Dietary inflammatory index and inflammatory markers in Brazilian adolescents.

OBJECTIVE: To evaluate the association between the inflammatory potential of the diet measured by the energy-adjusted diet inflammatory index (E-DII) and inflammatory markers in adolescents. METHODS: This cross-sectional study was conducted among 518 adolescents aged 18 and 19 years from São Luís, Maranhão, Brazil in 2016. A semiquantitative food frequency questionnaire (FFQ) was used to assess dietary intake from which E-DII scores were calculated to determine the inflammatory potential of the diet. The associations between E-DII and inflammatory markers (hs-CRP, IL-6, IL-4, TNF-α, and IFNγ) were analyzed using multivariable linear regression. The variables included in the adjusted model were identified using the directed acyclic graph. RESULTS: The diet of these adolescents was mostly pro-inflammatory; mean E-DII score was 1.71 and ranged from -2.44 to 5.58. Higher E-DII scores were positively associated with higher levels of IFNγ in the adjusted analysis (Adjusted Coef.: 1.19; 95%CI: 0.36-12.04). We observed no associations between E-DII and other inflammatory markers (hs-CRP, IL-6, IL-4, TNF-α). Study results indicate that E-DII is useful in evaluating the inflammatory potential of the diet of Brazilian adolescents. CONCLUSIONS: Cross-sectionally E-DII scores were positively associated with IFNγ concentrations. Future research should examine the association between changes in E-DII scores and levels of inflammatory markers longitudinally.

Chemical Profile and Biological Potential of Scaptotrigona Bee Products (Hymenoptera, Apidae, Meliponini): An Review.

Stingless bees belong to the Meliponini tribe and are widely distributed in the tropics and subtropics, where they perform important ecological services. Among the best distributed groups of stingless bees is the genus Scaptotrigona, which includes 22 species distributed throughout the neotropical region, including the area from Mexico to Argentina. Bees of this genus are responsible for the production of products such as honey, propolis, geopropolis and fermented pollen ("saburá"). This review aimed to provide an overview of the chemical composition and biological activities associated with derived products from stingless bees of the genus Scaptotrigona. The bibliographic review was carried out through searches in the Scopus, Web of Science, ScienceDirect and PubMed databases, including publications from 2003 to January 2023. The study of the chemodiversity of products derived from Scaptotrigona demonstrated the mainly presence of flavonoids, phenolic acids, terpenoids and alkaloids. It was also demonstrated that products derived from bees of the genus Scaptotrigona exhibit a wide range of biological effects, such as antibacterial, antioxidant, anti-inflammatory and antifungal activities, among other bioactivities. This review provides an overview of phytochemical and pharmacological investigations of the genus Scaptotrigona. However, it is essential to clarify the toxicity and food safety of these products.

Isoniazid Monoresistance and Antituberculosis Treatment Outcome in Persons With Pulmonary Tuberculosis in Brazil.

Background: The high burden of drug-resistant tuberculosis (TB) is a problem to achieve the goals of the End TB Strategy by 2035. Whether isoniazid monoresistance (Hr) affects anti-TB treatment (ATT) outcomes remains unknown in high-burden countries. Methods: We evaluated determinants of ATT outcome among pulmonary TB cases reported to the National Notifiable Disease Information System (SINAN) between June 2015 and June 2019, according to drug sensitivity testing (DST) results. Binomial logistic regression models were employed to evaluate whether Hr was associated with an unfavorable ATT outcome: death or failure, compared to cure or treatment completion. Results: Among 60 804 TB cases reported in SINAN, 21 197 (34.9%) were included in the study. In this database, the frequency of unfavorable outcomes was significantly higher in those with Hr in contrast to isoniazid-sensitive persons with pulmonary TB (9.1% vs 3.05%; P < .001). Using a binomial logistic regression model, Hr was independently associated with unfavorable outcomes (odds ratio, 3.34 [95% confidence interval, 2.06-5.40]; P < .001). Conclusions: Hr detected prior to ATT was predictive of unfavorable outcomes at the national level in Brazil. Our data reinforce the need for high-TB-burden countries to prioritize DST to detect Hr. Effective treatment regimens for Hr-TB are needed to improve outcomes.

The Xpert® MTB/RIF cycle threshold value predicts M. tuberculosis transmission to close contacts in a Brazilian prospective multicenter cohort.

BACKGROUND: The Xpert® MTB/RIF rapid molecular test provides a quantitative measure of Mycobacterium tuberculosis (Mtb) DNA in the form of cycle threshold (Ct) values. This information can be translated into mycobacterial load and used as a potential risk measure of bacterial spread for tuberculosis cases, which can impact infection control. However, the role of Ct values in assessing Mtb transmission to close contacts has not yet been demonstrated. METHODS: A prospective study was performed to investigate the association between Xpert® MTB/RIF Ct values and Mtb transmission to close contacts of patients with culture-confirmed pulmonary TB in a multi-center Brazilian cohort. We evaluated clinical and laboratory data, such as age, sex, race, smoking habits, drug use, alcohol use, chest radiograph, Xpert® MTB/RIF results among pulmonary tuberculosis cases, and QuantiFERON(QFT)-Plus results at baseline and after six months for close contacts who had a negative result at baseline. RESULTS: A total of 1,055 close contacts of 382 pulmonary tuberculosis cases were included in the study. The median Ct values from pulmonary tuberculosis cases of QFT-Plus positive (at baseline or six months) close contacts were lower compared with those who were QFT-Plus negative. An adjusted logistic regression demonstrated that reduced Ct values from the index cases were independently associated with QFT-Plus conversion from negative to positive (OR: 1.61, 95% CI: 1.12-2.32) after adjusting for clinical characteristics. CONCLUSION: Close contacts of pulmonary TB index cases exhibiting low Xpert MTB/RIF Ct values displayed higher rates of TB infection, reflecting Mtb transmission.

Antihypertensive treatment of end-stage renal disease patients on hemodialysis does not alter circulating ACE and ACE2 activity and angiotensin peptides.

Cardiovascular diseases (CVD) are the main causes of death in hemodialysis patients, representing a public health challenge. We investigated the effect of different antihypertensive treatments on circulating levels of renin-angiotensin system (RAS) components in end-stage renal disease (ESRD) patients on hemodialysis. ESRD patients were grouped following the prescribed antihypertensive drugs: ß-blocker, ß-blocker+ACEi and ß-blocker+AT1R blocker. ESDR patients under no antihypertensive drug treatment were used as controls. Blood samples were collected before hemodialysis sessions. Enzymatic activities of the angiotensin-converting enzymes ACE and ACE2 were measured through fluorescence assays and plasma concentrations of the peptides Angiotensin II (Ang II) and Angiotensin-(1-7) [Ang-(1-7)] were quantified using mass spectrometry (LC-MS/MS). ACE activity was decreased only in the ß-blocker+ACEi group compared to the ß-blocker+AT1R, while ACE2 activity did not change according to the antihypertensive treatment. Both Ang II and Ang-(1-7) levels also did not change according to the antihypertensive treatment. We concluded that the treatment of ESRD patients on hemodialysis with different antihypertensive drugs do not alter the circulating levels of RAS components.

Antiviral action of aqueous extracts of propolis from Scaptotrigona aff. postica (Hymenoptera; Apidae) against Zica, Chikungunya, and Mayaro virus

The limited availability of antivirals for new highly pathogenic strains of virus has become a serious public health. Therefore, news products against these pathogens has become an urgent necessity. Among the multiple sources for news antibiotics and antivirals, insect exudates or their products has become an increasingly frequent option. Insects emerged 350 million years ago and have showed a high adaptability and resistance to the most varied biomes. Their survival for so long, in such diferent environments, is an indication that they have a very efcient protection against environmental infections, despite not having a developed immune system like mammals. Since the ancient civilizations, the products obtained from the bee have been of great pharmacological importance, being used as antimicrobial, anti-infammatory, antitumor and several other functions. Investigations of biological activity of propolis have been carried out, mainly in the species Apis mellifera, and its product have showed activity against some important viruses. However, for the Meliponini species, known as stingless bees, there are few studies, either on their chemical composition or on their biological activities. The importance of studying these bees is because they come from regions with native forests, and therefore with many species of plants not yet studied, in addition to which they are regions still free of pesticides, which guarantees a greater fdelity of the obtained data. Previous studies by our group with crude hydroalcoholic extract of propolis demonstrated an intense antiviral activity against Herpes, infuenza, and rubella viruses. In this work, we chose to use aqueous extracts, which eliminates the presence of other compounds besides those originally present in propolis, in addition to extracting substances diferent from those obtained in alcoholic extracts. Therefore, this study aimed to identify, isolate and characterize compounds with antiviral efects from aqueous propolis extracts from Scaptotrigona af postica, in emerging viruses such as zicavirus, chikungunya, and mayaro virus. The evaluation of the antiviral activity of the crude and purifed material was performed by reducing infectious foci in VERO cell cultures. The results obtained with crude propolis, indicate a high reduction of zica virus (64×) and mayaro (128×) when was used 10% v/v of propolis. The reduction of chikungunya virus was of 256 fold, even when was used 5% v/v of propolis. The chemical characterization of the compounds present in the extracts was performed by high-pressure liquid chromatography. Through the purifcation of propolis by HPLC and mass spectrometry, it was possible to identify and isolate a peak with antiviral activity. This substance showed activity against all viruses tested. When purifed fraction was used, the reduction observed was of 16 fold for zicavirus, 32 fold for mayaro virus and 512 fold for chikungunya virus. Likewise, it was observed that the antiviral response was concentration dependent, being more intense when propolis was added 2 h after the viral infection. Now we are carrying out the chemical characterization of the purifed compounds that showed antiviral action.

Dietary inflammatory index and inflammatory markers in Brazilian adolescents

ABSTRACT OBJECTIVE To evaluate the association between the inflammatory potential of the diet measured by the energy-adjusted diet inflammatory index (E-DII) and inflammatory markers in adolescents. METHODS This cross-sectional study was conducted among 518 adolescents aged 18 and 19 years from São Luís, Maranhão, Brazil in 2016. A semiquantitative food frequency questionnaire (FFQ) was used to assess dietary intake from which E-DII scores were calculated to determine the inflammatory potential of the diet. The associations between E-DII and inflammatory markers (hs-CRP, IL-6, IL-4, TNF-α, and IFNγ) were analyzed using multivariable linear regression. The variables included in the adjusted model were identified using the directed acyclic graph. RESULTS The diet of these adolescents was mostly pro-inflammatory; mean E-DII score was 1.71 and ranged from -2.44 to 5.58. Higher E-DII scores were positively associated with higher levels of IFNγ in the adjusted analysis (Adjusted Coef.: 1.19; 95%CI: 0.36-12.04). We observed no associations between E-DII and other inflammatory markers (hs-CRP, IL-6, IL-4, TNF-α). Study results indicate that E-DII is useful in evaluating the inflammatory potential of the diet of Brazilian adolescents. CONCLUSIONS Cross-sectionally E-DII scores were positively associated with IFNγ concentrations. Future research should examine the association between changes in E-DII scores and levels of inflammatory markers longitudinally.

Driving after alcohol consumption among residents of Northeastern Brazil: National Health Survey 2019 / Conducción de vehículos después de consumir bebidas alcohólicas en residentes del Nordeste de Brasil: Encuesta Nacional de Salud 2019 / Condução de veículos após o consumo de bebidas alcoólicas em residentes do Nordeste do Brasil: Pesquisa Nacional de Saúde 2019

ABSTRACT Objective To estimate the prevalence of factors associated with drinking and driving in Northeastern Brazil. Methods This was a cross-sectional study conducted with participants from the 2019 National Health Survey, aged ≥ 18 years; the analysis of the association between sociodemographic variables and the outcome, stratified by sex, was performed using Poisson regression. Results The prevalence of drinking and driving was 21.0% ( 95%CI 19.9;23.2), with 24.6% ( 95%CI 22.7;26.5), in males and 10.1 % ( 95%CI 7.9;12.7), in females (p-value < 0.001); among men, younger age groups (PR = 1.70 - 95%CI 1.29;2.24), higher household income (PR = 1.74 - 95%CI 1.33;2.28), rural residence (PR = 1.48 - 95%CI 1.26;1.74) and motorcycle riding (PR = 1.29 - 95%CI 1.05;1.58) were associated with the event, while no association was observed among women. Conclusion Prevalence of drinking and driving was high in the Northeast region, especially among the male population; preventive measures targeting this group and intensified enforcement are necessary.

RESUMEN Objetivo Estimar la prevalencia y analizar factores asociados al consumo de alcohol y conducir en el Nordeste de Brasil. Métodos Estudio transversal con participantes de la Encuesta Nacional de Salud 2019, ≥ 18 años; se analizó la asociación entre variables sociodemográficas y el resultado, estratificadas por sexo, mediante regresión de Poisson. Resultados La prevalencia de beber y conducir fue del 21,0% (IC95% 19,9;23,2), 24,6% (IC95% 22,7;26,5) en hombres y 10,1% (IC95% 7,9;12,7) en mujeres (p-valor < 0,001); en hombres, franja etaria más joven (RP = 1,70 - IC95%1,29;2,24), mayor ingreso familiar (RP = 1,74 -IC95% 1,33;2,28), en áreas rurales (RP = 1,48 - IC95% 1,26;1,74) y conducir motocicleta (RP = 1,29 - IC95% 1,05;1,58) se asociaron al evento; en las mujeres no se observaron asociaciones. Conclusión La prevalencia de beber y conducir fue alta en el Nordeste específicamente entre hombres. Son necesarias medidas preventivas para esta población e intensificación de la supervisión.

RESUMO Objetivo Estimar a prevalência e analisar fatores associados ao hábito de beber e dirigir no Nordeste do Brasil. Métodos Estudo transversal, com participantes da Pesquisa Nacional de Saúde 2019, aos 18 anos ou mais de idade; analisou-se a associação entre variáveis sociodemográficas e o desfecho, estratificada segundo sexo, mediante regressão de Poisson. Resultados A prevalência de "beber e dirigir" de 21,0% (IC95% 19,9;23,2), 24,6% (IC95% 22,7;26,5) no sexo masculino e de 10,1% (IC95% 7,9;12,7) no feminino (p-valor < 0,001); nos homens, faixas etárias mais jovens (RP = 1,70 - IC95% 1,29;2,24), maior renda domiciliar (RP = 1,74 - IC95% 1,33;2,28), residência rural (RP = 1,48 - IC95% 1,26;1,74) e condução de motocicleta (RP = 1,29 - IC95% 1,05;1,58) associaram-se ao evento, enquanto nenhuma associação foi observada nas mulheres. Conclusão A prevalência de "beber e dirigir" alta no Nordeste, comparada à do Brasil, principalmente na população masculina; fazem-se necessárias medidas preventivas nesse público, e intensificação da fiscalização.

Histórico e panorama das mulheres na perícia oficial criminal (odontolegista) no Brasil / History and overview of women as forensic odontologists in the Brazilian criminal system

Forensic Dentistry is a dental specialty, historically marked by many "fathers", but few information about women in this context. The female insertion in the labor market still suffers from historical barriers, and the objective of this research was to identify the participation of the first women as Forensic Odontologists in the Brazilian Criminal Expert Services, and carry out an overview of the current number of professionals in this position and its proportion between the sexes. Data were collected on the first Forensic Odontologist in each state and the currently active professionals through the records from the Scientific Polices, Civil Polices, and Brazilian Transparency Databases for descriptive statistics. The first women as Forensic Odontologists in Brazil were from the states of Paraíba, Maranhão, and Pará (1981, 1982, and 1985, respectively). According to the Brazilian Federal Council of Dentistry, 59.69% of Specialists in Forensic Dentistry are women and in the states where data collection was possible, 57.89% of Official Forensic Odontologists are women. Despite being the majority, it is still necessary to standardize the nomenclature and create new official positions to strengthen the Forensic Odontologist profession, and encourage greater female participation. It is concluded that in 1981 there was the first Forensic Odontologist female in Brazil in the state of Paraíba and that today there is a better balance in the proportion of men and women in this position

A Odontologia Legal é uma especialidade marcada historicamente por muitas figuras "paternas", mas pouco é abordado sobre a participação das mulheres nesse contexto. A inserção feminina no mercado de trabalho ainda sofre barreiras históricas, sendo o objetivo deste trabalho a identificação da participação das primeiras mulheres na Perícia Oficial no Brasil, especificamente na condição de Peritas Odontolegistas, e realizar um panorama da quantidade atual de profissionais no cargo e sua proporção entre os sexos. Foram coletados dados sobre as primeiras mulheres a ocupar o cargo de Perita Oficial Odontolegista de cada estado e as Peritas Odontolegistas ativas atualmente por meio dos registros das Polícias Científicas, Polícias Civis e dados do Portal da Transparência para tabulação e estatística descritiva. Das respostas recebidas, as primeiras Peritas Odontolegistas Oficiais do Brasil foram dos estados da Paraíba, Maranhão e Pará, nos anos de 1981, 1982 e 1985, respectivamente. No cenário atual, de acordo com o Conselho Federal de Odontologia, 59,69% dos Especialistas em Odontologia Legal são mulheres e, nos estados onde foi possível a coleta dos dados, 57,89% dos Peritos Oficiais Odontolegistas são mulheres. Apesar de maioria na Odontologia Legal, ainda é necessário padronizar a nomenclatura e criar novos cargos oficiais no Brasil para fortalecer a profissão de Perito Odontolegista, incentivando uma maior participação feminina. Conclui-se que em 1981 tivemos a primeira Perita Oficial Odontolegista do Brasil, sendo tal fato no estado da Paraíba, e que hoje há um maior equilíbrio na proporção de homens e mulheres nesse cargo

Sugarcane: an unexpected habitat for black yeasts in Chaetothyriales.

Sugarcane (Saccharum officinarum, Poaceae) is cultivated on a large scale in (sub)tropical regions such as Brazil and has considerable economic value for sugar and biofuel production. The plant is a rich substrate for endo- and epiphytic fungi. Black yeasts in the family Herpotrichiellaceae (Chaetothyriales) are colonizers of human-dominated habitats, particularly those rich in toxins and hydrocarbon pollutants, and may cause severe infections in susceptible human hosts. The present study assessed the diversity of Herpotrichiellaceae associated with sugarcane, using in silico identification and selective isolation. Using metagenomics, we identified 5833 fungal sequences, while 639 black yeast-like isolates were recovered in vitro. In both strategies, the latter fungi were identified as members of the genera Cladophialophora, Exophiala, and Rhinocladiella (Herpotrichiellaceae), Cyphellophora (Cyphellophoraceae), and Knufia (Trichomeriaceae). In addition, we discovered new species of Cladophialophora and Exophiala from sugarcane and its rhizosphere. The first environmental isolation of Cladophialophora bantiana is particularly noteworthy, because this species up to now is exclusively known from the human host where it mostly causes fatal brain disease in otherwise healthy patients.

Contextualizing and optimizing novel strategies to improve the latent TB continuum of care: Insights from people living with HIV and health care providers in Brazil.

Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP's perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality.

Metagenomics reveals an abundance of black yeast-like fungi in the skin microbiome.

BACKGROUND: The skin is the first line of defence against communities of resident viruses, bacteria and fungi. The composition of the microbiome might change with factors related to the environment and host. The microbiome is dominated by bacteria. Dermatophytes and yeasts are the predominant fungi that are also involved in opportunistic infections of skin, hair and nails. Among environmental fungi, Chaetothyriales (black yeasts and relatives) are enriched by hydrocarbon pollution in domesticated habitats and comprise numerous species that cause mild-to-severe disease. METHODS: We investigated the presence of black fungi in the skin microbiome by conducting an analysis in the publicly available metagenomic SRA database (NCBI). We focused on the causative agents of chromoblastomycosis and phaeohyphomycosis and used barcodes and padlock probe sequences as diagnostic tools. RESULTS: A total of 132,159,577 MB was analysed and yielded 18,360 reads that matched with 24 species of black fungi. Exophiala was the most prevalent genus, and Cyphellophora europaea was the most abundant species. CONCLUSION: This study reveals the abundant presence of Chaetothyriales on the skin without necessarily being associated with infection. Most of the detected causal agents are known from mild skin diseases, while also species were revealed that had been reported from CARD9-deficient patients.

Translation and preliminary validation of the Brazilian family resources scale in a sample of parents of children with congenital Zika virus syndrome.

PURPOSE: Family-centered rehabilitative care optimizes outcomes for children with significant developmental disabilities. Family-centered services involve assessing family resources that promote positive developmental outcomes for children. Little is known regarding family resources in the context of caring for a child with developmental disabilities in Brazil due to an absence of validated measures. This study describes the translation and cultural adaptation of the Family Resource Scale and explored the measurement quality of the resulting measure (the Brazilian-Family Resource Scale, or B-FRS). METHODS: A rigorous serial translation process that emphasized linguistic accuracy as well as cultural adaptation was utilized. The resulting 27-item B-FRS was theoretically related and reflected the contextual intent of the original measure. RESULTS: A four-factor scoring approach yielded acceptable internal consistency estimates for the subscales and total scale score. Overall, low levels of family resources were reported by caregivers of children with Congenital Zika Syndrome. Low family resources were associated with parental depressive and stress-related symptoms. CONCLUSION: Confirmatory factor analysis of the B-FRS in a larger sample is recommended. Practitioners in Brazil should broadly consider family needs and resources to provide family-centered care that is effective for the child and engages the family in a way that highlights their strengths and promotes positive developmental trajectories.

Determinants of losses in the tuberculosis infection cascade of care among children and adolescent contacts of pulmonary tuberculosis cases: A Brazilian multi-centre longitudinal study.

Background: Approximately 10% of the global tuberculosis (TB) burden is in children. Identification, diagnosis, and early treatment of Mycobacterium tuberculosis infection (TBI) is critical to prevent progression to TB in children. The risk of TB, including severe disease, is highest in children <5 years old. We evaluated the cascade of TBI care among child and adolescent TB contacts to identify factors associated with losses in the cascade. Methods: Close contacts ≤ 18 years old of pulmonary TB patients enrolled between 2015 and 2019 in a multi-centre Brazilian cohort were followed for up to 24 months and classified according to age groups: <5 years, 5-9 years, 10-14 years and 15-18 years. Data on clinical investigation, radiographic examination, IGRA testing at baseline and 6 months, initiation and completion of TB preventive treatment (TPT) were collected. Multivariable regression analyses identified factors associated with TBI and losses in the cascade of care in children and adolescents. Findings: Among 1795 TB contacts initially identified, 530 (29·5%) were ≤18 years old. Losses for all steps in the cascade were especially high in children <5 years old (88%) because at this age all contacts are recommended to initiate TPT. As a proportion of all children, completion of TPT was low (between 10% and 13%) in all age-groups. Furthermore, multivariable regression revealed that younger age of contacts and TB index cases who were female, had pulmonary cavities, and persistent cough were independently associated with losses in the cascade of care among persons ≤18 years old. Interpretation: Losses in the TBI cascade were the highest among children <5 years, which was the group at highest risk for TB among the four age groups. The findings highlight the need to improve screening, initiation, and completion of TPT of young children who are close contacts of people with TB in Brazil. Funding: National Institutes of Allergy and Infectious Diseases.

Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), experienced in the 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and severe respiratory failure. In severe cases, COVID-19 manifests as a thromboinflammatory disease. Damage to the vascular compartment caused by SARS-CoV-2 has been linked to thrombosis, triggered by an enhanced immune response. The molecular mechanisms underlying endothelial activation have not been fully elucidated. We aimed to identify the proteins correlated to the molecular response of human umbilical vein endothelial cells (HUVECs) after exposure to SARS-CoV-2, which might help to unravel the molecular mechanisms of endothelium activation in COVID-19. In this direction, we exposed HUVECs to SARS-CoV-2 and analyzed the expression of specific cellular receptors, and changes in the proteome of HUVECs at different time points. We identified that HUVECs exhibit non-productive infection without cytopathic effects, in addition to the lack of expression of specific cell receptors known to be essential for SARS-CoV-2 entry into cells. We highlighted the enrichment of the protein SUMOylation pathway and the increase in SUMO2, which was confirmed by orthogonal assays. In conclusion, proteomic analysis revealed that the exposure to SARS-CoV-2 induced oxidative stress and changes in protein abundance and pathways enrichment that resembled endothelial dysfunction.

A Kunitz-type inhibitor from tick salivary glands: A promising novel antitumor drug candidate.

Salivary glands are vital structures responsible for successful tick feeding. The saliva of ticks contains numerous active molecules that participate in several physiological processes. A Kunitz-type factor Xa (FXa) inhibitor, similar to the tissue factor pathway inhibitor (TFPI) precursor, was identified in the salivary gland transcriptome of Amblyomma sculptum ticks. The recombinant mature form of this Kunitz-type inhibitor, named Amblyomin-X, displayed anticoagulant, antiangiogenic, and antitumor properties. Amblyomin-X is a protein that inhibits FXa in the blood coagulation cascade and acts via non-hemostatic mechanisms, such as proteasome inhibition. Amblyomin-X selectively induces apoptosis in cancer cells and promotes tumor regression through these mechanisms. Notably, the cytotoxicity of Amblyomin-X seems to be restricted to tumor cells and does not affect non-tumorigenic cells, tissues, and organs, making this recombinant protein an attractive molecule for anticancer therapy. The cytotoxic activity of Amblyomin-X on tumor cells has led to vast exploration into this protein. Here, we summarize the function, action mechanisms, structural features, pharmacokinetics, and biodistribution of this tick Kunitz-type inhibitor recombinant protein as a promising novel antitumor drug candidate.

Immunologic Biomarkers in Peripheral Blood of Persons With Tuberculosis and Advanced HIV.

Introduction: Tuberculosis (TB) is a common opportunistic infection among people living with HIV. Diagnostic tests such as culture, Xpert-MTB-RIF, and ULTRA have low sensitivity in paucibacillary TB disease; a blood biomarker could improve TB diagnostic capabilities. We assessed soluble factors to identify biomarkers associated with TB among persons with advanced HIV. Methods: A case-control (1:1) study was conducted, with participants from Rio de Janeiro and Manaus, Brazil. People living with HIV presenting with CD4 count ≤100 cells/mm3 were eligible to participate. Cases had culture-confirmed TB (N=15) (positive for Mycobacterium tuberculosis [Mtb]); controls had HIV-infection only (N=15). Study visits included baseline, month 2 and end of TB therapy, during which samples of peripheral blood were obtained. A panel containing 29 biomarkers including cytokines, chemokines and growth factors was utilized to assess candidate biomarkers using Luminex technology in cryopreserved EDTA plasma samples. We used neural network analysis, based on machine learning, to identify biomarkers (single or in combination) that best distinguished cases from controls. Additional multi-dimensional analyses provided detailed profiling of the systemic inflammatory environment in cases and controls. Results: Median CD4 count and HIV-1 RNA load values were similar between groups at all timepoints. Persons with TB had lower body mass index (BMI) (median=19.6, Interquartile Range [IQR]=18.6-22.3) than controls (23.7; IQR: 21.8 = 25.5, p=0.004). TB coinfection was also associated with increased frequency of other comorbidities. The overall profile of plasma cytokines, chemokines and growth factors were distinct between the study groups at all timepoints. Plasma concentrations of IL-15 and IL-10 were on average lower in TB cases than in controls. When used in combination, such markers were able to discriminate between TB cases and controls with the highest degree of accuracy at each study timepoint. Conclusion: Among persons with advanced HIV, plasma concentrations of IL-15 and IL-10 can be used in combination to identify TB disease regardless of time on anti-TB treatment.

Unique case of presumed ocular tuberculosis presenting as bilateral pseudoretinitis pigmentosa.

Ocular tuberculosis is often a challenging diagnosis with extremely diverse clinical manifestations and, most times, impractical bacilli isolation. Here we describe an unprecedented case of presumed ocular tuberculosis presenting with bilateral pseudoretinitis pigmentosa and retinal vasculitis.

The Effect of Diabetes and Prediabetes on Antituberculosis Treatment Outcomes: A Multicenter Prospective Cohort Study.

BACKGROUND: It is unclear whether diabetes or prediabetes affects unfavorable treatment outcomes and death in people with tuberculosis (PWTB). METHODS: Culture-confirmed, drug-susceptible PWTB, enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between 2015 and 2019 (N = 643) were stratified based on glycemic status according to baseline glycated hemoglobin. Unfavorable tuberculosis (TB) outcome was defined as treatment failure or modification, recurrence, or death; favorable outcome was cure or treatment completion. We corroborated the findings using data from PWTB reported to the Brazilian National System of Diseases Notification (SINAN) during 2015-2019 (N = 20 989). Logistic regression models evaluated associations between glycemic status and outcomes. RESULTS: In both cohorts, in univariate analysis, unfavorable outcomes were more frequently associated with smoking, illicit drug use, and human immunodeficiency virus infection. Diabetes, but not prediabetes, was associated with unfavorable outcomes in the RePORT-Brazil (adjusted relative risk [aRR], 2.45; P < .001) and SINAN (aRR, 1.76; P < .001) cohorts. Furthermore, diabetes was associated with high risk of death (during TB treatment) in both RePORT-Brazil (aRR, 2.16; P = .040) and SINAN (aRR, 1.93; P = .001). CONCLUSIONS: Diabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve TB treatment outcomes in persons with diabetes are needed.

Proteomic analysis identifies molecular players and biological processes specific to SARS-CoV-2 exposure in endothelial cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), experienced in the 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and severe respiratory failure. In severe cases, COVID-19 manifests as a thromboinflammatory disease. Damage to the vascular compartment caused by SARS-CoV-2 has been linked to thrombosis, triggered by an enhanced immune response. The molecular mechanisms underlying endothelial activation have not been fully elucidated. We aimed to identify the proteins correlated to the molecular response of human umbilical vein endothelial cells (HUVECs) after exposure to SARS-CoV-2, which might help to unravel the molecular mechanisms of endothelium activation in COVID-19. In this direction, we exposed HUVECs to SARS-CoV-2 and analyzed the expression of specific cellular receptors, and changes in the proteome of HUVECs at different time points. We identified that HUVECs exhibit non-productive infection without cytopathic effects, in addition to the lack of expression of specific cell receptors known to be essential for SARS-CoV-2 entry into cells. We highlighted the enrichment of the protein SUMOylation pathway and the increase in SUMO2, which was confirmed by orthogonal assays. In conclusion, proteomic analysis revealed that the exposure to SARS-CoV-2 induced oxidative stress and changes in protein abundance and pathways enrichment that resembled endothelial dysfunction.