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Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy causing progressive vision loss due to mutations in the CHM gene, leading to Rab escort protein 1 loss of function. CHM disease is characterized by a progressive degeneration of the choroid, the retinal pigment epithelium (RPE), and the retina. The RPE is a monolayer of polarized cells that supports photoreceptors, providing nutrients, growth factors, and ions, and removes retinal metabolism waste products, having a central role in CHM pathogenesis. Commonly used models such as ARPE-19 cells do not reproduce accurately the nature of RPE cells. Human induced pluripotent stem cells (hiPSCs) can be differentiated into RPE cells (hiPSC-RPE), which mimic key features of native RPE, being more suited to study retinal diseases. Therefore, we took advantage of hiPSCs to generate new human-based CHM models. Two isogenic hiPSC lines were generated through CRISPR/Cas9: a CHM knock-out line from a healthy donor and a corrected CHM patient line using a knock-in approach. The differentiated hiPSC-RPE lines exhibited critical morphological and physiological characteristics of native RPE, including the presence of the tight junction markers Claudin-19 and Zonula Occludens-1, phagocytosis of photoreceptor outer segments, pigmentation, a postmitotic state, and the characteristic polygonal shape. In addition, all the studied cells were able to form retinal organoids. This work resulted in the establishment of isogenic hiPSC lines, representing a new and important CHM cellular model. To our knowledge, this is the first time that isogenic cell lines have been developed to model CHM disease, providing a valuable tool for studying the mechanisms at the onset of RPE degeneration.
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In 2020, the European Commission published a regulation that states all producers of white paints containing titanium dioxide (TiO2) must provide a warning label on their products. Exposure during the production and application of products containing TiO2 can be harmful, and therefore these products must be labeled as "may cause cancer." The paint industry is a major user of TiO2 pigment. This study focuses on pigment release from three TiO2-based paints and discusses the effect of paint formulation, more precisely the Pigment Volume Concentration (PVC), to predict TiO2 pigment release from the paints during a simulated use phase and at the end of life (EoL). The use phase considered mild abrasion of painted panels that simulated cleaning or touching. The EoL phase was studied using leaching tests simulating landfill disposal. TiO2 release during both activities was evident with a high discrepancy between the three paints. While dry rubbing was similar for all paints, activities involving water present a high release link to paint matrix degradation. The paint pigment volume concentration and the paint permeability determines the TiO2 release during wet rubbing and leaching. This work represents an attempt to identify the paint permeability as a matrix-related parameter to predict TiO2 release and a way to use of this parameter to develop safer products.
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BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.
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Background: Incidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be 1 of the underlying mechanisms, but this has only been scarcely explored. Objectives: The purpose of this study was to assess the association between increased LA stiffness and CIS in young adults. Methods: In the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e' velocity (E/e')/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness. Results: Increased LA stiffness was found in 36% of patients and in 18% of controls (P < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders (P = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P < 0.05). Conclusions: LA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages. (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome [SECRETO]; NCT01934725).
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OBJECTIVE: 15-20% of identified pregnancies result in miscarriage, which may lead to persistent symptoms of psychological morbidities in some women. Healthcare satisfaction is among the factors believed to influence such negative psychological responses. Here, we present the results of a study conducted in Portugal that analyzes the relationship between healthcare satisfaction, information and support provision and perinatal grief symptoms. METHODS: In a cross-sectional study, symptoms of perinatal grief, degree of satisfaction with healthcare received, and information and support provision data were collected through an online survey aimed at women in Portugal who suffered a miscarriage. 873 were considered eligible. Correlations were performed between perinatal grief scores and healthcare satisfaction rates. Finally, the proportions of information and support received were compared after distributing the sample in groups according to their perinatal grief levels. RESULTS: Healthcare satisfaction correlated significantly with perinatal grief scores, the latter increasing as satisfaction levels decreased. 61.1% of our sample received information about the physical consequences of miscarriage and showed a significantly lower rate of above-threshold perinatal grief symptoms in this group. 18.2% received information about its mental health consequences, with no significant differences in above-threshold symptom rates. 11.7% were offered or recommended mental health support, but no significant differences in above-threshold symptom rates were found. CONCLUSION: Healthcare satisfaction and information on after-miscarriage physical changes correlated significantly with reduced perinatal grief rates after miscarriage. However, any effects of mental health information and psychological support provision need further studies. Training for healthcare providers dealing with pregnancy loss, implementing national guidelines that include follow-up on the parents' physical and psychological health, and including a specialized area in medical structures are advised.
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Aborto Espontâneo , Pesar , Satisfação do Paciente , Humanos , Feminino , Estudos Transversais , Portugal , Aborto Espontâneo/psicologia , Adulto , Gravidez , Inquéritos e Questionários , Pessoa de Meia-Idade , Apoio SocialRESUMO
Pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) exhibit favorable survival rates. However, for AML and ALL patients carrying KMT2A gene translocations clinical outcome remains unsatisfactory. Key players in KMT2A-fusion-driven leukemogenesis include menin and DOT1L. Recently, menin inhibitors like revumenib have garnered attention for their potential therapeutic efficacy in treating KMT2A-rearranged acute leukemias. However, resistance to menin inhibition poses challenges, and identifying which patients would benefit from revumenib treatment is crucial. Here, we investigated the in vitro response to revumenib in KMT2A-rearranged ALL and AML. While ALL samples show rapid, dose-dependent induction of leukemic cell death, AML responses are much slower and promote myeloid differentiation. Furthermore, we reveal that acquired resistance to revumenib in KMT2A-rearranged ALL cells can occur either through the acquisition of MEN1 mutations or independently of mutations in MEN1. Finally, we demonstrate significant synergy between revumenib and the DOT1L inhibitor pinometostat in KMT2A-rearranged ALL, suggesting that such drug combinations represent a potent therapeutic strategy for these patients. Collectively, our findings underscore the complexity of resistance mechanisms and advocate for precise patient stratification to optimize the use of menin inhibitors in KMT2A-rearranged acute leukemia.
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Histona-Lisina N-Metiltransferase , Leucemia Mieloide Aguda , Metiltransferases , Proteína de Leucina Linfoide-Mieloide , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteínas Proto-Oncogênicas , Humanos , Histona-Lisina N-Metiltransferase/genética , Proteína de Leucina Linfoide-Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Metiltransferases/antagonistas & inibidores , Metiltransferases/genética , Metiltransferases/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Sinergismo Farmacológico , Rearranjo Gênico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , MutaçãoRESUMO
This study explored clinical and sociodemographic moderators of treatment response to "Be a Mom", an internet-based cognitive behavioral therapy (iCBT) intervention, from baseline to postintervention, in women at high risk for postpartum depression (PPD). The study also assessed the stability of women's treatment gains from baseline to 4-months postintervention (follow-up). This open-label randomized controlled trial (RCT) involved a sample of 1,053 postpartum Portuguese women identified as being at high risk for PPD (i.e., having a score of 5.5 or higher on the Postpartum Depression Predictors Inventory-Revised); participants were allocated to "Be a Mom" intervention group or a waiting-list control group, and completed self-report measures at baseline, postintervention, and a 4-month follow-up (554 women completed follow-up assessments). Depressive and anxiety symptoms were measured using the Edinburgh Postnatal Depression Scale and the anxiety subscale of the Hospital Anxiety and Depression Scale, and flourishing/positive mental health was assessed with the Mental Health Continuum. Regression models and linear mixed models were used to examine moderators of treatment and the mid-term efficacy of the "Be a Mom" intervention, respectively. The results revealed that treatment completion, higher depression scores at baseline, and higher income levels were linked to greater symptom reduction and positive mental health enhancement. Moreover, the efficacy of the "Be a Mom" intervention was supported at the 4-month follow-up. The "Be a Mom" intervention appears to be an effective iCBT tool for reducing psychological distress and enhancing positive mental health in women at risk for PPD, with therapeutic improvements maintained over a 4-month period.
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Terapia Cognitivo-Comportamental , Depressão Pós-Parto , Humanos , Feminino , Adulto , Terapia Cognitivo-Comportamental/métodos , Depressão Pós-Parto/terapia , Depressão Pós-Parto/psicologia , Resultado do Tratamento , Ansiedade/terapia , Ansiedade/psicologia , Mães/psicologia , Intervenção Baseada em Internet , PortugalRESUMO
Group transdiagnostic cognitive-behavioral therapy (CBT) offers a promising solution for limited mental health access in Portugal. Understanding barriers to patient adherence is crucial for successful implementation. This study aimed to characterize the prospective acceptability and preferences for unified transdiagnostic CBT and group therapy in the Portuguese general population and explore their correlates. A sample of 243 participants (18-88 years old), recruited online, completed an online survey collecting information on sociodemographic and clinical characteristics, acceptability of transdiagnostic CBT treatments, specifically of Unified Protocol (UP), acceptability of group therapy, therapeutic format preferences, beliefs about group therapy and help-seeking attitudes. Most participants were receptive to and perceived as useful both unified transdiagnostic CBT and group therapy. Overall, participants presented significantly more favorable attitudes than unfavorable attitudes toward unified transdiagnostic CBT and group therapy (p < .001). Multivariate analyses revealed that (1) favorable attitudes toward transdiagnostic treatments were negatively associated with being employed and positively associated with living in an urban area, and higher efficacy scores; (2) unfavorable attitudes toward transdiagnostic treatments were positively associated with being married/cohabitating and negatively associated with vulnerability scores; (3) being female, living in an urban area, and higher efficacy and myth scores emerged as positive predictors of favorable attitudes toward group therapy; and (4) efficacy and vulnerability scores and help-seeking propensity emerged as negative predictors of unfavorable attitudes toward group therapy. These findings highlight the importance of delineating strategies to increase knowledge and acceptance of unified transdiagnostic CBT and group therapy in the Portuguese population, addressing specific individual characteristics.
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INTRODUCTION: Human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS) infection has been a serious health problem in pediatric age groups globally, and especially in African countries such as Angola. Our aim was to determine the prevalence rate, accumulate incidence rate, and mortality rate of HIV/AIDS infection in children under 14 years of age residing in four municipalities of Malanje (Malanje, Cacuso, Calandula, and Caculama), from 2010 to 2021. METHODOLOGY: This was a documentary research study, with data from 2010 to 2021, developed from a sample size of 10,984 children. RESULTS: The prevalence rate data showed a certain level of dispersion, and no relationship was identified in its behavior over the years (R2 = 0.0036). On the other hand, the accumulate incidence rate presented a tendency to decrease, indicating a moderate level of correlation in its behavior over the years (R2 = 0.4278). Finally, the mortality rate has been decreasing and presented a high correlation in its association with the years under analysis (R2 = 0.8142). Primary schooling and low purchasing power were frequent (60% and 82%, respectively) among the families of HIV-infected children under study. CONCLUSIONS: Despite the temporal variation of HIV in children under 14 years of age living in the different municipalities, there was a tendency of its diminishing in the later part of the period, from 2010 to 2021. Nevertheless, the key players should focus on strengthening community strategies for prevention, investigation, and diagnosis of HIV infections in this population.
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Infecções por HIV , Humanos , Angola/epidemiologia , Criança , Infecções por HIV/epidemiologia , Adolescente , Pré-Escolar , Masculino , Feminino , Incidência , Prevalência , Lactente , Seguimentos , Recém-NascidoRESUMO
INTRODUCTION: Schizophrenia is a debilitating disorder that affects a significant proportion of the population and leads to impaired functionality and long-term challenges. The first episode of psychosis (FEP) is a critical intervention stage for improving long-term outcomes. The GAPi program was established in São Paulo, Brazil to provide early intervention services and evaluate biomarkers in individuals with FEP. This article delineates the objectives of the GAPi program, detailing its innovative research protocol, examining the clinical outcomes achieved, and discussing the operational challenges encountered during its initial decade of operation. METHODS: The study comprised a prospective cohort of antipsychotic-naïve individuals with first-episode psychosis aged between 16 and 35 years. Participants were recruited from a public psychiatric facility in São Paulo. Emphasizing the initiative's commitment to early intervention, clinical assessments were systematically conducted at baseline and at two months, one year, two years, and five years of treatment to capture both short- and medium-term outcomes. Various assessment tools were utilized, including structured interviews, symptom scales, the Addiction Severity Index, and functional assessments. RESULTS: A total of 232 patients were enrolled in the cohort. Among them, 65.95â¯% completed the 2-month follow-up. Most patients presented with schizophrenia spectrum disorders, followed by bipolar disorder and major depressive disorder with psychotic features. Treatment response rates and remission rates were evaluated at different time points, with promising outcomes observed. The program also assessed socio-demographic factors, substance use, family history, and genetic and biomarker profiles, providing valuable data for research. DISCUSSION: The GAPi program has emerged as the largest ongoing cohort of antipsychotic-naïve first-episode psychosis in Latin America, contributing to the understanding of early psychosis in low- and middle-income countries. Despite operational challenges, the program has demonstrated efficacy in reducing the duration of untreated psychosis and in improving clinical outcomes. A multidisciplinary approach, including pharmacological treatment, psychosocial interventions, and family involvement, has been instrumental in enhancing treatment adherence and long-term prognosis. CONCLUSION: The GAPi program represents a valuable model for early intervention in first-episode psychosis and provides insights into the pathophysiology, treatment, and long-term outcomes of individuals with schizophrenia and related disorders. Continued research and resource allocation are essential for addressing operational challenges and expanding early intervention services in low- and middle-income countries.
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Intervenção Médica Precoce , Transtornos Psicóticos , Esquizofrenia , Humanos , Transtornos Psicóticos/terapia , Adulto , Masculino , Intervenção Médica Precoce/estatística & dados numéricos , Feminino , Adulto Jovem , Adolescente , Esquizofrenia/terapia , Brasil , Estudos Prospectivos , Avaliação de Resultados em Cuidados de Saúde , América LatinaRESUMO
Introduction: Obesity is a multifactorial disease associated with the development of many comorbidities. This disease is associated with several metabolic alterations; however, it has been shown that some individuals with obesity do not exhibit metabolic syndrome. Adipose tissue neutralizes the detrimental effects of circulating fatty acids, ectopic deposition, and inflammation, among others, through its esterification into neutral lipids that are stored in the adipocyte. However, when the adipocyte is overloaded, i.e., its expansion capacity is exceeded, this protection is lost, resulting in fatty acid toxicity with ectopic fat accumulation in peripheral tissues and inflammation. In this line, this study aimed to investigate whether polymorphisms in genes that control adipose tissue fat storage capacity are potential biomarkers for severe obesity susceptibility and also metabolic complications. Methods: This study enrolled 305 individuals with severe obesity (cases, BMI≥35 kg/m2) and 196 individuals with normal weight (controls, 18.5≤BMI≤24.9 kg/m2). Demographic, anthropometric, biochemical, and blood pressure variables were collected from the participants. Plasma levels of leptin, resistin, MCP1, and PAI1 were measured by Bio-Plex 200 Multiplexing Analyzer System. Genomic DNA was extracted and variants in DBC1 (rs17060940), SIRT1 (rs7895833 and rs1467568), UCP2 (rs660339), PPARG (rs1801282) and ADRB2 (rs1042713 and rs1042714) genes were genotyped by PCR allelic discrimination using TaqMan® assays. Results: Our findings indicated that SIRT1 rs7895833 polymorphism was a risk factor for severe obesity development in the overdominant model. SIRT1 rs1467568 and UCP2 rs660339 were associated with anthropometric traits. SIRT1 rs1467568 G allele was related to lower medians of body adipose index and hip circumference, while the UCP2 rs660339 AA genotype was associate with increased body mass index. Additionally, DBC1 rs17060940 influenced glycated hemoglobin. Regarding metabolic alterations, 27% of individuals with obesity presented balanced metabolic status in our cohort. Furthermore, SIRT1 rs1467568 AG genotype increased 2.5 times the risk of developing metabolic alterations. No statistically significant results were observed with Peroxisome Proliferator-Activated Receptor Gama and ADRB2 polymorphisms. Discussion/Conclusion: This study revealed that SIRT1 rs7895833 and rs1467568 are potential biomarkers for severe obesity susceptibility and the development of unbalanced metabolic status in obesity, respectively. UCP2 rs660339 and DBC1 rs17060940 also showed a significant role in obesity related-traits.
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OBJECTIVE: To assess the psychometric properties, i.e., reliability and construct validity of the 16-item Decisional Conflict Scale (DCS) and sub-scales in women with perinatal depressive symptoms in Norway and Portugal. METHODS: We included 415 women in Portugal and 163 in Norway (≥18 years) who were pregnant or had given birth in the last 12 months and presenting with active depressive symptoms. Women replied to the original DCS items. We conducted confirmatory factor analysis, estimated internal consistency reliability, and examined factorial invariance across country, perinatal status, and treatment uptake. RESULTS: The DCS factor model had good fit to the data, with all items loading significantly on their respective factor (.585 to .958). There was configural invariance of the DCS across countries, treatment, and perinatal status. The internal consistency of the total DCS (Cronbach's alpha) was .958, and for the subscales it ranged from .798 to .947. CONCLUSIONS: The DCS is a valid and reliable measure of the decisional conflict in women with perinatal depressive symptoms in Portugal and Norway. PRACTICE IMPLICATIONS: Measuring the extent of decisional conflict regarding treatment and the effect of multiple interventions towards its reduction, is critical to facilitate the decision-making process of women with perinatal mental illness.
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Conflito Psicológico , Tomada de Decisões , Depressão , Psicometria , Humanos , Feminino , Portugal , Noruega , Adulto , Gravidez , Depressão/psicologia , Reprodutibilidade dos Testes , Inquéritos e Questionários , Análise Fatorial , Gestantes/psicologiaRESUMO
OBJECTIVES: Muscle loss is one of the phenotypic criteria of malnutrition, is highly prevalent in patients with cirrhosis, and is associated with adverse outcomes. Mid-arm muscle circumference (MAMC) estimates the skeletal muscle mass and is especially helpful in cases of fluid overload. This study aimed to propose MAMC cutoff points for patients with cirrhosis and demonstrate its association with 1-year mortality. METHODS: This is an analysis of cohort databases from five reference centers in Brazil that included inpatients and outpatients with cirrhosis aged ≥18 y. The nutritional variables obtained were the MAMC (n = 1075) and the subjective global assessment (n = 629). We established the MAMC cutoff points stratified by sex based on the subjective global assessment as a reference standard for malnutrition diagnosis, considering the sensitivity, specificity, and Youden index. An adjusted Cox regression model was used to test the association of MAMC cutoff points and 1-year mortality. RESULTS: We included 1075 patients with cirrhosis, with a mean age of 54.8 ± 11.3 y; 70.4% (n = 757) male. Most patients had alcoholic cirrhosis (47.1%, n = 506) and were classified as Child-Pugh B (44.7%, n = 480). The MAMC cutoff points for moderate and severe depletion were ≤21.5 cm and ≤24.2 cm; ≤20.9 cm and ≤22.9 cm for women and men, respectively. According to these cutoff points, 13.8% (n = 148) and 35.1% (n = 377) of the patients had moderate or severe MAMC depletion, respectively. The 1-year mortality rate was 17.3% (n = 186). In the multivariate analysis adjusted for sex, age, MELD-Na, and Child-Pugh scores, a severe depletion in MAMC was an independent increased risk factor for 1-year mortality (HR: 1.71, 95% CI: 1.24-2.35, P < 0.001). Each increase of 1 cm in MAMC values was associated with an 11% reduction in 1-year mortality risk (HR: 0.89, 95% CI: 0.85-0.94, P < 0.001). CONCLUSIONS: Low MAMC classified according to the new cutoff points predicts mortality risk in patients with cirrhosis and could be used in clinical practice.
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Braço , Cirrose Hepática , Desnutrição , Músculo Esquelético , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Desnutrição/diagnóstico , Desnutrição/mortalidade , Cirrose Hepática/mortalidade , Cirrose Hepática/complicações , Brasil/epidemiologia , Adulto , Idoso , Estado Nutricional , Avaliação Nutricional , Modelos de Riscos Proporcionais , Estudos de Coortes , Sarcopenia/mortalidade , Sarcopenia/diagnósticoRESUMO
BACKGROUND: Postpartum depression (PPD) poses significant challenges, affecting both mothers and children, with substantial societal and economic implications. Internet-based cognitive behavioral therapy interventions (iCBT) offer promise in addressing PPD, but their economic impact remains unexplored. This study aimed to evaluate the cost-utility of Be a Mom, a self-guided iCBT intervention, compared with a waiting-list control among postpartum women at high risk of PPD. METHODS: This economic evaluation was conducted alongside a 14-month randomized controlled trial adopting a societal perspective. Participants were randomized to Be a Mom (n = 542) or a waitlisted control group (n = 511). Self-report data on healthcare utilization, productivity losses, and quality-adjusted life years (QALYs) were collected at baseline, post-intervention, and 4 and 12 months post-intervention. Incremental cost-effectiveness ratios (ICERs) were calculated, and cost-effectiveness acceptability curves were generated using nonparametric bootstrapping. Sensitivity analyses were conducted to assess result robustness. RESULTS: Over 14 months, Be a Mom generated a QALY gain of 0.0184 (0.0022, 0.0346), and cost savings of EUR 34.06 (-176.16, 108.04) compared to the control group. At a willingness to pay of EUR 20,000, Be a Mom had a 97.6 % probability of cost-effectiveness. LIMITATIONS: Results have limitations due to self-selected sample, potential recall bias in self-reporting, missing data, limited follow-up, and the use of a waiting-list control group. CONCLUSIONS: This study addresses a critical gap by providing evidence on the cost-utility of an iCBT intervention tailored for PPD prevention. Further research is essential to identify scalable and cost-effective interventions for reducing the burden of PPD.
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Terapia Cognitivo-Comportamental , Análise Custo-Benefício , Depressão Pós-Parto , Intervenção Baseada em Internet , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Feminino , Depressão Pós-Parto/prevenção & controle , Depressão Pós-Parto/economia , Depressão Pós-Parto/terapia , Adulto , Intervenção Baseada em Internet/economia , Terapia Cognitivo-Comportamental/economia , Terapia Cognitivo-Comportamental/métodos , Mães/psicologiaRESUMO
The transition from fossil fuels is in part limited by our inability to store energy at different scales. Batteries are therefore in high demand, and we need them to store more energy, be more reliable, durable and have less social and environmental impact. Silica-poly(vinyl alcohol) (PVA) composite aerogels doped with sodium perchlorate were synthesized as novel electrolytes for potential application in solid-state sodium batteries. The aerogels, synthesized by one-pot synthesis, are light (up to 214 kg m-3), porous (~85%), exhibit reduced shrinkage on drying (up to 12%) and a typical silica aerogel microstructure. The formation of a silica network and the presence of PVA and sodium perchlorate in the composite were confirmed by FTIR and TGA. The XRD analysis also shows that a predominantly amorphous structure is obtained, as crystalline phases of polymer and salt are present in a very reduced amount. The effects of increasing polymer and sodium salt concentrations on the ionic conductivity, assessed via electrochemical impedance spectroscopy, were studied. At a PVA concentration of 15% (w/w silica precursors), the sodium conduction improved significantly up to (1.1 ± 0.3) × 10-5 S cm-1. Thus, this novel material has promising properties for the envisaged application.
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Making research data findable, accessible, interoperable and reusable (FAIR) is typically hampered by a lack of skills in technical aspects of data management by data generators and a lack of resources. We developed a Template Wizard for researchers to easily create templates suitable for consistently capturing data and metadata from their experiments. The templates are easy to use and enable the compilation of machine-readable metadata to accompany data generation and align them to existing community standards and databases, such as eNanoMapper, streamlining the adoption of the FAIR principles. These templates are citable objects and are available as online tools. The Template Wizard is designed to be user friendly and facilitates using and reusing existing templates for new projects or project extensions. The wizard is accompanied by an online template validator, which allows self-evaluation of the template (to ensure mapping to the data schema and machine readability of the captured data) and transformation by an open-source parser into machine-readable formats, compliant with the FAIR principles. The templates are based on extensive collective experience in nanosafety data collection and include over 60 harmonized data entry templates for physicochemical characterization and hazard assessment (cell viability, genotoxicity, environmental organism dose-response tests, omics), as well as exposure and release studies. The templates are generalizable across fields and have already been extended and adapted for microplastics and advanced materials research. The harmonized templates improve the reliability of interlaboratory comparisons, data reuse and meta-analyses and can facilitate the safety evaluation and regulation process for (nano) materials.
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The change in land use in the Brazilian Cerrado modifies the dynamics of soil organic matter (SOM) and, consequently, carbon (C) stocks and their fractions and soil enzyme activities. This study evaluated the effect of brachiaria (Brachiaria decumbens Stapf.) intercropped with Arabica coffee (Coffea arabica L.) on the stock and fractions of soil carbon and enzyme activities. The experiment was arranged in a completely randomized block design with three replications and treatments in a factorial design. The first factor consisted of coffee with or without intercropped brachiaria, the second of Arabica coffee cultivars ('I.P.R.103' and 'I.P.R.99') and the third factor of the point of soil sampling (under the canopy (UC) and in inter-rows (I)). Soil was sampled in layers of 0-10, 10-20, 20-30, 30-40, 40-60 and 60-80 cm. Soil from the 0-10 cm layer was also used to analyze enzymatic activity. Significant effects of coffee intercropped with brachiaria were confirmed for particulate organic carbon (POC), with highest contents in the 0-10 and 20-30 cm layers (9.62 and 6.48 g kg-1, respectively), and for soil enzymes (280.83 and 180.3 µg p-nitrophenol g-1 for arylsulfatase and ß-glucosidase, respectively).
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The poultry industry is evolving towards antibiotic-free production to meet market demands and decelerate the increasing spread of the antimicrobial resistance. The growing need for antibiotic free products has challenged producers to decrease or completely stop using antimicrobials as feed supplements in broiler diet to improve feed efficiency, growth rate, and intestinal health. Natural feed additives (e.g., probiotics and phytobiotics) are promising alternatives to substitute antimicrobial growth promoters. The goal of our study was to characterize the effects of a Probiotic and an Essential Oils blend on broilers' performance and perform a time-series analysis to describe their excreta microbiome. A total of 320 Cobb 500 (1-day-old) chicks were raised for 21 d in 32 randomly allocated cages. Treatments consisted of 4 experimental diets: a basal diet, and a basal diet mixed with an Antibiotic (bacitracin methylene disalicylate), an essential oils blend (oregano oil, rosemary, and red pepper), or a Probiotic (Bacillus subtilis). Body weight (on 1, 10, and 21d), and feed intake (10d and 21d) were recorded and feed conversion ratio was calculated. Droppings were collected daily (1-21d) to characterize broilers' excreta microbiota by targeted sequencing of the bacterial 16S rRNA gene. The Probiotic significantly improved feed conversion ratio for starter phase 1 to 10d (P = 0.03), grower phase 10 to 21d (P = 0.05), and total period 1 to 21d (P = 0.01) compared to the Antibiotic. Feed supplements did not affect alpha diversity but did impact microbial beta diversity (P < 0.01). Age also impacted microbiome turnover as differences in alpha and beta diversity were detected. Furthermore, when compared to the basal diet, the probiotic and antibiotic significantly impacted relative abundance of Bifidobacterium (log2 fold change -1.44, P = 0.03), Intestinimonas (log2 fold change 0.560, P < 0.01) and Ligilactobacillus (log2 fold change -1.600, P < 0.01). Overall, Probiotic supplementation but not essential oils supplementation positively impacted broilers' growth performance by directly causing directional shifts in broilers' excreta microbiota structure.
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Ração Animal , Antibacterianos , Galinhas , Dieta , Suplementos Nutricionais , Óleos Voláteis , Probióticos , Salicilatos , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/microbiologia , Ração Animal/análise , Probióticos/administração & dosagem , Probióticos/farmacologia , Dieta/veterinária , Suplementos Nutricionais/análise , Óleos Voláteis/administração & dosagem , Óleos Voláteis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Bacitracina/farmacologia , Bacitracina/administração & dosagem , Distribuição Aleatória , Bacillus subtilis/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Masculino , Óleos de Plantas/farmacologia , Óleos de Plantas/administração & dosagemRESUMO
OBJECTIVES: The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. METHODS: Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. RESULTS: The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CONCLUSION: CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.
Assuntos
Acidente Vascular Cerebral , Vasculite Sistêmica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/diagnóstico , Vasculite Sistêmica/epidemiologia , Vasculite Sistêmica/diagnóstico , Fatores de Risco , Incidência , Idoso , Seguimentos , Estudos ProspectivosRESUMO
In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.