Abatacept inhibits Th17 differentiation and mitigates α-synuclein-induced dopaminergic dysfunction in mice.

Parkinson's disease (PD) is a multifaceted disease characterized by degeneration of nigrostriatal dopaminergic neurons, which results in motor and non-motor dysfunctions. Accumulation of α-synuclein (αSYN) in Lewy bodies is a key pathological feature of PD. Although the exact cause of PD remains unknown, accumulating evidence suggests that brain infiltration of T cells plays a critical role in the pathogenesis of disease, contributing to neuroinflammation and dopaminergic neurodegeneration. Here, we used a mouse model of brain-infused aggregated αSYN, which recapitulates motor and non-motor dysfunctions seen in PD patients. We found that αSYN-induced motor dysfunction in mice is accompanied by an increased number of brain-residing Th17 (IL17+ CD4+) cells, but not CD8+ T cells. To evaluate whether the modulation of T cell response could rescue αSYN-induced damage, we chronically treated animals with abatacept (8 mg/kg, sc, 3x per week), a selective T-cell co-stimulation modulator. We found that abatacept treatment decreased Th1 (IFNƔ+ CD4+) and Th17 (IL17+ CD4+) cells in the brain, rescued motor function and prevented dopaminergic neuronal loss in αSYN-infused mice. These results highlight the significance of effector CD4+ T cells, especially Th17, in the progression of PD and introduce novel possibilities for repurposing immunomodulatory drugs used for arthritis as PD-modifying therapies.

Relined fiberglass posts: influence of resin opacity on the bond strength to intraradicular dentin.

This study aimed to evaluate the bond strength between relined fiberglass posts with different composite resin opacities in different thirds of the intraradicular dentin. Thirty single-rooted premolars were endodontically treated and divided into three groups (n=10): fiberglass posts relined with translucent composite resin, fiberglass posts relined with opaque composite resin, and fiberglass posts without relining. After cementation of the posts, the specimens were cut perpendicular to the long axis of the tooth in slices of approximately 1.3 mm of each third to be analyzed (cervical, middle, and apical) and then subjected to the push-out test. The bond strength (MPa) data were subjected to Shapiro-Wilk normality tests and two-way repeated measures analysis of variance, considering the experimental groups and different regions as study factors. Tukey's post-hoc test (p<.05) was applied for comparisons between the groups. In the cervical third, higher values of bond strength were found for the group relined with translucent resin, with a statistically significant difference for the other groups. In the other regions, both opaque and translucent resins showed similar results, but both showed higher values of bond strength compared to fiberglass posts without relining. The bond strength of fiberglass posts to different thirds of intraradicular dentin is influenced by composite resin relining as well as the opacity of the resin. The use of translucent composite resin is a more effective alternative for fiberglass posts relining.

Relined fiberglass posts: influence of resin opacity on the bond strength to intraradicular dentin

Abstract This study aimed to evaluate the bond strength between relined fiberglass posts with different composite resin opacities in different thirds of the intraradicular dentin. Thirty single-rooted premolars were endodontically treated and divided into three groups (n=10): fiberglass posts relined with translucent composite resin, fiberglass posts relined with opaque composite resin, and fiberglass posts without relining. After cementation of the posts, the specimens were cut perpendicular to the long axis of the tooth in slices of approximately 1.3 mm of each third to be analyzed (cervical, middle, and apical) and then subjected to the push-out test. The bond strength (MPa) data were subjected to Shapiro-Wilk normality tests and two-way repeated measures analysis of variance, considering the experimental groups and different regions as study factors. Tukey's post-hoc test (p<.05) was applied for comparisons between the groups. In the cervical third, higher values of bond strength were found for the group relined with translucent resin, with a statistically significant difference for the other groups. In the other regions, both opaque and translucent resins showed similar results, but both showed higher values of bond strength compared to fiberglass posts without relining. The bond strength of fiberglass posts to different thirds of intraradicular dentin is influenced by composite resin relining as well as the opacity of the resin. The use of translucent composite resin is a more effective alternative for fiberglass posts relining.

Resumo Este estudo teve como objetivo avaliar a resistência de união entre pinos de fibra de vidro anatomizados com resinas compostas de diferentes opacidades em diferentes terços da dentina intrarradicular. Trinta pré-molares uniradiculares foram tratados endodonticamente e divididos em três grupos (n=10): pinos de fibra de vidro anatomizados com resina composta translúcida, pinos de fibra de vidro anatomizados com resina composta opaca e pinos de fibra de vidro sem anatomização. Após a cimentação dos pinos, os corpos de prova foram cortados perpendicularmente ao longo eixo do dente em fatias de aproximadamente 1,3 mm de cada terço a ser analisado (cervical, médio e apical) e posteriormente submetidos ao teste de push-out. Os dados de resistência de união (MPa) foram submetidos a testes de normalidade de Shapiro-Wilk e ANOVA dois fatores para análises repetidas, considerando os grupos experimentais e diferentes regiões como fatores de estudo. O teste post-hoc de Tukey (p=0,05) foi aplicado para comparações entre os grupos. No terço cervical foram encontrados maiores valores de resistência de união no grupo com anatomização com resina translúcida, com diferença estatisticamente significativa para os demais grupos. Nas demais regiões, tanto as resinas opacas quanto as translúcidas apresentaram resultados semelhantes, mas ambas apresentaram valores de resistência de união superiores aos pinos de fibra de vidro sem anatomização. A resistência de união dos pinos de fibra de vidro aos diferentes terços da dentina intrarradicular é influenciada pela anatomização da resina composta, bem como pela opacidade da resina. A utilização de resina composta translúcida é uma alternativa mais eficaz para a anatomização de pinos de fibra de vidro.

Do different adhesives influence the color stability and fluorescence of composite restorations after aging?

This study aimed to evaluate the influence of dental adhesive color on the chromatic stability and fluorescence intensity of composite resin restorations of different thicknesses. Ninety bovine enamel samples were obtained and restored with resin composite varying thicknesses of restorative material and enamel (1.0 mm enamel and 1.0 mm composite; 1.5 mm enamel and 0.5 mm composite; 0.5 mm enamel and 1.5 mm composite). The restorations were made of composite resin (Opallis E-bleach H) using different types of dental adhesives: Ambar, Ambar APS, and Single Bond Universal (n=10). The samples were subjected to color measurement tests in a spectrophotometer using CIEDE2000 and fluorescence intensity measurements before and after aging in a red wine coloring solution. Data were subjected to analysis of variance (ANOVA) and Tukey's test (α = 0.05). There were no statistically significant changes in color stability or fluorescence intensity for restorations made of different materials or thicknesses (p>0.05). Single Bond Universal showed greater color stability at 0.5 mm thickness (ΔE00 = 4.4 ± 1.6) compared to other thicknesses of the same material (p=0.003), as well as a greater difference in fluorescence intensity after aging at 1.5 mm thickness (-414.9 ± 103.8) compared to other materials (p=0.0002). Overall, it was concluded that the different adhesive systems did not influence the color stability and fluorescence of restorations of different thicknesses.

Chlamydia trachomatis, Neisseria gonorrhoeae and human papillomavirus infections of lower genital tract of Indigenous women from Xingu Indigenous Park.

INTRODUCTION: Xingu Indigenous Park (XIP) currently protects 16 ethnic Indigenous groups and is located in the central area of Brazil. XIP is the first and the largest Indigenous land to be recognized in the country. Community access is limited and restricted for the non-Indigenous population, and the Indigenous women are constantly dealing with shortages of medical care. High-risk human papillomavirus (HR-HPV) is the most common cause of cervical cancer and is detected in 99% of cervical precancers. HPV infections may be associated with bacterial agents such as Chlamydia trachomatis and Neisseria gonorrhoeae, which are also important causative agents of sexually transmitted infections and are responsible for the most frequent bacterial infections in the world. The present study evaluated the frequency and potential impact of Chlamydia trachomatis, Neisseria gonorrhoeae, and HR-HPV in the Indigenous women of XIP. METHODS: In this cross-sectional study, 992 cervical-vaginal samples were collected from Indigenous women, using a Cervex-Brush, and were immediately placed in a SurePath medium. All samples were submitted to the cobas® 4800 detection system for the identification of 14 different types of HR-HPV, and the multiplex Abbott RealTime CT/NG assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: HR-HPV was detected in 18.2% of women; 6% were positive for HPV16, 5% for HPV18, and 81% for other types of HR-HPV. Co-infections of HPV16 and other types was observed in 5% of women, and 3% had co-infections of HPV18 and other types. Moreover, 1.8% of women were positive for Chlamydia trachomatis, while Neisseria gonorrhoeae was not detected. In women with HR-HPV, 33% had Chlamydia trachomatis infections, 28% were positive for HR-HPV other than HPV16 or HPV18, and 5% had co-infections of HPV16 and the other types of HPV. Younger women were found to be more susceptible to HPV infections. CONCLUSION: The findings indicate a high frequency of HR-HPV and a considerable frequency of Chlamydia trachomatis in the Indigenous women of XIP. The detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and/or HR-HPV does not present evidence of a potential interrelationship for a combined pathogenic action in these women.

Comparison of Manual (2D) and Digital (3D) Methods in the Assessment of Simulated Facial Edema.

BACKGROUND: An edema assessment following dental surgeries is essential to improving the dental surgeon's technique and, consequentially, patient comfort. PURPOSE: Two-dimensional (2D) methods are limited in analyzing 3-dimensional (3D) surfaces. Currently, 3D methods are used to investigate postoperative swelling. However, there are no studies that directly compare 2D and 3D methods. The goal of this study is to directly compare 2D and 3D methods used in the assessment of postoperative edema. STUDY DESIGN AND SAMPLE: The investigators implemented a prospective, cross-sectional study with each subject serving as its own control. The sample was composed of dental student volunteers without facial deformities. PREDICTOR VARIABLE: The predictor variable is the method used to measure edema. After simulating edema, manual (2D) and digital (3D) techniques were used to measure edema. The manual method used direct facial perimeter measurements. The two digital methods were photogrammetry using a smartphone (iPhone 11, Apple Inc, Cupertino, California), and facial scanning with a smartphone application (Bellus3D FaceApp, Bellus3D Inc, Campbell, California) [3D measurements] MAIN OUTCOME VARIABLE: The coefficient of variation (CV) (CV = standard deviation /mean) was used to assess homogeneity of edema measurements. ANALYSIS: The Shapiro-Wilk and equal variance tests were applied to assess data homogeneity. Next, one-way analysis of variance was performed, followed by a correlation analysis. Finally, the data were submitted to Tukey's test. The statistical significance threshold was set at 5% (P < .05). RESULTS: The sample was composed of 20 subjects aged 18-38 years. The CV showed higher values using the manual (2D) method (47%; 4.88% ± 2.99), compared with the photogrammetry method (18%; 8.55 mm ± 1.52) and the smartphone application (21%; 8.97 mm ± 1.93). A statistically significant difference was observed between the manual method values and those of the other two groups (P < .001). There was no difference between the facial scanning and photogrammetry groups (3D methods) (P = .778) CONCLUSION AND RELEVANCE: Both digital measuring methods (3D) demonstrated greater homogeneity than the manual method in analyzing facial distortions caused by the same swelling simulation. Therefore, it can be affirmed that digital methods may be more reliable that manual methods for assessing facial edema.

Influence of thickness and degree of opacity of lithium disilicate on the degree of conversion and bond strength of resin cements.

The aim of this study was to evaluate the influence of various opacities and thicknesses of lithium disilicate on the degree of conversion (DC) of two resin cements and on their bond strength (BS) to the ceramic. Two hundred and forty ceramic samples of lithium disilicate with high translucency (HT), low translucency (LT), and medium opacity (MO) were obtained from IPS e. max CAD in five different thicknesses. Light-cured and dual-cured resin cements were used for DC (n = 9) and BS (n = 8). Cement samples were light-cured under ceramic samples and analyzed using a Raman confocal spectrometer to determine the DC. For BS, resin cement cylinders were fabricated using ceramic samples which were thsen subjected to a microshear bond strength test. The mean values were provided for statistical analysis. The increase in thickness resulted in a decrease in DC for both cements under all experimental conditions, but only affected the BS of the light-cured cement for the MO ceramic. Comparing the opacities, the most translucent ceramics with particular thicknesses exhibited higher DC values than the less translucent ceramics. The LT and MO ceramics with certain thicknesses exhibited the highest BS values than the HT. The dual-cured cement generally showed highest values in both analyses than the light-cured cement. A thicker and more opaque ceramic material can reduce the DC of the cement. The BS decreases with the increasing thickness of the more-opaque ceramics.

Immunoproteomics approach for the discovery of antigens applied to the diagnosis of canine visceral leishmaniasis.

In the present study, an immunoproteomic approach using Leishmania infantum parasites isolated from naturally infected dogs from an endemic region of the disease, was carried out to identify new antigens to be used in the diagnosis of canine visceral leishmaniasis (CVL). Protein extracts, obtained from parasites isolated from asymptomatic (CanLA) and symptomatic (CanLS) dogs, were used to perform the two-dimensional gels. Western Blotting assays were carried out by employing a pool of sera from dogs with visceral leishmaniasis (CanLA or CanLS), healthy dogs from an endemic area, or dogs with similar diseases associated with cross-reactions (babesiosis and ehrlichiosis). With these results, it was possible to exclude the spots that showed a cross-reactivity of the sera from groups of healthy dogs, and those with babesiosis or ehrlichiosis. Taken together, 20 proteins were identified, 15 of which have already been described in the literature and 5 of which are hypothetical. An immunogenomic screen strategy was applied to identify conserved linear B-cell epitopes in the identified hypothetical proteins. Two peptides were synthesized and tested in ELISA experiments as a proof of concept for the validation of our immunoproteomics findings. The results demonstrated that the antigens presented sensitivity and specificity values ranging from 81.93% to 97.59% and 78.14 to 85.12%, respectively. As a comparative antigen, a preparation of a Leishmania extract showed sensitivity and specificity values of 75.90% and 74.88%, respectively. The present study was able to identify proteins capable of being used for the serodiagnosis of canine visceral leishmaniasis.

Do different adhesives influence the color stability and fluorescence of composite restorations after aging?

Abstract This study aimed to evaluate the influence of dental adhesive color on the chromatic stability and fluorescence intensity of composite resin restorations of different thicknesses. Ninety bovine enamel samples were obtained and restored with resin composite varying thicknesses of restorative material and enamel (1.0 mm enamel and 1.0 mm composite; 1.5 mm enamel and 0.5 mm composite; 0.5 mm enamel and 1.5 mm composite). The restorations were made of composite resin (Opallis E-bleach H) using different types of dental adhesives: Ambar, Ambar APS, and Single Bond Universal (n=10). The samples were subjected to color measurement tests in a spectrophotometer using CIEDE2000 and fluorescence intensity measurements before and after aging in a red wine coloring solution. Data were subjected to analysis of variance (ANOVA) and Tukey's test (α = 0.05). There were no statistically significant changes in color stability or fluorescence intensity for restorations made of different materials or thicknesses (p>0.05). Single Bond Universal showed greater color stability at 0.5 mm thickness (ΔE00 = 4.4 ± 1.6) compared to other thicknesses of the same material (p=0.003), as well as a greater difference in fluorescence intensity after aging at 1.5 mm thickness (-414.9 ± 103.8) compared to other materials (p=0.0002). Overall, it was concluded that the different adhesive systems did not influence the color stability and fluorescence of restorations of different thicknesses.

Resumo O objetivo deste estudo foi avaliar a influência da cor do adesivo dental na estabilidade cromática e intensidade de fluorescência das restaurações de resina composta de diferentes espessuras. Foram obtidos noventa amostras de esmalte bovino que foram restaurados com resina composta, variando a espessura do material restaurador e do esmalte (1,0 mm de esmalte e 1,0 mm de compósito; 1,5 mm de esmalte e 0,5 mm de compósito; 0,5 mm de esmalte e 1,5 mm de compósito). As restaurações foram feitas de resina composta (Opallis E-bleach H) utilizando diferentes tipos de adesivos odontológicos: Ambar, Ambar APS, e Single Bond Universal (n=10). As amostras foram submetidas a testes de medição de cor em um espectrofotômetro usando CIEDE2000 e medições de intensidade de fluorescência antes e depois do envelhecimento em uma solução de coloração de vinho tinto. Os dados foram submetidos à análise de variância (ANOVA) e ao teste de Tukey (α = 0,05). Não houve mudanças estatisticamente significativas na estabilidade da cor ou intensidade de fluorescência para restaurações feitas de diferentes materiais ou espessuras (p>0,05). O Single Bond Universal mostrou maior estabilidade de cor a 0,5 mm de espessura (ΔE00 = 4,4 ± 1,6) em comparação com outras espessuras do mesmo material (p=0,03), bem como uma maior diferença na intensidade de fluorescência após o envelhecimento a 1,5 mm de espessura (-414,9 ± 103,8) em comparação com outros materiais (p=0,0002). Em geral, concluiu-se que os diferentes sistemas adesivos não influenciaram a estabilidade de cor e a intensidade de fluorescência das restaurações de diferentes espessuras.

Voice therapy with a respiratory approach in older adults: the practice of Brazilian speech-language-hearing therapists / Terapia vocal com abordagem respiratória em idosos: prática de fonoaudiólogos brasileiros

ABSTRACT Purpose: to investigate the practice of Brazilian speech-language-hearing therapists in voice therapy for older adults focused on breathing and verify possible associations between taking specific courses and having knowledge of respiratory parameters, between using incentive spirometers and respiratory devices, and between age and the use of these instruments. Methods: the sample had 156 specialists in voice, contacted via email, who answered a form in Google Forms. Specialists in voice with 3 or more years of experience were included, whereas those who did not fill out the questionnaire completely were excluded. The analysis addressed absolute and relative frequencies and associations with the chi-square test. Significance was set at 5%. Results: most participants took courses on respiratory approach. The use of facilitating sounds, vocal function exercises, and respiratory instruments stood out, with reported vocal improvements. The use of incentive spirometers was associated with respiratory devices, and age was associated with the use of respiratory instruments. Conclusion: speech-language-hearing therapists with expertise in voice provide voice therapy for dysphonic older people focusing on a respiratory approach. Professionals who use incentive spirometers also use respiratory devices. Older therapists are the ones who most use respiratory instruments and taking specific courses was not associated with knowledge on respiratory parameters.

RESUMO Objetivo: investigar a prática de fonoaudiólogos brasileiros em terapia vocal para idosos com ênfase na respiração e verificar possíveis associações entre realização de cursos específicos e conhecimento sobre parâmetros respiratórios, entre o uso de incentivadores e dispositivos respiratórios e entre a idade e o uso destes instrumentos. Métodos: participaram 156 especialistas em voz, contatados via e-mail, que responderam um formulário na plataforma Google Forms. Foram incluídos especialistas em voz, com experiência maior ou igual a três anos e excluídos aqueles que não preencheram o questionário completamente. Analisaram-se frequências absolutas e relativas e a associação pelo teste Qui-quadrado, com significância de 5%. Resultados: a maioria realizou cursos com abordagem respiratória. Destacaram-se: uso de sons facilitadores, exercícios de função vocal e uso de instrumentos respiratórios, com relatos de melhora vocal. Houve associação entre o uso de incentivadores e dispositivos respiratórios e entre idade e o uso de instrumentos respiratórios. Conclusão: fonoaudiólogos experts em voz realizam terapia vocal para idosos disfônicos com ênfase na abordagem respiratória. Profissionais que usam incentivadores respiratórios usam também os dispositivos respiratórios. Aqueles com mais idade são os que mais utilizam instrumentos respiratórios. A realização de cursos específicos não está associada ao conhecimento sobre parâmetros respiratórios.

Voice Therapy for Older Adults During the COVID-19 Pandemic in Brazil.

OBJECTIVE: To characterize the clinical practice of Brazilian speech-language-hearing therapists regarding voice therapy for older adults during the COVID-19 pandemic. METHODS: Cross-sectional survey conducted remotely. Data were collected through a form shared online with approximately 1.500 speech-language-hearing therapists. The form included voice therapy practice with older adults during the COVID-19 pandemic. It was responded by 155 voice experts. RESULTS: Most respondents were females with over 21 years' experience in vocal health care, working with both in-person therapy and teletherapy. Obtaining acoustic parameters and using therapy strategies for breathing and body training were the most reported changes in remote therapy during the pandemic. The main difficulties involved wearing masks in in-person therapy and assessing the voice in teletherapy. Patient adherence and goals reached were deemed positive by most participants. Associations were found between place and format of service; between patient adherence and goals reached; and between difficulties in teletherapy and use of complementary therapeutic resources. CONCLUSION: The COVID-19 pandemic led Brazilian speech-language-hearing therapists to change their clinical practice with older adults in both remote and in-person therapy. The main changes involved wearing masks in in-person therapy and assessing the voice in teletherapy. Remote therapy proved to be a safe and effective possibility.

Environmental impact of diets for dogs and cats.

Food production is responsible for almost one-quarter of the environmental impact and, therefore, its importance regarding sustainability should not be overlooked. The companion animal population is increasing, and an important part of pet food is composed of ingredients that have a high environmental impact. This study aimed to evaluate the impact of dry, wet, and homemade pet diets on greenhouse gas emission, land use, acidifying emission, eutrophying emissions, freshwater withdrawals, and stress-weighted water use. The wet diets were responsible for the highest impact, and dry diets were the type of diet that least impacted the environment, with a positive correlation between the metabolizable energy provided by animal ingredients and the environmental impact. It is necessary to consider the environmental impact of pet food since it is significant, and the population of pets tends to increase.

Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis.

Background: The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient's response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX). Results: Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81-0.95; p < 0.01; I2 = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79-0.94; p < 0.01; I2 = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05-1.36; p < 0.01; I2 = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68-1.00; p < 0.01; I2 = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding. Conclusion: According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.

Safety of biological therapy in patients with rheumatoid arthritis in administrative health databases: A systematic review and meta-analysis.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects the synovial fluid of joints, tendons, and some extra-articular sites. Biologic agents have been highly effective and are comparable in reducing RA symptoms, slowing disease progression, and improving physical function; however, concerns have been raised about the risks of several potential adverse effects. Thus, this study aimed to assess the safety of biological therapy in patients with rheumatoid arthritis in observational studies using administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science were searched from inception to 21 October 2021. The analysis was divided into five groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus csDMARDs; bDMARDs versus csDMARDs; abatacept versus bDMARDs; and TNFi versus Janus kinase inhibitors (JAKi). The adverse events were cancer, cardiovascular events, infection, herpes zoster, tuberculosis, and death. The methodological quality of the studies was assessed by the Newcastle-Ottawa Scale. A random-effects model estimated risk ratios with 95% confidence intervals. Results: Thirty-one studies were eligible for inclusion in the present systematic review, published from 2014 to 2021. A total of 1,039,398 RA patients were assessed. The 31 studies evaluated eleven different biological drugs. No significant differences were found regarding safety between TNFi versus non-TNFi (RR 1.08; 95% CI 0.92-1.28; p < 0.01; I2 = 93.0%), TNFi versus csDMARDs (RR 0.91; 95% CI 0.75-1.10; p < 0.01; I2 = 87.0%), bDMARDs versus csDMARDs (RR 0.99; 95% CI 0.82-1.20; p < 0.01; I2 = 93.0%), abatacept versus bDMARDs (RR 0.80; 95% CI 0.54-1.18; p < 0.01; I2 = 90.0%), and TNFi versus JAKi (RR 3.54; 95% CI 0.30-42.09; p = 0.01; I2 = 81.0%). In the subgroup analysis, among studies comparing abatacept to TNFi, a lower risk of cardiovascular events was associated with abatacept (RR 0.37; 95% CI 0.24-0.55). Conclusion: Our results do not suggest an increased risk of adverse events associated with biological therapy in treating RA patients, indicating a lower risk of cardiovascular events with abatacept than TNFi. However, these findings must be interpreted with caution given the limitations of this study and the low/very low certainty of the evidence. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier [CRD42020190838].

Ambulatório de Gênero e Sexualidades (AmbGen/ HC/ UNICAMP): relato da experiência do serviço / Gender and Sexualities Outpatient Clinic (AmbGen/ HC/UNICAMP): report of the service experience

0 Ambulatório de Género e Sexualidades (AmbGen) do Hospital das Clinicas da Universidade Estadual de Campinas é um dos poucos dispositivos públicos que acolhem população da infância e adolescência com variabilidade de género. A psiquiatria e psicologia investigam transtornos mentais, desencadeadores do sofrimento psíquico, disforias relacionados à incongruência de gênero e, no caso de crianças e adolescentes, acolhem as familías buscando compreensão da dinâmica familiar, esclarecimento de duvidas e estigmas. A intervenção hormonal na adolescência é possível em dois momentos: no inicio da puberdade, através de terapia medicamentosa visando blogueio puberal, e hormonização cruzada. A adequação corporal & identidade de género da pessoa trans, através da hormonização, é desejada pela maior parte dos adultos atendidos. A arteterapia realiza atendimentos nos quais busca fornecer padrões adequados à questões relevantes, utilizando- se de modalidades expressivas e vivências de processos criativos, uma maneira terapêutica diferenciada que propicia um ambiente acolhedor por um viés artístico. Características de género e voz são muito abrangentes. Sendo assim, a terapia fonoaudiológica a pessoas trans não se restringe apenas a produção vocal, mas também se relaciona a outros aspectos da comunicação e do discurso.

Voice therapy with a respiratory approach in older people: an integrative literature review / Terapia vocal com abordagem respiratória em idosos: revisão integrativa da literatura

ABSTRACT Purpose: to characterize voice therapy with a respiratory approach in dysphonic older people. Methods: a search made in PubMed, VHL, Scopus, Web of Science, and EMBASE. Original studies in English, Spanish, and Portuguese, addressing voice therapy in combination with a respiratory approach in the older population, were included. The analysis encompassed sex, age, associated etiology, session frequency and duration, exercise dosage, intervention, and benefits. Results: altogether, 1,425 articles were found, of which only nine were included in the review. In voice therapy for older people, the following strategies stood out: Vocal Function Exercises, Lee Silverman Voice Treatment®, ParkinSong, and tubes immersed in water. These approaches change the laryngeal muscle function and respiratory impulse and support and increase vocal intensity. The main therapeutic findings included improved auditory-perceptual, acoustic, and aerodynamic parameters, maximum phonation time, phonatory effort level, and voice quality. Conclusion: voice therapy with a respiratory approach characteristically used strategies aimed at both the general older population and those with neurological dysphonia. Their results showed improvement in frequency, resonance, intensity control, and breathing/phonation coordination.

RESUMO Objetivo: caracterizar a terapia vocal com abordagem respiratória em idosos disfônicos. Métodos: a busca foi realizada nas bases PubMed, BVS, Scopus, Web of Science e Embase. Foram incluídos estudos originais, nos idiomas inglês, espanhol e português, que tratassem sobre terapia vocal associada à abordagem respiratória na população idosa. Foram analisadas as variáveis gênero, faixa etária, etiologia associada, frequência e duração da sessão, dosagem de exercícios, intervenção e benefícios. Resultados: foram encontrados 1.425 artigos, porém, apenas nove foram incluídos na revisão. Na terapia vocal para idosos, destacaram-se as estratégias do Exercício de Função Vocal e o Método Lee Silverman®, além de outras, como o ParkinSong e o uso do tubo submerso em água. Tais abordagens modificam a função da musculatura laríngea, o impulso e o suporte respiratório, bem como o treino para aumento da intensidade vocal. Os principais resultados terapêuticos foram: melhora nos parâmetros perceptivo-auditivos, acústicos, aerodinâmicos, tempo máximo de fonação, nível de esforço fonatório e qualidade vocal. Conclusão: a terapia vocal com abordagem respiratória caracterizou-se pelo uso de estratégias direcionadas tanto à população idosa de forma geral, quanto a populações com disfonia neurológica, cujos resultados mostraram melhoria no controle de intensidade, frequência, ressonância e coordenação pneumofônica.

Influência da espessura e diferentes graus de opacidade do dissilicato de lítio no grau de conversão e resistência de união de cimentos resinosos / Influence of thickness and different degrees of opacity of lithium disilicate on the degree of conversion and bond strength of resin cements

O objetivo desse trabalho foi avaliar a influência de diferentes graus de opacidade e espessuras do dissilicato de lítio no grau de conversão de dois cimentos resinosos e na resistência de união dos mesmos à cerâmica. Duzentos e quarenta amostras cerâmicas de dissilicato de lítio (6x6 mm) foram obtidos a partir de blocos de IPS E-max CAD (Ivoclar Vivadent, Schaan, Liechtensten), nas opacidades HT (alta translucidez), LT (baixa translucidez) e MO (média opacidade), nas espessuras de 0,3 mm, 0,7 mm, 1,2mm, 1,7 mm, 2,0 mm. Para as análises do grau de conversão (n=9) e resistência de união (n=8) foram utilizados um cimento de ativação física (Variolink Esthetic LC) e um cimento dual (Multilink N). Para análise do grau de conversão, as amostras de cimento foram fotoativadas sob as amostras de cerâmica e levadas a um espectrômetro Raman confocal. Para o teste de resistência de união foram confeccionados cilindros de cimento resinoso sobre as amostras cerâmicas e submetidos ao ensaio de microcisalhamento. Os resultados mostraram que o aumento das espessuras causou diminuição no grau de conversão dos dois cimentos em todas as condições estudadas, porém só influenciou negativamente a resistência de união do cimento Variolink Esthetic LC quando unido à cerâmica na opacidade MO. Na comparação entre as opacidades, de maneira geral, a cerâmica de maior translucidez HT apresentou maiores valores de grau de conversão em comparação às outras opacidades. Já para resistência de união, em algumas espessuras as cerâmicas LT e MO apresentaram os maiores valores. O cimento dual Multilink N apresentou os maiores valores nas duas análises comparado ao cimento fotoativado Variolink Esthetic LC. Portanto, o aumento da espessura e da opacidade do material cerâmico podem promover uma diminuição no grau de conversão do cimento. A resistência de união também sofre uma diminuição com o aumento da espessura de cerâmicas mais opacas. No entanto, a maior translucidez do material não garante valores mais altos dessa mesma propriedade(AU)

This research aims to evaluate the influence of different degrees of opacity and thicknesses of lithium disilicate on the degree of conversion of two resin cements and on their bond strength to the ceramic. Two hundred and forty lithium disilicate ceramic samples (6x6 mm) were obtained from IPS E-max CAD (Ivoclar Vivadent, Schaan, Liechtensten), in HT, LT and MO opacities, with thicknesses of 0.3 mm, 0.7 mm, 1.2 mm, 1.7 mm, 2.0 mm. For degree of conversion (n=9) and bond strength analysis (n=8) a light cured (Variolink Esthetic LC) and a dual cured resin cement (Multilink N) were used. To analyze the degree of conversion, the cement samples were light cured under the ceramic samples and taken to a confocal Raman spectrometer. For the bond strength test, resin cement cylinders were made on the ceramic samples that were later subjected to a microshear. The results showed that the increase in thickness caused a decrease on degree of conversion of both cements in all the conditions studied, but it only had an influence on bond strength of Variolink LC cement for MO ceramic. Comparing the opacities, for the degree of conversion, the most translucent ceramics had higher conversion values compared to the less translucent ones in some thicknesses. As for bond strength, in some thicknesses the LT and MO ceramics showed the highest values. The dual cement Multilink showed the highest values of conversion degree and bond strength compared to Variolink Esthetic LC light-cured cement. The Multilink dual cement showed the highest values in both analyzes compared to the Variolink LC light-cured cement. Therefore, increasing the thickness and opacity of the ceramic material can promote a decrease in the degree of cement conversion. The bond strength also suffers a decrease with increasing thickness of more opaque ceramics and the greater translucency of the material does not guarantee higher values of this same property(AU)

Estudo de série de casos sobre voz e transexualidade: características acústicas de homens e mulheres trans brasileiras / Case series study on voice and transsexuality: acoustic characteristics of Brazilian trans men and women / Estudio de serie de casos sobre voz y transexualidad: características acústicas de hombres y mujeres trans brasileños

Objetivo: Descrever as características acústicas na voz de homens e mulheres trans. Método: Participaram desta pesquisa seis pessoas trans, dois homens e quatro mulheres trans, com idade superior a 18 anos. Foram utilizados o software SoundForge 10.0®, o Advanced Multi- Dimensional Voice Programm (MDVP-Adv) para extração das medidas da análise acústica computadorizada e o programa Analysis Synthesis Laboratory (Computerized Speech Lab - Kay Pentax®) para análise do filtro vocal. Resultados: Os valores dos formantes se mostraram menores quando comparados à literatura nacional e internacional. As medidas de f0 apresentaram valores abaixo do esperado ao gênero feminino e aumentados ao gênero masculino. Quanto às medidas de frequência fundamental máxima (fhi) e mínima (flo), os resultados apresentaram uma grande variabilidade, sugerindo instabilidade fonatória. Os resultados de jitter e shimmer e os parâmetros relacionados ao ruído, como o Índice de turbulência vocal (VTI) e Índice de fonação suave (SPI) mostraram-se incongruentes quando relacionados aos parâmetros de normalidade. A medida de ruído/harmônico NHR se mostrou maior que os valores de normalidade, sugerindo presença de ruído ou rouquidão durante a emissão. As medidas de tremor vocal (Fatr e Ftri) apresentaram distribuição anormal quando comparadas à literatura. Não foi possível observar relação nas análises das características acústicas entre os valores de referência e as pessoas participantes desta pesquisa. Conclusão: As medidas acústicas de vozes de homens e mulheres trans apresentam análises diferentes quando comparados à literatura, evidenciando fragilidade dos programas de análise vocal acústica que não contemplam a heterogeneidade cultural e as variadas identidades de gênero.

Objective: To describe the acoustic characteristics in the voice of trans men and women. Method: Six trans subjects, two men and four trans women, aged over 18 years participated in this study. The SoundForge 10.0® software was used to edit and select the vowel /a/, the Advanced Multi-Dimensional Voice Program (MDVP-Adv) for extraction of measurements from computerized acoustic analysis, and the Analysis Synthesis Laboratory program (Computerized Speech Lab - Kay Pentax®) for analysis of the vocal filter. Results: Formant values were lower when compared to national and international literature. The measures of f0 presented values below that expected for the female gender and increased to the male gender. Regarding the measures of the highest fundamental frequency (fhi) and the lowest (flo), the results showed great variability, suggesting phonatory instability. The results of jitter and shimmer and noise-related parameters, such as Voice Turbulence Index (VTI) and Soft Phonation Index (SPI), were incongruent when related to normality parameters. The noise / harmonic NHR measurement showed to be higher than the normal values, suggesting the presence of noise or hoarseness during the emission. Measurements of vocal tremor (Fatr and Ftri), presented an abnormal distribution when compared to the literature. It was not possible to observe relations in the analysis of the acoustic characteristics between the reference values and the people participating in this research. Conclusion: The acoustic measures of voices of trans people present different analysis when compared to the literature, evidencing the fragility of acoustic vocal analysis programs that do not contemplate the cultural heterogeneity and the varied gender identities.

Objetivo: describir las características acústicas en la voz de hombres y mujeres trans. Metodos: Seis personas trans, dos hombres y cuatro mujeres trans, mayores de 18 años participaron en esta investigación. El software SoundForge 10.0®, Programa de voz multidimensional avanzado (MDVP-Adv) se utilizaron para extraer las mediciones del análisis acústico computarizado y el programa del Laboratorio de síntesis de análisis (Laboratorio de habla computarizada - Kay Pentax®) para analizar el filtro vocal. Resultados: Los valores de los formantes demostraron ser más bajos en comparación con la literatura nacional e internacional. Las mediciones de f0 mostraron valores inferiores al esperado para el género femenino y aumentaron para el género masculino. En cuanto a las medidas de frecuencia fundamental máxima (fhi) y mínima (flo), los resultados mostraron una gran variabilidad, lo que sugiere inestabilidad fonatoria. Los resultados de jitter y shimmer y los parámetros relacionados con el ruido, como el índice de turbulencia vocal (VTI) y el índice de fonación suave (SPI) fueron incongruentes cuando se relacionaron con los parámetros de normalidad. La medida de ruido / armónicos NHR fue más alta que los valores normales, lo que sugiere la presencia de ruido o ronquera durante la emisión. Las mediciones del temblor vocal (Fatr y Ftri) mostraron una distribución anormal en comparación con la literatura. No fue posible observar una relación en el análisis de las características acústicas entre los valores de referencia y las personas que participan en esta investigación. Conclusión: Las medidas acústicas de las voces de las personas trans presentan diferentes análisis en comparación con la literatura, mostrando la fragilidad de los programas de análisis acústico vocal que no contemplan la heterogeneidad cultural y las diferentes identidades de género.

Innate immune memory mediates increased susceptibility to Alzheimer's disease-like pathology in sepsis surviving mice.

Sepsis survivors show long-term impairments, including alterations in memory and executive function. Evidence suggests that systemic inflammation contributes to the progression of Alzheimers disease (AD), but the mechanisms involved in this process are still unclear. Boosted (trained) and diminished (tolerant) innate immune memory has been described in peripheral immune cells after sepsis. However, the occurrence of long-term innate immune memory in the post-septic brain is fully unexplored. Here, we demonstrate that sepsis causes long-lasting trained innate immune memory in the mouse brain, leading to an increased susceptibility to Aß oligomers (AßO), central neurotoxins found in AD. Hippocampal microglia from sepsis-surviving mice shift to an amoeboid/phagocytic morphological profile when exposed to low amounts of AßO, and this event was accompanied by the upregulation of several pro-inflammatory proteins (IL-1ß, IL-6, INF-γ and P2X7 receptor) in the mouse hippocampus, suggesting that a trained innate immune memory occurs in the brain after sepsis. Brain exposure to low amounts of AßO increased microglial phagocytic ability against hippocampal synapses. Pharmacological blockage of brain phagocytic cells or microglial depletion, using minocycline and colony stimulating factor 1 receptor inhibitor (PLX3397), respectively, prevents cognitive dysfunction induced by AßO in sepsis-surviving mice. Altogether, our findings suggest that sepsis induces a long-lasting trained innate immune memory in the mouse brain, leading to an increased susceptibility to AßO-induced neurotoxicity and cognitive impairment.

Prognostic value of immunohistochemical markers in canine cutaneous mast cell tumours: A systematic review and meta-analysis.

Histological grading systems remain cornerstones in the prognosis of canine cutaneous mast cell tumours (MCTs), but the distinct biological behaviour of each tumour often necessitates the use of complementary markers. Although a plethora of immunohistochemical markers have been proposed as prognostic factors, few are presently applied in routine diagnosis. This systematic review and meta-analysis was designed to establish which immunohistochemical markers have verifiable prognostic value for cutaneous MCTs in dogs. A Boolean search of five databases identified 200 articles for screening, of which 73 were selected for full-text assessment and 24 ultimately included in the systematic review. Odds Ratio (OR) was adopted as the summary measure for subsequent meta-analysis but only 15 articles, relating to the immunomarkers Ki-67 (9), KIT (5), and BAX (2), provided either a value for OR or sufficient data to calculate this statistic. Meta-analysis verified that canine cutaneous MCTs with elevated expression of Ki-67 or BAX, as well aberrant immuno-expression of KIT, showed an increased odds of death, with respective OR values of 11.2 (95% CI 6.3-20.0; p < .01), 9.9 (95% CI 1.3-73.6; p = .03), and 4.1 (95% CI 1.1-15.3; p = .03). Despite KIT, Ki67, and BAX arise as suitable prognostic factor for canine MCTs, this study highlighted the lack of important clinical and statistical data in many published articles, rendering it impossible to complete the meta-analysis of several potentially valuable immunohistochemical markers.