FasL Expression in Articular Discs of Human Temporomandibular Joint and Association with Osteoarthrosis

Background Apoptosis is a programme of cell death which does not induce an inflammatory response. Recent previous research has suggested a correlation between temporomandibular internal derangement and apoptosis. Fas ligand (FasL) is an apoptosis‐inducing factor, known to trigger apoptosis through distinct signal pathways. This study aims to examine, by immunohistochemistry, the expression of FasL in temporomandibular joint (TMJ) articular discs of patients with anterior disc displacement with reduction (ADDwR) and without reduction (ADDwoR) in patients with and without osteoarthrosis (OA). Methods Forty‐two (n = 42) TMJ articular discs were divided into two cut‐offs: (i) 8 control, 17 ADDwR, 17 ADDwoR, and (ii) without OA (n = 25) and with OA (n = 17). The area of immunostaining was compared statistically between groups (P \u3c 0.05). Results Statistically significant differences were found in the expression of FasL in TMJ discs between the three groups (P = 0.001). ADDwR presented significant higher FasL expression when compared with ADDwoR (P \u3c 0.001). Significant higher FasL expression was observed in the group without OA (P = 0.001). All patients without OA presented ADDwR, while all the patients with OA presented ADDwoR. Conclusion A higher area of in situ immunostaining of FasL was found in temporomandibular discs with reduction, which is the less severe condition. Moreover, a reduced expression of FasL in the discs of patients with osteoarthrosis was found, suggesting that some aspects of apoptosis might underlie the progression of TMJ disorders

A new model of laryngitis: neuropeptide, cyclooxygenase, and cytokine profile

Objectives/Hypothesis: To develop and characterize a new model of laryngeal inflammation by analyzing the presence of neurogenic peptides and expression of cyclooxygenases (COX) and cytokines in the mucosa.Study Design: Laryngitis induced by nasogastric intubation (NGI) was evaluated by histopathologic changes of the mucosa, alterations in calcitonin gene related peptide (CGRP) and substance P (SP) neuropeptides in sensory fibers, and COX-1,2, and cytokine (interleukin [IL]-1, IL-6, IL-10, tumor necrosis factor [TNF]-alpha) expression in the laryngeal mucosa.Methods: Rats submitted to NGI for 1 to 5 weeks were compared with controls. Laryngeal sections were immunostained for stereologic analysis of SP and CGRP fiber density and number of mucosal cells expressing COX-2. Alterations in inflammatory mediators were evaluated by quantitative reverse-transcriptase polymerase chain reaction.Results: NGI induced metaplasia of the epithelium and narrowing of the laryngeal lumen because of hypertrophy of laryngeal glandules and edema. An initial decrease in CGRP- and SP-immunoreactive fibers in the laryngeal mucosa (1-3 wk) was reverted with time (5 wk). COX-2 expression in mucosal cells increased progressively, reaching a maximum level at 5 weeks, and was observed in mononuclear immune cells, which is indicative of a chronic inflammatory process. In regard to mRNA expression levels of inflammatory mediators, TNF-alpha was increased during the 5 week NGI, and IL-10 decreased during the 5 weeks,whereas IL-beta, IL-6, and COX-2 increased in the first 1 to 2 weeks and returned to baseline at 5 weeks.Conclusions: This NGI model results in laryngeal chronic inflammation without direct mechanical aggression of the mucosa and may contribute to the study of future therapeutic approaches to this pathology.FEDERFundação para a Ciência e Tecnologia (FCT) - POCTI/NSE/46399/2002Fundação Calouste Gulbenkian - projecto nº 7455

The selective COX-2 inhibitor etoricoxib reduces acute inflammatory markers in a model of neurogenic laryngitis but loses its efficacy with prolonged treatment

The selective COX-2 inhibitor Etoricoxib reduces acute inflammatory markers in a model of neurogenic laryngitis but loses its efficacy with prolonged treatment.OBJECTIVE: A randomised experimental study was used to evaluate the therapeutic effect of a selective cyclooxygenase-2 (COX-2) inhibitor in neurogenic laryngitis. MATERIALS AND METHODS: Male Wistar Han rats were subjected to the nasogastric intubation model (NGI) of laryngitis for 1 and 2 weeks. The NGI animals were divided into three groups: (1) treated with COX-2 inhibitor Etoricoxib, (2) vehicle and (3) non-intubated animals. A fourth group of animals was submitted to NGI only. Laryngeal sections were immunostained for substance P (SP) and calcitonin gene-related peptide (CGRP) fibre-immunoreactivity (IR) and quantification of COX-2 positive cells through stereological analysis. The expression of COX-2, interleukins IL-1beta, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-alpha) was determined by quantitative real time QRT-PCR. TREATMENT: Etoricoxib (6 mg/kg/day) was prepared in 0.9% sterile saline with 5% glucose (vehicle) and administered daily during 1 or 2 weeks. RESULTS: Treatment for 1 week with Etoricoxib attenuated the CGRP-IR fibre depletion, the COX-2-IR increased cell number and the TNF-alpha and COX-2 mRNA increased levels induced by NGI. Two weeks of treatment had no beneficial effect. CONCLUSIONS: Etoricoxib is effective in neurogenic laryngitis for limited periods of administration, indicating that selective COX-2 inhibitors should be evaluated in the future.This study was supported by Fundacao Calouste Gulbenkian Project No 74551 and Fundacao Grunenthal (Portugal)

Hematological and coagulation parameters as predictors of death by Coronavirus disease in hospitalized patients: a Brazilian follow-up study

This study aimed to evaluate the hematological and coagulation parameters according to the clinical outcomes of coronavirus disease (COVID-19). We analyzed the hematological and coagulation parameters of hospitalized patients with COVID-19 at admission, and two and three weeks during hospitalization. To assess the performance of these parameters in predicting poor outcomes, receiver operating characteristic (ROC) curves were created. We studied 128 patients with COVID-19 (59.2±17.7 years, 56% male). Non-survivors (n=54, 42%) presented significant alterations in hematological and coagulation parameters at admission, such as increased in white blood cells (WBC), neutrophil, and band cell counts, as well as elevated prothrombin time (PT), activated partial thromboplastin time, and D-dimer levels. During follow-up, the same group presented a gradual increase in D-dimer and PT levels, accompanied by a reduction in PT activity, hemoglobin, and red blood cell count (RBC). ROC curves showed that WBC, neutrophil, and band cell counts presented the best area under the curve (AUC) values with sensitivity and specificity of >70%; however, a logistic regression model combining all the parameters, except for RBC, presented an AUC of 0.89, sensitivity of 84.84%, and specificity of 77.41%. Our study shows that significant alterations in hematological and coagulation tests at admission could be useful predictors of disease severity and mortality in COVID-19

Memory Networks in Tinnitus: A Functional Brain Image Study

Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. the network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. the objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. Methods: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). the severity of tinnitus was assessed using the Tinnitus Handicap Inventory (THI). the images were processed and analyzed using Statistical Parametric Mapping (SPM8). Results: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE<0.05) was observed in patients with tinnitus compared with healthy controls. the average total THI score was 50.8+18.24, classified as moderate tinnitus. Conclusion: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Psiquiatria, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Radiol, Secao Med Nucl, São Paulo, BrazilHosp Israelita Albert Einstein, Inst Cerebro, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Fonoaudiol, São Paulo, BrazilUniv Western Australia, Med Res Ctr, Western Australian Ctr Hlth & Ageing, Perth, WA 6009, AustraliaUniversidade Federal de São Paulo, Dept Psiquiatria, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Radiol, Secao Med Nucl, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Fonoaudiol, São Paulo, BrazilFAPESP: FAPESP-2010/14804-6Web of Scienc

Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy – CADASIL

We report here neuroimaging findings of a  41 years-old female with molecular diagnosis of CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). CADASIL, the most common form of hereditary stroke, is characterized by headaches and relapsing strokes. More than 95% of patients present mutations of NOTCH3 gene. MRI, the best neuroimaging modality to investigate CADASIL can show lacunar infarcts and less-well demarcated T2 weighted hyperintensities characteristically located in subcortical white matter. There is no specific treatment for CADASIL. Anti-platelet agents such as aspirin might help to prevent new strokes. Other symptoms, like headache, seizures, or other neuropsychiatric manifestations should be appropriately treated

Genomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazil

Funding Information: Funding: This study was funded, in part, by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (Grant No. 001) and supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grant No. 17/1265–8 INCT-TB). JP is supported by Fundação para a Ciência e Tecnologia through Estímulo Individual ao Emprego Científico (CEECIND/00394/2017). Funding Information: The authors wish to thank TGen, C-Path and ReSeqTB for supporting WGS, and the Brazilian Network of Tuberculosis Research for enabling this partnership. The authors would also like to thank the Mycobacteria Laboratory at LACEN-RS/CEVS/SES-RS for performing and providing information on drug susceptibility testing. Funding: This study was funded, in part, by the Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - Brasil (Grant No. 001) and supported by Funda??o de Amparo ? Pesquisa do Estado do Rio Grande do Sul (Grant No. 17/1265?8 INCT-TB). JP is supported by Funda??o para a Ci?ncia e Tecnologia through Est?mulo Individual ao Emprego Cient?fico (CEECIND/00394/2017). Competing interests: None declared. Ethical approval: This project was approved by the Research Ethics Committee of the Funda??o Estadual de Produ??o e Pesquisa em Sa?de (Protocol No. 1.587.621 CAAE: 18269313.0.0000.5320). Data availability: M. tuberculosis genome data were deposited in the NCBI BioProject database (IDs: PRJNA535343, PRJNA639713 and PRJNA692642). Individual accession numbers for genomes analysed in this study are given in the online supplementary material. Publisher Copyright: © 2021 Elsevier LtdGenomic-based surveillance on the occurrence of drug resistance and its transmission dynamics has emerged as a powerful tool for the control of tuberculosis (TB). A whole-genome sequencing approach, phenotypic testing and clinical-epidemiological investigation were used to undertake a retrospective population-based study on drug-resistant (DR)-TB in Rio Grande do Sul, the largest state in Southern Brazil. The analysis included 305 resistant Mycobacterium tuberculosis strains sampled statewide from 2011 to 2014, and covered 75.7% of all DR-TB cases identified in this period. Lineage 4 was found to be predominant (99.3%), with high sublineage-level diversity composed mainly of 4.3.4.2 [Latin American and Mediterranean (LAM)/RD174], 4.3.3 (LAM/RD115) and 4.1.2.1 (Haarlem/RD182) sublineages. Genomic diversity was also reflected in resistance of the variants to first-line drugs. A large number of distinct resistance-conferring mutations, including variants that have not been reported previously in any other setting worldwide, and 22 isoniazid-monoresistant strains with mutations described as disputed in the rpoB gene but causing rifampicin resistance generally missed by automated phenotypic tests as BACTEC MGIT. Using a cut-off of five single nucleotide polymorphisms, the estimated recent transmission rate was 55.1%, with 168 strains grouped into 28 genomic clusters. The most worrying fact concerns multi-drug-resistant (MDR) strains, of which 73.4% were clustered. Different resistance profiles and acquisition of novel mutations intraclusters revealed important amplification of resistance in the region. This study described the diversity of M. tuberculosis strains, the basis of drug resistance, and ongoing transmission dynamics across the largest state in Southern Brazil, stressing the urgent need for MDR-TB transmission control state-wide.publishersversionpublishe

Effectiveness of a 16-month multicomponent and environmental schoolbased intervention for recovery of poor income overweight/obese children and adolescents: study protocol of the health multipliers program

Background: Excess of weight is a serious public health concern in almost all countries, afflicting people of different ages and socioeconomic backgrounds. Studies have indicated the need for developing treatment strategies that intervene directly in the obesogenic environment. This study aims to evaluate the effectiveness of a multi-component and environmental school-based intervention, lasting 16 months, on the recovery of the nutritional status of lowincome children and adolescents with overweight/obesity. Methods/study design: The study was conducted by the Center for Recovery and Nutritional Education (CREN) in Sao Paulo, Brazil. Two schools located in poor neighborhoods were selected for the intervention, between March 2016 and June 2017. The participants were all students aged 8 to 12 years fromthe two participating schools. At the beginning of the intervention, anthropometric measurements were carried out to assess the nutritional status of the students. For convenience, students from one of the schools were considered as the control group, while those from the other school formed the experimental group. The intervention in the experimental group (n = 438) consists of the following weekly activities at school: psychological counseling in groups, theoretical/practical nutrition workshops, and supervised physical education classes. In addition, theoretical and practical educational activities are held regularly for parents, teachers, and cooks. Students with excess of weight (>= 1 body mass index [BMI] - for-age Z score, n = 138) received clinical and nutritional care periodically at the outpatient care at CREN. Students enrolled in the control group (n = 353) participated in psychological counseling groups and theoretical/practical nutrition workshops for 6 months held in the school environment to provide motivation to entire classrooms. In the following 10 months, students with excess of weight from the control group (n = 125) were invited to attend the routine outpatient care at CREN. Discussion: This study is the first to assess the effectiveness of a multi-component and environmental school-based intervention for the recovery of low-income, overweight/obese children and adolescents. If positive, the results demonstrate the feasibility for the recovery of excess of weight in populations of similar conditions and age.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Sao Paulo, UNIFESP, Dept Physiol, Rua Botucatu 862,2 Andar,Vila Clementino, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Hlth & Soc Inst, Dept Publ Hlth & Collect Hlth, Santos, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Pediat, Sao Paulo, SP, BrazilCREN, Sao Paulo, SP, BrazilUNIFESP, Hlth & Soc Inst, Dept Publ Hlth & Collect Hlth, Santos, SP, BrazilUNIFESP, Dept Human Movement Sci, Santos, SP, BrazilUniv Sao Paulo, Dept Comp Sci, Inst Math & Stat, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Paulista Sch Med, UNIFESP, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Nephrol, UNIFESP, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Physiol, Rua Botucatu 862,2 Andar,Vila Clementino, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Hlth & Soc Inst, Dept Publ Hlth & Collect Hlth, Santos, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Pediat, Sao Paulo, SP, BrazilUNIFESP, Hlth & Soc Inst, Dept Publ Hlth & Collect Hlth, Santos, SP, BrazilUNIFESP, Dept Human Movement Sci, Santos, SP, BrazilUniv Fed Sao Paulo, Paulista Sch Med, UNIFESP, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Nephrol, UNIFESP, Sao Paulo, SP, BrazilFAPESP: 2014/22351-2Web of Scienc

Social distancing measures to control the COVID-19 pandemic: potential impacts and challenges in Brazil.

The COVID-19 pandemic has challenged researchers and policy makers to identify public safety measures forpreventing the collapse of healthcare systems and reducingdeaths. This narrative review summarizes the available evidence on the impact of social distancing measures on the epidemic and discusses the implementation of these measures in Brazil. Articles on the effect of social distancing on COVID-19 were selected from the PubMed, medRXiv and bioRvix databases. Federal and state legislation was analyzed to summarize the strategies implemented in Brazil. Social distancing measures adopted by the population appear effective, particularly when implemented in conjunction with the isolation of cases and quarantining of contacts. Therefore, social distancing measures, and social protection policies to guarantee the sustainability of these measures, should be implemented. To control COVID-19 in Brazil, it is also crucial that epidemiological monitoring is strengthened at all three levels of the Brazilian National Health System (SUS). This includes evaluating and usingsupplementary indicators to monitor the progression of the pandemic and the effect of the control measures, increasing testing capacity, and making disaggregated notificationsand testing resultstransparentand broadly available