S100A9 Drives the Chronification of Psoriasiform Inflammation by Inducing IL-23/Type 3 Immunity.

Psoriasis is a chronic inflammatory skin disorder driven by the IL-23/type 3 immune response. However, molecular mechanisms sustaining the chronicity of inflammation and psoriatic lesions remain elusive. Combining systematic analyses of several transcriptomic datasets, we delineated gene signatures across human psoriatic skin, identifying S100A9 as one of the most up-regulated genes, which was confirmed in lesioned skin from patients with psoriasis and preclinical psoriasiform skin inflammation models. Genetic ablation or pharmacologic inhibition of S100A9 alleviated Aldara-induced skin inflammation. By single-cell mapping of human psoriatic skin and bone marrow chimeric mice experiments, we identified keratinocytes as the major source of S100A9. Mechanistically, S100A9 induced IL-23 production by dendritic cells, driving the IL-23/type 3 immunity in psoriasiform skin inflammation. In addition, the cutaneous IL-23/IL-17 axis induced epidermal S100A9 expression in human and experimental psoriasis. Thus, we showed an autoregulatory circuit between keratinocyte-derived S100A9 and IL-23/type 3 immunity during psoriasiform inflammation, identifying a crucial function of S100A9 in the chronification of psoriasis.

The treatment of atypical hemolytic uremic syndrome with eculizumab in pediatric patients: a systematic review.

BACKGROUND: The atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy associated with high morbidity and high mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, was the first medication approved for treating aHUS in 2011. OBJECTIVE: The objective of this study is to evaluate the efficacy and safety of eculizumab treatment in pediatric patients with aHUS. DATA SOURCES: We consulted PubMed, Scopus, SciELO, and Cochrane Library databases in July 2021. The descriptors were as follows: "Atypical Hemolytic Uremic Syndrome," "aHUS," "eculizumab," "Pediatrics," "Pediatric," "Child," "Children," "Adolescent." STUDY ELIGIBILITY CRITERIA: The study eligibility criteria are as follows: clinical trials and observational studies that included pediatric patients with aHUS diagnosis and who were treated with eculizumab. PARTICIPANTS AND INTERVENTIONS: The participants are pediatric patients, up to 18 years old, with aHUS. The intervention was eculizumab treatment. STUDY APPRAISAL: For quality assessment, we used the Newcastle-Ottawa Scale, the National Institutes of Health (NIH) quality assessment tool for case series studies, and the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. RESULTS: The initial search retrieved 433 studies, from which 15 were selected after complete assessment: 9 cohorts, 4 case series, and 1 clinical trial. The publication date ranged from 2015 to 2021. In total, 940 pediatric patients were included, and 682 received eculizumab. All studies reported improvements in renal and hematological parameters in most of the patients treated with eculizumab. The mortality rate was 1.6% for all patients treated with eculizumab. LIMITATIONS: The number of studies is limited, and the included studies were methodologically heterogeneous. The studies were mostly observational and many had small sample sizes. CONCLUSIONS: Eculizumab appears to be safe and effective for the treatment of aHUS in pediatric patients. More research is necessary to establish long-term efficacy, safety, and time of discontinuation. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42021266255.

Sepsis expands a CD39+ plasmablast population that promotes immunosuppression via adenosine-mediated inhibition of macrophage antimicrobial activity.

Sepsis results in elevated adenosine in circulation. Extracellular adenosine triggers immunosuppressive signaling via the A2a receptor (A2aR). Sepsis survivors develop persistent immunosuppression with increased risk of recurrent infections. We utilized the cecal ligation and puncture (CLP) model of sepsis and subsequent infection to assess the role of adenosine in post-sepsis immune suppression. A2aR-deficient mice showed improved resistance to post-sepsis infections. Sepsis expanded a subset of CD39hi B cells and elevated extracellular adenosine, which was absent in mice lacking CD39-expressing B cells. Sepsis-surviving B cell-deficient mice were more resistant to secondary infections. Mechanistically, metabolic reprogramming of septic B cells increased production of ATP, which was converted into adenosine by CD39 on plasmablasts. Adenosine signaling via A2aR impaired macrophage bactericidal activity and enhanced interleukin-10 production. Septic individuals exhibited expanded CD39hi plasmablasts and adenosine accumulation. Our study reveals CD39hi plasmablasts and adenosine as important drivers of sepsis-induced immunosuppression with relevance in human disease.

Telomere Shortening and Psychiatric Disorders: A Systematic Review.

Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress ("Traumatic Stress Disorder" or "Anxiety Disorder" or "depression") and telomere length ("cellular senescence", "oxidative stress" and "telomere") was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.

Linking assessment instruments for brachial plexus injury to the international classification of functioning, disability and health.

BACKGROUND: Brachial plexus injuries (BPI) affect not only body structure and function, but also several aspects of individual's well-being. Considering the crescent need for assessing such patients through a biopsychosocial perspective, linking meaningful concepts of BPI instruments to the International Classification of Functioning, Disability and Health (ICF) provides a useful overview of how the ICF components are contemplated on the current measurements available. PURPOSE: To identify patient-reported outcome measures (PROMs) specifically designed for BPI assessment and link the content with the ICF. STUDY DESIGN: Content Analysis through ICF linking. METHODS: The study was conducted in two steps: the first one encompassed a literature review to identify questionnaires specifically designed for assessing patients with BPI, where two PROMs were eligible: the Brachial Assessment Tool (BrAT) and the Impact of Brachial Plexus Injury Questionnaire (IBPIQ); in the second phase, the items of such instruments were linked to the ICF by two independent reviewers, in accordance to the methodology proposed by Cieza et al. RESULTS: 54 different significant concepts were identified from the 74 questionnaire items and linked to 49 distinct ICF categories. The categories were mostly related to the activities and participation component (56.9%, n = 29), followed by body functions (27.45%, n = 14), body structures (9.8%, n = 5) and environmental factors component (1.96%, n = 1). CONCLUSION: The questionnaires developed for adults with BPI were BrAT and IBPIQ. Although both instruments presented with a diverse coverage of ICF components, their content had a major focus on activities and participation domain and poorly or did not addressed environmental factors. Thus, other instruments could be considered in a complementary way for clinical assessment.

Barriers to physical activity during the COVID-19 pandemic in adults: a cross-sectional study.

Social isolation due to the coronavirus disease 2019 (COVID-19) pandemic has reduced physical activity levels in both men and women. The identification of barriers to physical activity may assist in developing strategies to increase levels of physical activity during this pandemic. The study aim was identify the barriers to regular participation in physical during the COVID-19 pandemic in Brazilian adults. This cross-sectional study included 1570 [56.6% women; aged: 39.1 (37.7-40.7) years old] in social isolation due COVID-19. Barriers to physical activity were obtained using the validated questionnaires. "Laziness and fatigue" (50.2%), "lack of motivation" (31.2%), "lack of appropriate facilities/equipment/space" (17.4%), and "lack of time" (13.0%) were the barriers most prevalent in the study. Lack of motivation (OR = 1.49; 95% CI = 1.19-1.86) and lack of appropriate facilities/equipment/space (OR = 2.11; 95% CI = 1.57-2.83) were most associated with impacting physical activity levels due to the COVID-19, independent of sex, age, education level, days of social isolation and status weight. In conclusion, personal barriers to physical activity are common between both sexes, with lack of motivation and lack of appropriate facilities/equipment/space most associated with a decreased level of physical activity due to the COVID-19 pandemic.

NLRP12 controls arthritis severity by acting as a checkpoint inhibitor of Th17 cell differentiation.

Nucleotide oligomerization domain (NOD)-like receptor-12 (NLRP12) has emerged as a negative regulator of inflammation. It is well described that the Th17 cell population increases in patients with early Rheumatoid Arthritis (RA), which correlates with the disease activity. Here, we investigated the role of NLRP12 in the differentiation of Th17 cells and the development of experimental arthritis, using the antigen-induced arthritis (AIA) murine model. We found that Nlrp12-/- mice develop severe arthritis characterized by an exacerbated Th17-mediated inflammatory response with increases in the articular hyperalgesia, knee joint swelling, and neutrophil infiltration. Adoptive transfer of Nlrp12-/- cells into WT mice recapitulated the hyperinflammatory response seen in Nlrp12-/- mice and the treatment with anti-IL-17A neutralizing antibody abrogated arthritis development in Nlrp12-/- mice, suggesting that NLRP12 works as an inhibitor of Th17 cell differentiation. Indeed, Th17 cell differentiation markedly increases in Nlrp12-/- T cells cultured under the Th17-skewing condition. Mechanistically, we found that NLRP12 negatively regulates IL-6-induced phosphorylation of STAT3 in T cells. Finally, pharmacological inhibition of STAT3 reduced Th17 cell differentiation and abrogated hyperinflammatory arthritis observed in Nlrp12-/- mice. Thus, we described a novel role for NLRP12 as a checkpoint inhibitor of Th17 cell differentiation, which controls the severity of experimental arthritis.

Aplicabilidade da tomografia computadorizada cone beam na odontologia / Applicability of cone beam computerized tomography in dentistry

A Tomografia Computadorizada Cone Beam (TCCB) é um tipo de exame que possibilita visualização das imagens radiográficas em três dimensões. Os avanços tecnológicos na área da radiologia contribuíram com essa técnica, resultando em um diagnóstico rápido e preciso. O objetivo deste estudo consiste em estudar a aplicabilidade da Tomografia Computadorizada Cone Beam na odontologia. Trata-se de uma revisão bibliográfica da literatura onde foram realizadas consultas às seguintes plataformas digitais de dados bibliográficos: Scielo e PubMed. Os descritores utilizados na pesquisa foram: Tomografia, Tomografia por Raios X, Tomografia Computadorizada por Raios X e Tomografia Computadorizada de Feixe Cônico. O exame de TCCB auxilia em diversas áreas da odontologia. Na endodontia, colabora para o planejamento, tratamento e facilita a visualização de canais radiculares através de reconstruções em três dimensões. Em casos cirúrgicos, o exame permite um melhor planejamento da cirurgia, auxiliando no pré e pós operatório do paciente. Para avaliar possíveis alterações da articulação temporomandibular a TCCB é também indicada, pois oferece baixa dose de radiação e permite a realização de inúmeros cortes anatômicos, contribuindo para melhor investigação dessa articulação. Assim, a TCCB é um exame que fornece benefícios em diversas áreas da odontologia, possibilitando progressos no diagnóstico por imagem e trazendo grandes avanços tecnológicos para o radiodiagnóstico odontológico(AU)

Introduction: Cone Beam Computed Tomography (TCCB) is a type of examination that allows the visualization of radiographic images in three dimensions. Technological advances in radiology have contributed to this technique, resulting in rapid and accurate diagnosis. Objective: To study the applicability of Cone Beam Computed Tomography in dentistry. The aim of this study is to study the applicability of Cone Beam CT in dentistry. This is a bibliographical review of the literature where the following digital bibliographic data platforms were consulted: Scielo and PubMed. The descriptors used in the research were: Tomography, X-ray Tomography, X-ray Computed Tomography and Cone Beam Computed Tomography. The TCCB exam assists in several areas of dentistry. In endodontics, it collaborates to plan, treat and facilitate the visualization of root canals through reconstructions in three dimensions. In surgical cases, the examination allows a better planning of the surgery, assisting in the pre and post operative of the patient. In order to evaluate possible temporomandibular joint changes, CBT is also indicated, since it offers a low dose of radiation and allows the accomplishment of numerous anatomical cuts, contributing to a better investigation of this joint. Thus, the TCCB is an examination that provides benefits in several areas of dentistry, enabling progress in diagnostic imaging and bringing great technological advances to odontological radiodiagnosis(AU)

Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis.

Organ dysfunction is a major concern in sepsis pathophysiology and contributes to its high mortality rate. Neutrophil extracellular traps (NETs) have been implicated in endothelial damage and take part in the pathogenesis of organ dysfunction in several conditions. NETs also have an important role in counteracting invading microorganisms during infection. The aim of this study was to evaluate systemic NETs formation, their participation in host bacterial clearance and their contribution to organ dysfunction in sepsis. C57Bl/6 mice were subjected to endotoxic shock or a polymicrobial sepsis model induced by cecal ligation and puncture (CLP). The involvement of cf-DNA/NETs in the physiopathology of sepsis was evaluated through NETs degradation by rhDNase. This treatment was also associated with a broad-spectrum antibiotic treatment (ertapenem) in mice after CLP. CLP or endotoxin administration induced a significant increase in the serum concentrations of NETs. The increase in CLP-induced NETs was sustained over a period of 3 to 24 h after surgery in mice and was not inhibited by the antibiotic treatment. Systemic rhDNase treatment reduced serum NETs and increased the bacterial load in non-antibiotic-treated septic mice. rhDNase plus antibiotics attenuated sepsis-induced organ damage and improved the survival rate. The correlation between the presence of NETs in peripheral blood and organ dysfunction was evaluated in 31 septic patients. Higher cf-DNA concentrations were detected in septic patients in comparison with healthy controls, and levels were correlated with sepsis severity and organ dysfunction. In conclusion, cf-DNA/NETs are formed during sepsis and are associated with sepsis severity. In the experimental setting, the degradation of NETs by rhDNase attenuates organ damage only when combined with antibiotics, confirming that NETs take part in sepsis pathogenesis. Altogether, our results suggest that NETs are important for host bacterial control and are relevant actors in the pathogenesis of sepsis.

Estudo da sensibilização e da freqüência de aloanticorpos em pacientes candidatos ao transplante renal

A rejeição pelo hospedeiro ainda representa uma barreira para o completo sucesso do transplante de órgãos. A resposta humoral é causada pela produção de aloanticorpos, estando estes envolvidos tanto nas rejeições hiperagudas, agudas e crônicas. Um indivíduo é aloimunizado quando submetido a situações de exposição a estes aloantígenos (HLA ou MIC), como transfusões sanguíneas, transplantes prévios e gestações. O PRA (reatividade contra painel) é um método eficiente para detectar aloanticorpos no soro de pacientes que necessitem de um transplante. Para isso buscamos dentro de uma população de pacientes candidatos ao transplante renal a freqüência destes aloanticorpos e o perfil de sensibilização de cada paciente, inclusive a influência dos fatores sensibilizantes. Dos pacientes estudados entre os anos de 2008, 2009 e 2010, encontramos a presença de aloanticorpos Anti-HLA em 60% e de anti-MIC em 44% dos mesmos. Sendo que a maioria dos anticorpos estava direcionada contra HLA de classe I, presenteando 56%, sendo que destes 28% também apresentavam Anti-HLA de classe II. Dos pacientes que não estavam sensibilizados para anti-HLA, 64% também não possuíam anti-MIC. Quanto à sensibilização, vimos dentre os pacientes triados positivamente, cerca de 20% apresentavam pra de baixo risco, 43% apresentavam pra maior que 10% e menor que 50%, e os demais foram considerados hipersensibilizados. Quando avaliados os fatores aloimunizantes, vimos que gestações e transfusões estão ligadas aos pacientes sensibilizados, enquanto o retransplante está ligado ao perfil de hipersensibilização de alto risco. Quanto à freqüência de aloanticorpos Anti-HLA, o Anti-HLA B foi o mais freqüente dentre os demais Anti-HLA de classe I, sendo que o Anti-HLA DR, o mais freqüente dos anticorpos direcionados a classe II. O Anti-HLA de classe I mais freqüentes foram: Anti-HLA A23, B58 e Cw4, sendo que os menos freqüentes foram anti-HLA A74, B46 e Cw5. Os anticorpos mais freqüentes direcionado para a...

O processo de regulamentação da assistência médica suplementar no Brasil / the regulation process of the supplementary medical assistance in Brazil

O objetivo do estudo foi o desenvolvimento de investigações sobre a construção da assistência médica suplementar no Brasil e sua respectiva regulação, a partir de pesquisas acadêmicas disponíveis a respeito desse segmento do sistema de saúde, publicações das entidades representativas das operadoras, artigos publicados e dados estatísticos gerados pela agência Nacional de Saúde Suplementar - ANS e pelas próprias operadoras...

O Processo de regulamentação da Assistência Médica Suplementar no Brasil / The regulation process of the supplementary medical assistance in Brazil

OBJETIVO: O objetivo do estudo foi o desenvolvimento de investigações sobre a construção da assistência médica suplementar no Brasil e sua respectiva regulação, a partir de pesquisas acadêmicas disponíveis a respeito desse segmento do sistema de saúde, publicações das entidades representativas das operadoras, artigos publicados e dados estatísticos gerados pela Agência Nacional de Saúde Suplementar - ANS e pelas pró- prias operadoras. CONCLUSÃO: O mercado de planos e seguros de saúde apresentou um crescimento significativo nas últimas décadas, demandando do poder público a construção de um novo regime regulador, fato que traz a necessidade de aprofundar os conhecimentos dessa área, traçando um panorama da situação atual do setor e suas tendências no contexto da realidade do País, bem como procedendo à análise da dinâmica dessa expansão recente e suas possíveis repercussões na implantação do Sistema Único de Saúde ­ SUS.

OBJECTIVE: The aim of the study was the development of investigations over the construction of the supplementary medical assistance in Brazil and its respective regulation, beginning with available academic researches on this segment of the health system, publishings of the representative entities of the operators, published articles and statistical data produced by the Supplementary National Health Agency ­ (ANS) and by the operators themselves. CONCLUSION: The health and insurance plans market showed an important increase in the last decades, demanding from the authorities the construction of a new regulator norm, a fact that brings out the necessity to increase the knowledge on this area, plotting a picture of the present situation and its tendencies in the context of the Nation's reality, as well as proceeding in the analysis of the dynamics of this recent expansion and its possible repercussions in the Sole Health System ­ SUS implantation.