para análise de concordância e consistência interna (mínimo de 0,8). Resultados: o conteúdo é baseado nos principais antibióticos utilizados no manejo clínico de infecções em crianças hospitalizadas e na segurança do paciente. Obteve-se concordância absoluta em 60 dos 61 itens avaliados, o mínimo obtido foi 0,82 no índice de validação de conteúdo e 0,80 na concordância. Ajustes foram sugeridos pelos experts no enunciado de respostas de um caso específico e implementados para o aprimoramento da qualidade do conteúdo da tecnologia. Conclusão: o conteúdo do serious game Nurseped foi validado por enfermeiros experts em saúde da criança quanto aos casos clínicos, aos enunciados das perguntas e às respostas de múltipla escolha, além do feedback que apresenta ao usuário uma resposta baseada em evidências após o acerto ou erro do desafio.

Molecular landscape of the JAK2 gene in chronic myeloproliferative neoplasm patients from the state of Amazonas, Brazil.

JAK2V617F (dbSNP: rs77375493) is the most frequent and most-studied variant in BCR::ABL1 negative myeloproliferative neoplasms and in the JAK2 gene. The present study aimed to molecularly characterize variants in the complete coding region of the JAK2 gene in patients with BCR::ABL1 negative chronic myeloproliferative neoplasms. The study included 97 patients with BCR::ABL1 negative myeloproliferative neoplasms, including polycythemia vera (n=38), essential thrombocythemia (n=55), and myelofibrosis (n=04). Molecular evaluation was performed using conventional PCR and Sanger sequencing to detect variants in the complete coding region of the JAK2 gene. The presence of missense variants in the JAK2 gene including rs907414891, rs2230723, rs77375493 (JAK2V617F), and rs41316003 were identified. The coexistence of variants was detected in polycythemia vera and essential thrombocythemia. Thus, individuals with high JAK2V617F variant allele frequency (≥50% VAF) presented more thrombo-hemorrhagic events and manifestations of splenomegaly compared with those with low JAK2V617F variant allele frequency (<50% VAF). In conclusion, individuals with BCR::ABL1 negative neoplasms can display >1 variant in the JAK2 gene, especially rs2230722, rs2230724, and rs77375493 variants, and those with high JAK2V617F VAF show alterations in the clinical-laboratory profile compared with those with low JAK2V617F VAF.

HIV in MOTION: a community of practice on physical rehabilitation for and by people living with HIV and their allies.

Background: This paper describes the design, implementation, and evaluation of a community of practice (CoP), HIV in MOTION (HIM), to advance physical activity rehabilitation interventions with adults living with HIV, clinicians, researchers, and representatives from community-based organizations. We attracted a diverse audience of geographically dispersed people living with HIV, clinicians, exercise personnel, and trainees to eight HIM community of practice events that featured the clinical, research, and lived experience of people living with HIV. HIV in MOTION had (a) a domain related to physical rehabilitation, exercise, and social participation for people living with HIV; (b) a community of diverse individuals; and (c) a practice, that is, a series of sustained interactions online and offline, synchronous, and asynchronous. Our team included six diverse people living with HIV, two coordinators, and three academic researchers who planned, prepared, implemented, and evaluated each online session. To evaluate the HIV in MOTION CoP, we employed an evaluation framework composed of five criteria: Goals and Scope, Context and Structure, Process and Activities, Outcomes, and Impact. We collected quantitative and qualitative evaluative data using online evaluation, audiovisual archiving, and participant observations during the debriefing with all members of our team. Results: We widened the Goals and Scope of the HIV in MOTION CoP to include the HIV narrative of lived experiences, including autopathography, and participant storytelling. In matters of Context and Structure, we received explicit satisfaction with our governance and leadership. Also, being flexible to fit online formats was a productive strategy that made the HIV in MOTION CoP sessions agile and amenable to audiovisual archiving. Our indicators of success in Process, Activities, and Outcomes included participant retention online, elicited verbal interventions and comments in the chat room, and a rate of three repeat visits online. The indicators of success of Impact were the presence of voluntary and unscripted autopathography, the patient storytelling and how it reportedly caused changes in the participants, and the "legitimate peripheral participation" of emerging research and clinical students. In conclusion, we recommend our form of CoP for mixing the knowledge of diverse persons in this area. However, we recommend considering budget and burnout as serious challenges to sustainability.

Pulmonary exacerbations in early cystic fibrosis lung disease are marked by strong modulation of CD3 and PD-1 on luminal T cells.

Background: In chronic cystic fibrosis (CF) lung disease, neutrophilic inflammation and T-cell inhibition occur concomitantly, partly due to neutrophil-mediated release of the T-cell inhibitory enzyme Arg1. However, the onset of this tonic inhibition of T cells, and the impact of pulmonary exacerbations (PEs) on this process, remain unknown. Methods: Children with CF aged 0-5 years were enrolled in a longitudinal, single-center cohort study. Blood (n = 35) and bronchoalveolar lavage (BAL) fluid (n = 18) were collected at stable outpatient clinic visits or inpatient PE hospitalizations and analyzed by flow cytometry (for immune cell presence and phenotype) and 20-plex chemiluminescence assay (for immune mediators). Patients were categorized by PE history into (i) no prior PE, (ii) past history of PE prior to stable visit, or (iii) current PE. Results: PEs were associated with increased concentration of both pro- and anti-inflammatory mediators in BAL, and increased neutrophil frequency and G-CSF in circulation. PE BAL samples showed a trend toward an increased frequency of hyperexocytic "GRIM" neutrophils, which we previously identified in chronic CF. Interestingly, expression levels of the T-cell receptor associated molecule CD3 and of the inhibitory programmed death-1 (PD-1) receptor were respectively decreased and increased on T cells from BAL compared to blood in all patients. When categorized by PE status, CD3 and PD-1 expression on blood T cells did not differ among patients, while CD3 expression was decreased, and PD-1 expression was increased on BAL T cells from patients with current PE. Conclusions: Our findings suggest that airway T cells are engaged during early-life PEs, prior to the onset of chronic neutrophilic inflammation in CF. In addition, increased blood neutrophil frequency and a trend toward increased BAL frequency of hyperexocytic neutrophils suggest that childhood PEs may progressively shift the balance of CF airway immunity towards neutrophil dominance.

Academic performance beyond the metrics: A qualitative content analysis of nursing students' perceptions.

AIM: To explore the undergraduate nursing students' perceptions about the factors influencing their academic performance. BACKGROUND: Academic performance is the measure for the achievement of learning objectives and skills development. Thus, the literature on nursing education has already pointed out the factors associated with this construct. However, it is essential to understand the in-depth influencers of academic performance from the perspective of nursing students. For this, it is essential to analyze not only numerical indicators, but also to understand the perceptions of undergraduate students about the factors that can influence this performance. DESIGN: Descriptive study with qualitative approach. METHODS: Twenty-two undergraduate nursing students were recruited from a Brazilian public university. Interviews were collected and submitted to Content Analysis, thematic modality, and discussed according to references of critical and humanist education. RESULTS: Two thematic categories emerged from the interviews representing the students' perceptions: 1. The student - history and relationships, with the thematic axis quality of previous education, intrafamily processes and roles, family support, socioeconomic aspects, interpersonal relationships, copping with difficulties, mental health, and physical well-being; and 2. Academic experiences and their challenges, with the thematic axis academic adaptation, professor's didactics and preparation, structure and support provided by the University, management of study time, and participation in extracurricular activities. The students saw them as intervening factors in their academic performance, physical and psychological well-being, established interpersonal relationships (including the relation with peers and professors), family structure, socioeconomic aspects, academic conditions, and the transition to higher education. CONCLUSION: From the perspective of students, socio-historical aspects and constructs established in relationships with colleagues and professors at the university are directly related to their academic performance and directly influence their ability to achieve the proposed learning objectives and acquire essential competencies for their education.

Vacinas e desinformação: uma análise de conteúdo sobre fake newsapuradas por plataformas de debunkingem redes sociais / Vaccines and disinformation: a content analysis on fake news verified by debunking platforms on social networks / Vacunas y desinformación: un análisis de contenidos sobre fake news verificadas por las plataformas de debunking en las redes sociales

O impacto das fake news chegou à área da saúde e a desconfiança em relação às vacinas trouxe de volta doenças até então erradicadas. Mas como os discursos antivacinasão construídos nas redes sociais? Neste trabalho, 80fake news com foco nas vacinas foram coletadas de sites brasileiros que realizam debunking, uma estratégia de detecção e desmascaramento de desinformação e fake news. A partir da aplicação de um protocolo analítico, mapeamos as principais características presentes na elaboração dessas publicações. A análise de conteúdo revelou que o Facebook e o WhatsApp são as redes preferidas para esse tipo de compartilhamento. Cerca de 59% dos conteúdos são totalmente falsos e a maioria dos discursos destaca possíveis riscos das vacinas como estratégias de convencimento. As fontes mais referenciadas são supostamente médicos e cientistas, para criar confiabilidade. O levantamento aponta ainda que 60% das publicações apresentaram erros gramaticais e ortográficos na elaboração dos textos

The impact of fake news reached the health area and distrust in relation to vaccines brought back diseases that had been eradicated. But how are these anti-vaccine discourses constructed in social medias? In this paper, 80 fake news stories focusing on vaccines were collected through Brazilian websites that perform debunking, a strategy for detecting and unmasking misinformation and fake news. From the application of an analytical protocol, the main characteristics present in the elaboration of these publications were mapped. Content analysis revealed that Facebook and WhatsApp are the preferred medias for this type of sharing. About 59% of the contents are totally false and most of the speeches highlight the risks of vaccines as a convincing strategy. The most referenced sources are supposedly doctors and scientists to create re-liability. The survey also points out that 60% of publications have grammatical and spelling errors in the preparation of texts

El impacto de las fake news llegó al área de la salud y la desconfianza en las vacunas trajo de vuelta enfermedades erradicadas. Pero, ¿cómo se construyen los discursos antivacunas en las redes sociales? En este trabajo, se recopilaron 80 noticias falsas centradas en vacunas a través de sitios web brasileños que realizan debunking, una estrategia para detectar y desenmascarar información errónea y noticias falsas. A partir de la aplicación de un protocolo analítico, mapeamos las principales características presentes en la elaboración de estas publicaciones. El análisis de contenido reveló que Facebook y WhatsApp son las redes preferidas para este tipo de intercambio. Alrededor del 59% del contenido es completamente falso y la mayoría destaca los posibles riesgos de las vacunas como estrategias convincentes. Las fuentes más referenciadas son supuestamente médicos y científicos para crear confiabilidad. La encuesta señala que el 60% de las publicaciones tenían errores gramaticales y ortográficos

Acute Chagas disease associated with ingestion of contaminated food in Brazilian western Amazon.

OBJECTIVE: To describe clinical, epidemiological and management information on cases of acute Chagas disease (ACD) by oral transmission in the state of Amazonas in western Amazon. METHODS: Manual and electronic medical records of patients diagnosed with ACD at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) were included. RESULTS: There were 147 cases of acute CD registered from 10 outbreaks that occurred in the state of Amazonas between 2004 and 2022. The transmission pathway was through oral route, with probable contaminated palm fruit juice (açaí and/or papatuá), and involved people from the same family, friends or neighbours. Of 147 identified cases, 87 (59%) were males; cases were aged 10 months to 82 years. The most common symptom was the febrile syndrome (123/147; 91.8%); cardiac alterations were present in 33/100 (33%), (2/147; 1.4%) had severe ACD with meningoencephalitis, and 12 (8.2%) were asymptomatic. Most cases were diagnosed through thick blood smear (132/147; 89.8%), a few (14/147; 9.5%) were diagnosed by serology and (1/147; 0.7%) by polymerase chain reaction (PCR) and blood culture. In all these outbreaks, 74.1% of the patients were analysed by PCR, and Trypanosoma cruzi TcIV was detected in all of them. No deaths were recorded. The incidence of these foci coincided with the fruit harvest period in the state of Amazonas. CONCLUSION: The occurrence of ACD outbreaks in the Amazon affected individuals of both sexes, young adults, living in rural and peri-urban areas and related to the consumption of regional foods. Early diagnosis is an important factor in surveillance. There was a low frequency of cardiac alterations. Continuous follow-up of most patients was not carried out due to difficulty in getting to specialised centres; therefore, little is known about post-treatment.

SARS-CoV-2 intra-host diversity, antibody response, and disease severity after reinfection by the variant of concern Gamma in Brazil.

The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma in Amazonas during early 2021 fueled a second large COVID-19 epidemic wave and raised concern about the potential role of reinfections. Very few cases of reinfection associated with the VOC Gamma have been reported to date, and their potential impact on clinical, immunological, and virological parameters remains largely unexplored. Here we describe 25 cases of SARS-CoV-2 reinfection in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected with distinct viral lineages between March and December 2020 (B.1.1, B.1.1.28, B.1.1.33, B.1.195, and P.2) and reinfected with the VOC Gamma between 3 to 12 months after primo-infection. We found a similar mean cycle threshold (Ct) value and limited intra-host viral diversity in both primo-infection and reinfection samples. Sera of 14 patients tested 10-75 days after reinfection displayed detectable neutralizing antibodies (NAb) titers against SARS-CoV-2 variants that circulated before (B.1.*), during (Gamma), and after (Delta and Omicron) the second epidemic wave in Brazil. All individuals had milder or no symptoms after reinfection, and none required hospitalization. These findings demonstrate that individuals reinfected with the VOC Gamma may display relatively high RNA viral loads at the upper respiratory tract after reinfection, thus contributing to onward viral transmissions. Despite this, our study points to a low overall risk of severe Gamma reinfections, supporting that the abrupt increase in hospital admissions and deaths observed in Amazonas and other Brazilian states during the Gamma wave was mostly driven by primary infections. Our findings also indicate that most individuals analyzed developed a high anti-SARS-CoV-2 NAb response after reinfection that may provide some protection against reinfection or disease by different SARS-CoV-2 variants.

Clinical Features of COVID-19 in Patients with Congenital Central Hypoventilation Syndrome.

Background: The clinical course of COVID-19 in patients with congenital central hypoventilation syndrome (CCHS) is unknown. Methods: We conducted a cross-sectional questionnaire study in 43 patients with CCHS who had COVID-19. Results: The median age of patients was 11 [interquartile range (IQR) 6-22] years and 53.5% required assisted ventilation (AV) through tracheostomy. Disease severity ranged from asymptomatic infection (12%) to severe illness with hypoxemia (33%) and hypercapnia requiring emergency care/hospitalization (21%), increased AV duration (42%), increased ventilator settings (12%), and supplemental oxygen demand (28%). The median duration to return to baseline AV (n = 20) was 7 (IQR 3-10) days. Patients with polyalanine repeat mutations required increased AV duration compared with those with nonpolyalanine repeat mutations (P = 0.048). Patients with tracheostomy required increased oxygen during illness (P = 0.02). Patients aged ≥18 years took longer to return to baseline AV (P = 0.04). Conclusions: Our study suggests that all patients with CCHS should be vigilantly monitored during COVID-19 illness.