Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia.

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.

Indoor paint life cycle particle release: Safer-by-design products and the importance of choosing the right formula.

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.

Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults.

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).

The relationship between healthcare satisfaction after miscarriage and perinatal grief symptoms: A cross-sectional study on Portugal residents.

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.

GAPi: A description of the initiative for early psychosis intervention in Latin America and the short- to medium-term outcomes in early psychosis patients.

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, 65.95 % 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.

For Whom and for How Long Does the "Be a Mom" Intervention Work? A Secondary Analysis of Data From a Randomized Controlled Trial Exploring the Mid-Term Efficacy and Moderators of Treatment Response.

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.

Genetic variants in DBC1, SIRT1, UCP2 and ADRB2 as potential biomarkers for severe obesity and metabolic complications.

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.

HIV infection among children in Malanje province, Angola: a twelve-year follow-up study.

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.

Factors Associated with Prospective Acceptability and Preferences for Unified Transdiagnostic Cognitive-Behavioral Treatments and Group Therapy in the Portuguese General Population.

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.

Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

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.

A template wizard for the cocreation of machine-readable data-reporting to harmonize the evaluation of (nano)materials.

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.

Mid-arm muscle circumference cutoff points in patients with cirrhosis: Low muscle mass related to malnutrition predicts mortality.

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.

Silica-Poly(Vinyl Alcohol) Composite Aerogel: A Promising Electrolyte for Solid-State Sodium Batteries.

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.

Psychometric properties of the Decisional Conflict Scale in a sample of perinatal women with depressive symptoms: A study in Portugal and Norway.

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.

Economic evaluation of Be a Mom, a web-based intervention to prevent postpartum depression in high-risk women alongside a randomized controlled trial.

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.

Dynamics of Carbon and Soil Enzyme Activities under Arabica Coffee Intercropped with Brachiaria decumbens in the Brazilian Cerrado.

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).

Relapsing-remitting multiple sclerosis patients exhibit differential natural killer functional subpopulations.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) and has been known as T-cell mediated. However, the contribution of multiple cell types, notably natural killer (NK) cells, has also been reported. AIM: To quantify circulating total NK cells and its subpopulations, CD56 dim and bright, and to characterize the functional phenotype and IFN-γ and TNF-α production in relapsing-remitting patients treated with IFN-ß and in apparently healthy controls. RESULTS: CD56bright NK cells were found to be the least represented subpopulation. In relapse patients, the frequencies of IFN-γ-producing NK cells and their subpopulations were significantly decreased. In remission patients, CD56dim NK cells expressed high levels of HLA-DR and CD54. CONCLUSION: These results suggest that remission RRMS patients, although in an inactive stage of MS, present circulating NK cells with an activation phenotype, supporting the idea that NK cells may be relevant mediators in the MS pathophysiology.

Association of Meal Timing with Sleep Quality and Anxiety According to Chronotype: A Study of University Students.

There are several determinants of mental health symptoms, ranging from individual characteristics to social factors. Consistent with patterns in the general population, students with evening characteristics tend to exhibit more anxiety symptoms and poorer sleep quality compared to morning students. Meal timing also appears to affect sleep and may be associated with mental health symptoms. In this context, the aim of the present study was to investigate the association of the timing of the main and last meals of the day with sleep quality and anxiety levels, according to the chronotype of university students. This study was conducted in colleges in São Paulo, Brazil, and involved application of a questionnaire to 162 university students. The questionnaire collected sociodemographic information meal and study times, and included scales assessing eveningness and morningness, sleep quality, and anxiety. Students demonstrating a phase delay in both chronotype and dinner timing exhibited higher levels of anxiety compared to morning-type students. Although no associations were observed between meal timing and sleep quality, sleeping later was associated with poorer sleep quality. The study suggests that evening students and those who eat late at night are more prone to presenting mental health symptoms. More studies are needed to further investigate this association.

Standard Doses of Cholecalciferol Reduce Glucose and Increase Glutamine in Obesity-Related Hypertension: Results of a Randomized Trial.

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.

Characteristics and patient-reported outcomes of long-term lung cancer survivors.

Background: Due to advances in screening and treatment of lung cancer, there has been increased interest in long-term lung cancer survivors (LTLCS). The aim of this study was to evaluate the prevalence of LTLCS, their characteristics and patient-reported outcomes (PROs) of LTLCS. Methods: Cross-sectional study that included patients diagnosed with primary lung cancer between Jan 2012 and Dec 2016 whose overall survival (OS) was greater than 5 years. A self-administered questionnaire was applied, including European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), Patient Health Questionnaire-4 (PHQ-4) and two open questions regarding quality of life (QoL) and suggestions for improvements. Factors potentially related to QoL were analysed. Results: Of 767 lung cancer patients, 158 (20.6%) were LTLCS and LTLCS' proportion increased yearly. Most patients were male (70.9%) with median age of 65 [interquartile range (IQR), 56-71] years. Fifty-seven percent had adenocarcinoma, 66.2% were diagnosed at early stages but 8.9% were at stage IV. During follow-up, 77.1% quitted smoking, 31.8% had disease progression/relapse and 15.2% developed other tumours. Of all living LTLCS, 100 (85%) patients answered the PROs questionnaire. The median Global Health score was 66.67 (IQR, 50-83), social functioning had the best score and emotional functioning the worst. Pain and fatigue were the symptoms with the worst impact on QoL. PHQ-4 identified mental distress in 36% and patients with a lower QoL were more likely to present anxiety (35.3% vs. 9.4%, P=0.007) or depression (27.9% vs. 3%, P=0.006). In the open questions, patients reported pain (17%), lack of familiar/financial support (16%), dyspnoea (14%), depression (8%), concern for the future (8%) and limitations performing daily activities (8%) as the aspects with most impact in QoL. The most suggested measures were improvement of care provided by health institutions (25%) and better social support (16%). Conclusions: Prevalence of LTLCS is increasing and survivors may experience a high prevalence of anxiety and depression as well as a high disease burden affecting QoL. Therefore, it's important to provide multidisciplinary continuous patient-centred care and a careful follow-up for all lung cancer patients, including LTLCS.