Risk Factors for Early Lower Limb Re-Amputation in Vascular Diseases.

BACKGROUND: Numerous risk factors for lower limb amputations are known; however, this study aimed to identify risk factors for re-amputation in patients within 6 months from an initial lower limb amputation procedure. METHODS: This single-center retrospective cohort study was performed at the Hospital Regional Hans Dieter Schmidt in Brazil. The study included patients who were aged at least 18 years and had undergone lower limb amputation between 2013 and 2022. Patients who died while hospitalized and patients who were lost to follow-up after hospital discharge were excluded from the study. Patient age, sex, number of amputations, revision time, comorbidities, and potential risk factors were extracted from the physical therapy service database and electronic medical records of the hospital. Chi-squared test and student's t-test were used to identify statistical significance. RESULTS: A total of 652 patients were included, of which 35.2% (230) patients underwent re-amputation within 6 months of the first operation. We found that dialysis (P = 0.004; odds ratio [OR] 8.36, 95% confidence interval [CI] 3.09-20.5), smoking (P = 0.004; OR 1.67, 95% CI 1.18-2.35), and hypertension (P = 0.02; OR 1.55, 95% CI 1.09-2.19) were predictive factors for re-amputation within 6 months of lower limb amputation. CONCLUSIONS: Therefore, it is important to intervene early and provide additional support to patients undergoing lower limb amputation with these risk factors to reduce the potential for re-amputation in the future.

Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection.

Introduction: Dengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs). Methods and results: We analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach. Differential expression analysis identified 237 common differentially expressed genes (DEGs) between DVTs and NDI. Among them, 28 and 60 DEGs were up or downregulated by dengue vaccination during DVT2 and DVT3, respectively, with 20 DEGs intersecting across all three DVTs. Enriched biological processes of these genes included type I/II interferon signaling, cytokine regulation, apoptosis, and T-cell differentiation. Principal component analysis based on 20 common DEGs (overlapping between DVTs and our NDI validation dataset) distinguished dengue patients by disease severity, particularly in the late acute phase. Machine learning analysis ranked the ten most critical predictors of disease severity in NDI, crucial for the anti-viral immune response. Conclusion: This work provides insights into the NDI and vaccine-induced overlapping immune response and suggests molecular markers (e.g., IFIT5, ISG15, and HERC5) for anti-dengue-specific therapies and effective vaccination development.

Combinatorial multimer staining and spectral flow cytometry facilitate quantification and characterization of polysaccharide-specific B cell immunity.

Bacterial capsular polysaccharides are important vaccine immunogens. However, the study of polysaccharide-specific immune responses has been hindered by technical restrictions. Here, we developed and validated a high-throughput method to analyse antigen-specific B cells using combinatorial staining with fluorescently-labelled capsular polysaccharide multimers. Concurrent staining of 25 cellular markers further enables the in-depth characterization of polysaccharide-specific cells. We used this assay to simultaneously analyse 14 Streptococcus pneumoniae or 5 Streptococcus agalactiae serotype-specific B cell populations. The phenotype of polysaccharide-specific B cells was associated with serotype specificity, vaccination history and donor population. For example, we observed a link between non-class switched (IgM+) memory B cells and vaccine-inefficient S. pneumoniae serotypes 1 and 3. Moreover, B cells had increased activation in donors from South Africa, which has high-incidence of S. agalactiae invasive disease, compared to Dutch donors. This assay allows for the characterization of heterogeneity in B cell immunity that may underlie immunization efficacy.

Predictors of arteriovenous fistula maturation in hemodialysis patients: a prospective cohort from an ambulatory surgical center in Joinville, Brazil / Preditores da maturação de fístula arteriovenosa de pacientes em hemodiálise: coorte prospectiva de um centro cirúrgico ambulatorial, Joinville, Brasil

ABSTRACT Introduction: The high rate of arteriovenous fistula maturation failure is a concern in a scenario of growing numbers of patients on hemodialysis. Non-vascular factors tied to maturation success have not been fully discussed. Methods: This prospective observational cohort study included patients with CKD on dialysis or pre-dialysis prescribed arteriovenous fistula creation for the first time in an ambulatory surgical center in Joinville, Brazil, from January 2021 to July 2021. Anthropometric aspects, sociodemographic characteristics, comorbidities, and vascular parameters observed in Doppler ultrasound were analyzed. Variables associated with maturation were analyzed in multivariate models by logistic regression. Results: Eighty-eight of 145 participants (60.1%) were males. Included patients had a median age of 59 years. Successful arteriovenous fistula maturation occurred in 113 (77.9%) patients. Factors such as increased BMI, hematocrit, arm circumference, and skinfold thickness were associated with lower chances of arteriovenous fistula maturation in univariate analysis. On the other hand, larger vein and artery diameter and fistulas in the more proximal portion of the arm were associated with higher maturation success. In multivariate analysis, smoking and larger skinfold and arm circumference were associated with lower chances of successful maturation. Increased systolic blood pressure and vein diameter were associated with greater chance of success. Conclusion: In addition to the vascular parameters assessed in Doppler ultrasonography, factors related to obesity and/or nutritional aspects may influence arteriovenous fistula maturation.

Resumo Introdução: A alta taxa de falha na maturação da fístula arteriovenosa é motivo de preocupação para o crescente número de pacientes em hemodiálise. Os fatores não vasculares não foram totalmente estudados em relação ao sucesso da maturação. Métodos: Estudo de coorte prospectivo, observacional de pacientes com DRC diálise ou pré-diálise encaminhados para a primeira criação de fístula arteriovenosa em um centro cirúrgico ambulatorial de Joinville, Brasil, de janeiro de 2021 a julho de 2021. Aspectos antropométricos, características sociodemográficas, comorbidades, além de fatores vasculares verificados pelo ultrassom Doppler. As variáveis associadas à maturação foram analisadas em modelos multivariados por regressão logística. Resultados: Dos 145 pacientes participantes, 88 (60,1%) eram homens, com idade mediana de 59 anos. Houve sucesso na maturação da fístula arteriovenosa em 113 (77,9%) pacientes. Fatores como aumento do IMC, hematócrito, circunferência do braço e valor das dobras cutâneas foram associados a menor chance de maturação da fístula arteriovenosa na análise univariada. Por outro lado, o maior diâmetro da veia e da artéria e fístulas na porção mais proximal do membro superior foram associados a maior sucesso de maturação. Na análise multivariada, tabagismo, maior dobra cutânea e circunferência do braço foram associados a menor chance de sucesso da maturação. O aumento da pressão arterial sistólica e o do diâmetro da veia foram associados a maior chance de sucesso. Conclusão: Além dos aspectos vasculares avaliados pela ultrassonografia Doppler, fatores relacionados à obesidade e/ou a aspectos nutricionais podem influenciar a maturação da fístula arteriovenosa.

Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach.

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 severity (71 mild, 61 moderate, and 27 with severe symptoms) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid ß peptide, ß catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.

Interferome signature dynamics during the anti-dengue immune response: a systems biology characterization.

Dengue virus (DENV) infection manifests as a febrile illness with three distinct phases: early acute, late acute, and convalescent. Dengue can result in clinical manifestations with different degrees of severity, dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Interferons (IFNs) are antiviral cytokines central to the anti-DENV immune response. Notably, the distinct global signature of type I, II, and III interferon-regulated genes (the interferome) remains uncharacterized in dengue patients to date. Therefore, we performed an in-depth cross-study for the integrative analysis of transcriptome data related to DENV infection. Our systems biology analysis shows that the anti-dengue immune response is characterized by the modulation of numerous interferon-regulated genes (IRGs) enriching, for instance, cytokine-mediated signaling (e.g., type I and II IFNs) and chemotaxis, which is then followed by a transcriptional wave of genes associated with cell cycle, also regulated by the IFN cascade. The adjunct analysis of disease stratification potential, followed by a transcriptional meta-analysis of the interferome, indicated genes such as IFI27, ISG15, and CYBRD1 as potential suitable biomarkers of disease severity. Thus, this study characterizes the landscape of the interferome signature in DENV infection, indicating that interferome dynamics are a crucial and central part of the anti-dengue immune response.

Corrigendum to "Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities" [Heliyon 8 (11) (November 2022) Article e11368].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e11368.].

Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a broad spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS-CoV-2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID-19 patients in a cohort of 231 individuals, of which 161 were COVID-19 patients (72 with mild, 61 moderate, and 28 with severe disease) and 70 were healthy controls. Dysregulated IgG and IgA autoantibody signatures, characterized mainly by elevated concentrations, occurred predominantly in patients with moderate or severe COVID-19 infection. Autoantibody levels often accompanied anti-SARS-CoV-2 antibody concentrations while stratifying COVID-19 severity as indicated by random forest and principal component analyses. Furthermore, while young versus elderly COVID-19 patients showed only slight differences in autoantibody levels, elderly patients with severe disease presented higher IgG autoantibody concentrations than young individuals with severe COVID-19. This work maps the intersection of COVID-19 and autoimmunity by demonstrating the dysregulation of multiple autoantibodies triggered during SARS-CoV-2 infection. Thus, this cross-sectional study suggests that SARS-CoV-2 infection induces autoantibody signatures associated with COVID-19 severity and several autoantibodies that can be used as biomarkers of COVID-19 severity, indicating autoantibodies as potential therapeutical targets for these patients.

Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID-19 severity.

Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are several cyclins, cell division cycles, cyclin-dependent kinases, and mini-chromosome maintenance proteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and natural killer cells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.

Predictors of arteriovenous fistula maturation in hemodialysis patients: a prospective cohort from an ambulatory surgical center in Joinville, Brazil.

INTRODUCTION: The high rate of arteriovenous fistula maturation failure is a concern in a scenario of growing numbers of patients on hemodialysis. Non-vascular factors tied to maturation success have not been fully discussed. METHODS: This prospective observational cohort study included patients with CKD on dialysis or pre-dialysis prescribed arteriovenous fistula creation for the first time in an ambulatory surgical center in Joinville, Brazil, from January 2021 to July 2021. Anthropometric aspects, sociodemographic characteristics, comorbidities, and vascular parameters observed in Doppler ultrasound were analyzed. Variables associated with maturation were analyzed in multivariate models by logistic regression. RESULTS: Eighty-eight of 145 participants (60.1%) were males. Included patients had a median age of 59 years. Successful arteriovenous fistula maturation occurred in 113 (77.9%) patients. Factors such as increased BMI, hematocrit, arm circumference, and skinfold thickness were associated with lower chances of arteriovenous fistula maturation in univariate analysis. On the other hand, larger vein and artery diameter and fistulas in the more proximal portion of the arm were associated with higher maturation success. In multivariate analysis, smoking and larger skinfold and arm circumference were associated with lower chances of successful maturation. Increased systolic blood pressure and vein diameter were associated with greater chance of success. CONCLUSION: In addition to the vascular parameters assessed in Doppler ultrasonography, factors related to obesity and/or nutritional aspects may influence arteriovenous fistula maturation.

Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities.

Brazil experienced one of the most prolonged periods of school closures, and reopening could have exposed students to high rates of SARS-CoV-2 infection. However, the infection status of students and school workers at the time of the reopening of schools located in Brazilian cities is unknown. Here we evaluated viral carriage by RT-PCR and seroprevalence of anti-SARS-CoV-2 antibodies (IgM and IgG) by immunochromatography in 2259 individuals (1139 students and 1120 school workers) from 28 schools in 28 Brazilian cities. We collected the samples within 30 days after public schools reopened and before the start of vaccination campaigns. Most students (n = 421) and school workers (n = 446) had active (qRT-PCR + IgM- IgG- or qRT-PCR + IgM + IgG-/+) SARS-CoV-2 infection. Regression analysis indicated a strong association between the infection status of students and school workers. Furthermore, while 45% (n = 515) of the students and 37% (n = 415) of the school workers were neither antigen nor antibody positive in laboratory tests, 16% of the participants (169 students and 193 school workers) were oligosymptomatic, including those reinfected. These individuals presented mild symptoms such as headache, sore throat, and cough. Notably, most of the individuals were asymptomatic (83.9%). These results indicate that many SARS-CoV-2 infections in Brazilian cities during school reopening were asymptomatic. Thus, our study highlights the need to promote a coordinated public health effort to guarantee a safe educational environment while avoiding exacerbating pre-existent social inequalities in Brazil, reducing social, mental, and economic losses for students, school workers, and their families.

Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity.

Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS.

Therapeutics That Can Potentially Replicate or Augment the Anti-Aging Effects of Physical Exercise.

Globally, better health care access and social conditions ensured a significant increase in the life expectancy of the population. There is, however, a clear increase in the incidence of age-related diseases which, besides affecting the social and economic sustainability of countries and regions around the globe, leads to a decrease in the individual's quality of life. There is an urgent need for interventions that can reverse, or at least prevent and delay, the age-associated pathological deterioration. Within this line, this narrative review aims to assess updated evidence that explores the potential therapeutic targets that can mimic or complement the recognized anti-aging effects of physical exercise. We considered pertinent to review the anti-aging effects of the following drugs and supplements: Rapamycin and Rapamycin analogues (Rapalogs); Metformin; 2-deoxy-D-glucose; Somatostatin analogues; Pegvisomant; Trametinib; Spermidine; Fisetin; Quercetin; Navitoclax; TA-65; Resveratrol; Melatonin; Curcumin; Rhodiola rosea and Caffeine. The current scientific evidence on the anti-aging effect of these drugs and supplements is still scarce and no recommendation of their generalized use can be made at this stage. Further studies are warranted to determine which therapies display a geroprotective effect and are capable of emulating the benefits of physical exercise.

European Portuguese Language and Cultural Validation of the Chronic Obstructive Pulmonary Disease Assessment Test.

INTRODUCTION: The chronic obstructive pulmonary disease assessment test (CAT) is a self-administered questionnaire that measures health-related quality of life. GOLD proposes using this questionnaire, since it provides thorough coverage of the impact of chronic obstructive pulmonary disease (COPD) on well-being. This questionnaire has been widely used in daily clinical practice in Portugal, but it lacks validation for European Portuguese. The aim of this study was to carry out the cultural adaptation and validation of the CAT questionnaire so that the most appropriate version can be made available to Portuguese researchers and clinicians. MATERIAL AND METHODS: A cross-sectional descriptive study was performed involving 65 patients with COPD aged 40 years or older. CAT and the previously validated Portuguese-language version of the Clinical Questionnaire for COPD were applied between January 2019 and June 2019. The agreement between the two questionnaires was determined with Kappa agreement with a 95% confidence interval. Spearman correlation was used to find the correlation between two scores. RESULTS: The 65 patients included in the study were observed in a hospital-based pulmonology clinic [aged 68 ± 7 years; forced expiratory volume in 1 sec (FEV1) 49.86% ± 16.5% predicted]. CAT correlated significantly with all the domains and the overall score of the CCQ (0.47 < r < 0.75; p < 0.001). The bilingual patient interclass correlation coefficient was 0.922; Pearson's r = 0.928; p < 0.001. The Cronbach's alpha coefficient was 0.96 (p < 0.001). CONCLUSION: The European Portuguese version of the COPD Assessment Test is a valid instrument for measurement of health-related quality of life in COPD patients. The use of validated questionnaires is of great importance since it generates reliable and reproducible evidence for use either in research or clinical practice.

Introdução: O teste de avaliação da doença pulmonar obstrutiva crónica (CAT) é um questionário autoaplicável que mede a qualidade de vida relacionada com a saúde. As normas internacionais GOLD propõem o uso deste questionário, uma vez que traduz o impacto da doença pulmonar obstrutiva crónica (DPOC) no bem-estar. Este questionário tem sido amplamente utilizado na prática clínica diária em Portugal, mas carece de validação para o português europeu. Assim, o objetivo deste estudo foi realizar a adaptação cultural e validação do questionário CAT para que a sua versão mais adequada possa ser disponibilizada a investigadores e clínicos portugueses. Material e Métodos: Foi realizado um estudo transversal descritivo com 65 doentes com DPOC com 40 anos ou mais. O CAT e a versão em português previamente validada do questionário clínico para DPOC foram aplicados entre janeiro de 2019 e junho de 2019. A concordância entre os dois questionários foi determinada com o teste de concordância de Kappa com intervalo de confiança de 95%. A correlação de Spearman foi usada para avaliar a presença de uma correlação entre os dois scores. Resultados: Os 65 doentes incluídos no estudo foram observados em consulta de pneumologia hospitalar [idade 68 ± 7 anos; volume expiratório máximo no 1º segundo (FEV1) 49,86% ± 16,5% do previsto]. O CAT correlacionou-se significativamente com todos os domínios e com a pontuação geral do CCQ (0,47 < r < 0,75; p < 0,001). O coeficiente de correlação interclasse de doentes bilíngues foi de 0,922; R de Pearson = 0,928; p < 0,001. O coeficiente alfa de Cronbach foi de 0,96 (p < 0,001). Conclusão: A versão em português europeu do CAT é um instrumento válido para medir a qualidade de vida relacionada com a saúde em doentes com DPOC. A aplicação de questionários validados é fundamental, visto que gera evidência confiável e reprodutível para uso em ensaios clínicos ou na prática clínica.

Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States.

Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaki disease [KD]), and different respiratory infections (seasonal coronavirus, influenza, bacterial pneumonia). We observed that COVID-19 and HLH share immunological pathways (cytokine/chemokine signaling and neutrophil-mediated immune responses), including gene signatures that stratify COVID-19 patients admitted to the intensive care unit (ICU) and COVID-19_nonICU patients. Of note, among the common differentially expressed genes (DEG), there is a cluster of neutrophil-associated genes that reflects a generalized hyperinflammatory state since it is also dysregulated in patients with KD and bacterial pneumonia. These genes are dysregulated at the protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins that point to neutrophil hyperactivation in COVID-19 patients admitted to the intensive care unit. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils. Artificial intelligence modeling confirmed the strong association of these genes with COVID-19 severity. Thus, our work indicates putative therapeutic pathways for intervention.

Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity.

COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity.

Inclusão, formação e educação física: uma análise na perspectiva dos professores / Inclusion, teacher training and physical education: an analysis from the teachers' perspective / Inclusión, formación y educación física: un análisis desde la perspectiva del profesor

Este estudo teve como objetivo descrever a formação, na perspectiva da inclusão, de professores de Educação Física que atuam com alunos com deficiência nas escolas da Rede Municipal de Rio Grande ­ RS. Fizeram parte da amostra do estudo 17 professores. Foi aplicado um questionário sobre os dados de identificação e formação acadêmica na perspectiva da inclusão. Posteriormente, foi utilizada a técnica dos Grupos Focais com as temáticas: formação do professor de Educação Física e políticas públicas educacionais inclusivas. Os resultados obtidos sinalizam que os conhecimentos docentes relacionados à inclusão, estão ligados à pratica da sala de aula na escola, tendo um diálogo contínuo com os conhecimentos da formação inicial e continuada (AU).

The purpose of this study was to describe academic qualification in the perspective of inclusion of Physical Education teachers who works with students with disabilities in municipal schools in Rio Grande-RS. Seventeen teachers were involved in the sample. A questionnaire was sent on the identification data and academic background with a view to inclusion. After that, the Focus Group technic with the theme: the academic qualification of Physical Education teachers and public policies in inclusive education. The results has shown that the knowledge of the teachers toward inclusion has to do with teachers practice inside the classroom at school, keeping a continued dialogue between initial qualification and continuing qualification (AU).

Este estudio tuvo como objetivo describir la formación en la perspectiva de la inclusión de docentes de Educación Física que trabajan con estudiantes con discapacidad en las escuelas de la Red Municipal de Rio Grande - RS. 17 profesores formaron parte de la muestra del estudio. Se aplicó un cuestionario a los datos de identificación y formación académica desde la perspectiva de la inclusión. Posteriormente, se utilizó la técnica de Grupos Focales con los siguientes temas: formación de docentes de Educación Física y políticas públicas educativas inclusivas. Los resultados obtenidos indican que el conocimiento docente relacionado con la inclusión está vinculado a la práctica del aula en la escuela, teniendo un diálogo continuo con los conocimientos de la educación inicial y continua

Inclusão, formação e educação física: uma análise na perspectiva dos professores / Inclusion, teacher training and physical education: an analysis from the teachers' perspective / Inclusión, formación y educación física: un análisis desde la perspectiva del profesor

Este estudo teve como objetivo descrever a formação, na perspectiva da inclusão, de professores de Educação Física que atuam com alunos com deficiência nas escolas da Rede Municipal de Rio Grande ­ RS. Fizeram parte da amostra do estudo 17 professores. Foi aplicado um questionário sobre os dados de identificação e formação acadêmica na perspectiva da inclusão. Posteriormente, foi utilizada a técnica dos Grupos Focais com as temáticas: formação do professor de Educação Física e políticas públicas educacionais inclusivas. Os resultados obtidos sinalizam que os conhecimentos docentes relacionados à inclusão, estão ligados à pratica da sala de aula na escola, tendo um diálogo contínuo com os conhecimentos da formação inicial e continuada.

The purpose of this study was to describe academic qualification in the perspective of inclusion of Physical Education teachers who works with students with disabilities in municipal schools in Rio Grande-RS. Seventeen teachers were involved in the sample. A questionnaire was sent on the identification data and academic background with a view to inclusion. After that, the Focus Group technic with the theme: the academic qualification of Physical Education teachers and public policies in inclusive education. The results has shown that the knowledge of the teachers toward inclusion has to do with teachers practice inside the classroom at school, keeping a continued dialogue between initial qualification and continuing qualification.

Este estudio tuvo como objetivo describir la formación en la perspectiva de la inclusión de docentes de Educación Física que trabajan con estudiantes con discapacidad en las escuelas de la Red Municipal de Rio Grande - RS. 17 profesores formaron parte de la muestra del estudio. Se aplicó un cuestionario a los datos de identificación y formación académica desde la perspectiva de la inclusión. Posteriormente, se utilizó la técnica de Grupos Focales con los siguientes temas: formación de docentes de Educación Física y políticas públicas educativas inclusivas. Los resultados obtenidos indican que el conocimiento docente relacionado con la inclusión está vinculado a la práctica del aula en la escuela, teniendo un diálogo continuo con los conocimientos de la educación inicial y continua.

Confirmatory Evaluation of the Modified Medical Research Council Questionnaire for Assessment of Dyspnea in Patients with Chronic Obstructive Pulmonary Disease in Portugal.

INTRODUCTION: The Modified British Medical Research Council Questionnaire is considered an adequate and simple measure of breathlessness in chronic obstructive pulmonary disease. It is widely used in clinical practice in Portugal, but it still lacks confirmatory evaluation for the Portuguese setting. The aim of this study was to perform a cultural adaptation and validation of the Modified British Medical Research Council Questionnaire so that its most suitable version can be made available to researchers and clinicians in Portugal. MATERIAL AND METHODS: We performed a cross-sectional descriptive study involving patients with chronic obstructive pulmonary disease aged 40 years or older. We applied the Modified British Medical Research Council Questionnaire and the previously validated Portuguese-language version of the clinical questionnaire for chronic obstructive pulmonary disease between January and June 2019. We determined the agreement between the two questionnaires with kappa agreement, with a 95% confidence interval, and we used Spearman correlation to find a correlation between two scores. RESULTS: The study included 65 patients managed in a hospital pulmonology clinic (aged 68 ± 7 years; with predicted FEV1 of 49.86% ± 16.5%). The Modified British Medical Research Council scale correlated significantly with all the domains and the overall score of the clinical questionnaire for chronic obstructive pulmonary disease (0.46 < r < 0.68; p < 0.001). In bilingual patients, interclass correlation coefficient was 0.912 (p < 0.001). DISCUSSION: Our study showed that the Portuguese-language version of the Modified British Medical Research Council Questionnaire is feasible and externally valid when compared with a traditional and previously validated instrument. CONCLUSION: The Portuguese version of the Modified British Medical Research Council Questionnaire is a valid instrument for measurement of breathlessness in chronic obstructive pulmonary disease.

Introdução: O Questionário British Medical Research Council (mMRC) Modificado é considerado um instrumento adequado e simples para a medição da dispneia na doença pulmonar obstrutiva crónica (DPOC). Tem sido amplamente usado na prática clínica em Portugal, mas carece de avaliação confirmatória para o cenário português. O objetivo deste estudo é realizar a adaptação cultural e validação do Questionário British Medical Research Council Modificado para que a versão mais adequada possa estar disponível a investigadores e clínicos em Portugal. Material e Métodos: Realizamos um estudo descritivo e transversal com doentes com doença pulmonar obstrutiva crónica e idade ≥ 40 anos. Aplicamos o Questionário British Medical Research Council Modificado e o questionário clínico para a doença pulmonar obstrutiva crónica previamente validado para a língua portuguesa, entre janeiro e junho de 2019. Determinámos a concordância entre os dois questionários com kappa agreement, com 95% de intervalo de confiança, e usámos o coeficiente de correlação de Spearman para determinar a correlação entre os dois scores. Resultados: O estudo incluiu 65 doentes seguidos em consulta hospitalar de Pneumologia (idades de 68 ± 7 anos; com FEV1 49,86% ± 16,5% do predito). A Escala Modificada do British Medical Research Council correlacionou-se significativamente com todos os domínios e pontuação total do questionário clínico (0,46 < r < 0,68; p < 0,001). Nos doentes bilingues, o coeficiente de correlação interclasse foi 0,912 (p < 0,001). Discussão: O nosso estudo mostrou que a versão portuguesa do Questionário Modificado do British Medical Research Council apresenta exequibilidade e validade externa quando comparado com um instrumento tradicional e previamente validado. Conclusão: A versão portuguesa do Questionário Modificado do British Medical Research Council é um instrumento válido para a medição da dispneia na doença pulmonar obstrutiva crónica.

The network interplay of interferon and Toll-like receptor signaling pathways in the anti-Candida immune response.

Fungal infections represent a major global health problem affecting over a billion people that kills more than 1.5 million annually. In this study, we employed an integrative approach to reveal the landscape of the human immune responses to Candida spp. through meta-analysis of microarray, bulk, and single-cell RNA sequencing (scRNA-seq) data for the blood transcriptome. We identified across these different studies a consistent interconnected network interplay of signaling molecules involved in both Toll-like receptor (TLR) and interferon (IFN) signaling cascades that is activated in response to different Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis). Among these molecules are several types I IFN, indicating an overlap with antiviral immune responses. scRNA-seq data confirmed that genes commonly identified by the three transcriptomic methods show cell type-specific expression patterns in various innate and adaptive immune cells. These findings shed new light on the anti-Candida immune response, providing putative molecular pathways for therapeutic intervention.