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.

Elevated NS1 serum levels reduce CD119 expression and CXCL-10 synthesis in patients with dengue hemorrhagic fever.

BACKGROUND: The intensity of dengue virus (DV) replication and circulating non-structural protein 1 (NS1) levels may promote changes in the human immune response and favor severe forms of infection. We investigated the correlations between NS1 with CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels, and IFN-γ receptor α chain (CD119) expression, and CXCL10 production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IFN-γ in DV-infected patients with different clinical forms. METHODS: Dengue virus NS1, CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels were measured in 152 DV-infected patients with different clinical forms and 20 non-infected individuals (NI) using enzyme-linked immunosorbent assay (ELISA). In addition, we investigated the CXCL-10 production after in vitro IFN-γ stimulation of PBMCs from 48 DV-infected individuals (with different clinical forms of dengue fever) and 20 NI individuals using ELISA, and CD119 expression on CD14+ cells with flow cytometry. RESULTS: Patients with dengue hemorrhagic fever (DHF) had significantly higher NS1, CXCL-8, and CXCL-10 serum levels than those with classic dengue fever (DF). The response of PBMCs to IFN-γ stimulation was lower in patients with DHF than in those with DF or dengue with complications (DWC), with lower CD119 expression and reduced CXCL-10 synthesis. In addition, these alterations are associated with high NS1 serum levels. CONCLUSIONS: Patients with DHF reported high NS1 levels, low CD119 expression, and low CXCL-10 synthesis in PBMCs, which may be associated with infection progression and severity.

Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro.

Introduction: Single nucleotide variations (SNVs) are specific genetic variations that commonly occur in a population and often do not manifest phenotypically. However, depending on their location and the type of nucleotide exchanged, an SNV can alter or inhibit the function of the gene in which it occurs. Immunoglobulin G (IgG) receptor genes have exhibited several polymorphisms, including rs1801274, which is found in the FcgRIIa gene. The replacement of A with T results in a Histidine (H) to Arginine (R) substitution, altering the affinity of the IgG receptor for IgG subtypes and C-reactive protein (CRP). In this study, we analyzed rs1801274 and its functional implications concerning L. Infantum uptake and cytokine production. Methods: We genotyped 201 individuals from an endemic area for visceral leishmaniasis to assess the presence of rs1801274 using Taqman probes for a candidate gene study. Additionally, we included seventy individuals from a non-endemic area for a functional study. Subsequently, we isolated and cultivated one-week adherent mononuclear cells (AMCs) derived from the peripheral blood of participants residing in the non-endemic region in the presence of L. infantum promastigotes, with and without antigen-specific IgG and/or CRP. We analyzed the rate of phagocytosis and the production of nitric oxide (NO), tumor necrosis factor (TNF)-a, interleukin (IL)-10, IL-12 p70, IL-1b, IL- 6, and IL-8 in the culture supernatants. Results and discussion: In participants from the endemic region, the A/G (H/R isoform) heterozygous genotype was significantly associated with susceptibility to the disease. Furthermore, SNVs induced a change in the phagocytosis rate in an opsonin-dependent manner. Opsonization with IgG increased the production of IL-10, TNF-a, and IL-6 in AMCs with the H/R isoform, followed by a decrease in NO production. The results presented here suggest that the rs1801274 polymorphism is linked to a higher susceptibility to visceral leishmaniasis.

Metallic nanoparticles and treatment of cutaneous leishmaniasis: A systematic review.

BACKGROUND: Cutaneous leishmaniasis (LC) is an infectious vector-borne disease caused by parasites belonging to the genus Leishmania. Metallic nanoparticles (MNPs) have been investigated as alternatives for the treatment of LC owing to their small size and high surface area. Here, we aimed to evaluate the effect of MNPs in the treatment of LC through experimental, in vitro and in vivo investigations. METHODS: The databases used were MEDLINE/ PubMed, Scopus, Web of Science, Embase, and Science Direct. Manual searches of the reference lists of the included studies and grey literature were also performed. English language and experimental in vitro and in vivo studies using different Leishmania species, both related to MNP treatment, were included. This study was registered in PROSPERO (CRD42021248245). RESULTS: A total of 93 articles were included. Silver nanoparticles are the most studied MNPs, and L. tropica is the most studied species. Among the mechanisms of action of MNPs in vitro, we highlight the production of reactive oxygen species, direct contact of MNPs with the biomolecules of the parasite, and release of metal ions. CONCLUSION: MNPs may be considered a promising alternative for the treatment of LC, but further studies are needed to define their efficacy and safety.

A Global View of Pemphigus: Geographical Variations.

Pemphigus, an autoimmune intraepidermal bullous disease group with roughly eight distinct forms, includes pemphigus vulgaris (PV) and pemphigus foliaceus (PF) as its predominant global forms. Despite the increased utilization of global health records and reporting systems, epidemiological data remain limited and poorly categorized. Therefore, this study aimed to conduct a review to track, identify, and characterize cases of PV and PF published and categorized worldwide. A research question was formulated; studies were selected based on the inclusion criteria; and data from these publications were systematically collected, summarized, and presented using narrative descriptions. The search strategy yielded 3,212 articles, of which 95 underwent critical analysis and data extraction. Studies from 52 countries contributed to the dataset, covering various pemphigus variants. Notably, only two countries, Iran (18.87%) and South Korea (11.43%), accounted for approximately a third of the reported PV cases, while Brazil contributed 40.25% of the foliaceus variants cases documented in the literature. These findings offer valuable insights into the global distribution of pemphigus and inform future research and healthcare efforts.

Comparing the wound healing potential of natural rubber latex serum and F1-protein: An in vivo approach.

Chronic wounds pose significant health concerns. Current treatment options include natural compounds like natural rubber latex (NRL) from Hevea brasiliensis. NRL, particularly the F1 protein fraction, has demonstrated bioactivity, biocompatibility, and angiogenic effects. So far, there is no study comparing F1 protein with total NRL serum, and the necessity of downstream processing remains unknown. Here, we evaluated the angiogenic potential of F1 protein compared to total NRL serum and the need for downstream processing. For that, ion exchange chromatography (DEAE-Sepharose), antioxidant activity, physicochemical characterization, cell culture in McCoy fibroblasts, and wound healing in Balb-C mice were performed. Also, the evaluation of histology and collagen content and the levels of inflammatory mediators were quantified. McCoy fibroblast cell assay showed that F1 protein (0.01 %) and total NRL serum (0.01 %) significantly increased cell proliferation by 47.1 ± 11.3 % and 25.5 ± 2.5 %, respectively. However, the AA of F1 protein (78.9 ± 0.8 %) did not show a significant difference compared to NRL serum (77.0 ± 1.1 %). F1 protein and NRL serum were more effective in wound management in rodents. Histopathological analysis confirmed accelerated healing and advanced tissue repair. Similarly, the F1 protein (0.01 %) increased collagen, showing that this fraction can stimulate the synthesis of collagen by fibroblastic cells. Regarding cytokines production (IL-10, TNF-α, IFN-γ), F1 protein and NRL serum did not exert an impact on the synthesis of these cytokines. Furthermore, we did not observe statistically significant changes in dosages of enzymes (MPO and EPO) among the groups. Nevertheless, Nitric Oxide dosage was reduced drastically when the F1 protein (0.01 %) protein was applied topically. These findings contribute to the understanding of F1 protein and NRL serum properties and provide insights into cost-effectiveness and practical applications in medicine and biotechnology. Therefore, further research is needed to assess the economic feasibility of downstream processing for NRL-based herbal medicine derived from Hevea brasiliensis.

Vector species richness predicts local mortality rates from Chagas disease.

Vector species richness may drive the prevalence of vector-borne diseases by influencing pathogen transmission rates. The dilution effect hypothesis predicts that higher biodiversity reduces disease prevalence, but with inconclusive evidence. In contrast, the amplification effect hypothesis suggests that higher vector diversity may result in greater disease transmission by increasing and diversifying the transmission pathways. The relationship between vector diversity and pathogen transmission remains unclear and requires further study. Chagas disease is a vector-borne disease most prevalent in Brazil and transmitted by multiple species of insect vectors of the subfamily Triatominae, yet the drivers of spatial variation in its impact on human populations remain unresolved. We tested whether triatomine species richness, latitude, bioclimatic variables, human host population density, and socioeconomic variables predict Chagas disease mortality rates across over 5000 spatial grid cells covering all of Brazil. Results show that species richness of triatomine vectors is a good predictor of mortality rates caused by Chagas disease, which supports the amplification effect hypothesis. Vector richness and the impact of Chagas disease may also be driven by latitudinal components of climate and human socioeconomic factors. We provide evidence that vector diversity is a strong predictor of disease prevalence and give support to the amplification effect hypothesis.

Elevated NS1 serum levels reduce CD119 expression and CXCL-10 synthesis in patients with dengue hemorrhagic fever

ABSTRACT Background: The intensity of dengue virus (DV) replication and circulating non-structural protein 1 (NS1) levels may promote changes in the human immune response and favor severe forms of infection. We investigated the correlations between NS1 with CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels, and IFN-γ receptor α chain (CD119) expression, and CXCL10 production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IFN-γ in DV-infected patients with different clinical forms. Methods: Dengue virus NS1, CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels were measured in 152 DV-infected patients with different clinical forms and 20 non-infected individuals (NI) using enzyme-linked immunosorbent assay (ELISA). In addition, we investigated the CXCL-10 production after in vitro IFN-γ stimulation of PBMCs from 48 DV-infected individuals (with different clinical forms of dengue fever) and 20 NI individuals using ELISA, and CD119 expression on CD14+ cells with flow cytometry. Results: Patients with dengue hemorrhagic fever (DHF) had significantly higher NS1, CXCL-8, and CXCL-10 serum levels than those with classic dengue fever (DF). The response of PBMCs to IFN-γ stimulation was lower in patients with DHF than in those with DF or dengue with complications (DWC), with lower CD119 expression and reduced CXCL-10 synthesis. In addition, these alterations are associated with high NS1 serum levels. Conclusions: Patients with DHF reported high NS1 levels, low CD119 expression, and low CXCL-10 synthesis in PBMCs, which may be associated with infection progression and severity.

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.

Quantification of blood loss for the diagnosis of postpartum hemorrhage: a systematic review and meta-analysis.

OBJECTIVE: to compare the effectiveness of different diagnostic methods to estimate postpartum blood volume loss. METHODS: a systematic review of effectiveness according to PRISMA and JBI Protocol. Searches in PubMed/MEDLINE, LILACS, Scopus, Embase, Web of Science and CINAHL, with descriptor "Postpartum Hemorrhage" associated with keyword "Quantification of Blood Loss". Tabulated extracted data, presented in metasynthesis and meta-analysis was applied to quantitative data. To assess risk of bias, JBI Appraisal Tools were applied. RESULTS: fourteen studies were included, published between 2006 and 2021. Quantification of loss by any method was superior to visual estimation and is highly recommended, however the studies' high heterogeneity did not allow estimating this association. CONCLUSION: the studies' high heterogeneity, with a probable margin of error given the uncontrolled factors, indicates the need for further studies, however quantification proved to be effective in relation to visual estimate. PROSPERO registration CRD 42021234486.

Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches.

Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the Vibrio genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, 'vme-VAC/MST-1' based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant. In silico analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic Vibrio spp. However, further experimental analyses are required to measure the vaccine's effects In vivo.Communicated by Ramaswamy H. Sarma.

Potential Associations between Vascular Biology and Hodgkin's Lymphoma: An Overview.

Hodgkin's lymphoma (HL) is a lymphatic neoplasm typically found in the cervical lymph nodes. The disease is multifactorial, and in recent years, the relationships between various vascular molecules have been explored in the field of vascular biology. The connection between vascular biology and HL is intricate and the roles of several pathways remain unclear. This review summarizes the cellular and molecular relationships between vascular biology and HL. Proteins associated with various functions in vascular biology, including cytokines (TNF-α, IL-1, IL-13, and IL-21), chemokines (CXCL10, CXCL12, and CCL21), adhesion molecules (ELAM-1/VCAM-1), and growth factors (BDNF/NT-3, platelet-derived growth factor receptor-α), have been linked to tumor activity. Notable tumor activities include the induction of paracrine activation of NF-kB-dependent pathways, upregulation of adhesion molecule regulation, genome amplification, and effective loss of antigen presentation mediated by MHC-II. Preclinical study models, primarily those using cell culture, have been optimized for HL. Animal models, particularly mice, are also used as alternatives to complex biological systems, with studies primarily focusing on the physiopathogenic evaluation of the disease. These biomolecules warrant further study because they may shed light on obscure pathways and serve as targets for prevention and/or treatment interventions.

Progressive multifocal leukoencephalopathy triggered by COVID-19 in a previously asymptomatic person living with undiagnosed HIV infection.

This report presents the case of a 47-year-old male patient who worked as a mathematics teacher and experienced the sudden onset of disorientation, aphasia, and acalculia during an online class. The current study reveals the first documented case of HIV and progressive multifocal leukoencephalopathy with the detection of SARS-CoV-2 and human polyomavirus 2 (previously known as John Cunningham virus) in the cerebrospinal fluid. Furthermore, serum analysis revealed elevated concentrations of interleukin (IL)-6, IL-17, and IL-8, which are potential factors known to reduce the expression of tight junctions and adhesion molecules in the extracellular matrix, thereby affecting the permeability of the blood-brain barrier. Finally, the study discusses whether SARS-CoV-2 triggers or exacerbates progressive multifocal leukoencephalopathy.

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.

Breastfeeding prevalence in newborns of mothers with COVID-19: a systematic review.

OBJECTIVES: to compare exclusive breastfeeding prevalence versus artificial feeding in newborns of mothers with COVID-19. METHODS: a systematic review of prevalence, according to JBI. Searches in PubMed®, Embase, CINAHL, LILACS and Web of Science™ databases in August 2021. Cross-sectional, longitudinal or cohort studies were selected, without language and time limitations that showed breastfeeding prevalence or that allowed calculation. RESULTS: fifteen articles published in 2020 and 2021, cohort (60%) or cross-sectional (40%) were analyzed. The average of exclusive breastfeeding in mothers with COVID-19 was 56.76% (CI=39.90-72.88), and artificial breastfeeding, 43.23% (CI = 30.99 - 55.88), without statistically significant differences. CONCLUSIONS: despite the recommendations for maintaining breastfeeding, there was a reduction worldwide, when compared to periods prior to the pandemic. With advances in science, these rates have improved, showing the impact of evidence on practices. As limitations, study sources are cited. It is recommended to carry out new studies. PROSPERO registration CRD42021234486.

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.

Exploring the functionalization of Ti-6Al-4V alloy with the novel antimicrobial peptide JIChis-2 via plasma polymerization.

This study aimed to characterize the immobilization of the novel JIChis-2 peptide on the Ti-6Al-4V alloy, widely used in the biomedical sector. The antimicrobial activity of JIChis-2 was evaluated in the Gram-negative bacterium E. coli. Its immobilization occurred by inducing the formation of covalent bonds between the N-terminus of the peptides and the surface previously submitted to acrylic acid polymerization via the PECVD technique. Coated and uncoated surfaces were characterized by FTIR, AFM, SEM and EDX. Studies of global and localized corrosion were carried out, seeking to explore the effects triggered by surface treatment in an aggressive environment. Additionally, the ability of the functionalized material to prevent E. coli biofilm formation evidenced that the strategy to immobilize JIChis-2 in the Ti-6Al-4V alloy via PECVD of acrylic acid resulted in the development of a functional material with antibiofilm properties.