Identification of common MicroRNAs expression signatures in antiphospholipid syndrome and thromboembolic disease: A scoping review.

BACKGROUND: Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by distinct pathophysiological mechanisms leading to heterogeneous manifestations, including venous and arterial thrombosis. Despite the lack of specific markers of thrombosis risk in APS, some of the mechanisms responsible for thrombosis in APS may overlap with those of other thromboembolic diseases. Understanding these similarities is important for improving the assessment of thrombosis risk in APS. MicroRNAs (MiRNAs) are RNA molecules that regulate gene expression and may influence the autoimmune response and coagulation. PURPOSE: In this scoping review we aimed to investigate shared miRNAs profiles associated with APS and other thromboembolic diseases as a means of identifying markers indicative of a pro-thrombotic profile among patients with APS. DATA COLLECTION AND RESULTS: Through a comprehensive search of scientific databases, 45 relevant studies were identified out of 1020 references. miRs-124-3p, 125b-5p, 125a-5p, and 17-5p, were associated with APS and arterial thrombosis, while miRs-106a-5p, 146b-5p, 15a-5p, 222-3p, and 451a were associated with APS and venous thrombosis. Additionally, miR-126a-3p was associated with APS and both arterial and venous thrombosis. CONCLUSION: We observed that APS shares a common miRNAs signature with non-APS related thrombosis, suggesting that miRNA expression profiles may serve as markers of thrombotic risk in APS. Further validation of a pro-thrombotic miRNA signature in APS is warranted to improve risk assessment, diagnosis, and management of APS.

Association between interferon-I producing plasmacytoid dendritic cells and thrombotic antiphospholipid syndrome.

Background: Thrombotic risk in antiphospholipid syndrome (APS) is conferred by the association of antiphospholipid (aPL) antibodies (first hit) with additional pro-coagulant stimulus (second hit), such as inflammation. Among inflammatory responses, the production of large amounts of interferon (IFN)-I by plasmacytoid dendritic cells (pDCs) is at the basis of the pathophysiology of systemic autoimmune disorders, which raises the hypothesis that this mechanism could also be associated with vascular manifestations of APS. Purpose: Here, we determined the association of pDCs and IFN-I production with thrombotic APS. Research design: Patients with thrombotic primary (t-PAPS) and secondary APS (t-SAPS), asymptomatic aPL carriers and individuals without thrombosis (controls) were included. Data collection and analysis: Circulating pDCs and IFN-α intracellular expression (in the presence or not of oligodeoxynucleotides (CP) stimulus) were quantified by flow cytometry. The expression of five IFN-I inducing genes: ISG15, OASL, Ly6E, MX1, and OAS1 in mononuclear cells was determined by qPCR. Between-group differences were evaluated using chi-square or Kruskal-Wallis tests. Results: A total of 50 patients with t-PAPS, 50 patients with t-SAPS, 20 aPL carriers, and 50 individuals without thrombosis (controls) were included. Intracellular expression of IFN-α was increased after CPG stimulation in both t-SAPS (1.56%; IQR 1.07-2.02) and t-PAPS (0.96%; IQR 0.55-1.24), when compared to aPL carriers (0.71%; IQR 0.42-0.93) and controls (0.48%; IQR 0.24-0.78; p < .0001). ISG15, OASL, Ly6E, MX1, and OAS1 mRNA expressions were higher in t-SAPS (but not in t-PAPS) than in aPL carriers and controls. The expression of proteins and mRNA related to IFN-I response was similar between the triple aPL-positive profile and other aPL profiles. Conclusion: Our results indicate an association of IFN-I response and t-APS. Since IFN-I expression was not increased in aPL carriers or associated with a higher-risk aPL profile, this mechanism does not appear to be related to the presence of aPL alone. IFN-I response could possibly constitute a complementary mechanism for triggering clinical manifestations in APS.

Efficacy of a hypolipid diet in patients with primary antiphospholipid syndrome with dyslipidemia: a prospective study.

Although dyslipidemia is associated with poorer prognosis in antiphospholipid syndrome (APS), the management of lipid disorders can be challenging. While statins may increase the bleeding risk associated with anticoagulation, the effectiveness of hypolipid diet (HD) has not yet been established in patients with autoimmune disorders. In this study, we evaluated whether HD is associated with decreases in cholesterol levels in patients with thrombotic primary APS (t-PAPS) and dyslipidemia. Nutritional and lipid profiles were assessed before HD was initiated (baseline) and after 3 and 6 months with HD. A 24-h dietary recall was applied to assess the adherence to the diet. Forty-four patients were included, mean age was 43 years (± 12.93) and 65% were female. After HD was started, the intake of carbohydrates, lipids, saturated fats and cholesterol decreased, whereas dietary fiber intake increased. Levels of total cholesterol (TC) and non-high density lipoprotein cholesterol (non-HDL-C) decreased after 3 and 6 months of HD, as compared to baseline (P = 0.007 and P = 0.008). Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) values did not change during the study period. The mean body mass index (BMI) decreased from 28.4 to 27.8 kg/m2 after six months of HD (p < 0.0001). In subgroup analysis, the effects of HD were more pronounced in patients with high TC, LDL-C or non-HDL-C levels at baseline and in those without obesity or hypertension. Nutritional intervention is feasible among t-PAPS and could be an alternative therapy to modulate lipid metabolism in this population.

Aging and self-reported health in 114 Latin American cities: gender and socio-economic inequalities.

BACKGROUND: Understanding how urban environments influence people's health, especially as individuals age, can help identify ways to improve health in the rapidly urbanizing and rapidly aging populations. OBJECTIVES: To investigate the association between age and self-reported health (SRH) in adults living in Latin-American cities and whether gender and city-level socioeconomic characteristics modify this association. METHODS: Cross-sectional analyses of 71,541 adults aged 25-97 years, from 114 cities in 6 countries (Argentina, Brazil, Colombia, Chile, El Salvador, and Guatemala), as part of the Salud Urbana en America Latina (SALURBAL) Project. We used individual-level age, gender, education, and self-reported health (SRH) data from harmonized health surveys. As proxies for socioeconomic environment we used a city-level socioeconomic index (SEI) calculated from census data, and gross domestic product (GDP) per-capita. Multilevel Poisson models with a robust variance were used to estimate relative risks (RR), with individuals nested in cities and binary SRH (poor SHR vs. good SRH) as the outcome. We examined effect modification by gender and city-level socioeconomic indicators. RESULTS: Overall, 31.4% of the sample reported poor SRH. After adjusting for individual-level education, men had a lower risk of poor SRH (RR = 0.76; CI 0.73-0.78) compared to women, and gender modified the association between age and poor SRH (p-value of interaction < 0.001). In gender stratified models, the association between older age and poor SRH was more pronounced in men than in women, and in those aged 25-65 than among those 65+ (RR/10 years = 1.38 vs. 1.10 for men, and RR/10 years = 1.29 vs. 1.02 for women). Living in cities with higher SEI or higher GDP per-capita was associated with a lower risk of poor SRH. GDP per-capita modified the association between age (25-65) and SRH in men and women, with SEI the interaction was less clear. CONCLUSIONS: Across cities in Latin America, aging impact on health is significant among middle-aged adults, and among men. In both genders, cities with lower SEI or lower GDP per-capita were associated with poor SRH. More research is needed to better understand gender inequalities and how city socioeconomic environments, represented by different indicators, modify exposures and vulnerabilities associated with aging.

Loneliness and social disconnectedness in the time of pandemic period among Brazilians: evidence from the ELSI COVID-19 initiative.

Objectives: This study aimed at estimating the pre-pandemic and pandemic prevalence of loneliness and investigating the association of loneliness with social disconnectedness during social distancing strategies in the time of the COVID-19 pandemic period.Methods: We used data from the ELSI COVID-19 initiative with participants from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), which comprised 4,431 participants aged 50 years and over. Loneliness (hardly ever/some of the time/often) was assessed by the question "In the past 30 days, how often did you feel alone/lonely?". Social disconnectedness included information on social contacts through virtual talking (i.e. telephone, Skype, WhatsApp, or social media) and outside-home meetings with people living in another household. Covariates included sociodemographic and health related characteristics. Multinomial logistic regression models were used to estimate odds ratios (OR) with their 95% confidence interval (CI).Results: The overall prevalence of loneliness during the pandemic was 23.9% (95% CI 20.7-27.5); lower than in the pre-pandemic period (32.8%; 95% CI 28.6-37.4). In the pandemic period, 20.1% (95% CI 16.9-23.6) reported some of the time feeling lonely and 3.9% (95% CI 3.1-4.8) reported often feeling lonely. In the fully adjusted model, virtual talking disconnectedness (OR=1.67; 95% CI 1.09-2.56) was positively associated with some of the time feeling lonely and outside-home disconnectedness (OR=0.33; 95% CI 0.18-0.60) was negatively associated with often feeling lonely.Conclusion: Individuals with virtual talking disconnectedness and without outside-home disconnectedness are at higher risk of loneliness during the time of COVID-19 pandemic. Stimulating virtual talking connectedness might have the potential to diminish loneliness despite steep outside-home disconnectedness.

Self-perceived quality of life of primary antiphospholipid syndrome patients using vitamin K antagonist.

PURPOSE: Primary antiphospholipid syndrome (PAPS) is a chronic autoimmune disorder clinically characterized by thromboembolic events or obstetric complications. Prolonged anticoagulation therapy with vitamin K antagonists (VKA) is the treatment of choice for PAPS patients with thrombosis. However, the efficacy of VKA therapy depends on laboratory monitoring, dose adjustment, adequate lifestyle and adherence to treatment. Difficulties with VKA therapy can affect patients' self-perceived health related quality of life (HRQOL). This study aims to evaluate PAPS patients' HRQOL, therapy adherence and knowledge of treatment. METHODS: A general Medical Outcome Study Short Form-36 (SF-36) and the Duke Anticoagulation Satisfaction Scale (DASS) were used to access APS-patients self-perceived HRQOL. Treatment adherence was measured by the Treatment Measure Adhesion (TMA) - oral anticoagulant version instrument, and knowledge of VKA treatment was measured using the MedTake test. RESULTS: 66 PAPS patients using VKA were assessed. 63% of them were female; the mean age was 41.9 years old, approximately 60% had unprovoked venous thrombosis and one third of the patients had recurrent thrombotic events. The most impacted domain of DASS was "psychological impacts" and the factors associated to anticoagulation related poor HRQOL were: female sex, presence of arterial thrombosis and INR lability. Using the SF-36 instrument, PAPS-patients self-perceived HRQOL was poorer than that of the general Brazilian population and was associated with female sex and presence of cardiovascular risk factors. CONCLUSION: Despite the high adherence to treatment and knowledge of VKA therapy, self-perceived HRQOL is poor in patients with PAPS and is mainly affected by VKA therapy. Searching for better treatment options is warranted.

Association between plasmatic oxidative stress and thrombosis in primary antiphospholipid syndrome.

Antiphospholipid antibodies induce a pro-inflammatory and hypercoagulable state that lead to increased risk of thrombosis. Whether oxidative damage contributes thrombosis risk is a matter of debate. We evaluated the association between oxidative stress and thrombosis in primary antiphospholipid syndrome (t-PAPS). Plasma total antioxidant capacity and the levels of malondialdehyde (TBARs), carbonyl protein, and 8-isoprostane in plasma were determined in a group of patients with t-PAPS and in individuals without a history of thrombosis (controls) using commercial ELISA assays. The levels of these plasma markers of oxidative stress were compared between t-PAPS and controls using Mann-Whitney test. A total of 70 patients with t-PAPS and 74 controls were included. Overall, measurements of all plasma oxidative stress markers were similar between t-PAPS patients and controls. In a subgroup analysis, patients with t-PAPS and arterial thrombosis had a higher antioxidant capacity as compared to controls. Thrombotic PAPS was not associated with increased levels of oxidative stress markers, in comparison with individuals without thrombosis. Even though it is not possible to rule out that a mild oxidative damage, not detected by plasma markers, occurs in t-PAPS, our results suggest that measuring plasma oxidative stress markers has limited clinical relevance in t-PAPS.

Expression of tissue factor mRNA in thrombosis associated with antiphospholipid syndrome.

Tissue factor (TF) is a procoagulant protein associated with increased risk of thrombotic events in antiphospholipid syndrome (t-APS). The mechanisms by which TF levels are increased in APS have not yet been established. The aim of this study was to investigate whether TF mRNA expression is associated with TF levels and thrombosis in APS. We compared levels of circulating TF and high sensitivity C-reactive protein (hs-CRP) between t-APS and controls (individuals without thrombosis). The association between TF mRNA expression, quantified by real time quantitative polymerase chain reaction, and t-APS was accessed using regression analysis. We included 41 controls and 42 t-APS patients, mean age was 41 years old (SD 14) in both groups. Hs-CRP and TF levels were higher in t-APS patients (mean hs-CRP levels 0.81 mg/dL [SD 1.88] and median TF levels 249.0 pg/mL [IQR 138.77-447.61]) as compared to controls (mean hs-CRP levels 0.24 mg/dL [SD 0.26] and median TF levels 113.0 pg/mL [IQR 81.17-161.53]; P = 0.02 and P < 0.0001, respectively). There was no correlation between TF mRNA expression and TF levels in t-APS (r - 0.209, P = 0.19). TF mRNA expression was not associated with t-APS (adjusted OR 1.16; 95%CI 0.72-1.87). Despite circulating TF levels being higher in patients with t-APS than in controls, TF mRNA expression was similar between groups. The results demonstrate that TF mRNA expression is not associated with levels of circulating TF and hypercoagulability in t-APS.

Outcomes in hepatocellular carcinoma patients undergoing sorafenib treatment: toxicities, cellular oxidative stress, treatment adherence, and quality of life.

The study of toxicities induced by sorafenib, as well as the identification of possible mechanisms and biomarkers of these toxicities, is important to improve the treatment and quality of life of hepatocellular carcinoma (HCC) patients. This study focused on toxicities, cellular oxidative stress, adherence, and quality of life of 11 patients with HCC treated with sorafenib. Dermatotoxicity, myelotoxicity, gastro toxicity, nephrotoxicity, pain, and fatigue were investigated. For oxidative stress analysis, the peripheral blood mononuclear cells were isolated and mitochondrial superoxide anion production was measured using MitoSOX Red test. Medication adherence was evaluated based on Morisky-Green and MedTake tests. Quality of life assessment was performed using EORTC QLQ C-30 and QLQ HCC18 questionnaires. The results showed that hand-foot syndrome (45.5%), thrombocytopenia (45.5%), diarrhea (54.5%), pain (54.5%), and fatigue (36.4%) were the most prevalent toxicities. A non-statistically significant change in the levels of superoxide anion was observed after the sorafenib treatment (Wilcoxon test, P = 0.4131). Moreover, 81.8% of patients had high adherence, 100% knew the correct indication of sorafenib, 81.8% knew the correct intake and drug regimen, and 36.4% knew the correct dose of antineoplastic. There was a significant worsening in the emotional and pain domains of quality of life after the sorafenib (Wilcoxon test, P = 0.0313 and P = 0.0313, respectively). A production of superoxide anion was not correlated with toxicities (Spearman's correlation and Mann-Whitney U tests, P > 0.05). This study suggests that oxidative stress might not be the mechanism of sorafenib toxicities.

A multilevel model of life satisfaction among old people: individual characteristics and neighborhood physical disorder.

BACKGROUND: Considering the lack of studies that examine built environmental factors associated with life satisfaction among old people in developing countries, particularly those focused on Brazil, the aim of this study was to estimate the prevalence of life satisfaction among old adults residents in a Brazilian urban center and to investigate its association with individual characteristics and objective measures of the built environment. METHODS: A household survey (N = 832) in Belo Horizonte, Minas Gerais, Brazil (2008-2009) and a Systematic Social Observation (SSO) was used in this study. Life satisfaction was assessed through Self-Anchoring Ladder Scale, developed by Cantril, in 1965. Participants' answers were categorized as satisfied (rungs 6-10) and dissatisfied (rungs 0-5). A Multilevel Poisson regression analysis with robust variance was performed. RESULTS: The prevalence of satisfaction with life was approximately 82%. Higher prevalence of life satisfaction was significantly associated with old people who reported higher incomes, higher religious participation, who practice physical activity and who perceive their health as good and very good. In contextual level, results showed that when the contextual features were adjusted separately by the individual characteristics they were no longer significant. The results also showed a lower prevalence of life satisfaction among those living in neighborhoods with higher physical disorder, even after adjusting for individual and other contextual characteristics. CONCLUSIONS: The present findings suggest that life satisfaction should be assessed whenever evaluating urban redevelopment programs designed to improve neighborhood characteristics, reducing physical disorder, especially among old adults.

Cisplatin-induced human peripheral blood mononuclear cells' oxidative stress and nephrotoxicity in head and neck cancer patients: the influence of hydrogen peroxide.

Cisplatin is a widely used antineoplastic agent in the treatment of head and neck cancer. However, it is highly nephrotoxic. Oxidative stress is the main mechanism responsible for cisplatin-induced nephrotoxicity. The aim of this study was to characterize cisplatin-induced nephrotoxicity, oxidative stress in peripheral blood mononuclear cells, and the relationship between them. Twenty-four patients were included in the study. Patients had their blood collected prior to cisplatin administration, and 5 and 20 days after initiating therapy, to assess renal function and to determine oxidative stress with MitoSOX™Red, H2DCF-DA, and Amplex® Red tests. Renal function was assessed by measuring serum creatinine, creatinine clearance, and blood urea nitrogen (BUN). Serum creatinine and creatinine clearance were used to grade nephrotoxicity using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Compared to baseline values, the mean BUN and serum creatinine increased 135 and 100%, respectively, 5 days after cisplatin infusion. Mean creatinine clearance showed a 43% decrease compared to baseline value. Non-statistically significant changes in superoxide anion (O 2•- ), hydrogen peroxide (H2O2), and general reactive oxygen species production occurred. A higher production of H2O2 was correlated with variation in serum creatinine, and was associated with higher grades for serum creatinine increases and creatinine clearance reductions. Linear regression analyses showed an association between H2O2 production and serum creatinine, creatinine clearance, and BUN levels. These results were observed for 5 days following cisplatin administration. In conclusion, H2O2 production was significantly related to changes in all renal parameters that were evaluated, following the cisplatin infusion.

Deficiency of lncRNA MERRICAL abrogates macrophage chemotaxis and diabetes-associated atherosclerosis.

Diabetes-associated atherosclerosis involves excessive immune cell recruitment and plaque formation. However, the mechanisms remain poorly understood. Transcriptomic analysis of the aortic intima in Ldlr-/- mice on a high-fat, high-sucrose-containing (HFSC) diet identifies a macrophage-enriched nuclear long noncoding RNA (lncRNA), MERRICAL (macrophage-enriched lncRNA regulates inflammation, chemotaxis, and atherosclerosis). MERRICAL expression increases by 249% in intimal lesions during progression. lncRNA-mRNA pair genomic mapping reveals that MERRICAL positively correlates with the chemokines Ccl3 and Ccl4. MERRICAL-deficient macrophages exhibit lower Ccl3 and Ccl4 expression, chemotaxis, and inflammatory responses. Mechanistically, MERRICAL guides the WDR5-MLL1 complex to activate CCL3 and CCL4 transcription via H3K4me3 modification. MERRICAL deficiency in HFSC diet-fed Ldlr-/- mice reduces lesion formation by 74% in the aortic sinus and 86% in the descending aorta by inhibiting leukocyte recruitment into the aortic wall and pro-inflammatory responses. These findings unveil a regulatory mechanism whereby a macrophage-enriched lncRNA potently inhibits chemotactic responses, alleviating lesion progression in diabetes.

[Discrimination perceived by elderly adults in the use of health services: an integrative review]. / Discriminação percebida por adultos mais velhos no uso de serviços de saúde: uma revisão integrativa.

This paper analyzes the current evidence on discrimination perceived by elderly adults (> 50 years) in the use of health services and identifies factors associated with this discriminatory experience. It involved an integrative literature review, carried out on the Biblioteca Virtual de Saúde, CINAHL, Medline, Scopus, and Web of Science search websites, in June/2021. The key words used were social discrimination or ageism; middle-aged, or aged 80 and over or elderly; health services or health services for the elderly, including synonyms, in Portuguese, English, and Spanish. The search strategy identified 1,165 articles; 19 met the eligibility and inclusion criteria and were included in this integrative review. They comprise quantitative and qualitative studies published between 2002 and 2021; about 60% carried out in the United States and Australia. The prevalence of discrimination in the use of health services ranged from 2% to 42%. The report of discriminatory practices was associated with ethnic-racial characteristics, sex, age, sexual orientation, physical appearance, and social class. By giving visibility to the theme, this work aims to stimulate the definition of concrete ways to tackle discrimination, in an attempt to interrupt the perpetration of inequities in the health care area.

Este trabalho analisa as evidências atuais sobre a discriminação percebida por adultos mais velhos (> 50 anos) no uso de serviços de saúde e identifica os fatores associados a essa experiência. Trata-se de uma revisão integrativa da literatura, realizada a partir de pesquisa nos sítios eletrônicos Biblioteca Virtual de Saúde, CINAHL, Medline, Scopus e Web of Science, em junho de 2021. Foram utilizados os descritores: discriminação social ou ageismo; pessoa de meia-idade ou idoso de 80 anos ou mais ou idoso; e serviço de saúde ou serviço de saúde para idosos, incluindo sinônimos, nos idiomas português, inglês e espanhol. A estratégia de busca identificou 1.165 artigos; 19 cumpriram os critérios de elegibilidade e inclusão. O acervo inclui estudos quantitativos e qualitativos publicados entre 2002 e 2021; cerca de 60% realizados nos Estados Unidos e Austrália. A prevalência de discriminação no uso de serviços de saúde variou de 2% a 42%. O relato de práticas discriminatórias se mostrou associado a características étnico-raciais, sexo, idade, orientação sexual, aparência física e classe social. Ao dar visibilidade ao tema, este trabalho visa estimular a definição de formas concretas de enfrentamento à discriminação e interromper a perpetração de iniquidades no âmbito da atenção à saúde.

Social environment characteristics are related to self-rated health in four Latin America countries: Evidence from the SALURBAL Project.

We investigated the associations of social and built environment and demographic features of urban areas with self-rated health among adults living in four Latin American countries. We estimated multilevel models with harmonized data from 69,840 adults, nested in 262 sub-cities and 112 cities, obtained from the Salud Urbana en América Latina project. Poor self-rated health was inversely associated with services provision score at the sub-city-level and with social environment index at the city-level. We did not identify associations of built environment and demographic features with self-rated health. Approaches and policies to improve health in Latin American should be urban context-sensitive.

Evaluation of a gene signature related to thrombotic manifestations in antiphospholipid syndrome.

Thrombotic primary antiphospholipid syndrome (t-PAPS) is an acquired condition characterized by heterogeneous thrombotic manifestations, which is intriguing since venous and arterial thrombosis appear to have distinct pathogenesis. Gene expression analysis may constitute a new approach to evaluate potential similarities or differences between the clinical manifestations of t-PAPS. Recently, dysregulation of the ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 genes has been associated with both arterial and venous thrombosis in the general population. Therefore, the aim of this study was to examine whether ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression was associated with t-PAPS. Gene expression was quantified by qPCR of total leukocyte mRNA. In this case-control study, 102 t-PAPS patients, 17 asymptomatic antiphospholipid (aPL) carriers and 100 controls were evaluated. Increased expression of ANXA3 (P = 0.008) and TNFAIP6 (P = 0.001) and decreased expression of the TXK gene (P = 0.0001) were associated with an increased risk of t-PAPS compared to the control. ANXA3 upregulation was more evident in cases of arterial thrombosis and multiple thrombotic events. There was no difference in the expression of these genes between triple and non-triple aPL positivity. ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression levels were also similar between aPL carriers and controls (P = 0.77; P = 0.48; P = 0.08; P = 0.73, and P = 0.13, respectively). In conclusion, our results showed that genes related to hemostasis (ANXA3) and immunity (TNFAIP6, TXK) are dysregulated in t-PAPS compared to controls. Gene dysregulation was not detected in aPL carriers and was not related to the aPL profile, suggesting that this gene signature is related to thrombotic manifestations rather than to aPL burden. Our results suggest that innate immunity and hemostasis pathways are associated with t-PAPS at a molecular level and may play a role in disease severity.

A decreased trajectory of loneliness among Brazilians aged 50 years and older during the COVID-19 pandemic: ELSI-Brazil.

This study aimed to estimate prevalence of loneliness among older Brazilian adults over the first seven months of the COVID-19 pandemic and to identify the predictors of loneliness trajectories. Pre-pandemic data derived from face-to-face interviews of participants of the 2019-2020 Brazilian Longitudinal Study of Aging (ELSI-Brazil), which is a nationally representative study of community-dwelling individuals aged 50 years and over. Pandemic data were based on three rounds of telephone interviews among those participants, conducted from May to October 2020. Loneliness was measured by a single-item question, considering those who had at least two repeated measures. Explanatory variables included depression, living alone, leaving home in the last week, and virtual connectedness in the last month. Mixed-effects logistic regression was used to estimate odds ratios with their 95% confidence intervals (95%CI) and to investigate loneliness trajectories and their predictors. In total, 5,108 participants were included. The overall prevalence of loneliness in the pre-pandemic period was 33.1% (95%CI: 29.4-36.8), higher than the pandemic period (round 1: 23.6%, 95%CI: 20.6-26.9; round 2: 20.5%, 95%CI: 17.8-23.5; round 3: 20.6%, 95%CI: 17.1-24.6). A significant interaction (p ≤ 0.05) was evidenced only between depression and time; participants with depression showed a greater reduction in loneliness levels. Although loneliness levels in Brazil have decreased during the pandemic, this pattern is not present for all older adults. Individuals with depression had a more significant reduction, probably due to feeling closer to their social network members during the stay-at-home recommendations.

MicroRNA 205-5p and COVID-19 adverse outcomes: Potential molecular biomarker and regulator of the immune response.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The uncontrolled systemic inflammatory response, resulting from the release of large amounts of pro-inflammatory cytokines, is the main mechanism behind severe acute respiratory syndrome and multiple organ failure, the two main causes of death in COVID-19. Epigenetic mechanisms, such as gene expression regulation by microRNAs (miRs), may be at the basis of the immunological changes associated with COVID-19. Therefore, the main objective of the study was to evaluate whether the expression of miRNAs upon hospital admission could predict the risk of fatal COVID-19. To evaluate the level of circulating miRNAs, we used serum samples of COVID-19 patients collected upon hospital admission. Screening of differentially expressed miRNAs in fatal COVID-19 was performed by miRNA-Seq and the validation of miRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The Mann-Whitney test and receiver operating characteristic (ROC) curve were used to validate the miRNAs, whose potential signaling pathways and biological processes were identified through an in silico approach. A cohort of 100 COVID-19 patients was included in this study. By comparing the circulating levels of miRs between survivors and patients who died due to complications of the infection, we found that the expression of miR-205-5p was increased in those who died during hospitalization, and the expression of both miR-205-5p (area under the curve [AUC] = 0.62, 95% confidence interval [CI] = 0.5-0.7, P = 0.03) and miR-206 (AUC = 0.62, 95% CI = 0.5-0.7, P = 0.03) was increased in those who lately evolved to severe forms of the disease (AUC = 0.70, 95% CI = 0.6-0.8, P = 0.002)."In silico" analysis revealed that miR-205-5p has the potential to enhance the activation of NLPR3 inflammasome and to inhibit vascular endothelial growth factor (VEGF) pathways. Impaired innate immune response against SARS-CoV-2 may be explained by epigenetic mechanisms, which could form early biomarkers of adverse outcomes.

Thrombosis Occurrence in COVID-19 Compared With Other Infectious Causes of ARDS: A Contemporary Cohort.

Thrombosis occurrence in coronavirus disease 2019 (COVID-19) has been mostly compared to historical cohorts of patients with other respiratory infections. We retrospectively evaluated the thrombotic events that occurred in a contemporary cohort of patients hospitalized between March and July 2020 for acute respiratory distress syndrome (ARDS) according to the Berlin Definition and compared those with positive and negative real-time polymerase chain reaction results for wild-type severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using descriptive analysis. The association between COVID-19 and thrombotic risk was evaluated using logistic regression. 264 COVID-19-positive (56.8% male, 59.0 years [IQR 48.6-69.7], Padua score on admission 3.0 [2.0-3.0]) and 88 COVID-19-negative patients (58.0% male, 63.7 years [51.2-73.5], Padua score 3.0 [2.0-5.0]) were included. 10.2% of non-COVID-19 and 8.7% of COVID-19 patients presented ≥ 1 clinically relevant thrombotic event confirmed by imaging exam. After adjustment for sex, Padua score, intensive care unit stay, thromboprophylaxis, and hospitalization length, the odds ratio for thrombosis in COVID-19 was 0.69 (95% CI, 0.30-1.64). We, therefore, conclude that infection-induced ARDS carries an inherent thrombotic risk, which was comparable between patients with COVID-19 and other respiratory infections in our contemporary cohort.

The results of a 24-h pad test in Brazilian women.

INTRODUCTION AND HYPOTHESIS: The International Continence Society (ICS) adopted 1.3 g as the normative value for the 24-h pad test. We hypothesized that this cutoff value may not be valid for women who live in countries with high temperatures. METHODS: We documented the 24-h pad test values of continent women in Brazil and investigated the factors that can influence in vaginal humidity. RESULTS: The sample consisted of 257 participants. The temperatures ranged from 19°C to 27.8°C. The median increase in the weight of the pad was 1.9 g (1.4-3.0 g, 95th percentile 4.4 g). Pad test results differed significantly between pre- and postmenopausal women (p = 0.026). There was a significant difference in the pad weights of women who use hormone therapy (p = 0.003). CONCLUSIONS: The value of the 24-h pad test established by the ICS was not valid for the investigated sample. Environmental conditions, menopausal status, and use of hormone therapy can interfere with the values of the pad test.