Immune response of BALB/c mice infected with two strains of Corynebacterium pseudotuberculosis.

This work evaluated aspects of the immune response of BALB/c mice infected with Corynebacterium pseudotuberculosis (T1 and C57). The fifteen BALB/c mice were euthanized after 70 days of infection and morphologically evaluated, also analyzing the innate and adaptive immune responses. The C57 strain induced more pronounced morphological changes than the T1 strain. There was an increase in CD4+ and CD8+ T cells identified during infection with the C57 strain. Cytokines of the inflammatory profile IL-1α and IL-6 and regulatory IL-13 and IL-10 presented significant differences. Cytokines IL-2, IL-4, INF-γ, IL-22, IL-21, and IL-27 did not differ significantly between groups. The obtained results contribute to a better understanding of the type of response and the immunological mechanisms involved during infection with different strains of C. pseudotuberculosis.

Depression and associated factors among Brazilian adults: the 2019 national healthcare population-based study.

BACKGROUND: Mental disorders represent a major public health challenge worldwide, affecting 80% of people living in low- and middle-income countries. Depression, a mental disorder, is a chronic disease of long duration that causes changes in the brain, resulting from a combination of genetic, physiologic, environmental, and behavioral factors. The aim of this study was to investigate possible factors associated with depression in Brazilian adults. METHODS: A population-based, cross-sectional study was carried out using the public domain database of the 2019 National Health Survey, conducted in Brazil. Depression was considered the dependent variable, and through hierarchical analysis, predictor variables were investigated such as, at the distal level-socioeconomic variables, at the intermediate level-variables related to lifestyle behavior, health condition, and history, and at the proximal level-demographic variables. Logistic regression analysis was used to obtain the adjusted Odds Ratio and the respective 95% confidence interval to identify possible factors associated with depression. RESULTS: The study included 88,531 participant records with 10.27% diagnosed with depression. The adjusted association measurements, after selecting the independent variables in the hierarchical analysis, showed the following factors associated with depression with differing magnitudes: age, brown and white race/skin color, female sex, poor, very poor, or regular self-reported health condition, diagnosis of cardiovascular disease, work-related musculoskeletal disorder, history of smoking habit, and macroeconomic region. CONCLUSIONS: An effective strategy for preventing and managing depression in Brazilian adults must include the control of health status and lifestyle behavior factors, with actions and programs to reduce people's exposure to these factors, understanding that socioeconomic-demographic differences of each population can potentially reduce the disease burden.

Periodontitis is a factor associated with dyslipidemia.

OBJECTIVE: To investigate the association between the severity of periodontitis (exposure) and dyslipidemia (outcome). METHODS: This was a cross-sectional study of users of public health services. Periodontitis was defined using the Center for Disease Prevention and Control and the American Academy of Periodontology criteria. Lipid evaluation used data on systemic biomarkers. Dyslipidemia diagnosis was based on the Guidelines of total cardiovascular risk of the World Health Organization. Weight, height, waist circumference, and blood pressure were measured, and socioeconomic-demographic, lifestyle behavior factors, general and oral health conditions of the participants were collected. Hierarchical and logistic regression analyzes were used to determine the association between the exposures and the outcome. Odds Ratios, unadjusted and adjusted, and 95% confidence intervals were estimated. RESULTS: Of 1,011 individuals examined, 75.17% had dyslipidemia, and 84.17% had periodontitis, 0.2% with mild, 48.56% moderate, and 35.41% severe disease. The association between periodontitis and dyslipidemia was maintained through hierarchical analysis and in the multiple regression modeling, showing that the occurrences of dyslipidemia in the group with periodontitis, and its moderate and severe levels, were, respectively, 14%, 30%, and 16% higher compared with those without periodontitis. CONCLUSIONS: The results showed a positive association between moderate and severe periodontitis and dyslipidemia.

Obesity in young women is positively associated with periodontitis.

OBJECTIVE: This cross-sectional study was performed to investigate the association between excess body weight and periodontitis in adults, stratified by sex and age, and using different criteria for obesity. MATERIAL AND METHODS: Enrolled in the study were 345 individuals with a minimum age of 18 years who had attended the Public Health Service in the city of Salvador, Bahia, Brazil. All individuals underwent a complete periodontal examination and anthropometric measurements and answered a questionnaire regarding their socioeconomic, demographic, health, and lifestyle conditions. Excess body weight (exposure factor) was defined using body mass index (BMI) and waist circumference (WC). Prevalence ratios (PRs) and 95% confidence intervals (95%CI) were obtained by Poisson regression analysis with robust variance. RESULTS: Periodontitis was found in 74.2% of study participants, with the disease being more prevalent among those individuals with increased WC. The occurrence of overweight was 44.4% and that of obesity ranged from 29.9 to 70.8%, dependent upon the specific definition of obesity that was used. There was a positive association between obesity (WC > 88 cm) and periodontitis only among women, after adjustment for age, smoking habit, education level, diabetes, and family income (PRadjusted: 1.20; 95%CI: [1.01-1.44]). The magnitude of this positive association was higher among women aged 18 to 49 years when the outcome was severe periodontitis, and the exposure was obesity defined by WC. CONCLUSIONS: The findings draw attention to the high frequency of the diseases investigated: overweight, obesity and periodontitis. Moreover, obesity was positively associated with periodontitis in women and younger individuals, demonstrating that among those with obesity, there is a higher probability of having periodontitis. The smaller number study of men in the may have influenced the non-statistically significant association found in that group. CLINICAL RELEVANCE: Obese females and younger people are more likely to also have periodontitis. Periodontal evaluation and clinical management of individuals with obesity is recommended.

Obesity and periodontitis are not associated in pregnant women.

OBJECTIVE: The objective of this study was to investigate an association between obesity (exposure) and periodontitis (outcome) in pregnant women. BACKGROUND: This association was investigated and only five studies were identified as showing a positive association. However, some of these studies had limitations such as reduced sample sizes, inadequate exposure criteria and outcome measures, which question the internal validity of these investigations. METHODS: A cross-sectional study was carried out with a sample of 644 pregnant women of the public health service of the municipality of Santo Antônio de Jesus, Bahia, Brazil. Data were obtained by collecting of socioeconomic-demographic information, health behavior, health conditions, and reproductive history through an interview. Obesity was evaluated using body mass index adjusted for gestational age and expected weight gain. The diagnosis of periodontitis followed two criteria: (a) Center for Disease Prevention and Control and American Academy of Periodontology (CDC/AAP); (b) Gomes-Filho et al (2018) using criterion that also evaluated bleeding upon probing; Prevalence ratios and respective 95% confidence intervals were obtained by Poisson regression analysis. RESULTS: In accordance with the outcome diagnostic criterion, the frequency of periodontitis was 17.24% (Gomes-Filho et al) and 66.92% (CDC/AAP). The participants were classified as low weight (19.72%), adequate weight (42.39%), overweight (24.84%), and obesity (13.04%), based on the exposure diagnostic criterion. The low weight and overweight groups were excluded from the data analysis, giving a final sample of 357 pregnant women. The association between obesity in pregnant women and periodontitis was not statistically significant, after adjusting for confounders such as age, schooling level, alcoholic beverage consumption, alimentary and nutritional orientation, urinary infection, and dental flossing. CONCLUSIONS: The findings showed a high frequency of periodontitis, obesity, and overweight in the studied population but no association between obesity and periodontitis in pregnant women was found.

Periodontitis and respiratory diseases: A systematic review with meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the recent scientific literature addressing the association between periodontitis and asthma, chronic obstructive pulmonary disease (COPD), and pneumonia. MATERIALS AND METHODS: The search for studies was carried out using MEDLINE/PubMed, EMBASE, Lilacs, Web of Science, Scopus, and SciELO databases, including the gray literature (ProQuest). Reference lists of selected articles were also searched. Studies having varying epidemiological designs assessing the association between periodontitis and respiratory diseases in human subjects were eligible for inclusion. Three independent reviewers performed the selection of articles and data extraction. Fixed and random effects meta-analysis were performed for the calculation of the association measurements (Odds Ratio-OR) and 95% confidence intervals (95% CI). RESULTS: A total of 3,234 records were identified in the database search, with only 13 studies meeting the eligibility criteria and 10 studies contributed data for meta-analysis. Using a random effects models periodontitis was associated with asthma: ORadjusted: 3.54 (95% CI: 2.47-5.07), I2  = 0%; with COPD: OR adjusted: 1.78 (95% CI: 1.04-3.05), I2  = 37.9%; and with pneumonia: OR adjusted: 3.21 (95% CI: 1.997-5.17), I2  = 0%. CONCLUSIONS: The main findings of this systematic review validated an association between periodontitis and asthma, COPD and pneumonia.

Factors associated with dental caries, periodontitis and intra-oral lesions in individuals with HIV / AIDS.

This study aimed to investigate the factors associated with oral diseases in individuals with HIV/AIDS. A cross sectional study was carried out which included 312 individuals registered in the Specialized Care Services for HIV/AIDS in three municipalities of the State of Bahia: Feira de Santana, Santo Antonio de Jesus and Juazeiro, Brazil. Socioeconomic-demographic characteristics related to life style and to dental caries, periodontitis and intra-oral mucosal lesions were investigated in patients with HIV/AIDS infection. Prevalence Ratio with 95% Confidence Interval and significance level of 5% were employed for the statistical analysis. The majority of the individuals evaluated were male with a mean age (± standard deviation) of 41.5 ± 11.3 years, and a mean time of HIV infection diagnosis (± standard deviation) of 5.2 ± 4.4 years. The presence of dental caries was observed in 78.7% of the sample, periodontitis in 25.4% and 36.2% showed intra-oral lesions. Oral health status showed a statistically significant association with the following variables: gender, age, schooling level, current occupation, family income, past and current smoking, antiretroviral use time, latest viral burden dosage, latest CD4-positive T lymphocyte count, use of complete/partial dental prosthesis, need for dental prosthesis, and use of dental floss. With the exception of those factors directly related to HIV/AIDS i.e., antiretroviral use time, latest viral burden dosage and latest CD4-positive T lymphocyte count, the factors associated with oral diseases in this population were the same as those associated with oral diseases in the non-HIV/AIDS population.

Association between periodontitis and severe asthma in adults: A case-control study.

OBJECTIVE: To evaluate the association between periodontitis and severe asthma, with participants in treatment for severe asthma, controlled by therapy. METHODS: A case-control investigation was performed to compare 130 adults with severe asthma with 130 without asthma. Individuals with periodontitis were those with ≥4 teeth with ≥1 site with probing depth ≥4 mm, clinical attachment level ≥3 mm, and bleeding upon probing at the same site. Severe asthma diagnosis was based on Global Initiative for Asthma criteria. RESULTS: Association between exposure to periodontitis and severe asthma was found: ORcrude  = 2.98 (95% CI: 1.74-5.11). When confounders were considered, the association between exposure to periodontitis and severe asthma was maintained: ORadjusted  = 3.01-3.25. Individuals with periodontitis had about a threefold increased risk of severe asthma than those without periodontitis. Frequency of periodontitis in participants with severe asthma was greater than that of those without asthma (46.6% vs 22.3%, p ≤ .05). CONCLUSIONS: Association between periodontitis and severe asthma was observed. Further investigation is required to determine the direction of this relationship. It may be causal, but it may also be a consequence of the immunopathological process that characterizes asthma, or else, consequence of the medication used for treatment.

Humoral and cellular immune responses in mice against secreted and somatic antigens from a Corynebacterium pseudotuberculosis attenuated strain: Immune response against a C. pseudotuberculosis strain.

BACKGROUND: Corynebacterium pseudotuberculosis is the etiologic agent of caseous lymphadenitis (CL), a chronic disease that affects goats and sheep. CL is characterized by the formation of granulomas in lymph nodes and other organs, such as the lungs and liver. Current knowledge of CL pathogenesis indicates that the induction of humoral and cellular immune responses are fundamental to disease control. The aim of this study was to evaluate the humoral and cellular immune responses in BALB/c mice inoculated with a C. pseudotuberculosis strain isolated in the state of Bahia, Brazil. RESULTS: The lymphocyte proliferation and in vitro production of IFN-γ, IL-4, IL-10, IL-12 and nitric oxide by spleen cells stimulated with secreted and somatic antigens from the studied strain were evaluated. IgG subclasses were also analyzed. Results showed a significant increase of Th1-profile cytokines after 60 days post-inoculation, as well as an important humoral response, represented by high levels of IgG2a and IgG1 against C. pseudotuberculosis. CONCLUSION: The T1 strain of C. pseudotuberculosis was shown to induce humoral and cellular immune responses in BALB/c mice, but, even at a dosage of 1x10(7) CFU, no signs of the disease were observed.

Effect of maternal periodontitis and low birth weight--a case control study.

INTRODUCTION: Since the 1990s, evidence has been raised that there is an association between maternal periodontal disease and undesirable gestational events, for example low birth weight; this issue is controversial. OBJECTIVE: To evaluate whether there is an association between maternal periodontitis and low birth weight (LBW). METHODS: A case-control study was carried out on 951 mothers that had been cared for by the Brazilian Unified Health System in Petrolina-PE and Juazeiro-BA, Brazil. The case group (n = 269) consisted of mothers of newborns with birth weight <2500 g and a control group (n = 682) of mothers of newborns with birth weight ≥2500 g. An interview was realized, using a questionnaire as well as a full mouth examination to diagnose the periodontal condition. Women who had at least four teeth with probing depth ≥4 mm and clinical attachment loss ≥3 mm, with bleeding on probing at the same site, were diagnosed with periodontitis. The birth weight was obtained through the hospital book record. The main association was evaluated using the multivariate regression model, considering confounders. RESULTS: The frequency of periodontitis was 16.4% (case group) and 17.4% (control group). Periodontitis did not show an association with LBW (ORcrude = 0.92; 95% CI = 0.63-1.35), even after adjustment for the following confounders: maternal age, pre-gestational body mass index, number of pre-natal consultations, number of pregnancies, maternal schooling level, smoking habit during pregnancy and hypertension (ORadjusted = 1.00; 95% CI = 0.61-1.68). CONCLUSION: The findings of this study showed no association between maternal periodontal disease and low birth weight, even after appropriate adjustments for confounding factors.

Can periodontal infection induce genotoxic effects?

OBJECTIVE: This study aimed to evaluate the occurrence of chromosomal abnormalities, through micronuclei, and apoptosis by the sum of karyorrhexis, pyknosis and condensed chromatin in individuals with chronic periodontitis, gingivitis associated with biofilm and no periodontal disease. MATERIALS AND METHODS: This study included 72 individuals divided into three groups: gingivitis (n = 21), periodontitis (n = 24) and control (n = 27). Information on sociodemographic characteristics, health and lifestyle was obtained. Full mouth clinical examination was performed to define the periodontal condition. Exfoliated cells from gingival mucosa were collected for computation of micronuclei and nuclear changes indicative of apoptosis. The differences in the occurrence of endpoints (micronucleus, karyorrhexis, pyknosis and condensed chromatin) were evaluated using the conditional test to compare proportions in a rare events situation. RESULTS: There was no statistically significant difference in the occurrence of micronucleus (p > 0.1) between gingivitis, periodontitis and control groups. The occurrence of apoptosis was significantly higher among individuals with periodontitis compared to individuals with gingivitis (p < 0.05) and controls (p < 0.025). CONCLUSIONS: The findings showed that the inflammatory process generated by gingivitis and periodontitis is not related to a higher occurrence of chromosomal damage. However, the higher occurrence of apoptosis in individuals with periodontitis points to genotoxic effects induced by periodontal infection.

MAPK involvement in cytokine production in response to Corynebacterium pseudotuberculosis infection.

BACKGROUND: Caseous lymphadenitis (CL) is a contagious infectious disease of small ruminants caused by Corynebacterium pseudotuberculosis. Is characterized by the formation of abscesses in the lymph nodes and intestines of infected animals, induced by inflammatory cytokines. The production of cytokines, such as IL-10, TNF-α, IL-4 and IFN-γ, is regulated by mitogen-activated protein kinase (MAPK) pathway activation. The present study investigated the involvement of MAPK pathways (MAPK p38, ERK 1 and ERK 2) with respect to the production of cytokines induced by antigens secreted by C. pseudotuberculosis over a 60-day course of infection. CBA mice (n = 25) were divided into three groups and infected with 102 colony forming units (CFU) of attenuated strain T1, 102 CFU of virulent strain VD57 or sterile saline solution and euthanized after 30 or 60 days. Murine splenocytes were treated with specific inhibitors (MAPK p38 inhibitor, ERK 1/2 inhibitor or ERK 2 inhibitor) and cultured with secreted antigens obtained from pathogenic bacteria (SeT1 or SeVD57). RESULTS: The MAPK pathways evaluated were observed to be involved in the production of IL-10, under stimulation by secreted antigens, while the MAPK p38 and ERK 1 pathways were shown to be primarily involved in TNF-α production. By contrast, no involvement of the MAPK p38 and ERK 1 and 2 pathways was observed in IFN-γ production, while the ERK 2 pathway demonstrated involvement in IL-4 production only in the mouse splenocytes infected with VD57 under stimulation by SeT1. CONCLUSION: The authors hypothesize that MAPK p38 and ERK 1 pathways with respect to TNF-α production, as well as the MAPK p38 and ERK 1 and 2 pathways in relation to IL-10 production under infection by C. pseudotuberculosis are important regulators of cellular response. Additionally, the lack of the MAPK p38 and ERK 1/2 pathways in IFN-γ production in infected CBA murine cells stimulated with the two secreted/excreted antigens, in IL-4 production showing involvement only via the ERK 2 pathway under stimulation by SeT1 antigen during 60-day infection period with the virulent strain, suggests that these pathways regulated the production of pro-inflammatory and regulatory cytokines in the splenic cells of CBA mice.

Pathophysiological and Clinical Significance of Crotalus durissus cascavella Venom-Induced Pulmonary Impairment in a Murine Model.

Crotalus venom has broad biological activity, including neurotoxic, myotoxic, hematologic, and cytotoxic compounds that induce severe systemic repercussions. We evaluated the pathophysiological and clinical significance of Crotalus durissus cascavella (Cdc) venom-induced pulmonary impairment in mice. We conducted a randomized experimental study, involving 72 animals intraperitoneally inoculated with saline solution in the control group (CG), as well as venom in the experimental group (EG). The animals were euthanized at predetermined intervals (1 h, 3 h, 6 h, 12 h, 24 h, and 48 h), and lung fragments were collected for H&E and Masson histological analysis. The CG did not present inflammatory alterations in pulmonary parenchyma. In the EG, interstitial and alveolar swelling, necrosis, septal losses followed by alveolar distensions, and areas of atelectasis in the pulmonary parenchyma were observed after three hours. The EG morphometric analysis presented pulmonary inflammatory infiltrates at all time intervals, being more significant at three and six (p = 0.035) and six and 12 h (p = 0.006). The necrosis zones were significant at intervals of one and 24 h (p = 0.001), one and 48 h (p = 0.001), and three and 48 h (p = 0.035). Crotalus durissus cascavella venom induces a diffuse, heterogeneous, and acute inflammatory injury in the pulmonary parenchyma, with potential clinical implications for respiratory mechanics and gas exchange. The early recognition and prompt treatment of this condition are essential to prevent further lung injury and to improve outcomes.

Variants in interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes that modulate inflammatory response are associated with periodontitis.

OBJECTIVE: Evaluate the association of genetic variants of the interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes with periodontitis. METHODS: The study involved 117 individuals with periodontitis and 389 without periodontitis, all Brazilians, miscegenated. Individuals with periodontitis presented at least 4 teeth with ≥ 1 site with probing depth ≥ 4 mm; clinical attachment level ≥ 3 mm on the same site and bleeding upon stimulus. Genotyping was performed using the Infinium Multi-Ethnic AMR/AFR-8 Bead Chip focused on Hispanic and African American populations with approximately 2 million markers of the human genome. Multivariate logistic regression was performed to identify associations in additive, dominant and recessive models adjusted for covariates age, obesity, mouth breathing, flossing, asthma, and ancestry. RESULTS: In IFI16, the rs75985579-A is positively associated with periodontitis in the additive (Odds Ratio adjusted (ORadjusted) 2.65, 95% confidence interval (CI):1.25-5.60, p value: 0.007) and dominant models (ORadjusted 2.56, 95%CI:1.13-5.81, p value: 0.017). In AIM2, the rs76457189-G, is associated negatively with periodontitis in two genetic models evaluated, additive (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022) and dominant (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022). CONCLUSIONS: These results have shown that variants in the IFI16 and AIM2 genes are associated with periodontitis. Individuals with at least one A (adenine) allele of the rs75985579 (IFI16) are more than twice as likely to have periodontitis, while individuals with the G (guanine) allele of rs76457189 (AIM2) are less likely to be diagnosed with periodontitis, providing a negative association with periodontitis.

The leprosy reaction is associated with salivary anti-Porphyromonas gingivalis IgA antibodies.

The aim of the study was to evaluate the association between salivary anti-Porphyromonas gingivalis IgA antibodies and the leprosy reaction. The levels of salivary anti - P. gingivalis IgA antibodies, together with salivary flow and pH were measured in individuals diagnosed with leprosy and associated with the development of the leprosy reaction. Saliva was collected from 202 individuals diagnosed with leprosy at a reference leprosy treatment center, 106 cases with the leprosy reaction and 96 controls without the leprosy reaction. Anti - P. gingivalis IgA was evaluated by indirect immunoenzyme assay. Non-conditional logistic regression analysis was employed to estimate the association between antibody levels and the leprosy reaction. There was a positive statistically significant association between the levels of anti - P. gingivalis IgA and the presence of the leprosy reaction, controlling for confounders: age, sex, level of education and alcoholic beverage consumption: ORajusted: 2.55; IC 95%: 1.34-4.87. Individuals with leprosy who had high levels of salivary anti - P. gingivalis IgA had approximately twice as many chances of developing the leprosy reaction. The findings suggest a possible relationship between salivary anti - P. gingivalis IgA antibodies and the leprosy reaction.

Periodontitis in individuals with few remaining teeth and a high gingival bleeding index increases the probability of dyslipidemia.

BACKGROUND: Dyslipidemia, a silent multifactorial condition, is characterized by changes in blood lipid levels, affecting all socioeconomic strata, increasing the risk for atherosclerotic diseases. This study investigated whether there is an association between dyslipidemia and the combined exposure of periodontitis plus the number of remaining teeth, gingival bleeding, or caries. METHODS: A two-center cross-sectional study was conducted involving 1270 individuals, with a minimum age of 18 years. Socioeconomic and demographic data, health conditions, lifestyle parameters, and anthropometric, biochemical, and oral clinical examinations were performed. The exposures considered were the presence of periodontitis, dental caries, number of remaining teeth, and gingival bleeding. The outcome was dyslipidemia as defined by the Brazilian Guidelines on Dyslipidemia and Prevention of Atherosclerosis. The combined associations between periodontitis plus other oral health conditions and dyslipidemia were estimated using confounder-adjusted prevalence ratios (PRsingle , PRmultiple , for single and multiple covariable adjustments) with 95% confidence intervals (95% CIs), in a Poisson regression model with robust variance. RESULTS: The occurrence of dyslipidemia was 70.1% and periodontitis was 84.1%. A positive association between periodontitis and dyslipidemia existed: PRsingle  = 1.13; 95% CI: 1.01-1.26. Combined exposure of periodontitis plus <11 remaining teeth (PRmultiple  = 1.23; 95% CI: 1.05-1.43), as well as combined exposure of periodontitis plus ≥10% gingival bleeding and <11 remaining teeth (PRmultiple  = 1.22; 95% CI: 1.03-1.44), represented greater probabilities of 23% and 22% of individuals having a diagnosis of dyslipidemia. CONCLUSION: Periodontitis combined with fewer than 11 teeth doubled the likelihood of being diagnosed with dyslipidemia.

MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study.

BACKGROUND: The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response. OBJECTIVE: In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes. METHODS: This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured. RESULTS: The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively. CONCLUSIONS: These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.

Gene expression profile of chronic oral graft-versus-host disease.

Among the complications observed after allogeneic hematopoietic stem cell transplantation, graft-versus-host disease (GVHD) is the primary cause of post-transplant mortality. The oral cavity is the second most affected organ target in chronic GVHD. Tissue damage results from the upregulation of inflammatory mediators, which play a critical role in the immunopathogenesis of the disease. This case series observational study aims to evaluate the participation of cytokines, chemokines, transcription factors, and heat shock proteins in the pathogenesis of oral GVHD (oGVHD), describing the mRNA expression of 28 genes selected. Peripheral blood mononuclear cells were isolated from six participants with oGVHD and two without GVHD, and relative expression of transcripts with established roles as inflammatory mediators was determined in triplicate using the human RT2 Profiler™ PCR Array. The gene expression levels in the group with oGVHD were mainly up-regulated compared to those without GVHD. PBMC from oGVDH expressed consistently higher IFN-γ, TNF, IL-1ß, CCL2, HSP60 (HSPD1) and HSP90 (HSP90B1). These results can provide a basis for developing new molecular diagnostics and targets therapies for the clinical management of oGVHD.