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Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

Abstract Background Bloodstream infection (BSI) is associated with poor outcomes especially when effective antimicrobial therapy and control of infection source are delayed. As the frequency of Enterobacterales producing metallo-β-lactamases (MBL) and/or OXA-48–like carbapenemases is increasing in some United States (US) medical centres, effective antimicrobials to treat the infections caused by these organisms are urgently needed. Aztreonam-avibactam is under clinical development for treatment of infections caused by Gram-negative bacteria, including MBL producers. Objectives To evaluate the antimicrobial susceptibility of Enterobacterales causing BSI in US medical centres and compare the activity of aztreonam-avibactam with ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and other antimicrobials used to treat BSI. Methods 4,802 Enterobacterales were consecutively collected (1/patient) from 72 US medical centres in 2020–2022 and susceptibility tested by broth microdilution. Aztreonam-avibactam was tested with avibactam at a fixed concentration of 4 mg/L. A pharmacokinetic/pharmacodynamic susceptible breakpoint of ≤ 8 mg/L was applied for aztreonam-avibactam for comparison. Carbapenem-resistant Enterobacterales (CRE) isolates were tested for β-lactamase–encoding genes using Next-generation sequencing. Results Aztreonam-avibactam was highly active against Enterobacterales; only 2 isolates showed aztreonam-avibactam MICs > 8 mg/L: 1 meropenem-susceptible E. coli and 1 K. aerogenes (CRE). All carbapenemase producers and 98.0% of CRE were inhibited at an aztreonam-avibactam MIC of ≤ 8 mg/L. CRE susceptibility rates were 81.6% for ceftazidime-avibactam, 65.3% for meropenem-vaborbactam, 61.2% for imipenem-relebactam, and 87.8% for cefiderocol. Aztreonam-avibactam retained activity (MIC, ≤ 8 mg/L) against all (100.0%) meropenem-vaborbactam nonsusceptible (n = 17), 99.5% of imipenem-relebactam nonsusceptible (n = 206), and 90.0% of ceftazidime-avibactam nonsusceptible (n = 10) isolates. The most common carbapenemases were KPC-2/3 (57.1% of CREs), OXA-48–like (16.3%), and NDM (14.3%). A carbapenemase gene was not observed in 12.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were active against 100.0% of KPC producers, but ceftazidime-avibactam showed limited activity against MBL producers and meropenem-vaborbactam showed limited activity against OXA-48–like and MBL producers. The most active non–β-lactam comparators against CRE were gentamicin (49.0% susceptible) and amikacin (44.9% susceptible). Conclusions Aztreonam-avibactam demonstrated potent activity against a large collection of Enterobacterales isolated from patients with BSI in US hospitals, including CRE, MBL producers, and isolates resistant to recently approved β-lactamase inhibitor combinations.

INTRODUCTION: Aging is associated with changes in heart structure and function, and there are benefits of physical exercise in delaying these changes. OBJECTIVES: To characterize the heart of a geriatric cohort at a structural and functional level, and to evaluate the potential cardiac benefits of a personalized exercise intervention program. METHODS: Non-randomized intervention study, including a group of old adults from the AGA@4life cohort. Two echocardiographic evaluations were performed, at baseline and 3 months after the implementation of a multidisciplinary intervention program, integrating the practice of adapted physical exercise. Participants were divided into 2 groups: group 1 with low adherence to the exercise program (< 20% of sessions); group 2 with high adherence to the exercise program (> 90% of sessions). RESULTS: Characteristic heart changes were observed at baseline, mainly at the valvular level, with 89.2% (n = 33) cases of aortic fibrosis, 73% (n = 27) cases of mitral fibrosis, 51.2% (n = 19) cases of aortic regurgitation, and 68% (n = 25) cases of mitral regurgitation. After the intervention, significant changes were observed in several functional parameters in group 2, namely in the maximum velocity of the E' (p = 0.01) and S' (p = 0.02) mitral valve waves, and maximum velocity of the E' tricuspid valve wave (p = 0.02). Positive structural changes were also observed in group 2, namely a reduction in relative wall thickness (p = 0.03) and left ventricular diastolic diameter (p = 0.04). CONCLUSION: Personalized physical exercise implemented as part of a multidisciplinary intervention program is a useful non-pharmacological tool for maintaining adequate cardiac function and structure in the old adult.

The mission of higher education institutions (HEI) includes fostering conditions that enable student participation, and a commitment to their professional success. Pedagogical strategies which combine learning that goes beyond the university and involves a service-learning (SL) course carried out in the context of a pedagogical innovation programme of the University of Porto were examined. This examination included interviews with teachers, a focus group discussion with students and the analysis of logbooks and final reports to realize the potential of SL for improving employability. The results put into perspective the weaknesses and potentialities of SL courses at HEI and show that when academic learning is integrated with community experience, students gain both personal/social and academic skills. They also develop leadership and communication skills and critical awareness on the one hand and time and resources management and the ability to adapt and respond to challenges of the real world on the other, all seen as beneficial for the transition into the labour market.

ABSTRACT Objective: To traslate and validate of the Brazilian version of the SDI-2. Methods: This was a cross-sectional study. The cultural adaptation considered the stages of initial translation, synthesis of translations, evaluation by a committee of experts from different regions of Brazil, back-translation, and pre-test. The content validity and psychometric proprieties was assessed. Results: Ten specialists participated in the cultural adaptation of the SDI-2. The content validity showed a Content Validity Ratio (CVR) ≥ 0.75 (p = 0.05). A total of 674 subjects participated in the field study. The Exploratory Factorial Analysis (EFA) presented factor loads ≥ 0.445, and commonalities ≥ 0.40; and two dimensions represented 77% of the total variance explained. The Confirmatory Factorial Analysis CFA presented X2/df = 4.265; the Root Mean Square Error of Approximation RMSEA = 0.110; the Non-Normed Fit Index NNFI = 0.946; the Comparative Fit Index (CFI) = 0.963; the Goodness of Fit Index GFI = 0.986; and the Adjusted Goodness of Fit Index AGFI = 0.979 for a two-factor model. The coefficient values for the total SDI-2 score were 0.91 for Cronbach's alpha, 0.91 for McDonald's Omega, and 0.97 for the Greatest Lower Bound GLB coefficients. The invariance between sexes was 0.01 for the ΔCFI and ΔRMSEA, showing model stability for these two populations. Conclusion: The Brazilian version of the SDI-2 is self-report, valid, reliable and invariant across sex.

ABSTRACT This study reports the activity of cefiderocol against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. isolates collected from the United States and Europe, including Israel and Turkey, from 2020 to 2021. Among Enterobacterales, 2.8% were carbapenem nonsusceptible (CNSE); cefiderocol inhibited 96.6%/85.1% [Clinical Laboratory Standards Institute (CLSI)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints] of these isolates. Imipenem-relebactam, meropenem-vaborbactam, and ceftazidime-avibactam displayed susceptibilities lower than cefiderocol against CNSE isolates (67.4–84.6% susceptible, CLSI). Cefiderocol was the only agent active against CNSE isolates carrying metallo-β-lactamase (MBL) carbapenemase or multiple carbapenemase genes (84.6%–92.3% susceptible, CLSI). Approximately 18% of carbapenem-susceptible Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis carried extended-spectrum-β-lactamases and/or plasmid-borne AmpC-encoding genes; cefiderocol inhibited 99.8%–100.0% (CLSI) of these genotypic groups. Multi-drug resistance (MDR) phenotypes were observed in 16.9% and 52.5% of P. aeruginosa and A. baumannii-calcoaceticus isolates, respectively. Carbapenemase genes were rare (4.9%) among cephalosporin and/or carbapenem nonsusceptible P. aeruginosa, compared to 87.6% carriage in A. baumannii-calcoaceticus, respectively. Against the MDR and carbapenemase-carrying P. aeruginosa and A. baumannii-calcoaceticus subsets, cefiderocol was active against 98.6%/98.7% and 97.1%/97.4% (CLSI), respectively. Only 69 isolates (0.3%) across all species groups were identified as cefiderocol nonsusceptible per CLSI criteria (>4 mg/L). Cefiderocol was the most active agent in vitro against Enterobacterales, P. aeruginosa, and Acinetobacter spp., with uniform activity against all phenotypic- and genotypic-resistant subsets. Coupled with the low incidence of nonsusceptibility observed across species groups, these results demonstrate cefiderocol as an important option for treating infections caused by pathogens with diverse mechanisms of resistance in US and European hospitals.IMPORTANCEThe worldwide spread of multi-drug-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales and Acinetobacter spp. poses a serious challenge in healthcare settings as infections caused by these organisms are commonly refractory to many frontline therapeutic agents. Multiple global health organizations highlighted these pathogens as critical priorities for new antibiotic development, thus necessitating continued surveillance of the activities of currently available antimicrobial agents and circulating mechanisms of resistance. To meet this need, this study phenotypically and genotypically characterized priority Gram-negative pathogens collected from patients in US and European hospitals to examine the activity of cefiderocol and other currently available treatment options, including carbapenems and β-lactam-β-lactamase inhibitor combinations. The results presented here provide a detailed perspective to healthcare practitioners of cefiderocol’s broad applicability, manifested in high activity and low nonsusceptibility rates, across phenotypic and genotypic organism groups relative to other agents and further support its use against the most intransigent infections.

IntroductionImmunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC).MethodsOpen-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study.Results125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p

Introdução: A hanseníase é uma doença bacteriana endêmica causada pela Mycobacterium leprae sendo mais prevalente nos países em desenvolvimento. Se não tratada evolui de forma lenta e progressiva se tornando transmissível e desta forma pode afetar pessoas de qualquer idade ou sexo. No Brasil, segundo país do mundo em número de casos novos, é uma das principais causas de incapacidade física, pelo potencial de gerar lesões neurais. Objetivo: Analisar e correlacionar espacialmente a prevalência e características clínicas da Hanseníase no estado de São Paulo (SP) entre 2018 e 2022. Método: Trata-se de um estudo ecológico e exploratório com informações do DATASUS acerca dos casos de hanseníase nos municípios de SP, com análise da forma clínica de notificação e avaliação do grau de incapacidade física (GIF) em que os dados foram inseridos no TerraView para identificar autocorrelação espacial estimada pelo Índice de Moran (IM) e construção de mapas temáticos. Resultados: Entre os anos de 2018 a 2022 houve 7215 (16,27/100.000 Hab) casos de Hanseníase no Estado. É possível notar neste período uma queda de 17,02% no número de casos. Analisando pela classificação de Madri, houve 620 (8,59%) casos da forma indeterminada; 738 (10,22%) da tuberculóide; 3424 (47,45%) da dimorfa e 2025 (28,06%) da virchowiana. 418 (5,79%) casos foram ignorados ou não classificados. Explorando o GIF, indicador de perda da sensibilidade protetora e/ou deformidade visível pela lesão neural ou cegueira, 2843 (39,4%) foram classificados como grau 0; 2468 (34,2%) classificados como grau I e 1199 (16,6%) classificados como grau II. 705 (9,77%) casos foram deixados em branco ou não avaliados. O valor estimado do IM dos casos totais por 100.000 habitantes foi de 0.257 (p-valor: 0.01). No mapa temático é possível notar uma concentração de casos ao Norte do estado, na região de São José do Rio Preto e Araçatuba. É possível também identificar um acúmulo de casos de GIF 2 nas cidades de Ribeirão Preto, Sorocaba e Fernandópolis. Analisando a forma virchowiana, caracterizada como a mais contagiosa, as cidades com piores indicadores foram São Paulo, Campinas e Ribeirão Preto. Conclusão: Apesar da diminuição dos casos nos últimos anos, a doença ainda se encontra presente no estado de SP. Cerca de 50,74% dos acometidos apresentam algum nível de comprometimento funcional, conforme o GIF. Esses dados reforçam a importância das políticas públicas voltadas para a prevenção e tratamento da hanseníase, especialmente com foco na região norte do estado.

Introdução: A sífilis congênita é um problema de saúde pública significativo, podendo levar a diversos desfechos perinatais desfavoráveis e sequelas graves para a criança. No Brasil, os casos de sífilis congênita e gestacional continuam aumentando, destacando a necessidade de diagnóstico, tratamento e prevenção oportunos. A falta de acompanhamento adequado durante o pré-natal pode resultar em desfechos indesejados para o neonato, como hospitalização prolongada e impactos no neurodesenvolvimento. Apesar de muitos estudos se concentrarem nos aspectos clínicos da sífilis congênita, há uma lacuna na compreensão das experiências maternas, especialmente em relação aos aspectos afetivos e psicológicos. A importância das redes de apoio também é subestimada neste contexto, apesar de seu potencial para mitigar os efeitos da sífilis congênita. Objetivo: Conhecer as vivências de mães de crianças com sífilis congênita frente ao diagnóstico e hospitalização da criança. Método: Estudo descritivo, de abordagem qualitativa, fundamentado no conceito das redes de apoio social. Após aprovação ética, foram realizadas entrevistas individuais e semiestruturadas, submetidas à análise de conteúdo. Foram incluídas 14 mães de crianças com sífilis congênita em acompanhamento ambulatorial em um serviço de referência. Resultados: Identificou-se a culpa da mulher e sua responsabilização pela transmissão da sífilis congênita. As mulheres vivenciaram sentimentos de tristeza, dúvidas em relação ao filho, a concepção equivocada de tratar-se de uma doença incurável e o medo da morte da criança. A vivência da sífilis congênita foi permeada por estigma e preconceitos. A internação da criança foi um momento de choque, sobretudo diante da separação da criança, e da necessidade de realização de procedimentos invasivos. A perspectiva de melhora da criança, bem como o reconhecimento dos benefícios do tratamento, atrelado a fé e conformação de uma rede de apoio foram fundamentais no processo de superação. Conclusão: A presença da rede de apoio na jornada de enfrentamento da sífilis congênita é capaz de modular a experiência materna da doença, apontando para a necessidade de educação em saúde e ações mais inclusivas no contexto de saúde materno-infantil, desde o pré-natal.

Introdução: Doença citomegálica neurológica continua causando elevada morbidade e mortalidade em pessoas com aids avançada. Atualmente não existe consenso sobre o uso de pontos de corte de carga viral plasmática do citomegalovírus (CMV), no diagnóstico das complicações neurológicas causadas por esse vírus na aids avançada. Objetivo: Avaliar o desempenho da carga viral plasmática do CMV no diagnóstico de doença neurológica citomegálica em pessoas com aids avançada. Método: Estudo observacional, de coorte e retrospectivo, realizado em centro terciário de São Paulo, Brasil. Foram incluídos pacientes admitidos no hospital, durante o período de um ano, e que apresentaram os seguintes critérios: (i) diagnóstico confirmado de infecção por HIV-1; (ii) contagem de linfócitos T-CD4+ ≤ 100 células/µL; e (iii) coleta de carga viral plasmática do CMV na admissão hospitalar. Posteriormente foram identificados os pacientes com lesão de órgão-alvo citomegálica confirmada, incluindo a neurológica (encefalite e/ou polirradiculopatia). Calculou-se desempenho da carga viral do CMV (sensibilidade -Se-, especificidade -Es-, valor preditivo positivo -VPP-, valor preditivo negativo -VPN-, acurácia -Ac-, razão de verossimilhança positiva -RVP-, e razão de verossimilhança negativa -RVN- em pacientes com doença neurológica citomegálica, utilizando diversos pontos de corte de carga viral do CMV. Resultados: No período do estudo foram internadas 830 PVHIV e 245 (29.5%) delas foram incluídos. A mediana (IQR) de idade dos pacientes foi 38 (30-46) anos e 183 (74.7%) deles foram do sexo masculino. Durante a internação, 17 (6.9%) pacientes tiveram lesão de órgão-alvo pelo CMV: 6 (2.4%) apresentaram doença neurológica e 11 (4.5%) tiveram doença não neurológica. A presença de carga viral plasmática de CMV ≥ 1.000 UI/mL mostrou Se = 83.3%, Es = 78.7%, VPP = 8.9%, VPN = 99.5, Ac = 78.8%, RVP = 3.9 e RVN = 0.2 no diagnóstico de doença neurológica. Por outro lado, a presença de carga viral plasmática de CMV ≥ 30.000 UI/mL mostrou Se = 83.3%, Es = 97.5%, VPP = 45.4%, VPN = 99.6, Ac = 97.1%, RVP = 33.3 e RVN = 0.03 no diagnóstico de doença neurológica. Conclusão: O resultado do desempenho da carga viral plasmática de CMV ≥ 30.000 UI/mL sugere o uso potencial desse valor de corte no diagnóstico da doença neurológica citomegálica na prática clínica diária. Maiores estudos são necessários para confirmar esse achado e suas implicações terapêuticas.

BackgroundAlthough long-acting, injectable cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) has proven efficacious for HIV prevention in clinical trials, research is needed to guide effective implementation in real-world settings. Formative work with community members and health care providers (HCPs) is important to provide insight into the needs and contexts of specific populations and reveal potential barriers and facilitators for implementation projects. ObjectiveWe aimed to describe the results from formative work to develop an implementation package for CAB-LA PrEP within the ImPrEP CAB Brasil study. MethodsImPrEP CAB Brasil is an implementation study of same-day delivery of CAB-LA PrEP for young sexual and gender minority (SGM) groups (aged 18-30 years) in 6 existing oral PrEP public health clinics. We conducted formative research to prepare for the implementation of ImPrEP CAB Brasil through community mobilization, process mapping with HCPs with experience in CAB-LA, and focus group discussions (FGDs) with young SGM groups (n=92) and HCPs (n=20) to identify initial perceptions of facilitators and barriers for CAB-LA PrEP implementation, refine the mobile health (mHealth) educational tool, and evaluate the acceptability of using a text message appointment reminder intervention through WhatsApp. FGDs were recorded, transcribed, systematically coded, and analyzed with thematic categorization by trained researchers using a qualitative data analysis program ATLAS.ti (version 7). ResultsA community mobilization team comprising 34 SGM community leaders collaborated in creating a prototype for an mHealth educational tool and contributed to the planning of peer education activities. We created 3 process maps for each site to describe the initial visit, follow-up visits, and laboratory flow. The main challenge identified for same-day CAB-LA PrEP delivery was the extended duration of clinic visits due to the numerous laboratory tests and HIV counseling steps required. Proposed solutions included having point-of-care HIV rapid tests instead of laboratory tests and additional counseling staff. Barriers for CAB-LA PrEP implementation identified through FGDs were the training of HCPs, support for adherence to injection appointments, and stigma or discrimination against SGM groups and persons using PrEP. The mHealth educational tool and WhatsApp reminders were highly acceptable by SGM groups and HCPs, indicating their potential to support PrEP choice and adherence. Content analysis on the cultural appropriateness of the language and overall clarity of the material contributed to the refinement of the mHealth tool. ConclusionsStructured formative work with SGM persons and HCPs generated important refinements to context-specific materials and plans to launch ImPrEP CAB Brasil in public health clinics. Ongoing implementation monitoring will use the process maps to identify additional barriers and potential solutions to same-day delivery of CAB-LA PrEP. Summative evaluations are needed to measure the effectiveness of the mHealth educational tool to support PrEP choice and the use of WhatsApp appointment reminders.

Objetivos: A Fundação Hemominas é constituída por uma rede de 21 Unidades descentralizadas nas macrorregiões de Minas Gerais. Considerando a dimensão geográfica do estado, a distribuição de insumos partindo do Almoxarifado Central em Contagem, região metropolitana de Belo Horizonte para as Unidades regionais percorre grandes distâncias. O objetivo deste trabalho foi revalidar o envio de materiais críticos transportados à temperatura ambiente, do Almoxarifado Central para todas as Unidades da rede, pelo monitoramento das temperaturas de transporte, tempo de transporte e integridade da carga no ato do recebimento no destino final. Material e métodos: Foi feito o monitoramento dos envios de carga das rotas entre o Almoxarifado Central e as Unidades regionais, colocando-se os sensores de temperatura sobre a carga e utilizando manta térmica sobre o sensor e carga, buscando obter dados mais fidedignos relacionados aos insumos transportados e a carga de insumos críticos foi montada em pallets específicos e organizados de acordo com a ordem de descarregamento conforme logística da rota programada entre o Almoxarifado e as Unidades regionais. Foram distribuídos sobre a carga, 3 termômetros tipo data-logger, programados para registrar as temperaturas a cada 15 minutos. Como nova estratégia de transporte e monitoramento da temperatura, os pallets contendo os insumos críticos foram cobertos por uma manta laminada, de modo a ficarem menos sujeitos à ação de radiação térmica propagada através da lataria do baú de transporte do caminhão. Foram consideradas para análise o valor MKT (mean kinetic temperature ) fornecido pelo data-logger. Foram feitos 58 monitoramentos, somando-se todos os registros gerados durante as excursões nas 6 rotas programadas. Resultados: : A distância percorrida das 6 rotas foi de 338 km para distância final da rota mais curta a 664 km para distância final da rota mais longa, o que deu um tempo médio de percurso que variou de 26h a 44h20min. A média de MKT por rota variou de 21,8°C a 23,82°C, correspondendo respectivamente às rotas de menor e maior distância. Discussão: : Não houve uma correlação da média da MKT com o tempo gasto no percurso, sendo observada uma estabilidade das temperaturas médias cinéticas alcançadas durante o transporte, com a MKT apresentando valores muito similares em todas as rotas, apesar das grandes diferenças de distância entre elas. O maior valor MKT observado foi de 25,7°C, bem abaixo da MKT máxima estabelecida de 30°C. Os resultados também mostraram que a média da MKT e da temperatura média simples registrada durante os envios foi quase idêntica (correlação de Pearson > 0,99), demonstrando que não houve evidência de variações significativas ao longo do processo, onde a soma da temperatura e tempo de transporte pudessem prejudicar a integridade da carga. Conclusão: Em todas as rotas houve tempo de transporte superior a 24 h, mas a MKT se manteve em excelente nível nas rotas citadas, o que demonstrou que nosso processo de transporte é seguro e dentro das boas práticas estabelecidas. A adoção do parâmetro MKT (mean kinetic temperature ) se mostrou uma excelente escolha para monitoramento de transporte de cargas entre almoxarifados. Por fim, atribuímos ao uso da manta térmica a ótima estabilidade e homogeneidade da temperatura ao longo das excursões realizadas, mantendo um ambiente isotérmico desejável para este tipo de transporte.

Resumo Objetivo Analisar evidências sobre os custos financeiros de famílias no cuidado de crianças e adolescentes durante o tratamento oncológico. Métodos Revisão integrativa. As buscas foram realizadas nas bases de dados: PubMed, CINAHL, Scopus, Web of Science e EMBASE. Foram considerados artigos publicados em português, espanhol e inglês, nos últimos dez anos, com diferentes desenhos de estudo e que abordassem a temática. Para as buscas, foram utilizados os descritores controlados MeSH, dos títulos CINAHL e EMTREE, seus sinônimos e palavras-chave, interligados pelos operadores booleanos AND e OR. Resultados Foram incluídos 22 artigos. Os resultados foram descritos em categorias: Custos diretos (médicos e não médicos) e indiretos (condição laboral parental e renda familiar). Os custos médicos são aqueles associados a hospitalizações, tratamento e diagnóstico. Os principais elementos responsáveis pelas despesas não médicas foram viagens, alimentação e acomodação. O impacto na situação laboral das famílias é consequência da alta demanda de cuidados imposta aos cuidadores para o tratamento do câncer infantojuvenil. Em decorrência da mudança na situação de trabalho, as famílias precisam lidar com o risco e desdobramentos da diminuição ou perda de renda. Conclusão Os resultados indicam que as famílias assumem despesas médicas diretas e indiretas, bem como custos não relacionados à saúde decorrentes da doença. Além disso, são afetadas por custos indiretos, como perda de produtividade, impacto e mudanças no emprego, o que reduz significativamente a renda.

Objetivou-se avaliar o efeito da inclusão de nitrogênio não proteico (NNP) no suplemento e a influência de diferentes tempos de maturação sobre características físico-químicas no músculo de bovinos de corte (½ Angus + ½ Nelore) em pastejo. Foram utilizados 108 bifes do músculo Longissimus dorsi, retirados de 36 bovinos não castrados, com aproximadamente 20 meses de idade e peso corporal inicial de 400,33 ± 40,87 kg, em delineamento experimental inteiramente casualizado e esquema fatorial, com doze tratamentos, constituídos pela combinação de quatro dietas pré-abate e três tempos de maturação da carne, sendo um bife por unidade experimental totalizando nove repetições. As dietas pré-abate foram compostas por pasto e suplementação concentrada com baixo, médio e alto teor de NNP e controle (não suplementado). Não houve interação (p > 0,05) entre dietas e tempos de maturação (TM) sobre a luminosidade, teor de vermelho e intensidade de amarelo, pH e força de cisalhamento da carne. Independente dos TM, animais não suplementados apresentaram menor (p < 0,05) perda de água por cocção (5,92%) e carnes mais duras (3,32 kgf cm-3) que bovinos que receberam dieta com média concentração de NNP (2,62 kgf cm-3). Os animais que receberam dietas com baixa suplementação de NNP apresentaram carnes com maior (p < 0,05) pigmentação vermelha, além de bifes mais leves (p < 0,05) no pós-cocção do que bovinos não suplementados e aqueles alimentados com dieta contendo média suplementação de NNP. Independente das classes de NNP, a maturação realizada até o 9º dia é eficaz para aumentar a maciez da carne dos bovinos. Bovinos cruzados (½ Angus + ½ Nelore) que consomem dietas com baixa ou média suplementação de nitrogênio não proteico apresentam bifes com melhores condições de intensidade de cor vermelha e de maciez, respectivamente.

ABSTRACT OBJECTIVE To analyze the impact of the fiscal austerity policy (PAF) on health spending in Brazilian municipalities, considering population size and source of funds. METHODS The interrupted time series method was used to analyze the effect of the PAF on total expenditure, resources transferred by the Federal Government, and own/state per capita resources allocated to health in the municipalities. The time series analyzed covered the period from 2010 to 2019, every six months. The first semester of 2015 was adopted as the start date of the intervention. The municipalities were grouped into small (up to 100,000 inhabitants), medium (101,000 to 400,000 inhabitants), and large (over 400,000 inhabitants). The data was obtained from the Sistema de Informações sobre Orçamentos Públicos em Saúde (Information System on Public Health Budget). RESULTS The results for the national average of municipalities show that the PAF had a negative impact on the level of total expenditure and own/state resources allocated to health in the first half of 2015, without causing statically significant changes in the trends of any of the indicators analyzed in the period after 2015. Small municipalities saw a drop in total expenditure, while large municipalities saw a drop in own/state resources, and medium-sized municipalities saw a drop in both variables. There was no statistically significant drop in the volume of funds transferred by the Federal Government in the immediate aftermath of the implementation of the PAF in any of the municipal groups analyzed. In the medium-term, the PAF only had a negative impact on the large municipalities, which saw significant reductions in the trends of own/state resources and those transferred by the Union for health. CONCLUSION In general, the impact of the PAF on health financing in municipalities was immediate and based on the decrease in own/state resources allocated to health. In large municipalities, however, the impact lasted from 2015 to 2019, mainly affecting health expenditure from federal funds.

Brucella spp. are facultatively intracellular bacteria that can infect, survive, and multiply in various host cell types in vivo and/or in vitro. The genus Brucella has markedly expanded in recent years with the identification of novel species and hosts, which has revealed additional information about the cell and tissue tropism of these pathogens. Classically, Brucella spp. are considered to have tropism for organs that contain large populations of phagocytes such as lymph nodes, spleen, and liver, as well as for organs of the genital system, including the uterus, epididymis, testis, and placenta. However, experimental infections of several different cultured cell types indicate that Brucella may actually have a broader cell tropism than previously thought. Indeed, recent studies indicate that certain Brucella species in particular hosts may display a pantropic distribution in vivo. This review discusses the available knowledge on cell and tissue tropism of Brucella spp. in natural infections of various host species, as well as in experimental animal models and cultured cells.

Additive manufacturing for new constructions or repairing purposes may deal with the use of dissimilar materials. Hence, the influence of interface between the substrate layer and printed one is crucial. This study delves into the impact of printed layers on the microstructure and hardness of an upcycled AISI 303 alloy produced by Direct Energy Deposition. Chemical composition distribution, phase and grain size evolutions were studied, accompanied with microhardness measurements.Microscopic analysis through chemical composition mapping and using electron backscatter diffraction technique for crystallography analysis revealed that the interface structure is strongly affected by the distribution of chemical composition and the heat received from subsequent printing. That means, a dominant transformation of austenite to martensite/ferrite occurs at the first layer printed on the top of the substrate. This is confirmed by hardness measurements (442 ± 15 HV0.1). This dominance (global martensite/ferrite distribution of 42%) is attributed to the reduction of Cr, Ni and Mn contents in the first layer, caused by Marangoni convection currents. This study confirms that subsequent printing favors the evolution of martensite/ferrite to austenite (global distribution of 75%) and grain growth, leading to hardness decrease to around 295 ± 34 HV0.1, leaving small difference with the printed AISI 303 alloy with a hardness of 235 ± 18 HV0.1.

Abstract Objective: to analyze the meaning attributed by parents to the extended and permanent survival of childhood cancer. Method: qualitative narrative inquiry, developed with parents of adolescents and young adults who survived childhood cancer. Recruitment and data collection involved virtual and in-person approaches. The data were collected through semi-structured interviews. Data were analyzed according to reflective thematic analysis. Results: a total of ten parents were included in the study. Two thematic narrative syntheses were constructed: “Times of war”; and “Time of uncertain peace”, with their respective sub-themes. The cancer diagnosis marks the beginning of times of war in the parents’ lives. They experience cancer treatment as “highs and lows” with potential threats to their children’s lives. After that, “Time of uncertain peace” are reached, and the balance of the family unit is reestablished. However, the fear of recurrence makes the family peace uncertain, and its maintenance requires constant vigilance and attention to the signs and symptoms of a possible new battle. Conclusion: the results highlight the experience of being a parent of a childhood cancer survivor and can be applied to develop models of care centered on the survivors’ family.

Abstract Objective: to compare the decision-making of Nursing students, before and after theoretical training on basic life support, using the practice of high-fidelity simulation and medium-fidelity simulation. Method: an experimental study was developed, pre- and post-test type, with quantitative, descriptive and inferential analysis, with theoretical training on basic life support and clinical simulation practices, and with evaluation of knowledge and decision-making of Nursing students, at three different moments - before the simulation scenario (T0), after the simulation scenario (T1) and after clinical teaching (T2). Results: 51 students participated in the research, with an average age of 20.25±3.804, of which 92.2% were female. Statistically significant differences (F=6.47; p=0.039) were evident regarding the definition of the problem and development of objectives in decision-making in the experimental group. Conclusion: Nursing students demonstrate an adequate level of knowledge and a good decision-making process, based on the most current instruments produced by scientific evidence, in clinical simulation scenarios in basic life support, and this innovative methodology should be deepened in the Nursing teaching.

Background: Taurolidine exhibits broad antimicrobial activity and is a component of a recently FDA approved catheter lock solution (DefenCath®, taurolidine 13,500 μg/mL and heparin 1000 Units/mL) indicated for reducing the risk of catheter-related bloodstream infections (CRBSI) in adult patients receiving chronic hemodialysis through a central venous catheter (HD-CVC). FDA approval was based on a Phase 3 randomized trial (LOCK-IT-100) in which DefenCath showed a 71% reduction in CRBSI risk among HD-CVC patients as compared with heparin alone. Although individual isolates from the clinical program were not available for testing, this study evaluated the in vitro antimicrobial activity of taurolidine against a set of recent clinical isolates representative of those recovered from the LOCK-IT-100 trial and/or those commonly associated with CRBSI. Methods: 420 bacterial and 50 yeast isolates were selected from the SENTRY Antimicrobial Surveillance Program. All isolates were collected from the bloodstream of patients in the U.S. between 2018-2023. Isolates were tested for susceptibility to taurolidine and comparators using Clinical and Laboratory Standards Institute (CLSI) broth microdilution guidelines. JMI Laboratories produced susceptibility test panels for testing. CLSI-recommended quality control strains were also tested concurrently. MIC values were determined after 24 hours. Results: Taurolidine exhibited broad antimicrobial activity against all isolates tested (see table). Against gram-positive bacteria, taurolidine MIC50/90 values ranged from 256-512/512-1,024 μg/mL for S. aureus, Coagulase-negative Staphylococcus, Enterococcus species, and Viridans group streptococci. This activity was maintained regardless of methicillin susceptibility for Staphylococcal isolates or vancomycin resistance among Enterococcal species. Against gram-negative bacteria, taurolidine MIC50/90 values ranged from 256-1,024/512-2,048 μg/mL for Enterobacterales, P. aeruginosa, S. maltophilia, A. baumannii-calcoaceticus, and B. cepacia. This activity was maintained in both multidrug resistant Enterobacterales and P. aeruginosa isolates. Among Candida isolates, taurolidine MIC50/90 values ranged from 256-512/512 μg/mL for C. glabrata and C. parapsilosis while taurolidine MIC50/90 values of 4,096/4,096 μg/mL were observed for C. albicans. Conclusions: Taurolidine activity was very similar among a large collection of gram-positive, gram-negative, and yeast organisms. MIC90 values for all species/groups were ≤2,048 μg/mL, except C. albicans where an MIC90 of 4,096 μg/mL was observed. The activity of taurolidine was unaffected by resistance to antibiotics (i.e. methicillin, vancomycin, or multi-drug resistance) among gram-positive or gram-negative organisms. Based on these data, catheter lock solutions containing the broad-spectrum antimicrobial taurolidine at 13,500 μg/mL have the potential to prevent CRBSI caused by a variety of species, including those observed in the recent LOCK-IT-100 clinical trial and other common bloodstream pathogens

The literature shows that there are dimensions related to soil legislation and policy in the European Union contexts that can be better explored through bibliometric analysis, systematic reviews and quantitative approaches. Therefore, this research aims to analyse documents on soil legislation and policies, highlighting the specific cases of Portugal and the European Union (EU). The aim is to identify suggestions to improve the Portuguese and European Union soil policy instruments and measures. To achieve these objectives, a bibliometric analysis (considering text and bibliographic data) and systematic review were carried out, as well as a survey of the available soil legislation (considering qualitative data and quantitative analysis). The results show that soil legislation and policy have become more relevant in recent years and that concerns are about soil health, protection and safety, as well as risk mitigation, biodiversity preservation and the maintenance of ecosystem services. However, some topics could be further explored in future research, namely those related to multidisciplinarity, smart methodologies, soil salinisation, innovation and quantitative approaches to assessing policy impacts. This study presents suggestions that can be considered by the Portuguese and European Union policymakers to improve the respective soil legislation and policies. Defining a regulatory system for soils in the European Union has not been easy over time, although there have been attempts, given the specificities of the contexts related to soils and the reluctance of some member states to take certain measures. The approaches and analysis topics considered are innovative (there aren't many scientific documents on the topics that address bibliometric analysis and quantitative assessments with qualitative data) and bring novelty to the literature.

Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

Background The integration of diagnostic methods holds promise for advancing the surveillance of malaria transmission in both endemic and non-endemic regions. Serological assays emerge as valuable tools to identify and delimit malaria transmission, serving as a complementary method to rapid diagnostic tests (RDT) and thick smear microscopy. Here, we evaluate the potential of antibodies directed against peptides encompassing the entire amino acid sequence of the PvMSP-1 Sal-I strain as viable serological biomarkers for P. vivax exposure. Methods We screened peptides encompassing the complete amino acid sequence of the Plasmodium vivax Merozoite Surface Protein 1 (PvMSP-1) Sal-I strain as potential biomarkers for P. vivax exposure. Here, immunodominant peptides specifically recognized by antibodies from individuals infected with P. vivax were identified using the SPOT-synthesis technique followed by immunoblotting. Two 15-mer peptides were selected based on their higher and specific reactivity in immunoblotting assays. Subsequently, peptides p70 and p314 were synthesized in soluble form using SPPS (Solid Phase Peptide Synthesis) and tested by ELISA (IgG, and subclasses). Results This study unveils the presence of IgG antibodies against the peptide p314 in most P. vivax-infected individuals from the Brazilian Amazon region. In silico B-cell epitope prediction further supports the utilization of p314 as a potential biomarker for evaluating malaria transmission, strengthened by its amino acid sequence being part of a conserved block of PvMSP-1. Indeed, compared to patients infected with P. falciparum and uninfected individuals never exposed to malaria, P. vivax-infected patients have a notably higher recognition of p314 by IgG1 and IgG3.