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Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole-exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on NF-κB signaling. Nine rare, potentially deleterious variants were found in eight of 21 patients, located in IL17RC, IFNA10, or NLRP12 genes. Unlike the wild-type NLRP12 protein, which inhibits NF-κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C.
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Nanoformulations in vaccinology provide antigen stability and enhanced immunogenicity, in addition to providing targeted delivery and controlled release. In the last years, much research has been focused on vaccine development using virus-like particles, liposomes, emulsions, polymeric, lipid, and inorganic nanoparticles. Importantly, nanoparticle interactions with innate and adaptive immune systems must be clearly understood to guide the rational development of nanovaccines. This review provides a recap and updates on different aspects advocating nanoparticles as promising antigen carriers and immune cell activators for vaccination. Moreover, it offers a discussion of how the physicochemical properties of nanoparticles are modified to target specific cells and improve vaccine efficacy.
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Antígenos , Portadores de Fármacos , Nanopartículas , Vacunas , Humanos , Vacunas/administración & dosificación , Vacunas/inmunología , Animales , Antígenos/administración & dosificación , Antígenos/inmunología , Antígenos/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Sistema de Administración de Fármacos con Nanopartículas/químicaRESUMEN
Abstract To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.
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Anemia de Células Falciformes , HidroxiureaRESUMEN
Inga laurina is a plant species which produces edible fruits, and until now there is little information available concerning its nutritional, chemical and bioactive composition. In this study, we evaluated for the first time the proximate composition and mineral contents in its fruit (peel, pulp and seed), that is the traditionally consumed part. The seeds obtained the highest protein (19.52 g/100 g), carbohydrate (22.5 g/100 g) and mineral contents, mainly Cu, Cr, P, Mn, Se and Zn. The peel and pulp were excellent sources of fiber (4.5 and 11.05 g/100 g) as well as mineral content, with Cr and Cu standing out in the pulp. This study is notably the first to provide a detailed assessment of the nutritional compositions of traditionally consumed and not consumed parts of this fruit. Sensory analysis of the pulp was also performed, which indicated good acceptance. The antioxidant properties were characterized in the fruit, peels and leaves. The ABTS test showed that leaf supernatant hydroethanolic crude extract (EC50 = 2.70 µg/mL) and its corresponding ethyl acetate (EC50 = 1.68 µg/mL) and butanol (EC50 = 2.48 µg/mL) partitions presented higher antioxidant potential compared to the control Ginkgo biloba (EC50 = 12.17 µg/mL). The most active precipitate extract regarding DPPH was from the peel (EC50 = 13.30 µg /mL) and the most active partition was the ethyl acetate (EC50 = 13.37 µg/mL), both with better activity compared to the control Ginkgo biloba (EC50 = 46.97 µg/mL). The ethyl acetate partition (EC50 = 13.45 µg/mL) and butanol partition (EC50 = 7.97 µg/mL) from the leaves showed the highest antioxidant capacity. Thus, extracts and partitions from the peels and leaves were studied from a phytochemical point of view due to presenting the best results for antioxidant capacity. The presence of phenolic compounds such as myricetin-3-O-rhamnopyranoside, myricetin-3-O-(2â³-O-galloyl)-rhamnopyranoside and myricetin-3-O-(2â³,4â³-di-O-galloyl)-arabinopentoside-methyl ether were observed in the leaf crude extract and polar partitions, being reported for the first time in the Inga genus and Fabaceae family. Moreover, quercetin, quercetin-3-O-galatoctoside, quercetin-3-O-rhamnopyranoside, quercetin-3-O-(2â³-O-galloyl)-rhamnoside, and quercetin tri-hexose were identified in the peel crude extract and ethyl acetate partition, in which the galloyl derivative of quercetin was identified for the first time in I. laurina fruit peels. GC-MS enabled separating and identifying substances such as palmitic and stearic acids, and ethyl oleate. It is possible to conclude that I. laurina pulp can be a supplementary food as a source of phenolic compounds, and the other organs of the plant (leaves and peel) are rich in flavonoids with great antioxidant capacity, making this species a promising source of antioxidants.
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Acetatos , Antioxidantes , Fabaceae , Antioxidantes/química , Quercetina , Extractos Vegetales/química , Fenoles/análisis , Minerales , ButanolesRESUMEN
To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.
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Implementation of HCT programs is a high priority in Brazil, given the growing survival rates for children with SCD. Our data highlights a well-connected community of healthcare workers, but also reveals that the current level of HCT activities for SCD in Brazil is low. This underscores the urgent need for transition intervention. The key facilitators for successful HCT implementation in Brazil are strong leadership and a motivated workforce. However, community participation and finances are weak points that require implementation strategies during program implementation. Compared to the US, both Brazilian institutions scored significantly lower on all components needed for transition, emphasizing the need for intervention. This project is the first to evaluate the readiness for HCT implementation in a low- and middle-income country. Designing a context-specific HCT program that suits low-resource settings will improve outcomes for individuals with SCD in the country. (AU)
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BACKGROUND: Sickle cell anemia (SCA) is a genetic disease with great clinical heterogeneity and few viable strategies for treatment; hydroxyurea (HU) is the only widely used drug. Thus, the study of single nucleotide polymorphisms (SNPs) and the gene expression of MMPs 1, 2, 9, 7 and TIMPs 1 and 2, which are involved in the regulation of extracellular matrix, inflammation, and neuropathies, may provide further insights into the pathophysiology of the disease and elucidate biomarkers and molecules as potential therapeutic targets for patients with SCA. METHODS AND RESULTS: We evaluated 251 young individuals with SCA from northeastern Brazil. The groups were divided according to vaso-occlusive crisis (VOC) and cerebrovascular disease (CVD), compared to control individuals. SNP detection and gene expression assays were performed by real-time PCR, TaqMan system®. Both the expression levels of MMP1 gene, and the SNP MMP1-1607 1G/2G were associated with the risk of cerebral ischemic stroke (IS), and the expression of MMP1 was also associated with a higher frequency of VOC/year. Expression levels of MMP7, TIMP1, and TIMP2 were increased in patients conditioned to IS. The SNP 372T>C (rs4898) TIMP1 T alleles were more frequent in patients with > 5 VOC events/year. The SNP rs17576 of MMP9 showed differences in gene expression levels; it was increased in the genotypes AG, and AG+GG. CONCLUSION: The findings of this study, the SNPs, and expression provide initial support for understanding the role of MMPs-TIMPs in the pathophysiology of SCA in young patients.
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Anemia de Células Falciformes , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Compuestos Orgánicos Volátiles , Humanos , Metaloproteinasa 1 de la Matriz/genética , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/genética , Accidente Cerebrovascular/genética , Isquemia , Polimorfismo de Nucleótido Simple/genética , Metaloproteinasas de la Matriz/genética , Expresión GénicaRESUMEN
PURPOSE: To explore the evidence of the internal structure validity of the Roland-Morris Disability Questionnaire in older adults with low back pain. METHODS: This was a cross-sectional study of psychometric testing involving 528 older adults with low back pain. Internal structure validity was explored by exploratory factor analysis and semi-confirmatory factor analysis. Reliability was verified using Kuder-Richardson Formula 20, Cronbach's alpha, and McDonald's omega. Replicability was observed by the generalized H index. RESULTS: Roland-Morris Disability Questionnaire displayed two factors that assess "functional capacity" and "mobility". Eight items were excluded for presenting cross-loading (2 and 10), inadequate loading factors and communalities (18, 24, 13, and 12), or did not relate to the latent construct (15 and 22). Semi-confirmatory factor analysis indicated that the questionnaire had a good fitness model [X2 = 153.698 (p = 0.00001); RMSEA = 0.037; RMSR = 0.06; WRMR = 0.04; NNFI = 0.987; GFI = 0.979; AGFI = 0.971]. Reliability was acceptable (KR-20 = 0.79; Cronbach's alpha = 0.86; McDonald's Omega = 0.85), but replicability was poor in both factors (G-H factor 1 = 0.816-0.655; G-H factor 2 = 0.889-0.775). CONCLUSIONS: The most appropriate version of the Roland-Morris Disability Questionnaire to apply to older adults with low back pain has 16 items and assesses functional capacity and mobility. IMPLICATIONS FOR REHABILITATIONThe RMDQ-16 is the most appropriate version of the RMDQ to use in older adults with LBP;The RMDQ-16 is bidimensional and assesses "functional capacity" and "mobility";The poor replicability of the RMDQ-16 indicates that it will probably not be stable across studies, but it can be useful in a clinical setting.
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Dolor de la Región Lumbar , Humanos , Anciano , Dolor de la Región Lumbar/diagnóstico , Reproducibilidad de los Resultados , Estudios Transversales , Vida Independiente , Evaluación de la Discapacidad , Encuestas y Cuestionarios , Psicometría/métodos , Comparación TransculturalRESUMEN
Extrahepatic manifestations are common in people with hepatitis C virus (HCV). Cognitive changes are pointed out, but the mechanisms are still uncertain. The aim of this systematic review was to analyze studies involving spectroscopic magnetic resonance in people infected with HCV, which also included cognitive tests. The research occurred in six databases (Directory of Open Access Journals, Lilacs, Medcaribe, Medline, Scielo and ScienceDirect) and the selection of studies was carried out in two stages: search for titles and abstracts, then reading of the full articles, excluding those that did not meet the eligibility criteria. 12,888 titles and abstracts were selected, but only 6 articles were included in the review. Impairments in attention, concentration, speed of information processing, memory, verbal fluency and executive functions were identified as well as an increase in the Cho/Cr and mI/Cr ratios and a reduction in the NAA/Cr ratio in some included studies. Longitudinal studies, with more homogeneous samples and methods, as well as with better controlled confounding factors, are necessary to adequately identify the effect of HCV on the brain.
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Trastornos del Conocimiento , Hepatitis C Crónica , Humanos , Hepatitis C Crónica/patología , Imagen por Resonancia Magnética , Encéfalo/patología , CogniciónRESUMEN
The IL-22 pathway has been shown to play an important role in the pathogenesis of liver fibrosis. However, little is known about the role of single-nucleotide polymorphisms (SNPs) in IL-22-related genes in relation to the severity of liver fibrosis. This study aimed to investigate the association of polymorphisms in IL22 and IL22RA1 genes with the severity of liver fibrosis in patients with chronic hepatitis C. A total of 326 patients (165 with mild fibrosis and 161 with severe fibrosis) were included. Four SNPs in IL22 (rs1179251, rs2227473, rs1012356, and rs2227485) and two in IL22RA1 (rs4648936 and rs3795299) were evaluated by real-time PCR. No significant association was observed between the polymorphisms studied and the severity of liver fibrosis. The SNPs rs1179251, rs2227473, rs1012356, and rs2227485 in IL22 and rs4648936 and rs3795299 in IL22RA1 may not be involved in the pathogenesis of liver fibrosis in patients with chronic hepatitis C.
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Hepatitis C Crónica , Interleucinas , Cirrosis Hepática , Receptores de Interleucina , Humanos , Fibrosis , Genotipo , Hepatitis C Crónica/genética , Hepatitis C Crónica/patología , Interleucinas/genética , Interleucinas/metabolismo , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Polimorfismo de Nucleótido Simple , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Interleucina-22RESUMEN
A rare dihydoxyflavan-epicatechin proanthocyanidin, entcassiflavan-(4ßâ8)-epicatechin, was isolated from Dalbergia monetaria, a plant widely used by traditional people from the Amazon to treat urinary tract infections. The constitution and relative configuration of the compound were elucidated by HR-MS and detailed 1D- and 2D-NMR measurements. By comparing the experimental electronic circular dichroism (ECD) spectrum with the calculated ECD spectra of all 16 possible isomers, the absolute configuration, the interflavan linkage, and the atropisomers could be determined.
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Catequina , Dalbergia , Dicroismo Circular , Electrónica , Humanos , Estructura MolecularRESUMEN
Quantum dots (QDs) have stood out as nanotools for glycobiology due to their photostability and ability to be combined with lectins. Mannose-binding lectin (MBL) is involved in the innate immune system and plays important roles in the activation of the complement cascade, opsonization, and elimination of apoptotic and microbial cells. Herein, adsorption and covalent coupling strategies were evaluated to conjugate QDs to a recombinant human MBL (rhMBL). The most efficient nanoprobe was selected by evaluating the conjugate ability to labelCandida albicansyeasts by flow cytometry. The QDs-rhMBL conjugate obtained by adsorption at pH 6.0 was the most efficient, labelingca.100% of cells with the highest median fluorescence intensity. The conjugation was also supported by Fourier transform infrared spectroscopy, zeta potential, and size analyses.C. albicanslabeling was calcium-dependent; 12% and <1% of cells were labeled in buffers without calcium and containing EDTA, respectively. The conjugate promoted specific labeling (based on cluster effect) since, after inhibition with mannan, there was a reduction of 80% in cell labeling, which did not occur with methyl-α-D-mannopyranoside monosaccharide. Conjugates maintained colloidal stability, bright fluorescence, and biological activity for at least 8 months. Therefore, QDs-rhMBL conjugates are promising nanotools to elucidate the roles of MBL in biological processes.
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Puntos Cuánticos , Carbohidratos , Citometría de Flujo , HumanosRESUMEN
BACKGROUND: The mannose-binding lectin (MBL) plays an important role in innate immunity. Genetically determined variations in serum levels of MBL may influence the susceptibility and clinical outcome of dengue infection in early life. METHODS: We investigated the MBL2 gene polymorphisms and serum levels of MBL (total and functional) in children with asymptomatic (n=17) and symptomatic (n=29) primary dengue infections and age-matched uninfected children (n=84) enrolled in a birth cohort with dengue in Brazil. Polymorphisms of the MBL2 gene were assessed by reverse transcription-polymerase chain reaction (RT-PCR), whereas the enzyme-linked immunosorbent assay (ELISA) was used to quantify serum levels of MBL. RESULTS: We found that the X allele and YX genotype in the MBL2 were more frequent in the dengue cases than in the control group. Likewise, the LXPA haplotype was exclusively found in dengue cases, thus probably related to dengue infection in our setting. Moreover, we found a higher frequency of the O allele and AO genotype in the control group. Serum levels of total and functional MBL were higher in dengue naïve infants than in dengue cases. CONCLUSIONS: MBL2 variants related to lower production of serum MBL were associated with dengue infection in infants, whereas intermediate to high levels of total and functional serum MBL were associated with protection against dengue infection. These findings highlight the role of MBL2 variants and serum levels of MBL in the susceptibility of children to dengue disease at early ages.
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Dengue , Lectina de Unión a Manosa , Brasil/epidemiología , Niño , Dengue/epidemiología , Dengue/genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Lactante , Lectina de Unión a Manosa/genética , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030. In Brazil, efforts have been undertaken to achieve this goal; there are, however, great challenges. It is important to understand the disease profile in different regions of the country in order to design strategies to fight the disease nationwide. The objective of this study was to analyse the time trend of the incidence and mortality of hepatitis C in Brazil during the period from 2008 to 2018 according to sociodemographic and clinical characteristics. METHODS: All newly diagnosed cases of hepatitis C reported between 2008 and 2018, in all regions of Brazil, were included. The indicators were obtained from the databases of the Brazilian Ministry of Health. For the time series analysis, a joinpoint regression model was used. RESULTS: Between 2008 and 2018, 136,759 newly diagnosed cases of hepatitis C were reported considering anti-HCV and HCV RNA positivity, and 271,624 newly diagnosed cases were reported considering one or another positive test. The majority of the records were concentrated in the Southeast (61%) and South (26.2%) Regions. The joinpoint regression model indicated an increasing trend in the detection rate of hepatitis C in Brazil, but there was a decreasing trend in the mortality rate during the period analysed. CONCLUSIONS: Differences were observed in the time trend of hepatitis C and in the sociodemographic and clinical characteristics in different regions of Brazil. These data can provide support to design strategies for the elimination of hepatitis C in Brazil, according to regional particularities.
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Hepacivirus , Hepatitis C , Brasil/epidemiología , Hepacivirus/genética , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Humanos , Incidencia , Factores de TiempoRESUMEN
BACKGROUND: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC). We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea in a specialized hematology center in Brazil. METHODS: The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. The reasons for acute hospital visits were grouped as: 1) vaso-occlusive (VOC) pain, 2) infection, 3) anemia exacerbation, and 4) chronic organ damage complications. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period. RESULTS: In total, 1144 patients, median age 17 years (range 0-70), 903 (78.9%) with HbSS/HbSß0-thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions. Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2176.40/visit). Compared with other genotypes, individuals with HbSS/HbSß0-thalassemia were admitted more often (79% versus 21%, p < 0.0001), and their admission costs were higher ($1677.18 versus $1224.47/visit, p = 0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs. Costs of ED visits not resulting in admissions were lower among HbSS/HbSß0-thalassemia individuals with hydroxyurea MPR ≥65% compared with visits by patients with MPR <65% ($98.16/visit versus $182.46/visit, p = 0.0007). No difference in admission costs were observed relative to hydroxyurea use. DISCUSSION: In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Hydroxyurea may reduce ED costs among individuals with HbSS/HbSß0-thalassemia but is dependent on adherence level.
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Anemia de Células Falciformes , Adolescente , Adulto , Anciano , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/epidemiología , Niño , Preescolar , Costos y Análisis de Costo , Servicio de Urgencia en Hospital , Hospitalización , Humanos , Hidroxiurea/uso terapéutico , Lactante , Recién Nacido , Persona de Mediana Edad , Adulto JovenRESUMEN
AIMS: Liver fibrosis is the result of an exacerbated wound-healing response associated with chronic liver injury. Interleukin-22 (IL-22) plays a key role in liver disease, through either a protective or an adverse role, depending on the context. The relationship between IL-22 and its receptors IL-22R1 and IL-22BP (soluble inhibitor) in liver fibrosis is unknown. In this study, we assessed the presence and quantity of IL-22, IL-22R1, and IL-22BP-producing cells in liver tissues of patients with chronic hepatitis C. METHODS AND RESULTS: The number of IL-22-producing cells was significantly higher in stages F1, F2, and F3 when compared to F0 or F4 (p < 0.05). The immunostaining of IL-22R1 decreased as liver fibrosis increased from F1 to F4. On the other hand, the concentration of IL-22BP-producing cells was higher in patients with cirrhosis (F4). Furthermore, the IL-22BP:IL-22 ratio was highest in patients with cirrhosis. CONCLUSIONS: Our results suggest that IL-22, IL-22R1 and IL-22BP may be involved in the mechanisms of liver fibrosis in patients with chronic hepatitis C.
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Hepatitis C Crónica , Hepatitis C Crónica/complicaciones , Humanos , Interleucinas , Hígado , Cirrosis Hepática/complicaciones , Receptores de Interleucina , Interleucina-22RESUMEN
OBJECTIVE: To evaluate the impact of the Covid-19 pandemic on depressive symptoms and suicide risk among patients receiving treatment at a Public Health Psychosocial Addiction Care Center (CAPS AD III) in Porto Alegre, Brazil. METHODS: Questions from the Coronavirus Health Impact Survey (CRISIS) translated into Brazilian Portuguese were used to evaluate 70 patients' perceptions of and behaviors during the Covid-19 pandemic. Validated Brazilian versions of the Patient Health Questionnaire (PHQ-9) and the General Anxiety Disorder-7 (GAD-7) were used to evaluate the severity of depressive symptoms, suicide risk, and anxiety symptoms. A multiple logistic regression model was used to evaluate predictors of suicide risk in the sample. RESULTS: Around 70% of patients reported moderate depressive symptoms and 30% reported severe depressive symptoms, 17% of patients reported having thoughts of suicide or death on more than half of days and 10% reported having them daily. The logistic regression model identified history of alcohol use as the main predictor of suicide risk in (OR 13.0, p = 0.03). CONCLUSIONS: Individuals with a history of alcohol consumption had significantly higher suicide risk scores at a psychosocial public health care center in Brazil during the Covid-19 pandemic. This result may be important for devising better strategies and interventions to support this specific population profile.
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COVID-19 , Suicidio , Ansiedad/epidemiología , Brasil/epidemiología , COVID-19/epidemiología , Depresión/epidemiología , Humanos , Pandemias , Salud Pública , SARS-CoV-2RESUMEN
Abstract Objective To evaluate the impact of the Covid-19 pandemic on depressive symptoms and suicide risk among patients receiving treatment at a Public Health Psychosocial Addiction Care Center (CAPS AD III) in Porto Alegre, Brazil. Methods Questions from the Coronavirus Health Impact Survey (CRISIS) translated into Brazilian Portuguese were used to evaluate 70 patients' perceptions of and behaviors during the Covid-19 pandemic. Validated Brazilian versions of the Patient Health Questionnaire (PHQ-9) and the General Anxiety Disorder-7 (GAD-7) were used to evaluate the severity of depressive symptoms, suicide risk, and anxiety symptoms. A multiple logistic regression model was used to evaluate predictors of suicide risk in the sample. Results Around 70% of patients reported moderate depressive symptoms and 30% reported severe depressive symptoms, 17% of patients reported having thoughts of suicide or death on more than half of days and 10% reported having them daily. The logistic regression model identified history of alcohol use as the main predictor of suicide risk in (OR 13.0, p = 0.03). Conclusions Individuals with a history of alcohol consumption had significantly higher suicide risk scores at a psychosocial public health care center in Brazil during the Covid-19 pandemic. This result may be important for devising better strategies and interventions to support this specific population profile.
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The rapid annotation and identification by mass spectrometry techniques of flavonoids remains a challenge, due to their structural diversity and the limited availability of reference standards. This study applies a workflow to characterize two isoflavonoids, the orobol-C-glycosides analogs, using high-energy collisional dissociation (HCD)- and collision-induced dissociation (CID)-type fragmentation patterns, and also to evaluate the antioxidant effects of these compounds by ferric reducing antioxidant power (FRAP), 2,2'-azino-bis(3-ethylbenzothiazolin acid) 6-sulfonic acid (ABTS), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods. By the CID-type fragmentation, in positive mode and at all high-resolution mass spectrometry (HRMS) multiple stage, there were shown differences in the annotation of the compounds, mainly concerning some ratios of relative abundance. At CID-MS2 20 eV, the compounds could be efficiently characterized, because they present distinct base peaks [M + H]+ and [M + H-H2 O]+ for the orobol-8-C- and orobol-6-C-glycoside, respectively. Similarly, by the HCD-type fragmentation, in HRMS2 stage, differences between orobol analogs in both mode of ionization were observed. However, the HR HCD-MS2 at 80 eV, in positive mode, generated more ions and each isomer presented different base peaks ions, [0,2X]+ for the orobol-8-C-glycoside and [0,3X]+ for the orobol-6-C-glycoside. By the DPPH, the 8-C-derivative showed a very close value compared with the standard rutin and, in the ABTS method, a higher radical-scavenging activity. In both methods, the EC50 of orobol-8-C-glycoside was almost twice better compared with orobol-6-C-glycoside. In FRAP, both C-glycosides showed a good capacity as Fe+3 reducing agents. We could realize that combined MS techniques, highlighting the positive mode of ionization, can be used to evaluate the isoflavones analogs being useful to differentiate between the isomeric flavones; therefore, these data are important to mass spectrometry dereplication studies become more efficient. HIGHLIGHTS: The MS2, in positive mode of ionization, at low CID energies (15 and 20 eV) and at high HCD energies (50 eV), was suitable to characterize orobol 8 and 6-C-derivatives. Positive mode of ionization was effective to rapid annotation of each orobol C-glycoside. The orobol C-derivatives showed high radical scavenging effects. Orobol-8-C-glycoside showed higher antioxidant capacity.