Molecular Epidemiology of Mayaro Virus among Febrile Patients, Roraima State, Brazil, 2018-2021.

We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018-2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that these cases were caused by genotype D. Improved surveillance is needed to better determine the burden of MAYV in the Amazon Region.

A flow cytometry-based assay to measure neutralizing antibodies against SARS-CoV-2 virus.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has highlighted the need for serological assays that can accurately evaluate the neutralizing efficiency of antibodies produced during infection or induced by vaccines. However, conventional assays often require the manipulation of live viruses on a level-three biosafety (BSL3) facility, which presents practical and safety challenges. Here, we present a novel, alternative assay that measures neutralizing antibodies (NAbs) against SARS-CoV-2 in plasma using flow cytometry. This assay is based on antibody binding to the S protein and has demonstrated precision in both intra- and inter-assay measurements at a dilution of 1:50. The cut-off was determined using Receiver Operating Characteristic (ROC) analysis and the value of 36.01% has shown high sensitivity and specificity in distinguishing between pre-pandemic sera, COVID-19 patients, and vaccinated individuals. The efficiency significantly correlates with the gold standard test, PRNT. Our new assay offers a safe and efficient alternative to conventional assays for evaluating NAbs against SARS-CoV-2.

Onde está o sujeito? Reflexões sobre o materialismo e a dialética / Where's the subject? Reflections on materialism and dialectics / ¿Dónde está el sujeto? Reflexiones sobre el materialismo y la dialéctica

Buscamos uma análise acerca dos desdobramentos da questão do sujeito à luz das diversas críticas que a ela se levantaram nos anos pós-estruturalistas e diante da ascensão do neoliberalismo como ideologia dominante em todo o mundo. Relegada como questão metafísica da modernidade, ou como resíduo do cientificismo positivista, a categoria de sujeito tem sido notadamente objeto de desconstrução, ou, quando não, de simples rejeição. Se apoiando sobre um duplo questionamento, de sua possível pertinência para o pensamento psicológico e filosófico atual, como dos possíveis atores da transformação social diante das transformações sofridas que o capitalismo tardio impõe à categoria de proletariado, através do pensamento de Alain Badiou e Slavoj Zizek, tentamos afastar a tendência linguística que hoje pauta grande parte das análises sobre o sujeito e os processos subjetivos para tentar apontar a importância de uma teoria das verdades que renove as bases ontológicas do pensamento e a visão sobre a dialética materialista. Uma teoria do sujeito assentada sobre um conceito de verdade se mostra assim um potencial para repensar o homem enquanto criador. (AU)

We seek an analysis of the developments surrounding the issue of the subject in light of various critiques that have emerged in the post-structuralist years and in the face of the rise of neoliberalism as the dominant ideology worl-dwide. Relegated as a metaphysical question of modernity or as a residue of positivist scientism, the category of the subject has notably been a target of deconstruction, or, when not, outright rejection. Grounded in a dual inquiry into its possible relevance for current psychological and philosophical thought, as well as the potential actors of social transformation in the face of the changes imposed by late capitalism on the proletariat category, through the prospectives of Alain Badiou and Slavoj Zizek, we attempt to move away from the linguistic trend that currently guides a significant portion of analyses on the subject and subjective processes. Our aim is to emphasize the importance of a theory of truths that renews the ontological foundations of thought and the perspective on dialectical materialism. A theory of the subject anchored in a concept of truth thus proves to be a potential avenue for rethinking man as a creator. (AU)

Buscamos un análisis del desarrollo del tema del sujeto a la luz de las diversas críticas que surgieron en los años postestructuralistas y ante el surgimiento del neoliberalismo como ideología dominante a nivel mundial. Relegada como cuestión metafísica de la modernidad, o como residuo del cientificismo positi-vista, la categoría de sujeto ha sido notablemente objeto de deconstrucción o, cuando no, de simple rechazo. Partiendo de un doble cuestionamiento, de su posible relevancia para el pensamiento psicológico y filosófico actual, como de los posibles actores de la transformación social frente a las transforma-ciones que el capitalismo tardío impone a la categoría de proletariado, a través del pensamiento de Alain Badiou y Slavoj Zizek , intentamos quitar la tendencia lingüística que hoy guía la mayoría de los análisis sobre el tema y los procesos subjetivos para intentar señalar la importancia de una teoría de las verdades que renueve las bases ontológicas del pensamiento y la mirada sobre la dialéctica materialista. Una teoría del sujeto basada en un concepto de verdad muestra así un potencial para repensar al hombre como creador. (AU)

Does cross-education minimize the loss of muscle force and power and sEMG amplitude during short-term detraining in older women who are recreationally engaged in resistance training?

This study aimed to investigate whether 4 weeks of unilateral resistance training (RT) could attenuate the decline in muscle function in the contralateral limb of older women recreationally engaged in RT compared to control group (CTL). Twenty-four participants completed a 10-week RT before the cross-education (CR-Edu) phase and subsequent detraining. Afterward, participants were randomized into two groups: CTL (n = 8 women, n = 16 legs) who underwent 4 weeks of detraining without any training, and CR-Edu (n = 16 women, n = 16 legs) who performed 4 weeks of unilateral RT. Muscle force, power, and surface electromyography were measured unilaterally before and after the 4-week period, using five repetitions conducted at 40% and 60% of the 1RM. The results showed a reduction in muscle force at both 40% and 60% of 1RM, as well as a decrease in power at 60% of 1RM (P-time < 0.05) without significant differences between the two groups (P interaction > 0.05). There was a decline in power at 60% of 1RM (P-time < 0.05) but no significant change at 40% of 1RM (P-time > 0.05), and again, no significant differences were observed between the groups (P-interaction > 0.05). The surface electromyography of vastus lateralis decreased only in the CTL group (P-interaction < 0.05). Older women recreationally engaged in RT who perform in unilateral leg extension compared to a brief period of detraining seem not to retain muscle force and power, and sEMG amplitude of their homologous and contralateral limb.

Magnetic signature and X-ray fluorescence for mapping trace elements in soils originating from basalt and sandstone.

The knowledge of the lithological context is necessary to interpret trace elements concentrations in the soil. Soil magnetic signature (χ) and soil X-ray fluorescence (XRF) are promising approaches in the study of the spatial variability of trace elements and the environmental monitoring of soil quality. This research aimed to assess the efficiency of measurements of χ and XRF sensors for spatial characterization of zinc (Zn), manganese (Mn), and copper (Cu) contents in soils of a sandstone-basalt transitional environment, using machine learning modeling. The studied area consisted of the Western Plateau of São Paulo (WPSP), with soils originating from sandstone and basalt. A total of 253 soil samples were collected at a depth of 0.0-0.2 m. The soils were characterized by particle size and chemical analysis: organic matter (OM), cation exchange capacity (CEC), ammonium oxalate-extracted iron (Feo), sodium dithionite-citrate-bicarbonate-extracted iron (Fed), and sulfuric acid-extracted iron (Fet). Hematite (Hm), goethite (Gt), kaolinite (Kt), and gibbsite (Gb) contents were obtained by X-ray diffraction (XRD). Magnetite (Mt) and maghemite (Mh) contents were obtained by soil χ, while trace elements contents were obtained by XRF and predicted by χ. Descriptive analysis, the test of means, and correlation were performed between attributes. Zn, Mn, and Cu contents were predicted using the machine learning algorithm random forest, and the spatial variability was obtained using the ordinary kriging interpolation technique. Landscape dissections influenced iron oxides, which had the highest contents in slightly dissected environments. Trace elements contents were not influenced by landscape dissections, demonstrating that lithological knowledge is necessary to characterize trace elements in soils. The prediction models developed through the machine learning algorithm random forest showed that χ can be used to characterize trace elements. The similar spatial pattern of trace elements obtained by XRF and χ measurements confirm the applicability of these sensors for mapping it under lithological and landscape transition, aiming for sustainable strategic planning of land use and occupation.

SARS-CoV-2 uses CD4 to infect T helper lymphocytes.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.

Biochemical and Microbiological Aspects of the Oral Cavity of Children and Young People with Neurological Impairment and Oropharyngeal Dysphagia.

The components and the salivary flow have a direct influence on the composition of the oral microbiota of children and young people with oropharyngeal dysphagia, and studies have already demonstrated the excessive accumulation of supragingival dental calculus in individuals with enteral nutrition. This study aimed to compare the oral hygiene, biochemical, and microbiological aspects of the oral cavity of children and young people with neurological impairment and oropharyngeal dysphagia. Forty children and young people with neurological impairment and oropharyngeal dysphagia were enrolled and divided into two groups: group I, encompassing 20 participants fed via gastrostomy; and group II, encompassing 20 participants fed via the oral route. Oral hygiene and salivary pH and flow were assessed, and a polymerase chain reaction was performed to evaluate the messenger RNA expressions of Porphyromonas gingivalis, Tanerella forsythia, and Treponema denticola. In groups I and II, the mean Oral Hygiene Index-Simplified scores were 4 and 2, respectively, showing a significant difference; the mean Calculus Index scores were 2 and 0, respectively, showing a significant difference; and the mean pH was 7.5 and 6.0, respectively, showing a significant difference. Bacterial analysis indicated no association between the two groups. It can be concluded that children and young people who use gastrostomy had a poorer oral hygiene, greater dental calculus deposition, and higher salivary pH. The saliva of patients in both groups contained Porphyromonas gingivalis, Tanerella forsythia, and Treponema denticola.

Antigen-Specific Antibody Signature Is Associated with COVID-19 Outcome.

Numerous studies have focused on inflammation-related markers to understand COVID-19. In this study, we performed a comparative analysis of spike (S) and nucleocapsid (N) protein-specific IgA, total IgG and IgG subclass response in COVID-19 patients and compared this to their disease outcome. We observed that the SARS-CoV-2 infection elicits a robust IgA and IgG response against the N-terminal (N1) and C-terminal (N3) region of the N protein, whereas we failed to detect IgA antibodies and observed a weak IgG response against the disordered linker region (N2) in COVID-19 patients. N and S protein-specific IgG1, IgG2 and IgG3 response was significantly elevated in hospitalized patients with severe disease compared to outpatients with non-severe disease. IgA and total IgG antibody reactivity gradually increased after the first week of symptoms. Magnitude of RBD-ACE2 blocking antibodies identified in a competitive assay and neutralizing antibodies detected by PRNT assay correlated with disease severity. Generally, the IgA and total IgG response between the discharged and deceased COVID-19 patients was similar. However, significant differences in the ratio of IgG subclass antibodies were observed between discharged and deceased patients, especially towards the disordered linker region of the N protein. Overall, SARS-CoV-2 infection is linked to an elevated blood antibody response in severe patients compared to non-severe patients. Monitoring of antigen-specific serological response could be an important tool to accompany disease progression and improve outcomes.

Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study.

BACKGROUND: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013. METHODS: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses. FINDINGS: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins. INTERPRETATION: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings. FUNDING: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Heterogeneity of humoral response patterns in mildly symptomatic, non-hospitalized COVID-19 patients: A one-year longitudinal study.

The duration and protectiveness of antibodies against SARS-CoV-2 in infected subjects are still uncertain; nonetheless, anti-S-specific antibodies can contribute to protective immunity against new infections. It has been described that the level of antibodies produced in COVID-19 is related to the severity of symptoms, and the majority of the humoral response studies have been conducted in hospitalized patients who have been, then, followed over time. However, about 80% of SARS-CoV-2 infections in unvaccinated people are mild to asymptomatic, and this percentage reaches more than 95% in vaccinated individuals. Therefore, understanding the long-term dynamics of the antibody responses in this predominant part of the COVID-19-affected population is essential. In this study, we followed a cohort of individuals with mild COVID-19 who did not require hospitalization. We collected blood samples at sequential times after the SARS-CoV-2-positive qRT-PCR result. From 65 recruited patients, 50 had detectable antibodies at screening. Anti-SARS-CoV-2 IgM levels peaked around two weeks post-COVID-19 diagnostics, becoming undetectable after 65 days. IgG levels reached a peak in approximately one month and remained detectable for more than one year. In contrast to the levels of anti-SARS-CoV-2, antibody neutralization potency indexes persisted over time. In this study, humoral responses in mild COVID-19 patients persisted for more than one year. This is an important long-term follow-up study that includes responses from COVID-19 patients before and after vaccination, a scenery that has become increasingly difficult to evaluate due to the growing vaccination of the world human population.

Antibody cross-reactivity and evidence of susceptibility to emerging Flaviviruses in the dengue-endemic Brazilian Amazon.

OBJECTIVES: Several Flaviviruses can co-circulate. Pre-existing immunity to one virus can modulate the response to a heterologous virus; however, the serological cross-reaction between these emerging viruses in dengue virus (DENV)-endemic regions are poorly understood. METHODS: A cross-sectional study was performed among the residents of Manaus city in the state of Amazonas, Brazil. The serological response was assessed by hemagglutination inhibition assay (HIA), enzyme-linked immunosorbent assay, and neutralization assay. RESULTS: A total of 74.52% of the participants were immunoglobulin G-positive (310/416), as estimated by lateral flow tests. Overall, 93.7% of the participants were seropositive (419/447) for at least one DENV serotype, and the DENV seropositivity ranged between 84.8% and 91.0%, as determined by HIA. About 93% had antiyellow fever virus 17D-reactive antibodies, whereas 80.5% reacted to wild-type yellow fever virus. Zika virus (ZIKV) had the lowest seropositivity percentage (52.6%) compared with other Flaviviruses. Individuals who were DENV-positive with high antibody titers by HIA or envelope protein domain III enzyme-linked immunosorbent assay reacted strongly with ZIKV, whereas individuals with low anti-DENV antibody titers reacted poorly toward ZIKV. Live virus neutralization assay with ZIKV confirmed that dengue serogroup and ZIKV-spondweni serogroup are far apart; hence, individuals who are DENV-positive do not cross-neutralize ZIKV efficiently. CONCLUSION: Taken together, we observed a high prevalence of DENV in the Manaus-Amazon region and a varying degree of cross-reactivity against emerging and endemic Flaviviruses. Epidemiological and exposure conditions in Manaus make its population susceptible to emerging and endemic arboviruses.

Design and validation of equations for weight estimation in adolescents.

INTRODUCTION: Measuring weight is difficult to be carried out in bedridden people, with physical deformity or in emergency units. Under these circumstances, one option is to estimate the weight. OBJECTIVES: The aim of this study is to propose and validate equations for estimating the weight of Brazilian adolescents based on anthropometric variables related to body weight. METHODS: The study was developed based on a database created from data collection of a primary project, which had information from 662 Brazilian adolescents (10 to 19 years old). Based on the variables sex, age (days), weight (kg), height (m) and neck circumference (NC) (cm), equations for estimating weight of adolescents were proposed. The formulas were proposed after performing multiple linear regression models and subsequently tested and validated using appropriate statistical tests, considering 99% confidence. RESULTS: Two formulas were generated, the "Rucco Formulas-Adolescents", one for girls: -131.63091 + (0.00209 × A) + (37.57813 × H) + (3.71482 x NC) and another for boys: - 15.2854 + (-0.00414 × A)+ (14.30315 × H2)+ (0.04888 x NC2). Statistical test (R2) indicated that the proposed formulas are suitable for estimating weight. Low values of REQM and high values of CCI (> 0.8) also reinforce the quality of the proposed formulas. CONCLUSIONS: The current weight of adolescents can be estimated with adequate accuracy and precision using sex-specific "Rucco Formulas-Adolescents", generated from regression models using only three predictor variables.

Comportamento alimentar de crianças com transtorno do espectro autista / Eating behavior of children with autism spectrum disorder

RESUMO Objetivo: O objetivo deste estudo foi analisar o comportamento alimentar de crianças e adolescentes com transtorno do espectro autista. Métodos: Participaram deste estudo 21 crianças e adolescentes com TEA, na faixa etária de 2 a 14 anos de idade, de ambos os sexos. Foi aplicado um questionário sobre o comportamento alimentar com os 21 pais e/ou responsáveis das crianças. Esse instrumento é composto por 53 questões, distribuídas nas seguintes categorias: Motricidade na mastigação; Seletividade alimentar; Aspectos comportamentais; Sintomas gastrointestinais; Sensibilidade sensorial e Habilidades nas refeições. Resultados: A análise dos dados obtidos revela que as crianças com TEA apresentaram maiores alterações no comportamento alimentar nas categorias Seletividade alimentar (34,4%), Aspectos comportamentais (27,1%) e Motricidade na mastigação (21,9%). E houve correlação entre a categoria Motricidade na mastigação com todas as outras categorias. Houve também correlação entre seletividade alimentar com aspectos comportamentais e aspectos comportamentais com sensibilidade sensorial e habilidades nas refeições. Conclusão: Portanto, é possível observar que, no comportamento alimentar de crianças e adolescentes com TEA, há uma tendência a seletividade alimentar, comportamentos habituais durante as refeições e dificuldades motoras no que se refere à mastigação e à ingestão dos alimentos.

ABSTRACT Objective: The objective of this study was to analyze feeding behavior in children with autism spectrum disorder. Methods: Twenty-one children with autism spectrum disorder (ASD) participated in this study, aged 2 to 14 years old, of both sexes. A questionnaire on feeding behavior was applied to the 21 parents and/or responsible of the children. This instrument consists of 53 questions, distributed in the following categories: Motricity in chewing; Food selectivity; Behavioral aspects; Gastrointestinal symptoms; Sensory sensitivity and Skills in meals. Results: The analysis of the data obtained reveals that children with ASD showed greater changes in eating behavior in the categories Food selectivity (34.4%), Behavioral aspects (27.1%) and Motricity in mastication (21.9%). And there was a correlation between the chewing motricity category with all other categories. There was also a correlation between food selectivity with behavioral aspects and behavioral aspects with sensory sensitivity and mealtime skills. Conclusion: Therefore, it is possible to observe that in the eating behavior of children with autism spectrum disorder there is a tendency towards food selectivity, habitual behaviors during meals and motor difficulties with regard to chewing and food intake.

Prognostic factors in oropharyngeal squamous cell carcinoma in the state of São Paulo, Brazil: 10-year follow-up

Abstract Objective: To descriptively analyze the epidemiological data, clinical stage, and outcomes of oropharyngeal squamous cell carcinoma in the state of São Paulo, Brazil, and to estimate the influence of clinical stage and treatment type on overall and disease-free survival. Methods: We retrospectively analyzed epidemiological data from the São Paulo Cancer Center Foundation database relative to patients with oropharyngeal squamous cell carcinoma diagnosed between 2004 and 2014 in the state of São Paulo. Univariate and multivariate Cox regression analyses were performed to assess factors associated with the outcomes. A forward stepwise selection procedure was used. Survival curves were estimated by the Kaplan-Meier method and compared by the Gehan-Breslow-Wilcoxon test. Results: A total of 8075 individuals with oropharyngeal squamous cell carcinoma were identified. Of these, 86.3% were diagnosed at an advanced stage and 13.7% at an early stage. Only 27.2% of patients were treated surgically, whereas 57.5% were treated medically. Patients undergoing surgery had longer overall survival than those receiving medical treatment in both early- and advanced-stage oropharyngeal squamous cell carcinoma. However, there was no significant difference in disease-free survival between surgical and medical treatment. Conclusion: No significant difference in disease-free survival between medical and surgical treatment suggests similar complete remission rates with both approaches. Patients receiving medical treatment had shorter overall survival, which may be due to complications from chemotherapy and radiotherapy. However, we cannot confirm this relationship based on the data provided by the São Paulo Cancer Center Foundation. Prospective studies are warranted to assess whether the lower overall survival rate in patients receiving medical treatment is secondary to complications from chemotherapy and radiotherapy. Level of evidence: 2C.

Prognostic factors in oropharyngeal squamous cell carcinoma in the state of São Paulo, Brazil: 10-year follow-up.

OBJECTIVE: To descriptively analyze the epidemiological data, clinical stage, and outcomes of oropharyngeal squamous cell carcinoma in the state of São Paulo, Brazil, and to estimate the influence of clinical stage and treatment type on overall and disease-free survival. METHODS: We retrospectively analyzed epidemiological data from the São Paulo Cancer Center Foundation database relative to patients with oropharyngeal squamous cell carcinoma diagnosed between 2004 and 2014 in the state of São Paulo. Univariate and multivariate Cox regression analyses were performed to assess factors associated with the outcomes. A forward stepwise selection procedure was used. Survival curves were estimated by the Kaplan-Meier method and compared by the Gehan-Breslow-Wilcoxon test. RESULTS: A total of 8075 individuals with oropharyngeal squamous cell carcinoma were identified. Of these, 86.3% were diagnosed at an advanced stage and 13.7% at an early stage. Only 27.2% of patients were treated surgically, whereas 57.5% were treated medically. Patients undergoing surgery had longer overall survival than those receiving medical treatment in both early- and advanced-stage oropharyngeal squamous cell carcinoma. However, there was no significant difference in disease-free survival between surgical and medical treatment. CONCLUSION: No significant difference in disease-free survival between medical and surgical treatment suggests similar complete remission rates with both approaches. Patients receiving medical treatment had shorter overall survival, which may be due to complications from chemotherapy and radiotherapy. However, we cannot confirm this relationship based on the data provided by the São Paulo Cancer Center Foundation. Prospective studies are warranted to assess whether the lower overall survival rate in patients receiving medical treatment is secondary to complications from chemotherapy and radiotherapy. LEVEL OF EVIDENCE: 2C.

Impact of Microbiota Depletion by Antibiotics on SARS-CoV-2 Infection of K18-hACE2 Mice.

Clinical and experimental data indicate that severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection is associated with significant changes in the composition and function of intestinal microbiota. However, the relevance of these effects for SARS-CoV-2 pathophysiology is unknown. In this study, we analyzed the impact of microbiota depletion after antibiotic treatment on the clinical and immunological responses of K18-hACE2 mice to SARS-CoV-2 infection. Mice were treated with a combination of antibiotics (kanamycin, gentamicin, metronidazole, vancomycin, and colistin, Abx) for 3 days, and 24 h later, they were infected with SARS-CoV-2 B lineage. Here, we show that more than 80% of mice succumbed to infection by day 11 post-infection. Treatment with Abx had no impact on mortality. However, Abx-treated mice presented better clinical symptoms, with similar weight loss between infected-treated and non-treated groups. We observed no differences in lung and colon histopathological scores or lung, colon, heart, brain and kidney viral load between groups on day 5 of infection. Despite some minor differences in the expression of antiviral and inflammatory markers in the lungs and colon, no robust change was observed in Abx-treated mice. Together, these findings indicate that microbiota depletion has no impact on SARS-CoV-2 infection in mice.

Application of Fibrin Associated with Photobiomodulation as a Promising Strategy to Improve Regeneration in Tissue Engineering: A Systematic Review.

Fibrin, derived from proteins involved in blood clotting (fibrinogen and thrombin), is a biopolymer with different applications in the health area since it has hemostasis, biocompatible and three-dimensional physical structure properties, and can be used as scaffolds in tissue regeneration or drug delivery system for cells and/or growth factors. Fibrin alone or together with other biomaterials, has been indicated for use as a biological support to promote the regeneration of stem cells, bone, peripheral nerves, and other injured tissues. In its diversity of forms of application and constitution, there are platelet-rich fibrin (PRF), Leukocyte- and platelet-rich fibrin (L-PRF), fibrin glue or fibrin sealant, and hydrogels. In order to increase fibrin properties, adjuvant therapies can be combined to favor tissue repair, such as photobiomodulation (PBM), by low-level laser therapy (LLLT) or LEDs (Light Emitting Diode). Therefore, this systematic review aimed to evaluate the relationship between PBM and the use of fibrin compounds, referring to the results of previous studies published in PubMed/MEDLINE, Scopus and Web of Science databases. The descriptors "fibrin AND low-level laser therapy" and "fibrin AND photobiomodulation" were used, without restriction on publication time. The bibliographic search found 44 articles in PubMed/MEDLINE, of which 26 were excluded due to duplicity or being outside the eligibility criteria. We also found 40 articles in Web of Science and selected 1 article, 152 articles in Scopus and no article selected, totaling 19 articles for qualitative analysis. The fibrin type most used in combination with PBM was fibrin sealant, mainly heterologous, followed by PRF or L-PRF. In PBM, the gallium-aluminum-arsenide (GaAlAs) laser prevailed, with a wavelength of 830 nm, followed by 810 nm. Among the preclinical studies, the most researched association of fibrin and PBM was the use of fibrin sealants in bone or nerve injuries; in clinical studies, the association of PBM with medication-related treatments osteonecrosis of the jaw (MRONJ). Therefore, there is scientific evidence of the contribution of PBM on fibrin composites, constituting a supporting therapy that acts by stimulating cell activity, angiogenesis, osteoblast activation, axonal growth, anti-inflammatory and anti-edema action, increased collagen synthesis and its maturation, as well as biomolecules.

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

Identification and characterization of the anti-SARS-CoV-2 activity of cationic amphiphilic steroidal compounds.

The ongoing COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Treatment of COVID-19 patients is challenging, and specific treatments to reduce COVID-19 aggravation and mortality are still necessary. Here, we describe the discovery of a novel class of epiandrosterone steroidal compounds with cationic amphiphilic properties that present antiviral activity against SARS-CoV-2 in the low micromolar range. Compounds were identified in screening campaigns using a cytopathic effect-based assay in Vero CCL81 cells, followed by hit compound validation and characterization. Compounds LNB167 and LNB169 were selected due to their ability to reduce the levels of infectious viral progeny and viral RNA levels in Vero CCL81, HEK293, and HuH7.5 cell lines. Mechanistic studies in Vero CCL81 cells indicated that LNB167 and LNB169 inhibited the initial phase of viral replication through mechanisms involving modulation of membrane lipids and cholesterol in host cells. Selection of viral variants resistant to steroidal compound treatment revealed single mutations on transmembrane, lipid membrane-interacting Spike and Envelope proteins. Finally, in vivo testing using the hACE2 transgenic mouse model indicated that SARS-CoV-2 infection could not be ameliorated by LNB167 treatment. We conclude that anti-SARS-CoV-2 activities of steroidal compounds LNB167 and LNB169 are likely host-targeted, consistent with the properties of cationic amphiphilic compounds that modulate host cell lipid biology. Although effective in vitro, protective effects were cell-type specific and did not translate to protection in vivo, indicating that subversion of lipid membrane physiology is an important, yet complex mechanism involved in SARS-CoV-2 replication and pathogenesis.

Evaluation of the degradation of two bioabsorbable interference screws: an in-vivo study in sheep.

PURPOSE: To evaluate in-vivo degradation of two bioabsorbable interference screws. METHODS: Twenty-two crossbred Santa Inês ewes were used. A poly-DL-lactide (PDLLA) screw (70%/30%) was inserted in the right pelvic limb, and a PDLLA screw (70%) + ß-tri-calcium phosphate (ß-TCP) (30%) in the left pelvic limb. Animals were euthanized at one, four, seven and a half and 18 months after surgery. Plain radiography, computed tomography (CT), microCT, and histological analysis were accomplished. RESULTS: PDLLA screw was hypodense at all evaluation moments, but with progressive density increase along the central axis, whereas PDLLA/ß-TCP was initially hyperdense and progressively lost this characteristic. No adverse reactions were observed on histological evaluation. CONCLUSIONS: The inclusion of ß-TCP favors screw degradation since the PDLLA/ß-TCP screws evidenced a more intense degradation process than the PDLLA screws at the last evaluation. PDLLA screws showed higher bone production, evident around the screw thread, inside the lateral perforations, and in the central canal, whereas the PDLLA/ß-TCP screws presented less bone tissue at the implantation site.