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Abstract Since the 2000s, the number of immigrants has been growing in Brazil, as well as the cases of xenophobia. There are multiple explanations in the literature on the drivers of attitudes towards immigrants, which vary at the individual, regional and national analytical levels. We discuss and situate the argument of societal integration within the debate on whether social trust can reduce negative attitudes towards immigrants. We argue that social trust is key to reducing negative perceptions towards immigrants and a good predictor of attitudes in environments with strong perceived threat and prejudice, as is the case in Brazil. We empirically test whether greater generalized trust and trust in foreigners are related to a more positive attitude towards immigrants. Although this relationship has already been studied in other countries, to the best of our knowledge no study has yet been applied to the Brazilian case. Using data from the World Values Survey wave 7, and applying a logit model, our results corroborate that social trust has a positive impact on perceptions towards immigrants.

Abstract In food circular economy, the utilization of food manufacturing side streams (FMSS) offers significant potential instead of being discarded. However, reincorporating FMSS into the food value chain raises food safety concerns due to potential food hazards. This perspective explores food safety risks associated with circular management of FMSS by using a ‘Quad-Modal hazard dynamic’ approach with case studies. Future research and advancements in food safety control strategies are also discussed.

Objective Telemonitoring (TM) remotely monitors individuals’ health. Awareness of personal clinical data has resulted in improved glycaemic control in adults with type-2 diabetes mellitus (T2DM). However, its effects on their health-seeking behaviour remain unclear. This study aims to explore and understand the effects of a multicomponent TM system on self-efficacy in adults with T2DM.Design A qualitative study using semistructured interviews.Setting A public primary care clinic which is located at an estate in north-eastern Singapore with a population of about 300 000 multiethnic Asian residents.Participants 21 participants who completed 6 months of TM intervention which included immediate feedback on glucose and blood pressure readings, educational videos on exercise and nutrition, and personalised support with TM nurse when clinical parameters met high glucose or blood pressure thresholds.Results The health belief model was used to explain the participants’ behaviour change, including (1) immediate feedback from TM clinical parameters (blood pressure and glucose), raised their awareness of their health status and disease control to motivate behaviour change; (2) notification of higher glucose through TM allowed patients to reflect on their recent food consumption and nudged them to select healthier food options; (3) App teleeducation improved health literacy and supported lifestyle changes; (4) cues for action through personalised engagement with TM nurse and via automated reminders and (5) the TM system enhanced self-efficacy by modifying their multifaceted self-care behaviours.Conclusion TM heightened understanding among adults with T2DM of their potential for health complications and increased awareness of the benefits of proper diabetes management. It also helped lower the barriers to self-management and further enhanced their self-efficacy in self-care. The system and care team provided users with cues for health which was perceived to lead to adapting their lifestyle in order to achieve better health outcomes.Clinical Trials registration number NCT04306770

This paper proposes a multi-objective optimization model for designing a sustainable logistics system that determines the ideal logistic flow of an ultrafine mineral residue product, tailings, from Brucutu/MG to multiple destinations over a capable multimodal system. These tailings are extracted from iron ore and can be used as a partial substitute for raw materials in construction materials. This substitution can help avoid dangerous dams of iron ore tailings and save natural resources and greenhouse gas emissions in the civil construction chain. However, the distribution incurs logistical costs and resulting socio-environmental impacts. Therefore, logistics plays a fundamental role in making this substitution economically viable. The proposed model aims to maximize total profit while minimizing negative socio-environmental impacts and maximizing the positives. The resulting ideal multimodal logistic system is obtained based on sustainable pillars, demonstrating that a small decrease in profits can yield significant reductions in negative impacts and increases in positive externalities.

Abstract The deep sea environment is the largest environment and host some of the most extreme ecosystems on Earth, therefore, possessing a large and unique fish diversity that encompasses about 15% of all known species. Our knowledge about these fishes is still very limited in many biological fields basically due to the complexity to obtain specimens for research. In the present study, we describe the complete mitochondrial genome of Argentina brasiliensis, aiming a species characterization and the study of the phylogenetic relationships in the order Argentiniformes. The mitogenome is composed by 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region (D-loop), as found in other vertebrates. The phylogenetic results show that the order Argentiniformes is composed by two family groups the first formed by Argentinidae and Opisthoproctidae and the second formed by Bathylagidae and Microstomatidae. Additionally, we found that the genus Argentina is not monophyletic, and we suggest additional studies in the family Argentinidae to better investigate this question.

This paper proposes a methodology to evaluate and optimize the dynamic response of tall buildings under wind loading, controlled through semi-active Magneto-Rheological dampers (MR dampers). For this, a tall building, modeled as a 2D frame, is taken as case study and three structural control configurations are proposed. The original structural configuration of the building is the first configuration analyzed, called Uncontrolled Original (C1). In the second configuration, called Uncontrolled Optimized (C2), the fundamental frequency of the building is optimized via PSO algorithm as a function of its mass. Then, in the third configuration, Controlled Optimized (C3), a set of MR dampers with behavior formulated via the modified Bouc-Wen rheological model and controlled through the Linear Quadratic Regulator associated with the Clipped Optimal control strategy (LQR-CO) is applied to the structure. Finally, the dynamic response of the three scenarios under wind action is analyzed and compared to performance criteria established in the literature. The results demonstrate that the C3 configuration is the only one able of satisfying all the established performance criteria, proving that the proposed methodology y that combines structural optimization with MR dampers is a powerful tool for vibration control.

Abstract Testicular large B‐cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune‐privileged site and has recently been recognized as a distinct entity from diffuse large B‐cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B‐cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next‐generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations (p

Abstract Systematically predicting the effects of mutations on protein fitness is essential for the understanding of genetic diseases. Indeed, predictions complement experimental efforts in analyzing how variants lead to dysfunctional proteins that in turn can cause diseases. Here we present our new fitness predictor, FiTMuSiC, which leverages structural, evolutionary and coevolutionary information. We show that FiTMuSiC predicts fitness with high accuracy despite the simplicity of its underlying model: it was among the top predictors on the hydroxymethylbilane synthase (HMBS) target of the sixth round of the Critical Assessment of Genome Interpretation challenge (CAGI6) and performs as well as much more complex deep learning models such as AlphaMissense. To further demonstrate FiTMuSiC’s robustness, we compared its predictions with in vitro activity data on HMBS, variant fitness data on human glucokinase (GCK), and variant deleteriousness data on HMBS and GCK. These analyses further confirm FiTMuSiC’s qualities and accuracy, which compare favorably with those of other predictors. Additionally, FiTMuSiC returns two scores that separately describe the functional and structural effects of the variant, thus providing mechanistic insight into why the variant leads to fitness loss or gain. We also provide an easy-to-use webserver at https://babylone.ulb.ac.be/FiTMuSiC , which is freely available for academic use and does not require any bioinformatics expertise, which simplifies the accessibility of our tool for the entire scientific community.

Introdução: A nutrição apresenta importante papel na saúde e desempenho de atletas e desportistas sendo necessário um adequado aporte de nutrientes para a otimização dos resultados. Desta forma, o objetivo deste estudo foi avaliar o consumo alimentar e estado nutricional de praticantes de musculação. Materiais e Métodos: Foram coletados dados sociodemográficos, de consumo alimentar (dois recordatórios) e antropométricos (peso, altura e dobras cutâneas). As médias dos recordatórios foram comparadas com as referências da Dietary References Intakes (NASEN, 2017;2019) e da Sociedade Brasileira de Medicina do Exercício e do Esporte (SBME, 2009). Foi calculado o Índice de Massa Corporal (IMC) e % de gordura corporal. Resultados: Participaram do estudo 71 praticantes de musculação, a maioria em estado de eutrofia (63,4%), seguido de sobrepeso/obesidade (33,8%). A média do consumo de carboidratos foi significativamente inferior às recomendações, 41,7% do valor energético total (VET), enquanto, o consumo de lipídeos foi significativamente superior, 35,8% do VET. O consumo de vitamina D, potássio e fibras foi significativamente inferior às recomendações em ambos os gêneros, em contrapartida, o consumo de sódio foi significativamente superior. O consumo de ferro foi significativamente acima das recomendações entre os homens e significativamente inferior entre as mulheres. Conclusão: Foi observado consumo inadequado de carboidratos, proteínas, lipídios, vitamina D, potássio e fibras por praticantes de musculação em relação às recomendações, sendo necessário uma maior atuação do nutricionista nas academias a fim de promover a adequação do consumo alimentar.

Background Adoptive cell therapy using genetically modified T cells to express chimeric antigen receptors (CAR-T) has shown encouraging results, particularly in certain blood cancers. Nevertheless, over 40% of B cell malignancy patients experience a relapse after CAR-T therapy, likely due to inadequate persistence of the modified T cells in the body. IL15, known for its pro-survival and proliferative properties, has been suggested for incorporation into the fourth generation of CAR-T cells to enhance their persistence. However, the potential systemic toxicity associated with this cytokine warrants further evaluation.Methods We analyzed the persistence, antitumor efficacy and potential toxicity of anti-mouse CD19 CAR-T cells which express a membrane-bound IL15-IL15Rα chimeric protein (CD19/mbIL15q CAR-T), in BALB/c mice challenged with A20 tumor cells as well as in NSG mice.Results Conventional CD19 CAR-T cells showed low persistence and poor efficacy in BALB/c mice treated with mild lymphodepletion regimens (total body irradiation (TBI) of 1 Gy). CD19/mbIL15q CAR-T exhibits prolonged persistence and enhanced in vivo efficacy, effectively eliminating established A20 B cell lymphoma. However, this CD19/mbIL15q CAR-T displays important long-term toxicities, with marked splenomegaly, weight loss, transaminase elevations, and significant inflammatory findings in some tissues. Mice survival is highly compromised after CD19/mbIL15q CAR-T cell transfer, particularly if a high TBI regimen is applied before CAR-T cell transfer.Conclusion Tethered IL15-IL15Rα augments the antitumor activity of CD19 CAR-T cells but displays long-term toxicity in immunocompetent mice. Inducible systems to regulate IL15-IL15Rα expression could be considered to control this toxicity.

Introdução e objetivo: O aleitamento materno exclusivo (AME) e a alimentação complementar adequada destacam-se entre as práticas alimentares para a promoção da saúde materno-infantil. Desta forma, este estudo avaliou a relação entre práticas alimentares, estado nutricional infantil e gestacional, escolaridade materna e dano no DNA em crianças de um município do interior do sul do Brasil. Materiais e métodos: Estudo transversal, realizado com de crianças com idade entre 6 e 24 meses atendidas em uma Estratégia de Saúde da Família do município de Passo do Sobrado/RS. Analisou-se a alimentação e o nível de dano no DNA da criança. Também, classificou-se o estado nutricional da criança e gestacional da mãe, bem como a escolaridade materna. Resultados: Das 31 crianças avaliadas, verificou-se baixa prevalência de AME (29%), que se associou com a introdução precoce de papa salgada (p=0,002) e alimentos fontes de açúcares (p=0,017). Apesar de 58,1% das crianças apresentarem risco de sobrepeso e sobrepeso/obesidade, não houve associação com o tempo de AME (p=0,735). Ainda, verificou-se que 45,2% das mães apresentaram sobrepeso e obesidade para a idade gestacional, que não se associou com o estado nutricional atual das crianças (p=0,235). Quanto ao dano no DNA, observou-se uma frequência de células com micronúcleos significativamente maior (p=0,024) nas crianças que receberam AME entre 2-3 meses em relação ao AME até o sexto mês. Conclusão: Houve prevalência da prática de AME até seis meses de idade, o que foi associado à introdução precoce de alimentos e elevado consumo de alimentos não recomendados nesta faixa etária, bem como com danos no DNA.

The study evaluated the effect of a commercial polyphenol (ELIFE®) on the growth performance and antioxidant defense system of Penaeus vannamei juveniles. The study was completely randomized with three experimental groups and eight repetitions, divided into two 28-day phases. The experimental groups consisted of different dietary inclusion levels of ELIFE® (0.0, 0.5, and 1.0 g kg−1). Five shrimps were stocked in each experimental unit. Growth performance, oxidative stress, and enzymatic activity in shrimp hepatopancreas were assessed. In Phase 1, shrimp fed ELIFE®, regardless of inclusion level, displayed higher specific growth rate, final weight, and final length than the control group. In Phase 2, shrimp fed 1.0 g kg−1 ELIFE® showed higher final biomass and SGR than all other experimental groups; they also displayed increased reduced glutathione and glutathione-S-transferase activities. In both test phases, shrimp fed 1.0 g kg−1 ELIFE® presented increased glutathione reductase activity compared to all other experimental groups. In both test phases, shrimp fed ELIFE®, regardless of inclusion level, exhibited increased glutathione peroxidase activity compared to control groups. Thus, ELIFE® enhanced the antioxidant defense system of P. vannamei and led to better shrimp performance and survival. This study recommends dietary supplementation with 1.0 g kg−1 ELIFE® for P. vannamei juveniles.

The numerical study of floating offshore wind turbines (FOWTs) requires accurate integrated simulations which consider the aerodynamic, hydrodynamic, servo and elastic responses of these systems. In addition, the floating system dynamics couplings need to be included to calculate the excitation over the ensemble accurately. In this paper, a new tool has been developed for coupling NREL's aero-servo-elastic tool OpenFAST with the computational fluid dynamics (CFD) toolbox OpenFOAM. OpenFAST is used to model the rotor aerodynamics along with the flexible response of the different components of the wind turbine and the controller at each time step considering the dynamic response of the platform. OpenFOAM is used to simulate the hydrodynamics and the platform's response considering the loads from the wind turbine. The whole simulation environment is called OF2 (OpenFAST and OpenFOAM). The OC4 DeepCWind semi-submersible FOWT together with NREL's 5 MW wind turbine has been simulated using OF2 under two load cases. The purpose of coupling these tools to simulate FOWT is to obtain high-fidelity results for design purposes, thereby reducing the computational time compared with the use of CFD simulations both for the rotor aerodynamics, which usually consider rigid blades, and for the platform's hydrodynamics. The OF2 approach also allows us to include the aero-servo-elastic couplings that exist on the wind turbine along with the hydrodynamic system resolved by CFD. High-complexity situations of floating offshore wind turbines, like storms, yaw drifts, weather vanes or mooring line breaks, which imply high displacements and rotations of the floating platform or relevant non-linear effects, can be resolved using OF2, overcoming the limitation of many state-of-the-art potential hydrodynamic codes that assume small displacements of the platform. In addition, all the necessary information for the FOWT calculation and design processes can be obtained simultaneously, such as the pressure distribution at the platform components and the loads at the tower base, fairleads tension, etc. Moreover, the effect of turbulent winds and/or elastic blades could be taken into account to resolve load cases from the design and certification standards.

IntroductionSince the COVID-19 pandemic began, it has spread rapidly across the world and has resulted in recurrent outbreaks. This study aims to describe the COVID-19 epidemiology in terms of COVID-19 cases, deaths, ICU admissions, ventilator requirements, testing, incidence rate, death rate, case fatality rate (CFR) and test positivity rate for each outbreak from the beginning of the pandemic in 2020 till endemicity of COVID-19 in 2022 in Malaysia.MethodsData was sourced from the GitHub repository and the Ministry of Health’s official COVID-19 website. The study period was from the beginning of the outbreak in Malaysia, which began during Epidemiological Week (Ep Wk) 4 in 2020, to the last Ep Wk 18 in 2022. Data were aggregated by Ep Wk and analyzed in terms of COVID-19 cases, deaths, ICU admissions, ventilator requirements, testing, incidence rate, death rate, case fatality rate (CFR) and test positivity rate by years (2020 and 2022) and for each outbreak of COVID-19.ResultsA total of 4,456,736 cases, 35,579 deaths and 58,906,954 COVID-19 tests were reported for the period from 2020 to 2022. The COVID-19 incidence rate, death rate, CFR and test positivity rate were reported at 1.085 and 0.009 per 1,000 populations, 0.80 and 7.57%, respectively, for the period from 2020 to 2022. Higher cases, deaths, testing, incidence/death rate, CFR and test positivity rates were reported in 2021 and during the Delta outbreak. This is evident by the highest number of COVID-19 cases, ICU admissions, ventilatory requirements and deaths observed during the Delta outbreak.ConclusionThe Delta outbreak was the most severe compared to other outbreaks in Malaysia’s study period. In addition, this study provides evidence that outbreaks of COVID-19, which are caused by highly virulent and transmissible variants, tend to be more severe and devastating if these outbreaks are not controlled early on. Therefore, close monitoring of key epidemiological indicators, as reported in this study, is essential in the control and management of future COVID-19 outbreaks in Malaysia.

Major histocompatibility complex Class II (MHCII) proteins initiate and regulate immune responses by presentation of antigenic peptides to CD4+ T-cells and self-restriction. The interactions between MHCII and peptides determine the specificity of the immune response and are crucial in immunotherapy and cancer vaccine design. With the ever-increasing amount of MHCII-peptide binding data available, many computational approaches have been developed for MHCII-peptide interaction prediction over the last decade. There is thus an urgent need to provide an up-to-date overview and assessment of these newly developed computational methods. To benchmark the prediction performance of these methods, we constructed an independent dataset containing binding and non-binding peptides to 20 human MHCII protein allotypes from the Immune Epitope Database, covering DP, DR and DQ alleles. After collecting 11 known predictors up to January 2022, we evaluated those available through a webserver or standalone packages on this independent dataset. The benchmarking results show that MixMHC2pred and NetMHCIIpan-4.1 achieve the best performance among all predictors. In general, newly developed methods perform better than older ones due to the rapid expansion of data on which they are trained and the development of deep learning algorithms. Our manuscript not only draws a full picture of the state-of-art of MHCII-peptide binding prediction, but also guides researchers in the choice among the different predictors. More importantly, it will inspire biomedical researchers in both academia and industry for the future developments in this field.

A fungal polymerase chain reaction (PCR) amplifies conserved genes across diverse species, combined with the subsequent hybridization of amplicons using a specific oligonucleotide microarray, allowing for the rapid detection of pathogens at the species level. However, the performance of microarrays in diagnosing invasive mold infections (IMI) from infected tissue samples is rarely reported. During the 4-year study period, all biopsied tissue samples from patients with a suspected IMI sent for microarray assays were analyzed. A partial segment of the internal transcribed spacer (ITS) region was amplified by nested PCR after DNA extraction. Amplicons were hybridized with specific probes for a variety of mold species using an in-house oligonucleotide microarray. A total of 80 clinical samples from 74 patients were tested. A diagnosis of an IMI was made in 10 patients (4 proven, 1 probable, 3 possible, 2 clinical suspicion). The PCR/microarray test was positive for three out of four proven IMIs, one probable IMI, and one out of three possible IMIs. Two patients with positive PCR/microarray findings were considered to have clinical suspicion of an IMI, and their responsible physicians initiated antifungal therapy despite the absence of supporting microbiological and histological evidence. Clinical diagnoses were categorized into non-IMI and IMI groups (including proven, probable, possible, and clinical suspicion). The sensitivity and specificity of the microarray in diagnosing the IMIs were 70% and 95.7%, respectively, while the sensitivity and specificity of the culture and histological findings were 10%/96.3% and 40.0%/100%, respectively. PCR-based methods provide supportive microbiological evidence when culture results are inconclusive. The combination of a microarray with fungal culture and histology promotes the precise diagnosis of IMIs in difficult-to-diagnose patients.

Este artigo visa demonstrar as diferenças entre brancos e negros na obtenção de empréstimos em instituições financeiras, em razão de fatores influenciados pelo racismo estrutural presente na sociedade até os dias atuais, tais como sua renda, comportamento financeiro, score, falta de patrimônio, existência de bens móveis ou imóveis a serem dados em garantia, endereço, nível de escolaridade. Com a demonstração desta diferenciação o estudo também visa encontrar medidas a serem tomadas para que tal questão seja melhorada, com a diminuição de tais diferenças entre brancos e negros na obtenção de empréstimos, de forma a minorar os estragos que o racismo traz a esta população.

RESUMO Este artigo objetivou comparar o senso de autoeficácia dos professores da Pré-Escola e Ensino Fundamental I para ensinar estudantes público-alvo da Educação Especial (PAEE) na sala de aula regular da rede pública municipal e relacionar o senso de autoeficácia com dados demográficos e de atuação profissional. Participaram da pesquisa 17 professores da Pré-Escola e 27 do Ensino Fundamental 1 de um município do interior paulista. Os dados foram obtidos mediante questionário de caracterização e a Escala de Eficácia Docente para Práticas Inclusivas (EEDPI) via tendência central, dispersão e correlacionais. Quando comparados com os professores do Fundamental 1, os da Pré-Escola possuem mais idade, menos alunos em sala e sentem-se mais preparados para incluir. Os valores de autoeficácia foram semelhantes entre os grupos e são descritos os dados de correlação entre os instrumentos. Corroborou-se na sinalização da potência e sensibilidade da EEDPI para avaliação da autoeficácia docente e da influência do constructo no contexto educativo.

Abstract Background Releasing timely and relevant clinical guidelines is challenging for organizations globally. Priority-setting is crucial, as guideline development is resource-intensive. Our aim, as a national organization responsible for developing cardiovascular clinical guidelines, was to develop a method for generating and prioritizing topics for future clinical guideline development in areas where guidance was most needed. Methods Several novel processes were developed, adopted and evaluated, including (1) initial public consultation for health professionals and the general public to generate topics; (2) thematic and qualitative analysis, according to the International Classification of Diseases (ICD-11), to aggregate topics; (3) adapting a criteria-based matrix tool to prioritize topics; (4) achieving consensus through a modified-nominal group technique and voting on priorities; and (5) process evaluation via survey of end-users. The latter comprised the organization’s Expert Committee of 12 members with expertise across cardiology and public health, including two citizen representatives. Results Topics (n = 405; reduced to n = 278 when duplicates removed) were identified from public consultation responses (n = 107 respondents). Thematic analysis synthesized 127 topics that were then categorized into 37 themes using ICD-11 codes. Exclusion criteria were applied (n = 32 themes omitted), resulting in five short-listed topics: (1) congenital heart disease, (2) valvular heart disease, (3) hypercholesterolaemia, (4) hypertension and (5) ischaemic heart diseases and diseases of the coronary artery. The Expert Committee applied the prioritization matrix to all five short-listed topics during a consensus meeting and voted to prioritize topics. Unanimous consensus was reached for the topic voted the highest priority: ischaemic heart disease and diseases of the coronary arteries, resulting in the decision to update the organization’s 2016 clinical guidelines for acute coronary syndromes. Evaluation indicated that initial public consultation was highly valued by the Expert Committee, and the matrix tool was easy to use and improved transparency in priority-setting. Conclusion Developing a multistage, systematic process, incorporating public consultation and an international classification system led to improved transparency in our clinical guideline priority-setting processes and that topics chosen would have the greatest impact on health outcomes. These methods are potentially applicable to other national and international organizations responsible for developing clinical guidelines.

Learning achievement is something that cannot be separated from learning activities because learning achievement is the output of the learning process. Student achievement is influenced by two main factors, namely factors from within the student (Internal) and factors originating from outside the student or the environment (External). The research method used is quantitative data method. Qualitative research as a human instrument, serves to determine the focus of research, select informants as data sources, assess data quality, analyze data, interpret data and draw conclusions from the findings. The results of the study using t-test (partial) showed that the Teacher Teaching Method variable (X1) had an effect on the student achievement variable (Y), then the online learning method (X2) had an effect on student achievement (Y).

Introdução e objetivo: O bicarbonato de sódio, como agente ergogênico, tem sido proposto para atuar na melhora do desempenho dos corredores de distâncias longas, além de reduzir a fadiga muscular, reduzir a acumulação de lactato no músculo e no balanço ácido-base em atletas de várias modalidades esportivas. Portanto, este estudo objetivou avaliar e comparar o efeito da suplementação de bicarbonato de sódio no desempenho de corredores amadores numa prova simulada de 6 km. Materiais e métodos: estudo quase-experimental, com 12 corredores amadores, de ambos sexos e idade entre 18-57 anos. Em dias diferentes, os corredores ingeriram bicarbonato de sódio (0,15g • kg-1) ou não e participaram de 2 rústicas simuladas de 6km. Testes físicos específicos, como lactato sanguíneo, pH urinário e frequência cardíaca foram avaliados antes e após cada corrida. A percepção subjetiva da fadiga foi avaliada somente após a corrida. Resultados: O desempenho dos corredores não mostrou diferença significativa entre as corridas (p=0,771), no entanto, 41,67% dos corredores relataram uma diminuição na percepção de esforço após a suplementação de bicarbonato de sódio. A frequência cardíaca também não mostrou diferença significativa no repouso (p=0,978), após a corrida (p=0,592) ou na variação da frequência cardíaca (p=0,267). Entretanto, verificou-se um aumento significativo na variação do lactato sanguíneo após a suplementação de bicarbonato de sódio (p=0,048), bem como um aumento significativo no pH urinário (p=0,037). Conclusão: Nossos resultados demostraram que a suplementação de bicarbonato de sódio não melhorou o desempenho, mas melhorou a percepção subjetiva da fadiga, bem como aumentou a variação do lactato sanguíneo e do pH urinário.

OBJECTIVES This study aimed to develop susceptible-exposed-infectious-recovered-vaccinated (SEIRV) models to examine the effects of vaccination on coronavirus disease 2019 (COVID-19) case trends in Malaysia during Phase 3 of the National COVID-19 Immunization Program amidst the Delta outbreak. METHODS SEIRV models were developed and validated using COVID-19 case and vaccination data from the Ministry of Health, Malaysia, from June 21, 2021 to July 21, 2021 to generate forecasts of COVID-19 cases from July 22, 2021 to December 31, 2021. Three scenarios were examined to measure the effects of vaccination on COVID-19 case trends. Scenarios 1 and 2 represented the trends taking into account the earliest and latest possible times of achieving full vaccination for 80% of the adult population by October 31, 2021 and December 31, 2021, respectively. Scenario 3 described a scenario without vaccination for comparison. RESULTS In scenario 1, forecasted cases peaked on August 28, 2021, which was close to the peak of observed cases on August 26, 2021. The observed peak was 20.27% higher than in scenario 1 and 10.37% lower than in scenario 2. The cumulative observed cases from July 22, 2021 to December 31, 2021 were 13.29% higher than in scenario 1 and 55.19% lower than in scenario 2. The daily COVID-19 case trends closely mirrored the forecast of COVID-19 cases in scenario 1 (best-case scenario). CONCLUSIONS Our study demonstrated that COVID-19 vaccination reduced COVID-19 case trends during the Delta outbreak. The compartmental models developed assisted in the management and control of the COVID-19 pandemic in Malaysia.

BackgroundGlobally, the COVID-19 pandemic has affected the transmission dynamics and distribution of dengue. Therefore, this study aims to describe the impact of the COVID-19 pandemic on the geographic and demographic distribution of dengue incidence in Malaysia.MethodsThis study analyzed dengue cases from January 2014 to December 2021 and COVID-19 confirmed cases from January 2020 to December 2021 which was divided into the pre (2014 to 2019) and during COVID-19 pandemic (2020 to 2021) phases. The average annual dengue case incidence for geographical and demographic subgroups were calculated and compared between the pre and during the COVID-19 pandemic phases. In addition, Spearman rank correlation was performed to determine the correlation between weekly dengue and COVID-19 cases during the COVID-19 pandemic phase.ResultsDengue trends in Malaysia showed a 4-year cyclical trend with dengue case incidence peaking in 2015 and 2019 and subsequently decreasing in the following years. Reductions of 44.0% in average dengue cases during the COVID-19 pandemic compared to the pre-pandemic phase was observed at the national level. Higher dengue cases were reported among males, individuals aged 20–34 years, and Malaysians across both phases. Weekly dengue cases were significantly correlated (ρ = −0.901) with COVID-19 cases during the COVID-19 pandemic.ConclusionThere was a reduction in dengue incidence during the COVID-19 pandemic compared to the pre-pandemic phase. Significant reductions were observed across all demographic groups except for the older population (>75 years) across the two phases.

The objective was to evaluate the effects of partial replacement of fish meal with protein hydrolysates and a commercial product in the diets of Penaeus vannamei post-larvae on zootechnical performance, proximate chemical composition, digestive enzyme activity, and total hemocyte count. The experiment was conducted in a clear water recirculation system comprising 24 experimental units, each with 30 shrimp with an average weight of 0.2 g. The treatments were control, chicken protein hydrolysate (CPH), enzymatic hydrolysate of chicken feathers, Aquabite®, CPH + maltodextrin, and CPH + yeast, with four replicates each. The inclusion level of the different protein sources evaluated was 6%. At the end of the experiment, all shrimp were counted, weighed, and measured to determine the zootechnical performance. The body and feed chemical compositions, as well as the enzymatic activities of the hepatopancreas and the total hemocyte count in the hemolymph, were analyzed. The data obtained were subjected to ANOVA and Tukey’s test. There was no statistical difference between the treatments in any of the analyzed parameters. The results showed that all the evaluated protein hydrolysates can be used as partial substitutes for fish meal in P. vannamei diets during the nursery phase, maintaining equivalent and adequate digestive enzyme activities, health, growth, and body composition of the shrimp, in addition to being ecologically sustainable ingredients.

This study evaluated the inclusion of protein hydrolysates and a commercial product as a partial replacement for fish meals in the diet of Pacific white shrimp (Penaeus vannamei) during the grow-out phase. A recirculation system with 24 experimental units and a biological filter was used. The experimental design was completely randomized with six treatments: control; chicken protein hydrolysate (CPH); enzymatic hydrolysate of chicken feathers; Aquabite®; CPH + maltodextrin; CPH + yeast; and four replicates. After 50 days, the zootechnical performance and animal welfare parameters, centesimal carcass composition, digestive enzyme activity, and hemocyte count were evaluated. The treatments did not affect the zootechnical performance and total hemocyte count of the animals (p > 0.05). The evaluation of the antenna length indicated that all animals were in good health. The antenna length in treatment T5 was significantly greater (p > 0.05) than that in T4 and similar to that in treatments T3 and T6, demonstrating a positive influence of dietary protein hydrolysates. Concerning animal welfare, dietary protein hydrolysates influenced the length of the antenna (p < 0.05). The antenna length associated with different treatments indicated that the animals were in good welfare conditions in the production environment. With respect to body chemical composition, dry matter, ether extract, and ash were affected by the treatments (p < 0.05). Regarding the analysis of digestive enzymes, the treatments influenced the activities of amylase and trypsin (p < 0.05). The performance of the animals was satisfactory under all treatments, including enzymatic activity, demonstrating the possibility of using hydrolysates.

This paper investigates the syntactic–pragmatic behavior of two expletive-like elements, namely a and chiru, in Fornese and Cilentano, two Romance varieties spoken in Northern and Southern Italy, respectively. We argue that a and chiru are not bona fide expletive subjects but discourse-pragmatic expletives, which mark zero aboutness or the absence of an aboutness referent in an utterance. The investigation of Fornese and Cilentano points towards the existence of a sub-class of null-subject languages where aboutness as a discourse feature must be structurally satisfied by merging an overt or null topic in the syntactic spine of the clause. In the absence of such an element—for example, in thetic clauses—a discourse-pragmatic expletive is externally merged as a last-resort strategy to satisfy [uAboutness]. We argue that, in these null-subject languages, the satisfaction of the discourse feature [uAboutness] is an LF requirement, which is subject to a parametric choice. We show that, in Fornese, “default” [aboutness] is satisfied in SubjP, which is the canonical syntactic position for overt subjects within a cartographic approach. In Cilentano, on the other hand, [aboutness] is satisfied in a higher position within the C-domain, namely ShiftP, the canonical syntactic position that hosts overt aboutness/shift topics.

VP64 is the smallest transactivation domain that can be packaged together with the sgRNA into a single adeno-associated virus (AAV) vector. However, VP64-based CRISPRa often exerts modest activation to the target gene when only one sgRNA is used. Herein, we used PAM-flexible dual base editor-mediated mutagenesis and self-activation strategies to derive VP64 variants with gain-of-function mutations. First, we generated an HEK293FT transgenic clone to stably expressing pTK-CRISPRa-GFP. The sgRNA of CRISPRa was designed to target the TK promoter, thereby allowing self-activation of CRISPRa-GFP. Base editors were then used to randomly mutagenesis VP64 in this transgenic cell. VP64 with enhanced potency would translate into increment of GFP fluorescence intensity, thereby allowing positive selection of the desired VP64 mutants. This strategy has enabled us to identify several VP64 variants that are more potent than the wild-type VP64. ΔCRISPRa derived from these VP64 variants also efficiently activated the endogenous promoter of anti-aging and longevity genes (KLOTHO, SIRT6, and NFE2L2) in human cells. Since the overall size of these ΔCRISPRa transgenes is not increased, it remains feasible for all-in-one AAV applications. The strategies described here can facilitate high-throughput screening of the desired protein variants and adapted to evolve any other effector domains.

Background Potentially inappropriate prescribing (PIP) is common in primary care and is associated with adverse outcomes. Knowledge of the risk factors of PIP can be critical in designing PIP interventions, especially in guiding our understanding on how PIP occurs in primary care. Objective This systematic review examined factors associated with PIP, specific to primary care. Methods We searched PubMed, Embase, CINAHL, Web of Science, Scopus and PsycINFO for studies related to ‘older persons’, ‘primary care’ and ‘inappropriate prescribing’. Two reviewers conducted study selection, data extraction and quality appraisal. Factors associated with PIP were narratively synthesized. Results Of the 1017 articles identified, we included 25 articles and a total of 2,893,925 participants, with average age of 70.4–84.0 years. Risk factors of PIP could be classified into patient, physician and system factors. Patient factors were related to patient demographics (advanced age, lower education level and lower socioeconomic status), medical comorbidities (polypharmacy and multimorbidity) and lifestyle factors (unhealthy habits and use of over-the-counter medications). Physician and system factors included older, male, solo general practitioner (GP), higher number of visits of pharmaceutical sales representatives to GP, centrally located GP practice, and smaller number of older patients following up with GP, and medication source from public health system. Conclusions The findings provide contextual information to guide our understanding of PIP in primary care. Factors identified in this review can inform the design of complex interventions for PIP, as well as be used to develop risk prediction tools to identify high-risk groups who may require further interventions related to PIP.

ABSTRACT Objective: This study aimed to report the experience of medication-related osteonecrosis of the jaws (MRONJ) in osteoporotic patients for nine years, and their associated initiating factors. Materials and methods: The numbers of invasive oral procedures (IOP) (tooth extraction, dental implant placement, and periodontal procedures) and removable prostheses performed from January 2012 to January 2021 were obtained from the digital records of a large public dental center. There were an estimated 6,742 procedures performed in patients under osteoporosis treatment. Results: Two cases (0.03%) of MRONJ were registered in nine years amongst patients with osteoporosis who had dental treatment at the center. From the 1,568 tooth extractions, one patient (0.06%) developed MRONJ. There was also one case from the 2,139 removable prostheses delivered (0.05%). Conclusions: The prevalence of MRONJ associated with osteoporosis treatment was very low. The protocols adopted seem to be adequate for the prevention of this complication. The findings of this study reinforce the rare frequency of MRONJ associated with dental procedures in patients submitted to the pharmacological management of osteoporosis. An integral analysis of systemic risk factors and oral preventive strategies may be considered regularly in the dental treatment of these patients.

IntroductionCAR T-cell therapy has emerged as a promising new immuno-oncology treatment that engages the patient’s immune system to fight certain hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). In the European Union (EU), CAR T-cell therapies have been approved for relapsed/refractory (R/R) DLBCL patients since 2018, but patient access is often still limited or delayed. This paper is aimed at discussing challenges to access and possible solutions in the largest four EU countries.MethodsThe analysis relied on literature review, market data collection, since homogeneous data coming from registries were not available, and discussion with experts coming from all four countries.ResultsWe calculated that in 2020, between 58% and 83% of R/R DLBCL patients (EMA approved label population) or between 29% and 71% of the estimated medically eligible R/R DLBCL patients, were not treated with a licensed CAR T-cell therapy. Common challenges along the patient journey that may result in limited access or delays to CAR T-cell therapy were identified. These include timely identification and referral of eligible patients, pre-treatment funding approval by authorities and payers, and resource needs at CAR T-cell centers.DiscussionThese challenges, existing best practices and recommended focus areas for health systems are discussed here, with the aim to inform necessary actions for overcoming patient access challenges for current CAR T-cell therapies as well as for future cell and gene therapies.

A família é o primeiro ambiente social da criança e a base para seu desenvolvimento. Famílias de crianças com deficiência possuem necessidades específicas, advindas das demandas e das próprias características da deficiência em si. Conhecer essas famílias possibilita criar programas para auxiliá-las. Dessa forma, os objetivos da pesquisa foram: (a) identificar e analisar a satisfação parental e o suporte social de famílias de crianças com síndrome de Down e (b) relacionar a satisfação parental e o suporte social com os dados sociodemográficos das famílias. Participaram da pesquisa 15 responsáveis de crianças com síndrome de Down. As medidas avaliativas foram: Questionário Critério Brasil, Questionário de suporte social e Questionário de satisfação parental. Os dados obtidos foram quantitativos. Para correlacionar as variáveis foi utilizado o teste de correlação de Spearman. Os resultados indicaram que os pais sentiam prazer em ficar com o filho com deficiência, visto que os itens que obtiveram maiores médias de satisfação parental estavam relacionados às situações que valorizavam esses momentos. Com relação ao suporte social, a pessoa suportiva mais mencionada foi o/a cônjuge. Sobre a correlação entre variáveis, a idade dos participantes apresentou correlação positiva com o grau de satisfação em ser pai/mãe e com o suporte social recebido em momentos que necessitavam de ajuda emocional. Alguns itens da escala de Suporte Social também estavam positivamente correlacionados com itens da Escala de Satisfação Parental. Conclui-se que, conforme os pais ficam mais velhos aumenta o suporte social e sua satisfação parental e que tais variáveis estão correlacionadas entre si.

Introduction Dual/poly tobacco use is common among youths globally. However, in Malaysia information on dual/poly tobacco use is scarce, thus the present study examines the prevalence and factors associated with dual/poly tobacco users among school-going adolescents in Malaysia. Methods We derived data on tobacco and e-cigarette use among Malaysian adolescents from a nationwide school-based study conducted in 2016. A total of 13135 adolescents responded in the cross-sectional survey which used multistage sampling to select a representative sample of school-going adolescents aged 11–19 years. A standard validated questionnaire was used to obtain the data and multiple logistic regression was conducted to assess factors associated with dual/ poly tobacco use. Results The prevalence of dual/poly tobacco use was 6.5%, more than half of which were both conventional and e-cigarette users. Multivariable logistic regression revealed that the likelihood of dual tobacco use was significantly higher among males (AOR=14.73; 95% CI: 9.11–23.81), secondary school students, those aged 16–19 years (AOR=5.99; 95% CI: 4.04–8.87), natives of Sabah (AOR=7.41; 95% CI: 3.48–15.79), and those never been taught on the health hazards of tobacco at school, exposed to secondhand smoke (SHS) at home, school or other public areas, and had a positive perception of e-cigarettes and lower perception of the harms of tobacco smoking. Conclusions Although the prevalence of dual/poly users was still low among Malaysian school-going adolescents, proactive measures should be taken to reduce dual tobacco use among youth in Malaysia with focus on the factors identified in this study.

Introduction: The 2015 dengue outbreak in southern Taiwan caused substantial mortality. We analyzed the causes of death among these patients. Materials and methods: This retrospective study was conducted at a medical center in Tainan from August 2015 to December 2015. Dengue was diagnosed based on the detection of serum dengue NS1 antigen, IgM, or viral RNA in the blood. Causes of death were retrieved from chart reviews by three clinicians. Results: There were 4488 cases of dengue in the study hospital, with an in-hospital fatality rate of 1.3% (60 cases). The mean age of the 60 fatal cases was 73 years, among whom 90% were aged ≥65 years. Twenty-eight (46.7%) patients died of severe dengue, and 29 (48.3%) deaths were possibly related to dengue. Of the latter, 24 (40%) died of secondary infections. Thirteen cardiac arrest events, including out-of-hospital (5 events) and in-hospital (8) cardiac arrests in the emergency department, occurred during the dengue epidemic. Seven (53.8%) patients did not receive medical aid before the event. Of the 40 deaths that occurred within one week after hospitalization, 60% died of severe dengue. In contrast, 50% of 20 deaths that occurred one week after hospitalization were related to hospital-acquired infections, mainly pneumonia. Conclusion: Of 60 fatal cases, with a predominance of elderly patients, deaths were related to severe dengue within the first week after admission and secondary infections thereafter. The absence of medical care before cardiac arrest events highlights the importance of health education for warning signs of dengue.

Background/Purpose: Cytomegalovirus (CMV) viremia is associated with a higher mortality rate and prolonged intensive care unit (ICU) stay for critically ill patients. CMV infection causes transient but substantial immunosuppression for transplant recipients, increasing risk of fungal infection. The association between CMV viremia and invasive pulmonary aspergillosis (IPA) for critically ill patients is still unknown. Methods: We retrospectively analyzed patients received bronchoalveolar lavage (BAL), galactomannan test, influenza survey and blood CMV viral load test in ICUs of a university hospital between April 2017 and May 2020. Independent risks for IPA were analyzed by multivariable logistic regression. Results: A total of 136 patients were included. Twenty-one patients had IPA, 48 patients had CMV viremia and 22 patients had influenza. In a multivariable logistic regression model, patients with CMV viremia or influenza had higher IPA risk (adjusted odds ratio, 3.98 and 8.72; 95% CI, 1.26–12.60 and 2.64–28.82; p value = 0.019 and

Abstract Background The increasing role of exercise training in cancer care is built on evidence that exercise can reduce side effects of treatment, improve physical functioning and quality of life. We and others have shown in mouse tumor models, that exercise leads to an adrenalin-mediated increased influx of T and NK cells into the tumor, altering the tumor microenvironment (TME) and leading to reduced tumor growth. These data suggest that exercise could improve immune responses against cancer cells by increase immune cell infiltration to the tumor and potentially having an impact on disease progression. Additionally, there are data to suggest that infiltration of T and NK cells into the TME is correlates with response to immune checkpoint inhibitors in patients. We have therefore initiated the clinical trial HI AIM, to investigate if high intensity exercise can mobilize and increase infiltration of immune cells in the TME in patients with lung cancer. Methods HI AIM (NCT04263467) is a randomized controlled trial (70 patients, 1:1) for patients with non-small cell lung cancer. Patients in the treatment arm, receive an exercise-intervention consisting of supervised and group-based exercise training, comprising primarily intermediate to high intensity interval training three times per week over 6 weeks. All patients will also receive standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Blood samples and biopsies (ultrasound guided), harvested before, during and after the 6-week training program, will form basis for immunological measurements of an array of immune cells and markers. Primary outcome is circulating NK cells. Secondary outcome is other circulating immune cells, infiltration of immune cells in tumor, inflammatory markers, aerobic capacity measured by VO2 max test, physical activity levels and quality of life measured by questionnaires, and clinical outcomes. Discussion To our knowledge, HI AIM is the first project to combine supervised and monitored exercise in patients with lung cancer, with rigorous analyses of immune and cancer cell markers over the course of the trial. Data from the trial can potentially support exercise as a tool to mobilize cells of the immune system, which in turn could potentiate the effect of immunotherapy. Trial registration The study was prospectively registered at ClinicalTrials.gov on February 10th 2020, ID: NCT04263467. https://clinicaltrials.gov/ct2/show/NCT04263467

Abstract This paper aims to develop an automated web application to generate validated daily effective reproduction numbers (Rt) which can be used to examine the effects of super-spreading events due to mass gatherings and the effectiveness of the various Movement Control Order (MCO) stringency levels on the outbreak progression of COVID-19 in Malaysia. The effective reproduction number, Rt, was estimated by adopting and modifying an Rt estimation algorithm using a validated distribution mean of 3.96 and standard deviation of 4.75 with a seven-day sliding window. The Rt values generated were validated using thea moving window SEIR model with a negative binomial likelihood fitted using methods from the Bayesian inferential framework. A Pearson’s correlation between the Rt values estimated by the algorithm and the SEIR model was r = 0.70, p

A complex network of interactions exists between the olfactory, immune and central nervous systems. In this work we intend to investigate this connection through the use of an immunostimulatory odorant like menthol, analyzing its impact on the immune system and the cognitive capacity in healthy and Alzheimer’s Disease Mouse Models. We first found that repeated short exposures to menthol odor enhanced the immune response against ovalbumin immunization. Menthol inhalation also improved the cognitive capacity of immunocompetent mice but not in immunodeficient NSG mice, which exhibited very poor fear-conditioning. This improvement was associated with a downregulation of IL-1β and IL-6 mRNA in the brain´s prefrontal cortex, and it was impaired by anosmia induction with methimazole. Exposure to menthol for 6 months (1 week per month) prevented the cognitive impairment observed in the APP/PS1 mouse model of Alzheimer. Besides, this improvement was also observed by the depletion or inhibition of T regulatory cells. Treg depletion also improved the cognitive capacity of the APPNL-G-F/NL-G-F Alzheimer´s mouse model. In all cases, the improvement in learning capacity was associated with a downregulation of IL-1β mRNA. Blockade of the IL-1 receptor with anakinra resulted in a significant increase in cognitive capacity in healthy mice as well as in the APP/PS1 model of Alzheimer´s disease. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals, highlighting the potential of odors and immune modulators as therapeutic agents for CNS-related diseases.

O balé exige do praticante esforço e delicadeza na realização dos movimentos. O objetivo deste estudo foi avaliar hábitos alimentares, qualidade de vida e estado nutricional de crianças e adolescentes praticantes de balé. Trata-se de estudo transversal com todas as 35 crianças e adolescentes de 3 a 17 anos de um projeto social (Serra-ES). Utilizou-se questionário para identificar as situações sociodemográfica, história clí­nica, hábitos alimentares e qualidade de vida. O estado nutricional foi analisado por meio da antropometria (peso, altura, circunferência da cintura, prega cutânea tricipital e subescapular). Participaram da pesquisa os indiví­duos que tiveram o Termo de Consentimento Livre e Esclarecido assinado pelo respons´´avel e o projeto foi enviado ao comité de ética do Centro Universitário Católica de Vitória (Nº CAAE: 95651318.3.0000.5068). Os dados foram descritos em frequência absoluta e relativa. Os resultados demostraram que as crianças, em relação ao í­ndice P/I e E/I 95,8% (n=23) apresentavam-se adequada para a idade. As adolescentes 72,7% (n=8) apresentaram eutrofia (IMC/I), já em relação a E/I 100% (n=11) estavam adequadas para a idade. Constatou-se um consumo adequado dos grupos: leguminosas, leite e seus derivados, enquanto os demais grupos de alimentos estavam inadequados e se observou elevado consumo de guloseimas. Na qualidade de vida 97% (n=31) apresentaram boa qualidade de vida. As bailarinas estavam eutróficas, entretanto é necessária uma melhora nos hábitos alimentares que pode impactar no rendimento deste esporte. A qualidade de vida foi classificada como boa e isso pode estar relacionado a prática desta atividade fí­sica.

This work proposes a methodology to optimize a reinforced concrete structure. For this, the Whale Optimization Algorithm (WOA) algorithm was used, an algorithm from the group of metaheuristic algorithms, which presents an easy computational implementation. As a study object, a frame structure adapted from a real reinforced concrete building was used, subjected to the dynamic action of artificially generated synoptic wind. The objective function is to reduce the volume of concrete of the structure. For that, the dimensions of the cross-sections were used as design variables, and the maximum displacement at the top imposed by the ASCE / SEI 7-10 standard as a lateral constraint, as well as the maximum story drift between floors. In addition to this structural optimization, it was also proposed the use and optimization of Tuned Mass Dampers (TMD), in different quantities, positions and parameters, improving the dynamic response of the reinforced concrete building. The results show that for this situation it was possible to reduce the concrete volume of the structure by approximately 24%, respecting the maximum limit of displacement at the top required by the standard.

Abstract Professors may start teaching either out of love or out of convenience, with limited resources. This article provides a brief manual for planning, designing and implementing PS&IR courses. We discuss syllabi, from the basics to the inclusion of transversal topics, then present eight active learning strategies plus traditional lectures, and debate assessments. Although we consider the context of new teachers within Brazilian universities, we believe this is useful for professors from all countries and levels of experience. Thereby, we provide practical advice for teachers to live happily ever after in their pedagogical love story (even if it did not start that way).

O contato entre família e escola é de suma importância para a inclusão escolar dos alunos. A participação da família no processo de escolarização de alunos com deficiência intelectual é fundamental para o desenvolvimento do aluno. Sendo assim, para atender a temática da relação família e escola, foi realizado um estudo com objetivo de avaliar a opinião de professores sobre a relação entre família e escola após a realização de um curso de formação continuada. Para o método, foi desenvolvido e enviado um questionário (online) em forma de convite para 147 professores, concluintes de um curso de formação continuada de práticas pedagógicas inclusivas para a área da deficiência intelectual. O questionário foi estruturado contendo nove questões objetivas e uma questão aberta. Como resultado, infere-se que compreenderam a importância dessa relação e que tanto o relacionamento com os pais dos alunos, quanto as questões relativas as inclusões, são de responsabilidade de todos, além de ampliaram sua visão sobre a questão das parcerias.

The production of steamed cheese has a long tradition in Slovakia. Some of these cheeses have even received the PGI designation, which is a designation granted to products with specific geographical characteristics (Slovenská parenica, Zázrivské vojky, Zázrivský korbáčik, and Oravský korbáčik). In our study, eight samples of various unsmoked steamed cheese from small dairy farms (samples D, F, G, and H) and medium-sized farms (A, B, C, and E) were evaluated. Our work aimed to determine whether there are significant differences in sensory characteristics between samples from small and medium-sized dairy farms and whether there are differences in the preferences between these samples for consumers. Samples were evaluated by sensory analysis, where the assessors evaluated the characteristics of color, odor, texture, flavor, and overall appearance on a nine-point hedonic scale. Differences at a statistically significant level in the attributes of odor, texture, flavor, and overall appearance were confirmed (p 0.05). The results were processed using PCA, whereas can be seen from the graphic representation the carriers of all evaluated attributes were samples from medium-sized farms (except for sample D, which belonged to the first group of samples together with samples from medium-sized farms). We constructed a preferential map by combining internal and external mapping, while the internal data were formed by data obtained from assessors using sensory analysis and the external data came from an online questionnaire. Using the preferential mapping technique, we found out that samples from medium-sized dairy farms were classified as the most preferred samples which correspond with the results of sensory analysis.

Abstract Respiratory viruses can be detected in 18.3 to 48.9% of critically ill adults with severe respiratory tract infections (RTIs). The present study aims to assess the clinical significance of respiratory viruses in pragmatically selected adults in medical intensive care unit patients and to identify factors associated with viral respiratory viral tract infections (VRTIs). We conducted a prospective study on critically ill adults with suspected RTIs without recognized respiratory pathogens. Viral cultures with monoclonal antibody identification, in-house real-time polymerase chain reaction (PCR) for influenza virus, and FilmArray respiratory panel were used to detect viral pathogens. Multivariable logistic regression was applied to identify factors associated with VRTIs. Sixty-four (40.5%) of the included 158 critically ill adults had respiratory viruses detected in their respiratory specimens. The commonly detected viruses included influenza virus (20), followed by human rhinovirus/enterovirus (11), respiratory syncitial virus (9), human metapneumovirus (9), human parainfluenza viruses (8), human adenovirus (7), and human coronaviruses (2). The FilmArray respiratory panel detected respiratory viruses in 54 (34.6%) patients, but showed negative results for seven of 13 patients with influenza A/H3 infection. In the multivariable logistic regression model, patient characters associated with VRTIs included those aged

Indiví­duos com lesão medular (LM) podem apresentar alterações no sistema cardiovascular, como diminuição da variabilidade da frequência cardí­aca (VFC), decorrente da perda parcial e ou total da inervação autonômica. Nessa população, o exercí­cio fí­sico tem sido colocado como uma intervenção que pode minimizar essas disfunções cardiovasculares. Assim, o objetivo do presente estudo foi apresentar, por meio da revisão de literatura, o comportamento da VFC em indiví­duos com LM em resposta ao exercí­cio fí­sico agudo e crônico. A busca foi realizada nas bases de dados PubMed, Web of Science, Scielo e BVS. Foram utilizados os descritores: lesão medular AND variabilidade da frequência cardí­aca AND exercí­cio fí­sico (spinal cord injury, heart rate variability e physical exercise). Após a busca nas bases de dados foram encontrados 109 artigos sendo 65 no PubMed, 20 no Web of Science, 2 no Scielo e 22 na BVS. Desses, foram selecionados 12 artigos que preencheram os critérios de inclusão, sendo que, apenas 7 estudos avaliaram o efeito do exercí­cio fí­sico crônico na VFC e 5 artigos que avaliaram o efeito agudo. Indiví­duos com LM preservam a VFC no repouso, no entanto, apresentam alguns déficits na capacidade de realizar ajustes cardiovasculares quando submetidos à sobrecarga imposta pelo exercí­cio fí­sico agudo. E a maioria dos estudos não encontrou diferenças na VFC ao efetuar a análise após o exercí­cio fí­sico crônico, independentemente do tipo, duração e intensidade do exercí­cio fí­sico.

Background One of the main difficulties of adoptive cell therapies with chimeric antigen receptor (CAR)-T cells in solid tumors is the identification of specific target antigens. The tumor microenvironment can present suitable antigens for CAR design, even though they are not expressed by the tumor cells. We have generated a CAR specific for the splice variant extra domain A (EDA) of fibronectin, which is highly expressed in the tumor stroma of many types of tumors but not in healthy tissues.Methods EDA expression was explored in RNA-seq data from different human tumor types and by immunohistochemistry in paraffin-embedded tumor biopsies. Murine and human anti-EDA CAR-T cells were prepared using recombinant retro/lentiviruses, respectively. The functionality of EDA CAR-T cells was measured in vitro in response to antigen stimulation. The antitumor activity of EDA CAR-T cells was measured in vivo in C57BL/6 mice challenged with PM299L-EDA hepatocarcinoma cell line, in 129Sv mice-bearing F9 teratocarcinoma and in NSG mice injected with the human hepatocarcinoma cell line PLC.Results EDA CAR-T cells recognized and killed EDA-expressing tumor cell lines in vitro and rejected EDA-expressing tumors in immunocompetent mice. Notably, EDA CAR-T cells showed an antitumor effect in mice injected with EDA-negative tumor cells lines when the tumor stroma or the basement membrane of tumor endothelial cells express EDA. Thus, EDA CAR-T administration delayed tumor growth in immunocompetent 129Sv mice challenged with teratocarcinoma cell line F9. EDA CAR-T treatment exerted an antiangiogenic effect and significantly reduced gene signatures associated with epithelial-mesenchymal transition, collagen synthesis, extracellular matrix organization as well as IL-6-STAT5 and KRAS pathways. Importantly, the human version of EDA CAR, that includes the human 41BB and CD3ζ endodomains, exerted strong antitumor activity in NSG mice challenged with the human hepatocarcinoma cell line PLC, which expresses EDA in the tumor stroma and the endothelial vasculature. EDA CAR-T cells exhibited a tropism for EDA-expressing tumor tissue and no toxicity was observed in tumor bearing or in healthy mice.Conclusions These results suggest that targeting the tumor-specific fibronectin splice variant EDA with CAR-T cells is feasible and offers a therapeutic option that is applicable to different types of cancer.

This article explores the broad and undefined research field of the social impact of the arts. The effects of art and culture are often used as justification for public funding, but the research on these interventions and their effects is unclear. Using a co-word analysis of over 10,000 articles published between 1990 and 2020, we examined the characteristics of the field as we have operationalised it through our searches. We found that since 2015 this research field has expanded and consists of different epistemologies and methodologies, summarised in largely overlapping subfields belonging to the social sciences, humanities, arts education, and arts and health/therapy. In formal or informal learning settings, studies of theatre/drama as an intervention to enhance skills, well-being, or knowledge among children are most common in our corpus. A study of the research front through the bibliographic coupling of the most cited articles in the corpus confirmed the co-word analysis and revealed new themes that together form the ground for insight into research on the social impact of the arts. This article can therefore inform discussions on the social value of culture and the arts.