Identification of Leishmania infantum in blood donors from endemic regions for visceral leishmaniasis.

Visceral leishmaniasis is an endemic protozoonosis observed in over 60 countries, with over 500 000 new cases recorded annually. Although the diagnostic procedure of its symptomatic forms is well established, for asymptomatic patients, who represent about 85% of those infected, there is no consensus on the best method for its identification. Recent studies have presented molecular techniques as viable identification methods, with good sensitivity and specificity indices in asymptomatic individuals. Therefore, we aimed to use molecular methods to assess their effectiveness in identifying the presence of asymptomatic infection by Leishmania infantum (L. infantum) individuals from endemic regions of Brazil. Screening was performed by real-time polymerase chain reaction (qPCR) and confirmed by sequencing the cytochrome B gene. Of the 127 samples [from 608 blood donors who had participated in a previous study, of which 34 were positive by the enzyme-linked immunosorbent assay (ELISA) rK39] tested by qPCR, 31 (24.4%) were positive. In the sequencing of 10 qPCR-positive samples, five were identified as L. infantum. Complimentary samples of the ELISA rK39 and conventional PCR showed only reasonable and low agreement with qPCR, respectively. The qPCR confirmed the presence of infection in five of the 10 sequenced samples, ELISA confirmed three, and the conventional PCR confirmed none.

Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection.

Toxoplasma gondii (T. gondii) is an intracellular parasite responsible for causing toxoplasmosis. When infection occurs during pregnancy, it can produce severe congenital infection with ocular and neurologic damage to the infant. From the oral infection parasite reaches the intestine, causing inflammatory response, damage in tissue architecture and systemic dissemination. Macrophage migration inhibition factor (MIF) is a cytokine secreted from both immune and non-immune cells, including gut epithelial cells. MIF is described to promote inflammatory responses, to be associated in colitis pathogenesis and also to play role in maintaining the intestinal barrier. The aim of the present study was to evaluate the influence of the pregnancy and MIF deficiency on T. gondii infection in the intestinal microenvironment and to address how these factors can impact on the intestinal architecture and local cytokine profile. For this purpose, small intestine of pregnant and non-pregnant C57BL/6 MIF deficient mice (MIF-/-) and Wild-type (WT) orally infected with 5 cysts of ME-49 strain of T. gondii were collected on day 8th of infection. Intestines were processed for morphological and morphometric analyses, parasite quantification and for cytokines mensuration. Our results showed that the absence of MIF and pregnancy caused an increase in T. gondii infection index. T. gondii immunolocalization demonstrated that segments preferentially infected with T. gondii were duodenum and ileum. The infection caused a reduction in the size of the intestinal villi, whereas, infection associated with pregnancy caused an increase in villi size due to edema caused by the infection. Also, the goblet cell number was increased in the ileum of MIF-/- mice, when compared to the corresponding WT group. Analyses of cytokine production in the small intestine showed that MIF was up regulated in the gut of pregnant WT mice due to infection. Also, infection provoked an intense Th1 response that was more exacerbated in pregnant MIF-/- mice. We also detected that the Th2/Treg response was more pronounced in MIF-/- mice. Altogether, our results demonstrated that pregnancy and MIF deficiency interferes in the balance of the intestinal cytokines and favors a Th1-immflamatory profile, which in turn, impact in the development of pathology caused by T. gondii infection in the intestinal microenvironment.

Parasitological and immunological evaluation of cattle experimentally infected with Trypanosoma vivax.

Trypanosoma vivax infection causes relevant economical impact due to high morbidity and mortality leading to negative impact on local livestock. Despite parasitological and serological methods are used for the diagnosis of T. vivax infection, gaps regarding sensitivity and specificity of these methods still represent a challenge. The present study aimed to compare the kinetics of parasitological and serological parameters in cattle experimentally infected with T. vivax along with immunophenotypic analysis of whole blood leukocytes. Based on the parasitemia profile the analysis were performed in three distinct periods, referred as pre-patent, patent and post-treatment. Distinct kinetics of anti-T. vivax IgM and IgG were observed during the pre-patent, patent and post-treatment periods. Increased levels of WC1+ γδ T-cells were observed throughout the infection with strong correlations with other biomarkers observed during post-treatment period. Our findings demonstrated that there is a important participation of Monocytes:CD14+; NK-cells:CD335+ and WC1+ γδ T-cells that coincide with the peak of parasitemia and also with the adaptive immunity, specially CD4+ T-cells in T. vivax infection. The knowledge of the immune response is important not only for understanding the biology of the parasite in the host, but for the design of new treatment strategies for trypanosome infections.

Salivary Gland Extract of Kissing Bug, Triatoma lecticularia, Reduces the Severity of Intestinal Inflammation through the Modulation of the Local IL-6/IL-10 Axis.

Triatomines are known for their role as vectors of the causative agent of Chagas disease. The occurrence of an arsenal of molecules in their saliva is able to suppress vertebrate immune responses. Thus, it is reasonable to assume that the presence of molecules with therapeutic potential in their saliva is able to constrain inflammation in immune-mediated diseases. Thus, mice were exposed to dextran sulfate sodium (DSS) in drinking water uninterruptedly during 6 consecutive days and treated with T. lecticularia salivary gland extract (SGE) (3, 10, or 30 µg) or vehicle (saline) (n = 6/group). At the highest dose (30 µg), an improvement in clinical outcome and macroscopic aspects of the intestine were observed. This observation was followed by amelioration in histopathological aspects in the colon especially when the doses of 10 and 30 µg were used. Regardless of the concentration used, treatment with T. lecticularia SGE significantly reduced the levels of the inflammatory cytokine IL-6 in the intestine. The production of the anti-inflammatory cytokine IL-10 was positively impacted by the concentrations of 3 and 30 µg. Our results suggest that the presence of molecules in the T. lecticularia SGE is able to attenuate clinical outcome and colon shortening and improve intestinal architecture besides reducing the production of IL-6 and inducing a local production of IL-10 in the intestine.

Th1/Th17-Related Cytokines and Chemokines and Their Implications in the Pathogenesis of Pemphigus Vulgaris.

Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-3. Despite the variety of findings, the chemokine and cytokine profiles that characterize the immune response in the disease are still poorly explored. Thus, 20 PV patients and 20 controls were grouped according to gender, ethnicity, place of residence, and clinical parameters of the disease. Then, the levels of chemokines and of Th1/Th2/Th17/Treg/Th9/Th22-related cytokines were assessed in the serum. PV patients had higher levels of inflammatory Th1/Th17 cytokines (IFN-γ, IL-17, and IL-23), as well as higher levels of CXCL8 and reduced levels of Th1/Th2-related chemokines (IP-10 and CCL11). However, no differences in the levels of IL-2, IL-6, TNF-α, IL-1ß, IL-4, IL-9, IL-12, TGF-ß, IL-33, MCP-1, RANTES, and MIP-1α were found between PV patients and their control counterparts. Furthermore, PV patients with skin lesions had higher serum levels of IL-6 and CXCL8 when compared to PV patients without lesions. Taken together, our findings describe the role of cytokines and chemokines associated with Th1/Th17 immune response in PV patients. Finally, these data are important for better understanding of the immune aspects that control disease outcome, and they may also provide important information about why patients develop autoantibodies against desmogleins.

Morinda citrifolia (Noni) Fruit Juice Reduces Inflammatory Cytokines Expression and Contributes to the Maintenance of Intestinal Mucosal Integrity in DSS Experimental Colitis.

Morinda citrifolia L. (noni) has been shown to treat different disorders. However, data concerning its role in the treatment of intestinal inflammation still require clarification. In the current study, we investigated the effects of noni fruit juice (NFJ) in the treatment of C57BL/6 mice, which were continuously exposed to dextran sulfate sodium (DSS) for 9 consecutive days. NFJ consumption had no impact on the reduction of the clinical signs of the disease or on weight loss. Nonetheless, when a dilution of 1 : 10 was used, the intestinal architecture of the mice was preserved, accompanied by a reduction in the inflammatory infiltrate. Regardless of the concentration of NFJ, a decrease in both the activity of myeloperoxidase and the key inflammatory cytokines, TNF-α and IFN-γ, was also observed in the intestine. Furthermore, when NFJ was diluted 1 : 10 and 1 : 100, a reduction in the production of nitric oxide and IL-17 was detected in gut homogenates. Overall, the treatment with NFJ was effective in different aspects associated with disease progression and worsening. These results may point to noni fruit as an important source of anti-inflammatory molecules with a great potential to inhibit the progression of inflammatory diseases, such as inflammatory bowel disease.

Assessment of angiogenesis modulators in pregnant women with pre-eclampsia: a case-control study.

PURPOSE: This study aimed to evaluate the serum concentration of factors associated with placental angiogenesis in pre-eclamptic and normotensive pregnant women. METHODS: This was a prospective, cross-sectional, case-control study in which the pro-angiogenic factors PlGF, VEGF and IL-10, and the anti-angiogenic factors IL-6, IL-17 and TNF-α of 55 pregnant women (31 with pre-eclampsia-PE and 24 normotensive), with gestational age ≥20 weeks, were measured in maternal blood through the enzyme-linked immunosorbent assay (ELISA). The Mann-Whitney and Kruskal-Wallis tests were used for comparison between groups. RESULTS: Serum PIGF was reduced in the group of pregnant women with PE when compared with the normotensive women (493.2 ± 55.1 pg/mL vs. 4.4 ± 26.5 pg/mL; p < 0.001). There was no significant difference in PlGF levels in the pre-eclamptic pregnant women in relation to gestational age or proteinuria levels (p > 0.05). The serum levels of VEGF, IL-17, IL-10 and TNF-α were lower in the pregnant women with PE when compared with their normotensive peers, while the IL-6 levels were higher; however, this difference was not statistically significant (p > 0.05). CONCLUSION: Serum PlGF levels were reduced in the pregnant women with PE and were unrelated to disease severity. Serum levels of VEGF, IL-17, IL-10 and TNF-α were reduced in the pre-eclamptic pregnant women when compared with their normotensive peers, without statistically significant differences.

Inflammation Biomarkers of Advanced Disease in Nongingival Tissues of Chronic Periodontitis Patients.

Chronic periodontitis is a multifactorial inflammatory disease that affects supporting structures of the teeth. Although the gingival response is largely described, little is known about the immune changes in the alveolar bone and neighboring tissues that could indicate periodontal disease (PD) activity. Then, in this study we identified the ongoing inflammatory changes and novel biomarkers for periodontitis in the tissues directly affected by the destructive disease in PD patients. Samples were collected by osteotomy in 17 control subjects during extraction of third molars and 18 patients with advanced PD, in which alveoloplasty was necessary after extraction of teeth with previous extensive periodontal damage. Patients presented mononuclear cells infiltration in the connective tissue next to the bone and higher fibrosis area, along with increased accumulation of IL-17(+) and TRAP(+) cells. The levels of TNF-α and MMP-2 mRNA were also elevated compared to controls and a positive and significant correlation was observed between TNF-α and MMP-2 mRNA expression, considering all samples evaluated. In conclusion, nongingival tissues neighboring large periodontal pockets present inflammatory markers that could predict ongoing bone resorption and disease spreading. Therefore, we suggested that the detailed evaluation of these regions could be of great importance to the assessment of disease progression.

IL-17-expressing CD4⁺ and CD8⁺ T lymphocytes in human toxoplasmosis.

This study aimed to measure the synthesis of Th1 and Th2 cytokines by mononuclear cells after culture with live T. gondii and identified Th17 (CD4(+)) and Tc17 (CD8(+)) cells in toxoplasma-seronegative and toxoplasma-seropositive parturient and nonpregnant women. Cytometric bead arrays were used to measure cytokine levels (IL-2, TNF-α, IFN-γ, IL-4, IL-5, and IL-10); immunophenotyping was used to characterize Th17 and Tc17 cells, and the cells were stained with antibodies against CD4(+) and CD8(+) T cells expressing IL-17. The addition of tachyzoites to cell cultures induced the synthesis of IL-5, IL-10, and TNF-α by cells from seronegative parturient women and of IL-5 and IL-10 by cells from seropositive, nonpregnant women. We observed a lower level of IL-17-expressing CD4(+) and CD8(+) T lymphocytes in cultures of cells from seronegative and seropositive parturient and nonpregnant women that were stimulated with tachyzoites, whereas analysis of the CD4(+) and CD8(+) T cell populations showed a higher level of CD4(+) T cells compared with CD8(+) T cells. These results suggest that the cytokine pattern and IL-17-expressing CD4(+) and CD8(+) T lymphocytes may have important roles in the inflammatory response to T. gondii, thus contributing to the maintenance of pregnancy and control of parasite invasion and replication.

New immunological aspects of peri-implantitis.

BACKGROUND: The authors compared the levels of HIF1-α, VEGF, TNF-α, and IL-10 in peri-implant crevicular fluid between patients with or without peri-implantitis. HIF-1α levels were significantly high in the peri-implantitis possibly due to hypoxia triggered by persistent inflammation. OBJECTIVE: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. METHODS: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. RESULTS: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. CONCLUSION: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis. BACKGROUND: Higher levels of HIF-1α in patients with peri-implantitis occurred possibly due to persistent hypoxia triggered by inflammation. BACKGROUND: Tissue hypoxia in peri-implantitis induced increase in HIF-1α consequently increased VEGF and angiogenesis, contributing to the persistence of inflammation.

Comparative Analysis of TNF-alpha, TNF-R1, and TNF-R2 in Patients with Low-impact Fractures Due to Osteoporosis.

Objective To analyze the serum levels of TNF-alpha and its TNF-R1 and TNF-R2 receptors in the blood of patients with low-impact fractures due to osteoporosis, comparing between genders and with healthy patients. Methods The present study was conducted with a blood sample of 62 patients, divided into patients with osteoporosis and healthy patients. The results were obtained using the ELISA method. Cytokine concentrations were determined based on the absorbance values obtained. Results Serum TNF-alpha levels were undetectable in female patients, while in males they were found only in one patient, with no significant difference. Similar results were found in the analyses of TNF-R1 and TNF-R2 levels, a significant increase in levels of TNF-alpha receptors in the groups of patients with osteoporosis compared with the control group in both sexes. There was no significant difference between the sexes in the dosage of both receptors within the group with osteoporosis. There was also a positive and significant correlation in the levels of TNF-R1 and TNF-R2 only in women. Conclusion The significant increase in TNF-R1 and TNF-R2 levels in women with osteoporosis suggest that the release and expression of these receptors may be contributing differently to the development of osteoporosis in men and women.

Effects of complementary spiritual therapy on stress, anxiety, burnout syndrome and hematological parameters of professionals in a public hospital: a randomized controlled trial.

OBJECTIVES: This randomized controlled trial evaluated the stress, anxiety, and burnout of professionals exposed to complementary spiritist therapy (CST), which consists in therapeutic resources as prayer, Spiritist passe, fluidic water and spiritual education or control. METHODS: Seventy-six professionals were randomized to CST or control: to maintain the routine for 5 weeks. The ISSL scale, anxiety and depression Beck's indices, Maslach instrument, subjective well-being and WHOQOL-BREF were used at baseline and five-week. Blood count and cytokine dosage were collected at baseline, one-week and five-week. Analysis using the intention to treat approach. RESULTS: The means of variation of stress (exhaustion phase) between baseline and five-week were -1.50 ± 3.31 in the CST and 0.72 ± 3.50 in the control (p=0.036), effect size for CST group was d=0.65, which is considered medium effect. CST showed decrease in emotional exhaustion and negative affects, and increase in lymphocytes, erythrocyte parameters and platelets between the baseline and five-week (p<0.05). Reduction in IL-1ß and increase in total lymphocyte count were observed with 2-3 sessions per week, but that does not maintain when the number of sessions is decreased. Participants receiving ≥7 sessions reduced emotional exhaustion, depersonalization and stress, and improved hematological parameters throughout the study (p<0.05). CONCLUSIONS: CST may be effective in reducing stress (exhaustion phase) compared to control. Higher frequency of interventions promotes better psychic state, evidenced by large effect size for emotional exhaustion in burnout, and improves hematological parameters of professionals.

Macrophage Migration Inhibitory Factor contributes to drive phenotypic and functional macrophages activation in response to Toxoplasma gondii infection.

Cytokines are small molecules secreted by numerous cells. Macrophage Migration Inhibitory Factor (MIF) is a cytokine initially described due to its function of inhibiting random macrophage migration. Currently, new functions have been described for MIF, such as stimulating inflammatory functions in response to infections by microorganisms including, Toxoplasma gondii. However, the primordial MIF function related to macrophages has been little addressed. The main purpose of the study was to recapitulate MIF function on macrophages in response to T. gondii infection. To achieve this goal, peritoneal macrophages were collected from C57BL/6WT and Mif1-/- mice after recruitment with thioglycolate. Macrophages were cultured, treated with 4-Iodo-6-phenylpyrimidine (4-IPP), and infected or not by T. gondii for 24 h. Following this, the culture supernatant was collected for cytokine, urea and nitrite analysis. In addition, macrophages were evaluated for phagocytic activity and T. gondii proliferation rates. Results demonstrated that T. gondii infection triggered an increase in MIF production in the WT group as well as an increase in the secretion of IL-10, TNF, IFN-γ, IL-6 and IL-17 in the WT and Mif1-/- macrophages. Regarding the comparison between groups, it was detected that Mif1-/- macrophages secreted more IL-10 compared to WT. On the other hand, the WT macrophages produced greater amounts of TNF, IFN-γ, IL-6 and IL-17. Urea production was more pronounced in Mif1-/- macrophages while nitrite production was higher in WT macrophages. T. gondii showed a greater ability to proliferate in Mif1-/- macrophages and these cells also presented enhanced phagocytic activity. In conclusion, T. gondii infection induces macrophage activation inciting cytokine production. In presence of MIF, T. gondii infected macrophages produce pro-inflammatory cytokines compatible with the M1 activation profile. MIF absence caused a dramatic reduction in pro-inflammatory cytokines that are balanced by increased levels of urea and anti-inflammatory cytokines. These macrophages presented increased phagocytic capacity and shared features activation with the M2 profile.

Inflammatory Response and Activation of Coagulation after COVID-19 Infection.

SARS-CoV-2 (COVID-19) infection is responsible for causing a disease with a wide spectrum of clinical presentations. Predisposition to thromboembolic disease due to excessive inflammation is also attributed to the disease. The objective of this study was to characterize the clinical and laboratory aspects of hospitalized patients, in addition to studying the pattern of serum cytokines, and associate them with the occurrence of thromboembolic events. METHODOLOGY: A retrospective cohort study with 97 COVID-19 patients hospitalized from April to August 2020 in the Triângulo Mineiro macro-region was carried out. A review of medical records was conducted to evaluate the clinical and laboratory aspects and the frequency of thrombosis, as well as the measurement of cytokines, in the groups that presented or did not present a thrombotic event. RESULTS: There were seven confirmed cases of thrombotic occurrence in the cohort. A reduction in the time of prothrombin activity was observed in the group with thrombosis. Further, 27.8% of all patients had thrombocytopenia. In the group that had thrombotic events, the levels of IL1b, IL-10, and IL2 were higher (p < 0.05). CONCLUSIONS: In the studied sample, there was an increase in the inflammatory response in patients with thrombotic events, confirmed by the increase in cytokines. Furthermore, in this cohort, a link was observed between the IL-10 percentage and an increased chance of a thrombotic event.

Staphylococcus aureus and Enterococcus faecium isolated from pigeon droppings (Columba livia) in the external environment close to hospitals.

BACKGROUND: Domestic pigeons carry pathogens in their droppings, posing a potential public health problem. METHODS: The phenotypic and genotypic antimicrobial resistances of Staphylococcus aureus and Enterococcus faecium in the feces of urban pigeons near hospitals with intensive care units were measured. RESULTS: Twenty-nine samples showed Enterococcus growth, whereas one was positive for S. aureus. The S. aureus isolate was sensitive to the antibiotics tested via antibiogram, however resistance genes were identified. E. faecium isolates showed phenotypic resistance to gentamicin, erythromycin, and ciprofloxacin. CONCLUSIONS: Antimicrobial profiles harmful to health were demonstrated in bacterial pathogens isolated from the external environment of hospitals.

Role of Cytokines, Chemokines and IFN-γ+ IL-17+ Double-Positive CD4+ T Cells in Patients with Multiple Sclerosis.

Multiple sclerosis is mediated by self-reactive myelin T and B cells that lead to axonal and myelin damage. The immune response in multiple sclerosis involves the participation of CD4+ T cells that produce cytokines and chemokines. This participation is important to find markers for the diagnosis and progression of the disease. In our work, we evaluated the profile of cytokines and chemokines, as well as the production of double positive CD4+ T cells for the production of IFNγ IL-17 in patients with multiple sclerosis, at different stages of the disease and undergoing different treatments. We found that relapsing-remitting patients had a significant increase in IL-12 production. About IL-5, its production showed significantly higher levels in secondarily progressive patients when compared to relapsing-remitting patients. IFN-γ production by PBMCs from secondarily progressive patients showed significantly higher levels. This group also had a higher percentage of CD4+ IFNγ+ IL-17+ T cells. The combination of changes in certain cytokines and chemokines together with the presence of IFNγ+ IL-17+ double positive lymphocytes can be used to better understand the clinical forms of the disease and its progression.

Blood DNA methylation marks discriminate Chagas cardiomyopathy disease clinical forms.

Chagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) ≥ 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology.

Clinical-Epidemiology Aspect of Inpatients With Moderate or Severe COVID-19 in a Brazilian Macroregion: Disease and Countermeasures.

COVID-19, also known as coronavirus disease 2019, is an infectious viral disease caused by SARS-CoV-2, a novel coronavirus. Since its emergence, its epidemiology has been explored; however, for some regions of the world, COVID-19's behavior, incidence, and impact remain unclear. In continental nations like Brazil, this lack of knowledge results in nonuniform control, prevention, and treatment measures, which can be controversial in some locations. This study aimed to describe the epidemiological profile of patients with COVID-19 in the macroregion of Triângulo Sul in the state of Minas Gerais (MG), Brazil. Between March 25 and October 21, 2020, data were collected and statistically analyzed from 395 hospitalized patients in the city of Uberaba, MG, suspected to have moderate or severe forms of the disease. Of the 395 suspected cases, 82% were confirmed to be positive for COVID-19. The mean age of positive patients was 58.4 years, and 60.76% were male. Following these patients throughout their hospitalization, a mortality rate of 31.3% was observed. In the population positive for COVID-19, the risk of death increased by 4% for each year of the patient's age. Likewise, the older the patient, the longer their hospitalization and the higher the risk of developing acute respiratory failure. Among the treatments tested in patients, heparin was associated with protection against mortality, and the absence of anticoagulant use was linked to a more than six times greater risk of death. Finally, comorbidities in patients with COVID-19 were positively correlated with increased hospitalization time. In summary, this study revealed that age, presence of comorbidities, length of hospitalization, and drug treatment considerably altered COVID-19's lethality. To understand infection rates and the factors involved in COVID-19's lethality, knowledge of the local epidemiology is necessary.

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.

The relationship between heart rate variability and serum cytokines in chronic chagasic patients with persistent parasitemia.

BACKGROUND: Persistent parasitemia, immunological, and autonomic nervous system impairments may play an important role in the evolution and clinical outcome of the chronic phase of Chagas' disease by triggering functional cardiovascular changes. METHODS: Three groups were evaluated: 17 chronic chagasic patients with the indeterminate form (IChD), 12 chronic chagasic patients with cardiac forms (ChHD), and 29 individuals as a healthy control group. Parasitemia was assessed by polymerase chain reaction; hemoculture, heart rate variability by linear and nonlinear methods, and interleukin (IL)-1ß, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, and tumor necrosis factor-α, and interferon (IFN)-γ serum cytokines were assessed by enzyme-linked immune assay. RESULTS: Twenty-nine chronic chagasic patients were positive for parasitemia (17 IChD and 12 ChHD). Heart rate variability parameters in baseline condition and after cold face test were significantly decreased in chagasic patients compared to controls. Tilt tests showed no alteration. However, using nonlinear indices, ChHD patients presented lower values compared to IChD and controls. Differences in the expression of serum cytokines were observed between chagasic patients and controls. However, among the groups, ChHD presented higher median values of IL-10 and lower of IFN-γ compared to IChD. CONCLUSION: Both chagasic groups present an autonomic impairment using linear methods. The nonlinear methods revealed that the ChHD group had a higher cardiovascular risk. Serum cytokine concentrations between chagasic patients were similar. However, ChHD showed higher concentrations of IL-10 and lower of IFN-γ, suggesting some established process of immune regulation.