COVID-19 Inflammatory Syndrome: Lessons from TNFRI and CRP about the Risk of Death in Severe Disease.

Background/Objectives: Cytokine storm in severe COVID-19 is responsible for irreversible tissue damage and death. Soluble mediators from the TNF superfamily, their correlation with clinical outcome, and the use of TNF receptors as a potent predictor for clinical outcome were evaluated. Methods: Severe COVID-19 patients had the levels of soluble mediators from the TNF superfamily quantified and categorized according to the clinical outcome (death versus survival). Statistical modeling was performed to predict clinical outcomes. Results: COVID-19 patients have elevated serum levels from the TNF superfamily. Regardless of sex and age, the sTNFRI levels were observed to be significantly higher in deceased patients from the first weeks following the onset of symptoms. We analyzed hematological parameters and inflammatory markers, and there was a difference between the groups for the following factors: erythrocytes, hemoglobin, hematocrit, leukocytes, neutrophils, band cells, lymphocytes, monocytes, CRP, IL-8, IFN-γ, IL-10, IL-6, IL-4, IL-2, leptin MIF sCD40L, and sTNFRI (p < 0.05). A post hoc analysis showed an inferential capacity over 70% for some hematological markers, CRP, and inflammatory mediators in deceased patients. sTNFRI was strongly associated with death, and the sTNFRI/sTNFRII ratio differed between outcomes (p < 0.001; power above 90%), highlighting the impact of these proteins on clinical results. The final logistic model, including sTNFRI/sTNFRII and CRP, indicated high sensitivity, specificity, accuracy, and an eight-fold higher odds ratio for an unfavorable outcome. Conclusions: The joint use of the sTNFRI/sTNFRII ratio with CRP proves to be a promising tool to assist in the clinical management of patients hospitalized for COVID-19.

Maternal deaths caused by eclampsia in Brazil: a descriptive study from 2000 to 2021.

Objective: Eclampsia is a hypertensive disorder that occurs during pregnancy and can lead to death. The literature has gaps by not providing comprehensive data on the epidemiology of the disease, restricting analysis to limited temporal intervals and geographical locations. This study aims to characterize the epidemiological profile of women who died from eclampsia in Brazil from 2000 to 2021. Methods: The maternal mortality data were obtained from the Sistema de Informações sobre Mortalidade, with the following variables of interest selected: "Federative Unit," "Year," "Age Range," "Race/Color," and "Education Level." The collection of the number of live births for data normalization was conducted in the Sistema de Informações sobre Nascidos Vivos. Statistical analyses were performed using GraphPad Prism, calculating odds ratio for variables and fixing number of deaths per 100,000 live births for calculating maternal mortality ratio (MMR). Results: There was a downward trend in maternal mortality rate during the study period. Maranhão stood out as the federative unit with the highest MMR (17 deaths per 100.000 live births). Mothers aged between 40 and 49 years (OR = 3.55, CI: 3.11-4.05) presents higher MMR. Additionally, black women showed the highest MMR (OR = 4.67, CI: 4.18-5.22), as well as mothers with no educational background (OR = 5.83, CI: 4.82-7.06). Conclusion: The epidemiological profile studied is predominantly composed of mothers with little or no formal education, self-declared as Black, residing in needy states and with advanced aged. These data are useful for formulating public policies aimed at combating the issue.

Maternal deaths caused by eclampsia in Brazil: a descriptive study from 2000 to 2021

Abstract Objective Eclampsia is a hypertensive disorder that occurs during pregnancy and can lead to death. The literature has gaps by not providing comprehensive data on the epidemiology of the disease, restricting analysis to limited temporal intervals and geographical locations. This study aims to characterize the epidemiological profile of women who died from eclampsia in Brazil from 2000 to 2021. Methods The maternal mortality data were obtained from the Sistema de Informações sobre Mortalidade, with the following variables of interest selected: "Federative Unit," "Year," "Age Range," "Race/Color," and "Education Level." The collection of the number of live births for data normalization was conducted in the Sistema de Informações sobre Nascidos Vivos. Statistical analyses were performed using GraphPad Prism, calculating odds ratio for variables and fixing number of deaths per 100,000 live births for calculating maternal mortality ratio (MMR). Results There was a downward trend in maternal mortality rate during the study period. Maranhão stood out as the federative unit with the highest MMR (17 deaths per 100.000 live births). Mothers aged between 40 and 49 years (OR = 3.55, CI: 3.11-4.05) presents higher MMR. Additionally, black women showed the highest MMR (OR = 4.67, CI: 4.18-5.22), as well as mothers with no educational background (OR = 5.83, CI: 4.82-7.06). Conclusion The epidemiological profile studied is predominantly composed of mothers with little or no formal education, self-declared as Black, residing in needy states and with advanced aged. These data are useful for formulating public policies aimed at combating the issue.

Understanding the Relationship between Vaccine Supply Dead Space and Wasted COVID-19 Vaccine Doses.

INTRODUCTION: By July 2023, Brazil had administered approximately 540 million COVID-19 vaccine doses. This study aimed to quantify wasted doses resulting from dead space in vaccine supplies. METHODS: The vaccine supply was initially weighed, filled with distilled water, and expelled to simulate administration. Weighing it again after the application determined the dead space volume. Descriptive analyses calculated the waste rate/wasted dose count. RESULTS: The estimated total number of wasted vaccine doses using supplies with the lowest dead space was 62,097,338. CONCLUSIONS: Syringe dead space is a crucial factor in dose wastage, directly influencing the number of wasted doses.

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.

Understanding the Relationship between Vaccine Supply Dead Space and Wasted COVID-19 Vaccine Doses

ABSTRACT Introduction: By July 2023, Brazil had administered approximately 540 million COVID-19 vaccine doses. This study aimed to quantify wasted doses resulting from dead space in vaccine supplies. Methods: The vaccine supply was initially weighed, filled with distilled water, and expelled to simulate administration. Weighing it again after the application determined the dead space volume. Descriptive analyses calculated the waste rate/wasted dose count. Results: The estimated total number of wasted vaccine doses using supplies with the lowest dead space was 62,097,338. Conclusions: Syringe dead space is a crucial factor in dose wastage, directly influencing the number of wasted doses.

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.

Congenital transmission of Mexican strains of Trypanosoma cruzi TcIa: interaction between parasite and human placental explants.

Congenital transmission of Chagas disease plays an important role in endemic countries because it is not a diagnosis that is encountered frequently in prenatal care. Due to limited information regarding congenital transmission of Trypanosoma cruzi in Mexico, the present study aimed to investigate protozoan infectivity and modulation of immune responses in human placental explants infected with T. cruzi Ia Mexican strains. The Inc-5 strain showed increased infectivity and modulated IL-1ß, IL-10 and TLR-4, decreasing their expression after 24 h of infection. Both strains (Inc-5 and Ninoa) stimulated the production of TNF-α and decreased IL-6 levels 96 h after infection. An important detachment of the syncytiotrophoblast caused by infection with T. cruzi was observed after 24 h of infection. In this study, ex vivo infection of human placental villi was performed to better understand interactions involving parasitic T. cruzi and human placental tissue. It was concluded that the strains of TcIa present parasitism in placental tissue, modulation of the innate immune system of the placenta, and cause intense detachment of the syncytiotrophoblast, a fact that may be more associated with abortion and premature birth events than the congenital transmission itself, justifying the low rate of this transmission mechanism by this genotype.

In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi.

Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Despite the efforts and distinct methodologies, the search of antigens for diagnosis, vaccine, and drug targets for the disease is still needed. The present study is aimed at identifying possible antigens that could be used for diagnosis, vaccine, and drugs targets against T. cruzi using reverse vaccinology and molecular docking. The genomes of 28 T. cruzi strains available in GenBank (NCBI) were used to obtain the genomic core. Then, subtractive genomics was carried out to identify nonhomologous genes to the host in the core. A total of 2630 conserved proteins in 28 strains of T. cruzi were predicted using OrthoFinder and Diamond software, in which 515 showed no homology to the human host. These proteins were evaluated for their subcellular localization, from which 214 are cytoplasmic and 117 are secreted or present in the plasma membrane. To identify the antigens for diagnosis and vaccine targets, we used the VaxiJen software, and 14 nonhomologous proteins were selected showing high binding efficiency with MHC I and MHC II with potential for in vitro and in vivo tests. When these 14 nonhomologous molecules were compared against other trypanosomatids, it was found that the retrotransposon hot spot (RHS) protein is specific only for T. cruzi parasite suggesting that it could be used for Chagas diagnosis. Such 14 proteins were analyzed using the IEDB software to predict their epitopes in both B and T lymphocytes. Furthermore, molecular docking analysis was performed using the software MHOLline. As a result, we identified 6 possible T. cruzi drug targets that could interact with 4 compounds already known as antiparasitic activities. These 14 protein targets, along with 6 potential drug candidates, can be further validated in future studies, in vivo, regarding Chagas disease.

Trypanosoma cruzi Mexican Strains Differentially Modulate Surface Markers and Cytokine Production in Bone Marrow-Derived Dendritic Cells from C57BL/6 and BALB/c Mice.

Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in the immune response against Trypanosoma cruzi, the causative agent of Chagas disease. In vitro and in vivo studies have shown that the modulation of these cells by this parasite can directly affect the innate and acquired immune response of the host in order to facilitate its biological cycle and the spreading of the species. Many studies show the mechanisms by which T. cruzi modulates DCs, but the interaction of these cells with the Mexican strains of T. cruzi such as Ninoa and INC5 has not yet been properly investigated. Here, we evaluated whether Ninoa and INC5 strains evaded the immunity of their hosts by modulating the biology and function of murine DCs. The CL-Brener strain was used as the reference strain. Herein, it was demonstrated that Ninoa was more infective toward bone marrow-derived dendritic cells (BMDCs) than INC5 and CL-Brener strains in both BMDCs of BALB/c and C57BL/6 mice. Mexican strains of T. cruzi induced different cytokine patterns. In BMDCs obtained from BALB/c mice, Ninoa strain led to the reduction in IL-6 and increased IL-10 production, while in C57BL/6 mice Ninoa strain considerably increased the productions of TNF-α and IL-10. Also, Ninoa and INC5 differentially modulated BMDC expressions of MHC-II, TLR2, and TLR4 in both BALB/c and C57BL/6 mice compared to Brazilian strain CL-Brener. These results indicate that T. cruzi Mexican strains differentially infect and modulate MHC-II, toll-like receptors, and cytokine production in DCs obtained from C57BL/6 and BALB/c mice, suggesting that these strains have developed particular modulatory strategies to disrupt DCs and, consequently, the host immune responses.