Anti-RBD IgG antibodies from endemic coronaviruses do not protect against the acquisition of SARS-CoV-2 infection among exposed uninfected individuals.

Background: The Coronaviridae family comprises seven viruses known to infect humans, classified into alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1), which are considered endemic. Additionally, it includes SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome), and the novel coronavirus SARS-CoV-2, responsible for COVID-19. SARS-CoV-2 induces severe respiratory complications, particularly in the elderly, immunocompromised individuals and those with underlying diseases. An essential question since the onset of the COVID-19 pandemic has been to determine whether prior exposure to seasonal coronaviruses influences immunity or protection against SARS-CoV-2. Methods: In this study, we investigated a cohort of 47 couples (N=94), where one partner tested positive for SARS-CoV-2 infection via real-time PCR while the other remained negative. Plasma samples, collected at least 30 days post-PCR reaction, were assessed using indirect ELISA and competition assays to measure specific antibodies against the receptor-binding domain (RBD) portion of the Spike (S) protein from SARS-CoV-2, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1. Results: IgG antibody levels against the four endemic coronavirus RBD proteins were similar between the PCR-positive and PCR-negative individuals, suggesting that IgG against endemic coronavirus RBD regions was not associated with protection from infection. Moreover, we found no significant IgG antibody cross-reactivity between endemic coronaviruses and SARS-CoV-2 RBDs. Conclusions: Taken together, results suggest that anti-RBD antibodies induced by a previous infection with endemic HCoVs do not protect against acquisition of COVID-19 among exposed uninfected individuals.

The glycosaminoglycan-binding chemokine fragment CXCL9(74-103) reduces inflammation and tissue damage in mouse models of coronavirus infection.

Introduction: Pulmonary diseases represent a significant burden to patients and the healthcare system and are one of the leading causes of mortality worldwide. Particularly, the COVID-19 pandemic has had a profound global impact, affecting public health, economies, and daily life. While the peak of the crisis has subsided, the global number of reported COVID-19 cases remains significantly high, according to medical agencies around the world. Furthermore, despite the success of vaccines in reducing the number of deaths caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there remains a gap in the treatment of the disease, especially in addressing uncontrolled inflammation. The massive recruitment of leukocytes to lung tissue and alveoli is a hallmark factor in COVID-19, being essential for effectively responding to the pulmonary insult but also linked to inflammation and lung damage. In this context, mice models are a crucial tool, offering valuable insights into both the pathogenesis of the disease and potential therapeutic approaches. Methods: Here, we investigated the anti-inflammatory effect of the glycosaminoglycan (GAG)-binding chemokine fragment CXCL9(74-103), a molecule that potentially decreases neutrophil transmigration by competing with chemokines for GAG-binding sites, in two models of pneumonia caused by coronavirus infection. Results: In a murine model of betacoronavirus MHV-3 infection, the treatment with CXCL9(74-103) decreased the accumulation of total leukocytes, mainly neutrophils, to the alveolar space and improved several parameters of lung dysfunction 3 days after infection. Additionally, this treatment also reduced the lung damage. In the SARS-CoV-2 model in K18-hACE2-mice, CXCL9(74-103) significantly improved the clinical manifestations of the disease, reducing pulmonary damage and decreasing viral titers in the lungs. Discussion: These findings indicate that CXCL9(74-103) resulted in highly favorable outcomes in controlling pneumonia caused by coronavirus, as it effectively diminishes the clinical consequences of the infections and reduces both local and systemic inflammation.

Is There a Relationship Between Birth Quartile and Vertical Jump Performance Among Young Male Elite Volleyball Athletes?

Vertical jump is an important skill that influences volleyball performance. In this study, we analyzed the relationship between vertical jump performance and birth quartile of Brazilian male youth volleyball players. We calculated chi-square goodness-of-fit tests to compare the athletes' birthdate distributions in quarters of their birth years (Q1, Q2, Q3, and Q4) according to player age categories (U17, U18, U19, and U21). We calculated one-way ANOVAs to compare spike jump and block jump heights of players born in different quarters of the same year. Overall, we found a relative age effect (i.e., more players with birth dates early in the birth year) in U17 (p < .001), U18 (p < .001), U19 (p < .001), and U21 (p = .04). Regarding vertical jump performance, U18 athletes born in Q2 reached higher spike jump heights (p = .006) and block jump heights (p = .002) than athletes born in Q4, and U19 athletes born in Q1 reached higher block jump heights than athletes born in Q3 (p = .049). There were no significant differences in vertical jump performance across birth quartiles among U17 and U21 athletes. Thus, a relative age effect was present in all age categories but not always reflected in vertical jump performance. Volleyball coaches and policymakers are still advised to employ strategies to ensure fairer opportunities for players born later in the year of their eligibility dates, as we found RAE to be sometimes, but not always, related to higher spike or block jump heights even among these older adolescents and young adult athletes.

A clindamycin acetylated derivative with reduced antibacterial activity inhibits articular hyperalgesia and edema by attenuating neutrophil recruitment, NF-κB activation and tumor necrosis factor-α production.

We recently demonstrated that clindamycin exhibits activities in acute and chronic models of pain and inflammation. In the present study, we investigated the effects of clindamycin and a clindamycin acetylated derivative (CAD) in models of acute joint inflammation and in a microbiological assay. Joint inflammation was induced in mice by intraarticular (i.a.) injection of zymosan or lipopolysaccharide (LPS). Clindamycin or CAD were administered via the intraperitoneal route 1 h before zymosan or LPS. Paw withdrawal threshold, joint diameter, histological changes, neutrophil recruitment, tumor necrosis factor-α (TNF-α) production and phosphorylation of the IκBα and NF-κB/p65 were evaluated. In vitro assays were used to measure the antibacterial activity of clindamycin and CAD and also their effects on zymosan-induced TNF-α production by RAW264.7 macrophages. Clindamycin exhibited activity against Staphylococcus aureus and Salmonella Typhimurium ATCC® strains at much lower concentrations than CAD. Intraarticular injection of zymosan or LPS induced articular hyperalgesia, edema and neutrophil infiltration in the joints. Zymosan also induced histological changes, NF-κB activation and TNF-α production. Responses induced by zymosan and LPS were inhibited by clindamycin (200 and 400 mg/kg) or CAD (436 mg/kg). Both clindamycin and CAD inhibited in vitro TNF-α production by macrophages. In summary, we provided additional insights of the clindamycin immunomodulatory effects, whose mechanism was associated with NF-κB inhibition and reduced TNF-α production. Such effects were extended to a clindamycin derivative with reduced antibacterial activity, indicating that clindamycin derivatives should be investigated as candidates to drugs that could be useful in the management of inflammatory and painful conditions.

Does Relative Age Effect Exist in Paralympic Sport? A Study With Brazilian Paralympic Swimmers.

A Relative Age Effect (RAE), by which young athletes with birthdates early in a calendar year have experienced a team selection advantage that persists throughout their careers, has been found to be prevalent in many sports. However, this phenomenon has not been investigated in the Paralympic sports context. Thus, we aimed to investigate the prevalence of RAE among male and female Brazilian Paralympic swimmers. Data from 694 ranked athletes were collected from the 2021 Brazilian Paralympic Swimmers National rankings. Athletes' birthdates were divided into four quarters (Q1, Q2, Q3, and Q4) according to their month of birth. Chi-Square (χ2) goodness-of-fit tests were used to compare the observed and expected distributions of athletes born in each quarter, based on sex (male and female), impairment type (physical, visual, and intellectual), and swim stroke competition (freestyle, medley, backstroke, butterfly, and breaststroke). The observed birthdates distributions were different from expected in males (χ2 = 11.647; p = 0.009) and females (χ2 = 8.899; p = 0.031), for athletes with physical impairments (χ2 = 10.443; p = 0.015); and for athletes who competed in freestyle (χ2 = 16.683; p = 0.001), medley (χ2 = 12.343; p = 0.006) and backstroke (χ2 = 8.025; p = 0.045) races. Even though our results demonstrated asymmetric distributions of Brazilian Paralympic swimmers' birthdates in many of the analyses, we could not establish the classical prevalence of athletes born at the beginning of the year that defines RAE. Therefore, the selection process of Brazilian Paralympic swimmers does not seem to be influenced by the athletes' time of birth.

Age-related accumulation of B-1 cell progenitors in mice reflects changes in miR15a/16-1 expression and radioresistance capacity.

Hyperproliferative diseases such as Chronic Lymphocytic Leukemia (CLL) and Systemic Lupus Erythematosus (SLE) are potentially related to some disturbance in the apoptosis pathway, specifically in B-1a cells (CD5+). Accumulation of B-1a cells in lymphoid organs, bone marrow or periphery is observed in some leukemia experimental murine models along aging. It is known that aging also increases the healthy B-1 cell population. However, it is not yet clear if it happens due to self-renewal of mature cells or proliferation of progenitor cells. Herein we demonstrated that the B-1 cell precursor population (B-1p) from bone marrow of middle-aged mice is higher than from young mice. Also, these aged cells are more resistant to irradiation and have downregulation of microRNA15a/16. Alterations in these microRNAs expression and in Bcl-2 regulation were already described in human hematological malignancies and new therapeutically approaches focus on that axis. This finding could explain the early events related to cell transformation during aging and correlate with beginning of symptoms in hyperproliferative diseases. Moreover, studies have already reported these pro-B-1 as a contributor to the origin of other leukemia (Acute Myeloid Leukemia - AML). Our results point to a possible relation between B-1 cell precursors and hyperproliferation during aging. We hypothesized that this population could be maintained until the mature status of the cell or reveal changes that result in re-activation of precursor in adult bone marrow, culminating in accumulation of B-1 cells later. Based on this, B-1 cell progenitor could represent an origin for B cell malignancies and a new candidate target to diagnose and treatments in the future.

ZnO-Based Electrochemical Immunosensor to Assess Vaccine-Induced Antibody-Mediated Immunity against Wild-Type and Gamma SARS-CoV-2 Strains.

The evaluation of serological responses to COVID-19 is crucial for population-level surveillance, developing new vaccines, and evaluating the efficacy of different immunization programs. Research and development of point-of-care test technologies remain essential to improving immunity assessment, especially for SARS-CoV-2 variants that partially evade vaccine-induced immune responses. In this work, an impedimetric biosensor based on the immobilization of the recombinant trimeric wild-type spike protein (S protein) on zinc oxide nanorods (ZnONRs) was employed for serological evaluation. We successfully assessed its applicability using serum samples from spike-based COVID-19 vaccines: ChAdOx1-S (Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech). Overall, the ZnONRs/ spike-modified electrode displayed accurate results for both vaccines, showing excellent potential as a tool for assessing and monitoring seroprevalence in the population. A refined outcome of this technology was achieved when the ZnO immunosensor was functionalized with the S protein from the P.1 linage (Gamma variant). Serological responses against samples from vaccinated individuals were acquired with excellent performance. Following studies based on traditional serological tests, the ZnONRs/spike immunosensor data reveal that ChAdOx1-S vaccinated individuals present significantly less antibody-mediated immunity against the Gamma variant than the BNT162b2 vaccine, highlighting the great potential of this point-of-care technology for evaluating vaccine-induced humoral immunity against different SARS-CoV-2 strains.

Influência do efeito da idade relativa no futsal masculino escolar de Mato Grosso: análise de acordo com a categoria / Influence of the relative age effect on male school futsal in Mato Grosso: a category-based analysis / Influencia del efecto de la edad relativa en el fútbol sala escolar masculino de Mato Grosso: análisis de acuerdo con la categoría

O objetivo deste estudo foi analisar a existência e a influência do Efeito da Idade Relativa (EIR) em estudantes-atletas de futsal masculino de Mato Grosso de acordo com a categoria etária. A amostra foi composta por 486 estudantes-atletas masculinos de futsal de Mato Grosso das categorias A (15 a 17 anos) e B (12 a 14 anos) que disputaram os Jogos Escolares Mato-grossenses e os Jogos Estudantis de Seleções Mato-Grossenses de 2021. Para análise, foram realizados testes qui-quadrado (χ2) de aderência. Os resultados mostraram a presença do EIR na análise geral e nas categorias A e B, com maior representação de atletas nascidos no primeiro trimestre do ano. Conclui-se que o EIR é um fenômeno presente em estudantes-atletas de futsal masculino do estado de Mato Grosso.

The objective of this study was to analyze the existence and influence of the Relative Age Effect (RAE) in male Mato Grosso's futsal student-athletes according to age category. The sample consisted of 486 male futsal student-athletes from Mato Grosso, in categories A (15 to 17 years old) and B (12 to 14 years old) who competed in the 2021 Mato Grosso School Games and the Mato Grosso Student Selections Games. For analysis, chi-square (χ2) goodness of fit tests were performed. Results showed the presence of RAE in the overall analysis and in categories A and B, with a greater representation of athletes born in the first quarter of the year. It is concluded that RAE is a phenomenon present in male futsal student-athletes in the state of Mato Grosso.

El objetivo de este estudio fue analizar la existencia e influencia del Efecto de la Edad Relativa (EER) en estudiantes-atletas de fútbol sala masculino de Mato Grosso de acuerdo con la categoría de edad. La muestra estuvo compuesta por 486 estudiantes-atletas masculinos de fútbol sala de Mato Grosso de las categorías A (15 a 17 años) y B (12 a 14 años) que compitieron en los Juegos Escolares de Mato Grosso y los Juegos Estudiantiles de Selecciones de Mato-Grosso (Brasil) de 2021. Para el análisis, se realizaron pruebas estadísticas de ajuste chi-cuadrado (χ2). Los resultados mostraron la presencia del EER en el análisis general y en las categorías A y B, con una mayor representación de atletas nacidos en el primer trimestre del año. Se concluye que el EER es un fenómeno presente en estudiantes-atletas de fútbol sala masculino del estado de Mato Grosso.

Ouratea spectabilis and its Biflavanone Ouratein D Exert Potent Anti-inflammatory Activity in MSU Crystal-induced Gout in Mice.

Gouty arthritis (GA) is an inflammatory arthritis triggered by the deposition of monosodium urate monohydrate (MSU) crystals, causing pain, inflammation, and joint damage. Several drugs are currently employed to manage acute flares of GA, but they either have limited effectiveness or induce severe adverse reactions. Ouratea spectabilis is traditionally used in Brazil to treat gastric ulcers and rheumatism. The ethanolic extract of O. spectabilis stems (OSpC) and four biflavanones (ouratein A - D) isolated thereof were evaluated in a murine model of GA induced by the injection of MSU crystals. The underlying mechanism of action of ouratein D was investigated in vitro in cell cultures by measurement of IL-1ß levels by ELISA and Western blot analysis. The administration of OSpC (10, 30 or 100 mg/Kg, p. o.) reduced the migration of total inflammatory cells, monocytes, and neutrophils and diminished the levels of IL-1ß and CXCL1 in the synovial tissue. Among the tested compounds, only ouratein D (1 mg/Kg) reduced the migration of the inflammatory cells and it was shown to be active up to 0.01 mg/Kg (equivalent to 0.34 nM/Kg, p. o.). Treatment of pre-stimulated THP-1 cells (differentiated into macrophages) or BMDMs with ouratein D reduced the release of IL-1ß in both macrophage lines. This biflavanone reduced the activation of caspase-1 (showed by the increase in the cleaved form) in supernatants of cultured BMDMs, evidencing its action in modulating the inflammasome pathway. The obtained results demonstrate the anti-gout properties of O. spectabilis and point out ouratein D as the bioactive component of the assayed extract.

The Relative Age Effect in Male and Female Brazilian Elite Volleyball Athletes of Varied Competitive Levels.

Volleyball is a popular sport in Brazil, and the relative age effect (RAE) is known to occur within it; but less is known of how RAE relates to elite Brazilian volleyball players' age, sex, and competitive levels. We aimed to investigate RAE prevalence with data from two seasons of play among players in the Superliga A (2020/2021 and 2021/2022 seasons), and Superliga B (2021 and 2022 seasons) made available from the Brazilian Volleyball Confederation (CBV), the club's official website, or direct consultation with the CBV. After removing duplicate data, we grouped these 1,063 athletes by their dates of birth, sex, and competition level (Superliga A or B). We divided players' birth dates into quarters (Q1: January-March, Q2: April-June, Q3: July-September and Q4: October-December) and into semesters, and we performed chi-square (χ2) tests to investigate RAE prevalence according to the players' sex and competitive level. RAE was prevalent overall (χ2 = 33.198; p < .001), among males (χ2 = 24.48; p < .001) and females (χ2 = 11.23; p < .011). Regarding competition level, RAE was evident among males in both Superliga A (χ2 = 14.581; p = 0.002), and B (χ2 = 13.985; p = 0.003), and among females in Superliga B (χ2 = 9.204; p = 0.027), but not Superliga A (χ2 = 4.012; p = 0.26). Thus, the RAE phenomenon operated differently for male and female Brazilian volleyball players according to their competitive level. We discuss the implications of these findings.

Electrochemical Immunosensors Based on Zinc Oxide Nanorods for Detection of Antibodies Against SARS-CoV-2 Spike Protein in Convalescent and Vaccinated Individuals.

Even after over 2 years of the COVID-19 pandemic, research on rapid, inexpensive, and accurate tests remains essential for controlling and avoiding the global spread of SARS-CoV-2 across the planet during a potential reappearance in future global waves or regional outbreaks. Assessment of serological responses for COVID-19 can be beneficial for population-level surveillance purposes, supporting the development of novel vaccines and evaluating the efficacy of different immunization programs. This can be especially relevant for broadly used inactivated whole virus vaccines, such as CoronaVac, which produced lower titers of neutralizing antibodies. and showed lower efficacy for specific groups such as the elderly and immunocompromised. We developed an impedimetric biosensor based on the immobilization of SARS-CoV-2 recombinant trimeric spike protein (S protein) on zinc oxide nanorod (ZnONR)-modified fluorine-doped tin oxide substrates for COVID-19 serology testing. Due to electrostatic interactions, the negatively charged S protein was immobilized via physical adsorption. The electrochemical response of the immunosensor was measured at each modification step and characterized by scanning electron microscopy and electrochemical techniques. We successfully evaluated the applicability of the modified ZnONR electrodes using serum samples from COVID-19 convalescent individuals, CoronaVac-vaccinated with or without positive results for SARS-CoV-2 infection, and pre-pandemic samples from healthy volunteers as controls. ELISA for IgG anti-SARS-CoV-2 spike protein was performed for comparison, and ELISA for IgG anti-RBDs of seasonal coronavirus (HCoVs) was used to test the specificity of immunosensor detection. No cross-reactivity with HCoVs was detected using the ZnONR immunosensor, and more interestingly, the sensor presented higher sensitivity when compared to negative ELISA results. The results demonstrate that the ZnONRs/spike-modified electrode displayed sensitive results for convalescents and vaccinated samples and shows excellent potential as a tool for the population's assessment and monitoring of seroconversion and seroprevalence.

Dependência e política social no Brasil: reflexões sobre os desafios do Serviço Social / Addiction and social policy in Brazil: reflections on the challenges of Social Work

Resumo: Objetivamos realizar uma reflexão sobre os desafios enfrentados para a materialização da política social no Brasil. Embasamo-nos nas leituras de Rui Mauro Marini e Florestan Fernandes quanto ao entendimento da formação econômico-social brasileira. Em nossos resultados, destacamos que a condição dependente, com presença da autocracia burguesa, imprime a manutenção da superexploração da força de trabalho e o aviltamento das políticas sociais em detrimento da acumulação capitalista.

Abstract: We aim to carry out a reflection on the challenges faced for the materialization of social policy in Brazil. We base ourselves on the readings of Rui Mauro Marini and Florestan Fernandes in understanding the Brazilian socio-economic formation. In our results, we highlight that the dependent condition, with the presence of bourgeois autocracy, diminishes the maintenance of the super-exploitation of the work force, and in the debasement of social policy to the detriment of capitalist accumulation.

The Therapeutic Effect of Phosphopeptide P140 Attenuates Inflammation Induced by Uric Acid Crystals in Gout Arthritis Mouse Model.

Gout is a painful form of inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints. The aim of this study was to investigate the effect of peptide P140 on the inflammatory responses in crystal-induced mouse models of gout and cell models including MSU-treated human cells. Injection of MSU crystals into the knee joint of mice induced neutrophil influx and inflammatory hypernociception. Injection of MSU crystals subcutaneously into the hind paw induced edema and increased pro-inflammatory cytokines levels. Treatment with P140 effectively reduced hypernociception, the neutrophil influx, and pro-inflammatory cytokine levels in these experimental models. Furthermore, P140 modulated neutrophils chemotaxis in vitro and increased apoptosis pathways through augmented caspase 3 activity and reduced NFκB phosphorylation. Moreover, P140 increased the production of the pro-resolving mediator annexin A1 and decreased the expression of the autophagy-related ATG5-ATG12 complex and HSPA8 chaperone protein. Overall, these findings suggest that P140 exerts a significant beneficial effect in a neutrophilic inflammation observed in the model of gout that can be of special interest in the design of new therapeutic strategies.

Prevalence of the Relative Age Effect in Elite Brazilian Volleyball: An Analysis Based on Gender, the Playing Position, and Performance Indicators.

Athletes born closer to an arbitrary cut-off date are more likely to reach an elite level in sport, which is supported by a phenomenon called the relative age effect (RAE). It is important to determine whether this phenomenon is present in a sport to minimize this selection bias. This study aimed to investigate the prevalence of RAE in elite volleyball athletes, considering the influence of gender, the playing position (Setter, Middle, Libero, Opposite, and Outside Hitter) and the performance level (attack points, aces, and block points). The sample comprised 203 male and 193 female athletes competing in the Superliga A in the 2020/2021 season, which was equivalent to all of the teams of the championship. The data collection was performed during May and June, 2021. Athletes were organized according to gender, the playing position, and performance in the Superliga. For performance variables, athletes were separated based on the median value (90.0), and classified as high- or low-performance. Chi-squared tests were performed to verify differences between birth date distributions in relation to the aforementioned variables. Results indicated overrepresentation of relatively older male athletes (Q1 = 35.96%; Q2 = 27.59%; Q3 = 19.21%; Q4 = 17.24%), especially in Middles, Opposites, and Outside Hitters, regardless of their performance level. Considering females, no differences were found. Our findings suggest that RAE operates differently for men and women in elite Brazilian volleyball. The characteristics of the games played by male and female elite athletes may lead to different talent selection processes, affecting the likelihood of RAE prevalence.

Absence of CCR2 Promotes Proliferation of Alveolar Macrophages That Control Lung Inflammation in Acute Respiratory Distress Syndrome in Mice.

Acute respiratory distress syndrome (ARDS) consists of uncontrolled inflammation that causes hypoxemia and reduced lung compliance. Since it is a complex process, not all details have been elucidated yet. In a well-controlled experimental murine model of lipopolysaccharide (LPS)-induced ARDS, the activity and viability of macrophages and neutrophils dictate the beginning and end phases of lung inflammation. C-C chemokine receptor type 2 (CCR2) is a critical chemokine receptor that mediates monocyte/macrophage activation and recruitment to the tissues. Here, we used CCR2-deficient mice to explore mechanisms that control lung inflammation in LPS-induced ARDS. CCR2-/- mice presented higher total numbers of pulmonary leukocytes at the peak of inflammation as compared to CCR2+/+ mice, mainly by enhanced influx of neutrophils, whereas we observed two to six-fold lower monocyte or interstitial macrophage numbers in the CCR2-/-. Nevertheless, the time needed to control the inflammation was comparable between CCR2+/+ and CCR2-/-. Interestingly, CCR2-/- mice presented higher numbers and increased proliferative rates of alveolar macrophages from day 3, with a more pronounced M2 profile, associated with transforming growth factor (TGF)-ß and C-C chemokine ligand (CCL)22 production, decreased inducible nitric oxide synthase (Nos2), interleukin (IL)-1ß and IL-12b mRNA expression and increased mannose receptor type 1 (Mrc1) mRNA and CD206 protein expression. Depletion of alveolar macrophages significantly delayed recovery from the inflammatory insult. Thus, our work shows that the lower number of infiltrating monocytes in CCR2-/- is partially compensated by increased proliferation of resident alveolar macrophages during the inflammation control of experimental ARDS.

The oldest unvaccinated Covid-19 survivors in South America.

BACKGROUND: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. RESULTS: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. CONCLUSION: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

Potent anti-inflammatory activity of the lectin-like domain of TNF in joints.

In view of the crucial role of tumor necrosis factor (TNF) in joint destruction, TNF inhibitors, including neutralizing anti-TNF antibodies and soluble TNF receptor constructs, are commonly used therapeutics for the treatment of arthropathies like rheumatoid arthritis (RA). However, not all patients achieve remission; moreover, there is a risk of increased susceptibility to infection with these agents. Spatially distinct from its receptor binding sites, TNF harbors a lectin-like domain, which exerts unique functions that can be mimicked by the 17 residue solnatide peptide. This domain binds to specific oligosaccharides such as N'N'-diacetylchitobiose and directly target the α subunit of the epithelial sodium channel. Solnatide was shown to have anti-inflammatory actions in acute lung injury and glomerulonephritis models. In this study, we evaluated whether the lectin-like domain of TNF can mitigate the development of immune-mediated arthritis in mice. In an antigen-induced arthritis model, solnatide reduced cell influx and release of pro-inflammatory mediators into the joints, associated with reduction in edema and tissue damage, as compared to controls indicating that TNF has anti-inflammatory effects in an acute model of joint inflammation via its lectin-like domain.

O papel da sociedade civil na inovação e incorporação de dispositivos médicos no Brasil / The role of civil society in the innovation and incorporation of medical devices in Brazil

Objetivo: Abordar o contexto normativo quanto aos processos de participação social nas fases de Pesquisa, Desenvolvimento e Inovação (PD&I) e aos processos de regulação sanitária e de avaliação para incorporação de tecnologias no Sistema Único de Saúde (SUS). Métodos: Pesquisa exploratória descritiva com revisão dos referenciais normativos e análise documental: i) nos marcos regulatórios de inovação brasileiros; ii) na regulação sanitária pela Agência Nacional de Vigilância Sanitária (Anvisa); e iii) na avaliação e incorporação de dispositivos médicos na Comissão Nacional de Incorporação de Tecnologias em Saúde no SUS (Conitec). Resultados: Nos sites das instituições governamentais de fomento à Ciência, Tecnologia e Inovação (CT&I) vinculadas ao Ministério da Ciência, Tecnologia e Inovações (MCTI), observaram-se mecanismos de participação social estabelecidos na legislação. No contexto regulatório, a participação social se insere desde a construção dos regulamentos até etapas-chave do ciclo de vida da tecnologia. Na avaliação de tecnologias, verificou-se ampliação das estratégias de participação, a exemplo da "perspectiva do paciente" na plenária. Entre 64 chamadas públicas realizadas, cinco foram sobre dispositivos médicos. Conclusão: Evidenciou-se a importância da participação social em todas etapas do ciclo de vida dos dispositivos médicos, tendo em vista as especificidades dessas tecnologias. A Anvisa e a Conitec têm ampliado os mecanismos de participação para além dos preconizados em lei. Já nas etapas de PD&I, as iniciativas são incipientes, sendo localizadas ações conforme previsão legal. A ampliação de mecanismos de participação efetiva favorece a construção de soluções para minimizar os desafios de saúde, além de promover maior transparência, valor para a sociedade e confiança nas decisões em saúde brasileira.

Objective: To address the normative context regarding the processes of social participation in the phases of Research, Development and Innovation (RD&I), sanitary regulation and assessment for incorporation of technologies into SUS. Methods: Descriptive exploratory research with review of normative references and document analysis: i) in the regulatory milestones of Brazilian Innovation; ii) sanitary regulation by the National Health Surveillance Agency (Anvisa); and iii) in the assessment and incorporation of medical devices in the National Committee for Health Technology Incorporation into SUS (Conitec). Results: In the websites of government institutions that support RD&I linked to the MCTI, mechanisms of social participation established in the legislation were observed. In the regulatory context, social participation is inserted since the construction of regulations until key stages of the technology lifecycle. In the assessment of medical devices, we verified an expansion of engagement strategies, such as the "patient perspective" in the plenary meeting. From its 64 public calls, five were directed to medical devices. Conclusion: The importance of social participation in the

Modular Label-Free Electrochemical Biosensor Loading Nature-Inspired Peptide toward the Widespread Use of COVID-19 Antibody Tests.

Limitations of the recognition elements in terms of synthesis, cost, availability, and stability have impaired the translation of biosensors into practical use. Inspired by nature to mimic the molecular recognition of the anti-SARS-CoV-2 S protein antibody (AbS) by the S protein binding site, we synthesized the peptide sequence of Asn-Asn-Ala-Thr-Asn-COOH (abbreviated as PEP2003) to create COVID-19 screening label-free (LF) biosensors based on a carbon electrode, gold nanoparticles (AuNPs), and electrochemical impedance spectroscopy. The PEP2003 is easily obtained by chemical synthesis, and it can be adsorbed on electrodes while maintaining its ability for AbS recognition, further leading to a sensitivity 3.4-fold higher than the full-length S protein, which is in agreement with the increase in the target-to-receptor size ratio. Peptide-loaded LF devices based on noncovalent immobilization were developed by affording fast and simple analyses, along with a modular functionalization. From studies by molecular docking, the peptide-AbS binding was found to be driven by hydrogen bonds and hydrophobic interactions. Moreover, the peptide is not amenable to denaturation, thus addressing the trade-off between scalability, cost, and robustness. The biosensor preserves 95.1% of the initial signal for 20 days when stored dry at 4 °C. With the aid of two simple equations fitted by machine learning (ML), the method was able to make the COVID-19 screening of 39 biological samples into healthy and infected groups with 100.0% accuracy. By taking advantage of peptide-related merits combined with advances in surface chemistry and ML-aided accuracy, this platform is promising to bring COVID-19 biosensors into mainstream use toward straightforward, fast, and accurate analyses at the point of care, with social and economic impacts being achieved.