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Advancing data analysis tools for proteome-wide cross-linking mass spectrometry (XL-MS) requires ground-truth standards that mimic biological complexity. Here we develop well-controlled XL-MS standards comprising hundreds of recombinant proteins that are systematically mixed for cross-linking. We use one standard dataset to guide the development of Scout, a search engine for XL-MS with MS-cleavable cross-linkers. Using other, independent standard datasets and published datasets, we benchmark the performance of Scout and existing XL-MS software. We find that Scout offers an excellent combination of speed, sensitivity and false discovery rate control. The results illustrate how our large recombinant standard can support the development of XL-MS analysis tools and evaluation of XL-MS results., (© 2024. The Author(s).)

Background: Overlapping sarcopenia and malnutrition may increase the risk of readmission in surgical oncology. Overlapping probable sarcopenia/malnutrition was found in 4.6% of 238 patients and the 30-day unplanned readmission rate was 9.0%. In multivariate analysis, the overlap of probable sarcopenia and malnutrition was a significant predictor for the 30-day unplanned readmission (OR= 8.10, 95%CI= 1.20-0.55; p=0.032)., Background: ■ Probable sarcopenia plus malnutrition was significantly associated with unplanned readmission., Background: ■ Overlap of probable sarcopenia and malnutrition was an independent risk factor for readmission., Background: ■ Certification of whether the patient is malnourished and/or sarcopenic preoperatively is necessary., Background: ■ SARC-F and subjective global assessment can effectively and easily assess sarcopenia and malnutrition at admission., Objective: To assess the 30-day unplanned readmission rate and its association with overlapping probable sarcopenia and malnutrition after major oncological surgery., Methods: A prospective bicentric observational cohort study performed with adult oncological patients undergoing major surgery. The primary outcome was unplanned readmission within 30 days after discharge and the association with probable sarcopenia and malnutrition. Nutritional status and probable sarcopenia were assessed just prior to surgery. Patients classified using subjective global assessment, as B and C were malnourished. Probable sarcopenia was defined using SARC-F (strength, assistance with walking, rise from a chair, climb stairs, falls) questionnaire ≥4 points and low HGS (handgrip strength) <27kg for males and <16kg for females., Results: Two hundred and thirty-eight patients (51.7% female) with a median age of 60 years were included. The 30-day readmission rate was 9.0% (n=20). Univariate analysis showed an association of malnutrition (odds ratio (OR) = 4.84; p=0.024) and probable sarcopenia (OR = 4.94; p=0.049) with 30-day readmission. Furthermore, when both conditions were present, the patient was almost nine times more likely to be readmitted (OR = 8.9; p=0.017). Multivariable logistic regression analysis showed that overlapping probable sarcopenia and malnutrition was an independent predictor of 30-day unplanned readmission (OR = 8.10, 95% confidence interval (95%CI) 1.20-0.55; p=0.032)., Conclusion: The 30-day unplanned readmission rate was 9.0%, and the overlap of probable sarcopenia and malnutrition is an independent predictor for the 30-day unplanned readmission after major oncologic surgery.

We present RawVegetable 2.0, a software tailored for assessing mass spectrometry data quality and fine-tuned for cross-linking mass spectrometry (XL-MS) applications. Building upon the capabilities of its predecessor, RawVegetable 2.0 introduces four main modules, each providing distinct and new functionalities: 1) Pair Finder, which identifies ion doublets characteristic of cleavable cross-linking experiments; 2) Diagnostic Peak Finder, which locates potential reporter ions associated with a specific cross-linker; 3) Precursor Signal Ratio, which computes the ratio between precursor intensity and the total signal in an MS/MS scan; and 4) Xrea, which evaluates spectral quality by analyzing the heterogeneity of peak intensities within a spectrum. These modules collectively streamline the process of optimizing mass spectrometry data acquisition for both Proteomics and XL-MS experiments. RawVegetable 2.0, along with a comprehensive tutorial is freely accessible for academic use at: http://patternlabforproteomics.org/rawvegetable2.

Importance: Overweight and obesity affect 340 million adolescents worldwide and constitute a risk factor for poor mental health. Understanding the association between body mass index (BMI) and mental health in adolescents may help to address rising mental health issues; however, existing studies lack comprehensive evaluations spanning diverse countries and periods., Objective: To estimate the association between BMI and mental health and examine changes over time from 2002 to 2018., Design, Setting, and Participants: This was a repeated multicountry cross-sectional study conducted between 2002 and 2018 and utilizing data from the Health Behaviour in School-aged Children (HBSC) survey in Europe and North America. The study population consisted of more than 1 million adolescents aged 11 to 15 years, with all surveyed children included in the analysis. Data were analyzed from October 2022 to March 2023., Main Outcomes and Measures: Mental health difficulties were measured by an 8-item scale for psychological concerns, scoring from 0 to 32, where a higher score reflects greater psychosomatic issues. BMI was calculated using weight divided by height squared and adjusted for age and sex. Data were fitted by multilevel generalized additive model. Confounders included sex, living with parents, sibling presence, academic pressure, the experience of being bullied, family affluence, screen time, and physical activity., Results: Our analysis of 1 036 869 adolescents surveyed from 2002 to 2018, with a mean (SD) age of 13.55 (1.64) years and comprising 527 585 girls (50.9%), revealed a consistent U-shaped association between BMI and mental health. After accounting for confounders, adolescents with low body mass and overweight or obesity had increased psychosomatic symptoms compared to those with healthy weight (unstandardized β, 0.14; 95% CI, 0.08 to 0.19; unstandardized β, 0.27; 95% CI, 0.24 to 0.30; and unstandardized β, 0.62; 95% CI, 0.56 to 0.67, respectively), while adolescents with underweight had fewer symptoms (unstandardized β, -0.18; 95% CI, -0.22 to -0.15). This association was observed across different years, sex, and grade, indicating a broad relevance to adolescent mental health. Compared to 2002, psychosomatic concerns increased significantly in 2006 (unstandardized β, 0.19; 95% CI, 0.11 to 0.26), 2010 (unstandardized β, 0.14; 95% CI, 0.07 to 0.22), 2014 (unstandardized β, 0.48; 95% CI, 0.40 to 0.56), and 2018 (unstandardized β, 0.82; 95% CI, 0.74 to 0.89). Girls reported significantly higher psychosomatic concerns than boys (unstandardized β, 2.27; 95% CI, 2.25 to 2.30). Compared to primary school, psychosomatic concerns rose significantly in middle school (unstandardized β, 1.15; 95% CI, 1.12 to 1.18) and in high school (unstandardized β, 2.12; 95% CI, 2.09 to 2.15)., Conclusions and Relevance: Our study revealed a U-shaped association between adolescent BMI and mental health, which was consistent across sex and grades and became stronger over time. These insights emphasize the need for targeted interventions addressing body image and mental health, and call for further research into underlying mechanisms.

Competing Interests: Authors report no conflicts of interest.

The aim of this study was to evaluate the effect of non-surgical periodontal treatment in the expression of chemokine receptors, in individuals with Periodontitis, associated or not with Diabetes. Pilot study, which included patients (n = 45) with Periodontitis, associated (n = 25) or not (n = 20) with Diabetes, submitted to the non-surgical periodontal treatment for one month. The expression of chemokine receptors CCR2, CCR5, and CX3CR1 at the mRNA level was evaluated in the peripheral mononuclear cells, as well as the expression of these receptors at the protein level was verified in monocyte subtypes (classical, intermediate, and non-classical monocytes). There was higher expression of CCR2 and CCR5 receptors at the initial visit in the group with Diabetes, with no differences for CX3CR1 (p = 0.002; p = 0.018, and p = 0.896, respectively), without differences after treatment. There was higher expression of CCR2 and CCR5 proteins in the group with Diabetes at the initial visit for classical, intermediate, and nonclassical monocytes, with no differences for CX3CR1 (CCR2: p = 0.004; p = 0.026; p = 0.024; CCR5: 0.045; p = 0.045; p = 0.013; CX3CR1: p = 0.424; p = 0.944; p = 0.392, respectively), without differences after the end of treatment. Concerning each group separately, there were reductions in the expression of CCR2 as well as CCR5 in classical, intermediate, and nonclassical monocytes, and reduction of CX3CR1 in classical monocytes after treatment in the group with Diabetes (p = 0.003; p = 0.006; p = 0.039; p = 0.007; p = 0.006; p = 0.004; p = 0.019, respectively), without differences in the group without Diabetes. The expression of the chemokine receptors CCR2 and CCR5, in patients with Periodontitis associated with Diabetes, is favorably modified after the end of the non-surgical periodontal treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Authors report no conflicts of interest.

The functions of cellular organelles and sub-compartments depend on their protein content, which can be characterized by spatial proteomics approaches. However, many spatial proteomics methods are limited in their ability to resolve organellar sub-compartments, profile multiple sub-compartments in parallel, and/or characterize membrane-associated proteomes. Here, we develop a cross-link assisted spatial proteomics (CLASP) strategy that addresses these shortcomings. Using human mitochondria as a model system, we show that CLASP can elucidate spatial proteomes of all mitochondrial sub-compartments and provide topological insight into the mitochondrial membrane proteome. Biochemical and imaging-based follow-up studies confirm that CLASP allows discovering mitochondria-associated proteins and revising previous protein sub-compartment localization and membrane topology data. We also validate the CLASP concept in synaptic vesicles, demonstrating its applicability to different sub-cellular compartments. This study extends the scope of cross-linking mass spectrometry beyond protein structure and interaction analysis towards spatial proteomics, and establishes a method for concomitant profiling of sub-organelle and membrane proteomes., (© 2024. The Author(s).)

Aim: To assess the impact of adult body mass index (BMI) trajectories on the risk of obesity-related noncommunicable diseases (NCDs) in the U.S. adults after adjustment for sociodemographic and lifestyle factors., Methods: Data were extracted from the National Health and Nutrition Examination Survey conducted from 2007 to 2018, including male and female participants aged 29-59 years. Rao-Scott adjusted chi-square was employed to detect associations between categorical variables in descriptive analyses. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for NCDs and BMI trajectories, adjusted for sociodemographic and lifestyle factors. Kaplan-Meier curves illustrated the cumulative incidence over time., Results: Analyses were carried out on 15 721 participants and revealing significant differences among BMI trajectories in terms of demographic, lifestyle, and health characteristics. The overall prevalence of NCDs was 28.0% (95%CI:26.6-28.9). The cumulative incidence over time was higher in the high increase, moderate increase, and mixed trajectory groups, with a correspondingly higher cumulative risk (p < 0.001). Non-overweight trajectory was considered reference category in Cox models. The BMI trajectories were independently associated with an increased risk of NCDs, even after adjusting for potential confounders (HR: 1.7; 95%CI: 1.4-1.9 for moderate increase; HR: 3.6; 95%CI: 3.2-4.1 for high increase; and HR: 2.4; 95%CI: 2.1-2.7, for mixed). Furthermore, differences between males and females were also observed., Conclusion: The transition to and persistence of obesity into adulthood increases the risk of NCDs. The implementation of targeted interventions with long-term monitoring of BMI may be beneficial in the prevention of future obesity-related NCDs., (© 2023 Wiley Periodicals LLC.)

Background: Self-harm is considered an important public health issue and is comprised by a wide range of definitions and behaviours. It is estimated that suicide affects more than 700,000 individuals every year, although, globally, there is a lack of evidence on other self-harm behaviour, such as attempted suicide. The objective of this study is to report and examine temporal trends of notifications, hospitalisations related to self-harm and suicide rates in Brazil between 2011 and 2022, as well as investigating differences in sociodemographic characteristics, methods, and region., Methods: This ecological study used secondary, Brazilian Health Information System data between 2011 and 2022. Self-harm notifications were collected from the Notifiable Diseases Information System (SINAN); self-harm hospitalisations from the Hospital Information System (SIH), and suicide data from the Mortality Information System (SIM). We calculated self-harm notifications, hospitalisations, and suicide rates by sex, age, race, region, and overall. We assessed time-related trends using Joinpoint regression analyses., Findings: From 2011 to 2022, 720,480 self-harm notifications, 104,458 self-harm hospitalisations, and 147,698 suicides were recorded in Brazil. In this period, self-harm notifications (AAPC: 21.13 (CI: 17.50, 25.33)) and suicide (AAPC: 3.70 (CI: 3.05, 4.38)) have increased in the country. Male adults (25-59 years old) and the elderly (>60 years old) continue to be the groups most affected by suicide, with respective rates of 9.59 and 8.60/100,000 in 2022. However, the largest percentage increases have been seen in young people (AAPC: 6.14 (CI: 4.57, 7.88)). The Indigenous population had the highest self-harm notification (103.72, 10,000) and suicide (16.58/100,000) rates, but the lowest hospitalisation rates (1.14/100,000) in 2022), compared to the overall population (70.06, 7.27, and 4.69/100,000, respectively, in 2022)., Interpretation: The observed trend of increased self-harm notifications and suicide rates suggests the need for a greater allocation of resources to strategies to prevent self-harm and suicide. The Indigenous population seems to be the group with less access to healthcare., Funding: Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award number R01MH128911-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., Competing Interests: Authors report no conflicts of interest., (© 2024 The Authors.)

There is a strong, bidirectional association between social disadvantage and poor mental health. The risk of experiencing mental health problems is particularly enhanced by factors associated with living in poverty. Thus, economic interventions may be effective in reducing the burden of mental health issues in these populations. This article explores the evidence based on one specific type of economic intervention on mental health, that is, supplementing household income through cash transfers. This narrative evidence is supplemented by an in-depth analysis of one of the world's largest national cash transfer programs, the Bolsa Família program, in Brazil. We report that evidence from multiple contexts clearly demonstrates that cash transfers are highly effective in reducing the burden of mental health issues and reducing mental health disparities. We then consider the specific mechanisms through which cash transfers influence mental health. Finally, we discuss the need for these interventions and, referring to the Brazilian case study, explore potential strategies for their implementation at scale and the implications for research and policy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: Oral supplements containing carbohydrates (CHOs) can be used to reduce preoperative fasting time. The aim of this study was to investigate the early metabolic and acute phase responses to a clear, oral supplement containing CHO and whey protein (WP) in young, healthy volunteers during a fasting-induced organic response., Methods: In this controlled crossover clinical trial, volunteers were randomized into groups after a 12-h fast: the CHO+WP group consumed 200 mL CHO enriched with WP (n = 30); the CHO group members consumed 200 mL water plus maltodextrin (n = 30), and the Fast group was fasted only (n = 30). Blood samples were collected after fasting and 3 h after ingestion of the supplement. The samples were analyzed for glucose, glycated hemoglobin, insulin, C-reactive protein, β-hydroxybutyrate, triacylglycerols, albumin, chlorine, and sodium. After 7 d, the groups were inverted, so all volunteers entered the three groups., Results: The nutritional intervention did not change the biochemical parameters related to the acute phase response or insulin resistance; however, there was a statistically significant reduction (P < 0.001) in serum β-hydroxybutyrate in the CHO+WP group (0.05 ± 0.08 mmol/L) compared with the other two groups (Fast group: 0.11 ± 0.08 mmol/L; CHO group: 0.09 ± 0.13 mmol/L)., Conclusions: After overnight fasting, the oral supplement containing CHO and WP decreased ketosis. These findings may help select the most efficient oral supplement to be given 2 to 3 h before elective surgeries., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The current study aims to evaluate the effect of non-surgical periodontal treatment on the modulation of monocyte phenotype, in the presence or absence of diabetes., Materials and Methods: The identification, quantification, and phenotypic characterization of monocyte subtypes (classical, intermediate, and non-classical) were performed by flow cytometry, at baseline and 1 month after the end of non-surgical periodontal treatment, in patients with periodontitis, associated or not with diabetes., Results: There was an increase in non-classical monocytes after treatment and a reduction in intermediate monocytes, without differences for the classical subtype, regardless of the diabetes status. Furthermore, there was a reduction in intermediate monocytes and an increase in non-classical and classical monocytes after treatment in the diabetes group, while no significant differences were observed for classical, intermediate, and non-classical monocytes in the group without diabetes. Comparisons between the two groups showed significant differences for classical, intermediate, and non-classical monocytes at baseline; these differences were not found one month after treatment., Conclusions: Non-surgical periodontal treatment leads to modulation of monocytes to a less inflammatory phenotype, especially in individuals with diabetes., Clinical Relevance: A better understanding of the role of these biomarkers in the periodontitis contex may constitute a new strategic target for a better treatment of patiens with diabetes associated to periodontitis., Clinical Trial Registration: Brazilian Registry of Clinical Trials-RBR-35szwc. Jhefferson Miranda Alves and Danielle Borges Germano contributed equality to this study and should be considered first authors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Previous studies in Australia, Canada, and Brazil, found that suicide among ethnic minority groups is higher than in the general population. Indigenous peoples in Brazil have been reported to have a high suicide rate, with reports of suicide clusters occurring in several communities. The objective of this study was to report trends in countrywide suicide rates among Indigenous peoples in Brazil between 2000 and 2020, and to compare these with the non-Indigenous population., Methods: This ecological study used Indigenous suicide data collected from all regions of Brazil during a 21-year period, between 2000 and 2020. We used suicide estimates from the Mortality Information System (SIM), available at the Brazilian Health Ministry website (DATASUS). Suicide mortality rates by state and region were calculated using the estimated Indigenous population from the 2010 census, and estimated population proportions for the other years. We performed a trend analysis and compared trends in suicide between the Indigenous and non-Indigenous population during the period studied., Findings: Suicide rates among Indigenous Brazilians have reached more than two and a half times the levels for the overall Brazilian population in 2020 (17.57 suicide deaths versus 6.35 suicide deaths per 100,000 inhabitants, respectively). The Central-West region of Brazil had the highest suicide rates among Indigenous Brazilians over the study period, reaching 58.8 deaths/100,000 inhabitants in 2008. The younger age group (10-24 years old) had the highest suicide rates for all the years studied. Time-series analyses showed a trend of statistically significant increases in suicide rates in Brazil for both the Indigenous and non-Indigenous population during the study period. The North region, and specifically Amazonas state, has shown a decisive increase in suicide rates among the Indigenous populations. The suicide rate for Indigenous people in Brazil, excluding cases in Amazonas and Mato Grosso do Sul states, were similar to those for the entire Brazilian population, showing that the Indigenous peoples who are the most vulnerable to suicide reside in these locations., Interpretation: While there were statistically significant increases in suicide rates for all Brazilians over the study period, they remained alarmingly high among Indigenous people, compared to their non-Indigenous counterparts. The high suicide rates among Indigenous people, and younger individuals in particular (aged between 10 and 24), reinforces the need for specific prevention strategies for these populations. Further studies should be concentrated on determining risk factors in distinct ethnic groups, specifically within regions experiencing an elevated risk, such as the states of Amazonas and Mato Grosso do Sul., Funding: Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award number R01MH128911-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., Competing Interests: Authors report no conflicts of interest., (© 2023 The Author(s).)

Aim: To evaluate the lipid-lowering and antiplatelet combined strategies on the expression of the receptors CCR2, CCR5, and CX3CR1 and the percentage of CCR2, CCR5, and CX3CR1 cells in monocyte subtypes after acute myocardial infarction., Methods: Prospective, randomized, open-label study, with blinded analyses of endpoints (PROBE, ClinicalTrials.gov Identifier: NCT02428374, registration date: April 28, 2015). Participants were treated with rosuvastatin 20 mg or simvastatin 40 mg plus ezetimibe 10 mg, as well as ticagrelor 90 mg or clopidogrel 75 mg. The chemokine receptors CCR2, CCR5, and CX3CR1 were analyzed by real-time polymerase chain reaction as well as the percentages of CCR2, CCR5, and CX3CR1 cells in the monocyte subtypes (classical, intermediate, and non-classical), which were quantified by flow cytometry, at baseline, and after 1 and 6 months of treatment., Results: After comparisons between the three visits, regardless of the treatment arm, there was an increase in CCR2 expression after treatment, as well as an increase in intermediate monocytes CCR2+ and a reduction in non-classical monocytes CCR2+ at the end of treatment. There was also a lower expression of CCR5 after treatment and an increase in classical and non-classical monocytes CCR5+. Concerning CX3CR1, there were no differences in the expression after treatment; however, there were reductions in the percentage of intermediate and non-classical monocytes CX3CR1+ at the end of treatment., Conclusions: The results suggest the persistence of the inflammatory phenotype, known as trained immunity, even with the highly-effective lipid-lowering and antiplatelet therapies. Geriatr Gerontol Int 2023; 23: 700-707., (© 2023 Japan Geriatrics Society.)

Objective. Adjuvant therapy with sodium-glucose cotransport 2 inhibitors (SGLT2i) in type 1 diabetes (T1D) is associated with an improvement in glycemic control, but increases the risk of diabetic ketoacidosis (DKA). However, real-life studies in individuals with T1D under continuous subcutaneous insulin infusion (CSII) are still scarce. We present the first real-life study performed in patients with T1D exclusively treated with CSII. The aim of the present study was to assess the metabolic impact and safety of SGLT2i in T1D individuals under CSII. Methods. Retrospective study includes 34 T1D adult individuals under CSII, who started SGLT2i until 30th June 2021. Data regarding the glycemic control and acute diabetes complications at the moment of introduction of SGLT2i and after 3, 6, and 12 months of use were collected. Results. Twenty-three individuals were included. Comparing with the moment of SGLT2i introduction after 3, 6, and 12 months of use, there was a statistically significant increase of time in range (TIR) (∆ T3M =12.8%; ∆ T6M =11.5%; ∆ T12M =11.1%), and a decrease in time above range (∆ T3M =13.6%; ∆T6M=11.9%; ∆ T12M =10.5%). There were no significant differences in time below the range. Mean glucose and mean glucose management indicator significantly reduced in the 3 evaluated moments. A significant reduction in median weight was also observed (∆ T6M =2 kg; ∆ T12M =4.5 kg). Two patients (8.7%) developed mild euglycemic DKA during SGLT2i treatment, both were women and had body mass index (BMI) <27 kg/m 2 . One of them had a total daily insulin dose (TDDI) reduction of 26.9% after 3 months of use. Conclusions. The use of SGLT2i, as an adjuvant treatment in T1D individuals under CSII, was associated with a significant increase of TIR without increasing time in hypoglycemia. It also had a weight benefit. Careful use in selected participants is necessary to reduce the occurrence of DKA., (© 2023 Vania Benido Silva et al., published by Sciendo.)

Objectives: To evaluate the association between nutritional status in early adulthood and the burden of noncommunicable diseases (NCDs); To evaluate the influence of sociodemographic factors and lifestyle on the outcomes of BMI kg/m 2  ≤24.9, ≥25.0, and ≥30.0; to estimate the population attributable fraction (PAF) to BMI elevated at 25 years old in the burden of NCDs in American adults., Methods: We used data from 15 721 American adults participating in the National Health and Nutrition Examination Survey from 2007 to 2018. The Hazard Ratio (HR), Incidence Rate Ratio (IRR), and 95% confidence intervals (CI) were estimated in the proportional risk regression models of Cox (entire population) and Poisson (restricted to non-patients), respectively. The proportionality of the risk between the burden of NCDs and BMI at 25 years old was drawn by the Kaplan-Meier curve, and the PAF was calculated. All analyses were adjusted taking into account the sample weights., Results: Health disparities (sex, age, race/ethnicity, education, poverty index, and education level), and lifestyle (physical activity, smoking, and alcohol consumption) influenced the current nutritional status. Cumulative survival in overweight and obese groups decreased considerably over time (p < .0001). Being overweight and obese in adulthood may increase the risk of early NCDs (HR: 1.68, 95% CI: 1.54-1.84 and HR: 2.87, 95% CI: 2.56-3.21, respectively). About 22.72% (95% CI: 19.99-25.36, p < .001) of the burden NCDs could have been avoided if overweight at age 25 had been prevented., Conclusions: Monitoring weight change from young adulthood can provide a sensitive and useful clinical measure for early detection of adverse trends in NCDs risk., (© 2023 Wiley Periodicals LLC.)

Purpose: We investigated the impact of nanoformulations on the dose-exposure-response relationship of clozapine (CZP), a low-solubility antipsychotic with serious adverse effects, using a popPK/PD approach., Methods: We evaluated the pharmacokinetics and PK/PD profiles of three coated polymeric CZP-loaded nanocapsules functionalized with polysorbate 80 (NCP80), polyethylene glycol (NCPEG), and chitosan (NCCS). Data on in vitro CZP release by dialysis bag, plasma pharmacokinetic profiles in male Wistar rats (n = 7/group, 5 mg kg -1 , i.v.), and percentage of head movements in a stereotyped model (n = 7/group, 5 mg kg -1 , i.p.) were integrated using a sequential model building approach (MonolixSuite TM -2020R1-Simulation Plus)., Results: A base popPK model developed with CZP solution data collected after the i.v. administration of CZP was expanded to describe the changes in drug distribution caused by nanoencapsulation. Two additional compartments were inserted into the NCP80 and NCPEG models, and a third compartment was included in the NCCS model. The nanoencapsulation showed a decrease in the central volume of distribution for NCCS (V1NCpop = 0.21 mL), while for FCZP, NCP80, and NCPEG, it was ~1 mL. The peripheral distribution volume was higher for the nanoencapsulated groups (19.1 and 129.45 mL for NCCS and NCP80, respectively) than for FCZP. The popPK/PD model showed a formulation-dependent plasma IC 50 , with 20-, 50-, and 80-fold reductions compared to the CZP solution (NCP80, NCPEG, and NCCS, respectively)., Conclusion: Our model discriminates the coatings and describes the peculiar PK and PD behavior of nanoencapsulated CZP, especially NCCS, making it an exciting tool for evaluating the preclinical performance of nanoparticles., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Upon activation, vinculin reinforces cytoskeletal anchorage during cell adhesion. Activating ligands classically disrupt intramolecular interactions between the vinculin head and tail domains that bind to actin filaments. Here, we show that Shigella IpaA triggers major allosteric changes in the head domain, leading to vinculin homo-oligomerization. Through the cooperative binding of its three vinculin-binding sites (VBSs), IpaA induces a striking reorientation of the D1 and D2 head subdomains associated with vinculin oligomerization. IpaA thus acts as a catalyst producing vinculin clusters that bundle actin at a distance from the activation site and trigger the formation of highly stable adhesions resisting the action of actin relaxing drugs. Unlike canonical activation, vinculin homo-oligomers induced by IpaA appear to keep a persistent imprint of the activated state in addition to their bundling activity, accounting for stable cell adhesion independent of force transduction and relevant to bacterial invasion., Competing Interests: Declaration of interests The IpaA constructs in this study are associated with the patent N°PVT/EP2016/073287.2016 with no restriction for academic research but with restriction for commercial use., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Complex protein mixtures typically generate many tandem mass spectra produced by different peptides coisolated in the gas phase. Widely adopted proteomic data analysis environments usually fail to identify most of these spectra, succeeding at best in identifying only one of the multiple cofragmenting peptides. We present PatternLab V (PLV), an updated version of PatternLab that integrates the YADA 3 deconvolution algorithm to handle such cases efficiently. In general, we expect an increase of 10% in spectral identifications when dealing with complex proteomic samples. PLV is freely available at http://patternlabforproteomics.org.

Chemokine receptors are fundamental in many processes related to cardiovascular diseases, such as monocyte migration to vessel walls, cell adhesion, and angiogenesis, among others. Even though many experimental studies have shown the utility of blocking these receptors or their ligands in the treatment of atherosclerosis, the findings in clinical research are still poor. Thus, in the current review we aimed to describe some promising results concerning the blockade of chemokine receptors as therapeutic targets in the treatment of cardiovascular diseases and also to discuss some challenges that need to be overcome before using these strategies in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Background: Early nutritional therapy may aggravate hypophosphatemia in critically ill patients., Aim: To investigate the influence of the type nutritional therapy on the survival of critically-ill malnourished patients at refeeding hypophosphatemia risk., Methods: Retrospective cohort study including malnourished, critically-ill adults, admitted from June 2014-December 2017 in an intensive care unit (ICU) at a tertiary hospital. Refeeding hypophosphatemia risk was defined as low serum phosphorus levels (<2.5 mg/dL) seen at two timepoints: before the initiation and at day 4 of the nutritional therapy. Patients receiving enteral nutrition (EN) were compared with those receiving supplemental parenteral nutrition (SPN-EN plus parenteral nutrition). Primary outcome was 60 d survival. Secondary endpoint was the incidence of refeeding hypophosphatemia risk., Results: We included 468-321 patients (68.6%) received EN and 147 (31.4%) received SPN. The mortality rate was 36.3% (n = 170). Refeeding hypophosphatemia risk was found in 116 (24.8%) patients before and in 177 (37.8%) at day 4 of nutritional therapy. The 60 d mean survival probability was greater for patients receiving SPN both before (42.4 vs. 22.4%, p = 0.005) and at day 4 (37.4 vs. 25.8%, p = 0.014) vs. patients receiving EN at the same timepoints. Cox regression showed a hazard ratio of 3.3 and 2.4 for patients at refeeding hypophosphatemia risk before and at day 4 of EN, respectively, compared to the SPN group at the same timepoints., Conclusion: Refeeding hypophosphatemia risk was frequent in malnourished ICU patients and the survival for patients receiving SPN seemed associated with better survival than EN only., Competing Interests: Conflict of Interests All authors have no conflict of interests to declare., (Copyright © 2023. Published by Elsevier Inc.)

Rheumatoid arthritis (RA) is a systemic autoimmune disease that impairs mobility. How does sensory information influence postural responses in people with RA? The aim of this study was to evaluate the postural control of people with RA during a sensory organization test, comparing how sensory information influences postural responses in people with rheumatoid arthritis compared with healthy people. Participants were 28 women with rheumatoid arthritis (RA group) and 16 women without any rheumatoid disease (Control group CG). The Sensory Organization Test (SOT) was performed on a Smart Balance Master ® (NeuroCom International, Inc., Clackamas, OR, USA) and center of pressure (COP) was measured. SOT conditions: SOT1 (eyes open, fixed support surface and surround; SOT2) eyes closed, fixed support surface and surround; and SOT5) eyes closed, sway-referenced support surface, and fixed surround. To compare the demographic and clinical aspects between groups, independent t -test or Mann-Whitney's U-test were used. Differences were found between groups. Between SOT conditions, for CG and RA, COP was faster for SOT-5 than SOT-1, while SOT-1 and SOT-2 presented similar COP velocity. For SOT-2 and SOT-5, COP was larger for the RA group. For both groups, SOT-1 presented the smallest COP, and SOT-5 showed the largest COP.

Importance: Conditional cash transfers (CCTs) have been consistently associated with improvements to the determinants of maternal health, but there have been insufficient investigations regarding their effects on maternal mortality., Objective: To evaluate the association between being a Bolsa Família program (BFP) beneficiary and maternal mortality and to examine how this association differs by duration of BFP receipt, maternal race, living in rural or urban areas, the Municipal Human Development Index (MHDI), and municipal primary health care coverage., Design, Setting, and Participants: This cross-sectional analysis was nested within the 100 Million Brazilian Cohort. Girls and women aged 10 to 49 years (hereinafter referred to as women) who had at least 1 live birth were included, using data from Brazilian national health databases linked to the 100 Million Brazilian Cohort (January 1, 2004, to December 31, 2015). Propensity score kernel weighting was applied to control for sociodemographic and economic confounders in the association between BFP receipt and maternal mortality, overall and stratified by different subgroups (race, urban or rural area, and MHDI), and duration of BFP receipt. Data were analyzed from July 12, 2019, to December 31, 2022., Main Outcome(s) and Measures: Maternal death., Results: A total of 6 677 273 women aged 10 to 49 years were included in the analysis, 4056 of whom had died from pregnancy-related causes. The risk of maternal death was 18% lower in women who received BFP (weighted odds ratio [OR], 0.82 [95% CI, 0.71-0.93]). A longer duration receiving BFP was associated with an increased reduction in maternal mortality (OR for 1-4 years, 0.85 [95% CI, 0.75-0.97]; OR for 5-8 years, 0.70 [95% CI, 0.60-0.82]; OR for ≥9 years, 0.69 [95% CI, 0.53-0.88]). Receiving BFP was also associated with substantial increases in the number of prenatal appointments and interbirth intervals. The reduction was more pronounced in the most vulnerable groups., Conclusions and Relevance: This cross-sectional analysis nested within the 100 Million Brazilian Cohort found an association between BFP receipt and maternal mortality. This association was of greater magnitude in women with longer exposure to BFP and in the most vulnerable groups. These findings reinforce evidence that programs such as BFP, which have already proven effective in poverty reduction, have great potential to improve maternal survival.

Background: New formulas including a nitrogenous source to maltodextrin have been reported as preoperative beverages 2-3 h before anesthesia in the elective procedure. Whey protein is a potential candidate for the composition of this clear oral supplement. This study aimed to investigate the gastric residual volume (GRV) of healthy volunteers 3 h after the ingestion of an oral supplement containing carbohydrates (CHO) alone or combined with whey protein (WP)., Methods: This crossover clinical trial design includes young, healthy male volunteers with normal body mass index. Magnetic resonance imaging (MRI) scan of the upper abdomen to measure the GRV was performed in the participants in three phases: (1) after a fasting period of 8 h; (2) immediately after the ingestion of 200 mL of a clear supplement containing: (2a) 10 g of WP and 54 g of CHO (74% glucose and 26% maltodextrin)-WP + CHO group or (2b) 12.5% maltodextrin (25 g)-CHO group; and (3) after 3 h of the ingestion of both types of supplements. A week interval was programmed between phases 2a and 2b., Results: There was no significant difference (p = 0.91; within-group comparison) of the mean ± SD of the GRV between phase 1 (WP + CHO: 23.45 ± 14.01; CHO: 25.03 ± 15.17 cm 3 ; p = 0.78; between-groups comparison) and phase 3 (WP + CHO: 25.66 ± 9.31; CHO: 23.45 ± 13.58 cm 3 , p = 0.86; between-groups comparison). The GRV of phase 2 (WP + CHO: 206.43 ± 23; CHO: 203.99 ± 12.18 cm 3 ; p = 0.82; between-groups comparison) was significantly greater (p < 0.01; within-group comparison) than both other two phases., Conclusion: The GRV after 3 h of the ingestion of either WP + CHO or CHO oral supplement returns to basal fast condition implying that gastric emptying after this interval of time is significantly completed., Trial Registration: Registered and posted on the ClinicalTrials.gov public website with Identifier: NCT05573854., (© 2022. The Author(s).)

Depression and interpersonal violence are issues of increasing public health concern globally, especially in low-and-middle income countries. Despite the known relationship between interpersonal violence and an increased risk of depression, there is a need to further characterise the experience of depression in those who have experienced violence, to better develop screening and treatment interventions. A cross-sectional analysis was conducted on responses from the 2019 Brazilian National Health Survey. The prevalence of depression (both clinician-diagnosed, and Patient Health Questionnaire (PHQ-9) screened) were estimated by type of violence experienced in the preceding 12 months (none, physical violence, sexual violence, physical and sexual violence, or threat of violence). Logistic regression models assessed the associations between violence and depression after adjusting for socioeconomic and demographic factors. Of 88,531 respondents, 8.1% experienced any type of violence. Compared to those not experiencing violence, those who experienced any type of violence had a higher prevalence of clinician-diagnosed or PHQ-9-screened depression (e.g. the prevalence of clinician-diagnosed depression was 18.8% for those experiencing sexual violence compared to 9.5% for those not experiencing violence). Both undiagnosed and untreated depression were also more prevalent in those experiencing any type of violence. In logistic regression models, any experience of violence was associated with a higher odds of depression (e.g. aOR = 3.75 (95% CI: 3.06-4.59) for PHQ-9-detected depression). Experiencing violence was also associated with a higher likelihood of having depression which was undiagnosed (e.g. in those who experienced sexual violence: aOR of 3.20, 95% CI 1.81-5.67) or untreated (e.g. in those who experienced physical and sexual violence: aOR = 8.06, 95% CI 3.44-18.9). These findings highlight the need to consider screening for depression in those affected by violence, and to prioritise mental healthcare in communities affected by violence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Harding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Physical, emotional, and social changes, including exposure to poverty, abuse, or violence, increases youth vulnerability to mental illness. These factors interfere with development, limit opportunities, and hamper achievement of a fulfilling life as adults. Addressing these issues can lead to improved outcomes at the population level and better cost-effectiveness for health services. Cash transfer programs have been a promising way to address social drivers for poor mental health. However, it is still unclear which pathways and mechanisms explain the association between socioeconomic support and lower mental illness among youth. Therefore, we will evaluate the effect of social drivers on youth mental health-related hospitalizations and suicide, test mechanisms and pathways of a countrywide socioeconomic intervention, and examine the timing of the intervention during the life course., Methods: We will combine individual-level data from youth national hospitalization, mental health disorders and attempted suicide, suicide registries and notifications of violence, with large-scale databases, including "The 100 Million Brazilian Cohort", over an 18-year period (2001-2018). Several approaches will be used for the retrospective quasi-experimental impact evaluations, such as Regression Discontinuity Designs, Propensity Score Matching and difference-in-differences, combined with multivariable regressions for cohort analyses. We will run multivariate regressions based on hierarchical analysis approach to evaluate the association between important social drivers (mental health care, demographic and economic aspects) on mental health-related hospitalizations and suicide among youth. Furthermore, we will perform microsimulations to generate projections regarding how mental health-related hospitalizations and suicide trends will be in the future based on the current state, and how BFP implementation scenarios will affect these trends., Discussion: The results of this project will be of vital importance to guide policies and programs to improve mental health and reduce mental health-related hospitalizations and suicide in youth. It will provide information to improve the effectiveness of these programs worldwide. If cash transfers can decrease mental health problems among youth and reduce suicide., Competing Interests: The authors have declared that no competing interests exist.

This paper aims to discuss the issue of diversity from its incorporation into the training of health professionals through the analysis of the National Curriculum Guidelines (DCN) of two Brazilian undergraduate health courses: medicine and psychology. Thus, it debates the concept of diversity from the contribution of the social sciences, considering the multiple concepts in the nature of social and cultural differences, breaking with essentialist concepts of difference. Reflecting on how diversity appears in the curricular guidelines of these courses, it analyzes from recent studies how this has been considered in training and the main challenges. Intersectionality is an essential political theoretical framework to apprehend the articulation of multiple differences and inequalities acting in a dynamic, fluid, and flexible way from particular historical contexts. Thus, it is sensitive to address the issue of diversity in the training of health professionals. We highlight the importance of studying differences, suggesting an analytical framework that articulates discourses, practice, subjectivation, and social relationships.

Multimorbidity is a global health issue impacting the quality of life of all ages. Multimorbidity with a mental disorder is little studied and is likely to have been affected by the COVID-19 pandemic. We used a survey of 14,007 respondents living in Brazil to investigate whether people who already had at least one chronic medical condition had more depression and anxiety symptoms during social distancing in 2020. Generalized linear models and structural equation modelling were used to estimate the effects. A 19 % and 15 % increase in depressive symptoms were found in females and males, respectively, for each unit of increase in the observed value of reported chronic disease. Older subjects presented fewer symptoms of depression and anxiety. There was a 16 % increase in anxiety symptoms in females for each unit increase in the reported chronic disease variable and a 14 % increase in males. Younger subjects were more affected by anxiety symptoms in a dose-response fashion. High income was significantly related to fewer depressive and anxiety symptoms in both males and females. Physical activity was significantly associated with fewer anxiety and depression symptoms. Structural equation modelling confirmed these results and provided further insight into the hypothesised paths., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Multimorbidity, or the occurrence of two or more chronic conditions, is a global challenge, with implications for mortality, morbidity, disability, and life quality. Psychiatric disorders are common among the chronic diseases that affect patients with multimorbidity. It is still not well understood whether psychiatric symptoms, especially depressive symptoms, moderate the effect of multimorbidity on cognition., Methods: We used a large (n=2,681) dataset to assess whether depressive symptomatology moderates the effect of multimorbidity on cognition using structural equation modelling., Results: It was found that the more depressive symptoms and chronic conditions, the worse the cognitive performance, and the higher the educational level, the better the cognitive performance. We found a significant but weak (0.009; p = 0.04) moderating effect., Conclusion: We have provided the first estimate of the moderating effect of depression on the relation between multimorbidity and cognition, which was small. Although this moderation has been implied by many previous studies, it was never previously estimated., Competing Interests: The authors report no conflicts of interest.

Introduction: Studies have indicated that gait intervention programmes with minimalist shoes are effective for reducing pain, improving functionality and reducing knee joint overload in older women with knee osteoarthritis (OA). Other clinical trials with knee and foot muscle strength training and/or dynamic balance training have also shown clinical and functional effectiveness. Despite promising strategies, there is no evidence of the combination of shoes with gait intervention programmes. Thus, the objective of this randomised clinical trial is to investigate the effects of therapeutic programme of muscular resistance, balance and gait exercises with and without the use of low-cost, flexible shoes on the clinical, functional and biomechanical aspects of older women with medial knee OA., Methods and Analysis: This randomised controlled trial with blinded evaluators will involve 36 older women. Twenty-four older women with knee OA (medial compartment) will be randomised to the intervention groups with minimalist shoes (GIC; n=12) or in a barefoot condition (GID; n=12), and 12 older women to the control group (n=12). The intervention protocol will consist of knee-foot muscle resistance and static balance training, reactive and proactive dynamic balance training, and gait training with visual feedback. The intervention will have a duration of two consecutive months, twice a week, totalling 16 sessions. The primary outcomes will be walking pain measured by Visual Analogue Scale and questionnaires: Western Ontario McMaster Universities Osteoarthritis Index and Lequesne Algofunctional. The secondary outcomes will be: 6-min walk test, Falls Risk Awareness Questionnaire, Timed Up and Go Test, and distribution of plantar load during gait and balance by pressure platform. Data will be analysed according to an intention-to-treat approach., Ethics and Dissemination: This study involves human participants and was approved by the ethics committee of the Universidade Santo Amaro, School Medicine, São Paulo/SP, Brazil (N°4.091.006). Participants gave informed consent to participate in the study before taking part. Investigators will communicate trial results to participants and healthcare professionals through scientific databases, social media, publications and conferences., Trial Registration Number: RBR-10j4bw25 in Brazilian Clinical Trial Registry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The consumption of soft drinks has increased considerably in recent decades, mainly cola soft drinks. Excessive consumption of cola-based soft drinks is associated with several diseases and cognitive decline, particularly memory impairment. Furthermore, diets with high sugar can promote insulin resistance, metabolic syndrome, and dyslipidemia., Aim: Thus, the present study aimed to evaluate the effect of cola soft drink intake on behavioral alterations and oxidative damage in 2-, 8- and 14- month-old male Wistar rats., Methods: The soft drink groups drank soft drink and/or water ad libitum during 67 days, the control groups ingested only water. Radial-arm maze and Y-maze were used to evaluate spatial memory, open-field to evaluate the habituation memory, and inhibitory avoidance to evaluate aversive memory. The behavioral tests started at the day 57 and finished at day 67 of treatment. At 68th day, the rats were killed; frontal cortex and hippocampus were dissected to the analysis of antioxidants enzymes catalase (CAT) and superoxide dismutase (SOD); and the oxidative markers thiobarbituric acid reactive substances (TBARS) and dichloro-dihydro-fluorescein diacetate (DCFH) were measured in the hippocampus., Results and Discussion: The cola-based soft drink intake caused memory impairment in the radial-arm maze, Y-maze task, and open-field in the 2- and 8-month-old rat, but not in the 14-month-old. There were no difference among groups in the inhibitory avoidance test. In the frontal cortex, soft drink intake reduced CAT activity in the 8-month-old rats and SOD activity in the 8- and 14-month-old rats. In the hippocampus, the soft drink increased CAT activity in 2- and 8-month-old rats, increased DCFH levels at all ages, and increased TBARS levels in 2-month-rats. Therefore, the results show that long-term soft drink intake leads to memory impairment and oxidative stress. The younger seems to be more susceptible to the soft drink alterations on behavior; however, soft drink caused alterations in the oxidative system at all ages evaluated., (Copyright © 2022. Published by Elsevier Inc.)

Transgender people deal with intense discrimination in every aspect of life. These experiences increase when they face family rejection. The research on social and family environment surrounding gender transition has been largely overlooked. We examine the meanings of family and health, and how these intersect, among trans people and their family members in a health service in Brazil. We conducted a qualitative study (between December 2017 and July 2018), an ethnography with the triangulation of three sources: interviews with 8 transgender men, 8 transgender women and 5 family members; a focus group with another 8 transgender men and approximately 100 h of field observation. Our study shows that family and health are interpreted as ideal protective environments, and seen as causes of disappointment, abandonment and illness. The meanings of family and health are interconnected and constituted in relation to each other. We also found that there are differences within these meanings of family and health when we consider the ethnicity and the economic status of the participants. The participants reported that the society education towards transsexuality is fundamental to improving trans people's quality of life. Our results challenge health services to provide comprehensive healthcare and assure health equity for transgender people.

Objective: Hospital costs in surgery constitute a burden for the health system in all over the world. Multimodal protocols such as the ACERTO project enhance postoperative recovery. The aim of this study was to analyze the hospital costs in patients undergoing major digestive surgical procedures with or without the perioperative care strategies proposed by the ACERTO project., Methods: Retrospective data from elective patients undergoing major digestive surgical procedures in a university hospital between January 2002 and December 2011 were collected. The investigation involved two phases: between January 2002 and December 2005, covering cases admitted before the implementation of the ACERTO protocol (pre-ACERTO period), and cases operated between January 2006 and December 2011, after implementation (ACERTO period). The primary outcome was the comparison of hospital costs between the two periods. As secondary end point, we compared length of stay (LOS), postoperative complications, surgical-site infection (SSI) rate, and mortality., Results: We analyzed 381 patients (239 of the pre-ACERTO period and 142 of the ACERTO period) who underwent major procedures on the gastrointestinal tract. Patients operated after within the ACERTO protocol postoperative LOS had a median of 3 days shorter (p=0.001) when compared with pre-ACERTO period [median (IQR): 10 (12) days vs. 13 (12) days]. Mortality was similar between the two periods. Postoperative complications risk, however, was 29% greater (RR: 1.29; 95%CI 1.11-1.50) in the pre-ACERTO period (p=0.002). SSI risk was also greater in pre-ACERTO period (RR: 1.33; 95%CI 1.14-1.50). Costs (mean and SE) per patients were R$24,562.84 (1,349.33) before the implementation and R$19,912.81 (1,459.89) after the ACERTO protocol (p=0.02)., Conclusion: The implementation of the ACERTO project in this University Hospital reduced the hospital costs in major digestive procedures. Moreover, the implementation of this modern perioperative care strategy also reduced postoperative complications, SSI risks, and LOS.

Background and Aim: We sought to prospectively assess the impact of intermittently scanned continuous glucose monitoring (isCGM) initiation in the glycaemic control and quality of life (QoL) in type 1 diabetes mellitus (T1DM) patients followed in real-live conditions., Methods: Prospective, observational, cohort, single-centre and single-arm study conducted between September 2018 and March 2020, enrolling adults with T1DM with at least one year of diagnosis, interested in using isCGM. After training at isCGM initiation, CGM metrics and QoL were assessed at baseline and 12 months., Results: Thirty-six individuals (55.6% male) were included; median age at inclusion was 49.0 (43.5-62.5)years and the mean(±SD) duration of T1DM was 25.5 ± 12.0 years. Median (interquartile range) HbA1c decreased from 7.6(7.0-8.7)% to 7.4(6.8-7.7)% at 12 months (p = 0.02), driven by the subgroup of individuals with baseline HbA1c ≥ 7.5%. The number of scans per day increased from 7.0(5.5-10.0) to 10.0(7.0-14.0) but no correlation was found between the number of daily scans and CGM metrics. Total daily insulin dose remained unchanged, however the proportion of basal insulin decreased, and the proportion of bolus insulin increased over time. Multiple QoL subscales scores improved significantly, including disease-burden subscale for which TIR proved to be a significant predictive factor., Conclusion: isCGM improved both glycaemic control, namely time in range, time below range and glycaemic variability, as well as QoL scores in the long term. The increase of the bolus insulin proportion suggests a behavioural change. However, the appraisal of our results must consider our substantial rate of drop-out limiting the external validity of our findings., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Socioeconomic factors have been consistently associated with suicide, and economic recessions are linked to rising suicide rates. However, evidence on the impact of socioeconomic interventions to reduce suicide rates is limited. This study investigates the association of the world's largest conditional cash transfer programme with suicide rates in a cohort of half of the Brazilian population., Methods and Findings: We used data from the 100 Million Brazilian Cohort, covering a 12-year period (2004 to 2015). It comprises socioeconomic and demographic information on 114,008,317 individuals, linked to the "Bolsa Família" programme (BFP) payroll database, and nationwide death registration data. BFP was implemented by the Brazilian government in 2004. We estimated the association of BFP using inverse probability of treatment weighting, estimating the weights for BFP beneficiaries (weight = 1) and nonbeneficiaries by the inverse probability of receiving treatment (weight = E(ps)/(1-E(ps))). We used an average treatment effect on the treated (ATT) estimator and fitted Poisson models to estimate the incidence rate ratios (IRRs) for suicide associated with BFP experience. At the cohort baseline, BFP beneficiaries were younger (median age 27.4 versus 35.4), had higher unemployment rates (56% versus 32%), a lower level of education, resided in rural areas, and experienced worse household conditions. There were 36,742 suicide cases among the 76,532,158 individuals aged 10 years, or older, followed for 489,500,000 person-years at risk. Suicide rates among beneficiaries and nonbeneficiaries were 5.4 (95% CI = 5.32, 5.47, p < 0.001) and 10.7 (95% CI = 10.51, 10.87, p < 0.001) per 100,000 individuals, respectively. BFP beneficiaries had a lower suicide rate than nonbeneficiaries (IRR = 0.44, 95% CI = 0.42, 0.45, p < 0.001). This association was stronger among women (IRR = 0.36, 95% CI = 0.33, 0.38, p < 0.001), and individuals aged between 25 and 59 (IRR = 0.41, 95% CI = 0.40, 0.43, p < 0.001). Study limitations include a lack of control for previous mental disorders and access to means of suicide, and the possible under-registration of suicide cases due to stigma., Conclusions: We observed that BFP was associated with lower suicide rates, with similar results in all sensitivity analyses. These findings should help to inform policymakers and health authorities to better design suicide prevention strategies. Targeting social determinants using cash transfer programmes could be important in limiting suicide, which is predicted to rise with the economic recession, consequent to the Coronavirus Disease 2019 (COVID-19) pandemic., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: VP is an Academic Editor on PLOS Medicine’s editorial board. All of the authors declare that they have approved the final version.

Aims: The mental health of slum residents is under-researched globally, and depression is a significant source of worldwide morbidity. Brazil's large slum-dwelling population is often considered part of a general urban-poor demographic. This study aims to identify the prevalence and distribution of depression in Brazil and compare mental health inequalities between slum and non-slum populations., Methods: Data were obtained from Brazil's 2019 National Health Survey. Slum residence was defined based on the UN-Habitat definition for slums and estimated from survey responses. Doctor-diagnosed depression, Patient Health Questionnaire (PHQ-9)-screened depression and presence of undiagnosed depression (PHQ-9-screened depression in the absence of a doctor's diagnosis) were analysed as primary outcomes, alongside depressive symptom severity as a secondary outcome. Prevalence estimates for all outcomes were calculated. Multivariable logistic regression models were used to investigate the association of socioeconomic characteristics, including slum residence, with primary outcomes. Depressive symptom severity was analysed using generalised ordinal logistic regression., Results: Nationally, the prevalence of doctor diagnosed, PHQ-9 screened and undiagnosed depression were 9.9% (95% confidence interval (CI): 9.5-10.3), 10.8% (95% CI: 10.4-11.2) and 6.9% (95% CI: 6.6-7.2), respectively. Slum residents exhibited lower levels of doctor-diagnosed depression than non-slum urban residents (8.6%; 95% CI: 7.9-9.3 v. 10.7%; 95% CI: 10.2-11.2), while reporting similar levels of PHQ-9-screened depression (11.3%; 95% CI: 10.4-12.1 v. 11.3%; 95% CI: 10.8-11.8). In adjusted regression models, slum residence was associated with a lower likelihood of doctor diagnosed (adjusted odds ratio (adjusted OR): 0.87; 95% CI: 0.77-0.97) and PHQ-9-screened depression (adjusted OR: 0.87; 95% CI: 0.78-0.97). Slum residents showed a greater likelihood of reporting less severe depressive symptoms. There were significant ethnic/racial disparities in the likelihood of reporting doctor-diagnosed depression. Black individuals were less likely to report doctor-diagnosed depression (adjusted OR: 0.66; 95% CI: 0.57-0.75) than white individuals. A similar pattern was observed in Mixed Black (adjusted OR: 0.72; 95% CI: 0.66-0.79) and other (adjusted OR: 0.63; 95% CI: 0.45-0.88) ethnic/racial groups. Slum residents self-reporting a diagnosis of one or more chronic non-communicable diseases had greater odds of exhibiting all three primary depression outcomes., Conclusions: Substantial inequalities characterise the distribution of depression in Brazil including in slum settings. People living in slums may have lower diagnosed rates of depression than non-slum urban residents. Understanding the mechanisms behind the discrepancy in depression diagnosis between slum and non-slum populations is important to inform health policy in Brazil, including in addressing potential gaps in access to mental healthcare.

Purpose: Understanding long-term patterns of suicide methods can inform public health policy and prevention strategies. In Brazil, firearm-related policies may be one salient target for suicide prevention. This study describes trends in method-specific suicide at the national and state-levels in Brazil, with a particular focus on firearm-related suicides., Methods: Brazilian mortality data for suicide and undetermined intent among people aged 10 years and older between 2000 and 2017 were obtained from the National Mortality Information System. We examined national and state-level trends in age-standardised suicide rates for hanging, self-poisoning, firearms, jumping from a high place, other, and unspecified methods. We also compared total rates of mortality from suicide and undetermined intent over the period. Applying Joinpoint regression, we tested changes in trends of firearm-specific suicide rates., Results: The total suicide rate increased between 2000 and 2017. Rates of hanging, self-poisoning by drugs or alcohol and jumping from a high place showed the largest increases, while firearm-specific suicide rates decreased over the study period. Trends in methods of suicide varied by sex and state., Conclusion: It is of public health concern that suicide rates in Brazil have risen this millennium. Restricting access to firearms might be an effective approach for reducing firearm-specific suicides, especially in states where firearm availability remains particularly high. Treatment and management of substance misuse may also be an important target for suicide prevention policies. More work is needed to understand the causes of rising suicide rates in Brazil and to improve the mental health of the population., (© 2021. The Author(s).)

The Tocantins-Araguaia Basin is one of the largest river systems in South America, located entirely within Brazilian territory. In the last decades, capital-concentrating activities such as agribusiness, mining, and hydropower promoted extensive changes in land cover, hydrology, and environmental conditions. These changes are jeopardizing the basin's biodiversity and ecosystem services. Threats are escalating as poor environmental policies continue to be formulated, such as environmentally unsustainable hydropower plants, large-scale agriculture for commodity production, and aquaculture with non-native fish. If the current model persists, it will deepen the environmental crisis in the basin, compromising broad conservation goals and social development in the long term. Better policies will require thought and planning to minimize growing threats and ensure the basin's sustainability for future generations., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives. Immune reconstitution therapies (IRT), which include antibody-based cell-depleting therapies targeting CD52+ (alemtuzumab) or CD20+ (rituximab, ocrelizumab) leukocytes, are approved for the treatment of multiple sclerosis. Thyroid autoimmunity is a common adverse effect of alemtuzumab treatment, Graves' disease (GD) being the most prevalent manifestation. To date, thyroid autoimmunity events have not been reported with CD20-targeting monoclonal antibodies. Case Report. A 59-year-old woman with primary progressive multiple sclerosis with no prior personal history of thyroid disease or autoimmunity, was diagnosed with GD 6 months following the first ocrelizumab infusion. She was asymptomatic and had no signs of ophthalmopathy. Due to the temporal association of GD diagnosis with ocrelizumab infusion, absence of symptoms and our experience with alemtuzumab-induced GD, we decided for an active surveillance strategy and antithyroid drugs were not started. She underwent spontaneous resolution of hyperthyroidism with thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) negativity and a mild and transitory period of subclinical hypothyroidism, while she continued the biannually ocrelizumab administration schedule. To present date, she has maintained close clinical and biochemical surveillance with normal TSH, free thyroxine (fT4) and free triiodothyronine (fT3) levels and undetectable TRAb. Conclusions. This is the first case of GD reported after ocrelizumab administration. The timing, onset and course of this case is similar to alemtuzumab-induced GD, usually interpreted as an "immune reconstitution syndrome"; however, ocrelizumab cell count depletion is inferior in severity, cell population affected and duration of depletion. This case highlights the importance of pre-screening and follow-up with thyroid function tests in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to unravel the causes of thyroid autoimmunity., (© 2021 Diana Borges Duarte et al., published by Sciendo.)

The inactivation of bacteria Escherichia coli (E. coli) by non-thermal plasma (NTP) was investigated using argon, air and 1:1 mixture of air/Ar as plasma gas on five different reactors. The experiments were carried out in triplicate in each reactor, using 60 mL of distilled water pre-inoculated with E.coli. The physical-chemical analysis of pH, conductivity, nitrite, nitrate and temperature were performed soon after of 10 min of NTP treatment. The microbiological analysis of E. coli inactivation was performed using 100 μL samples withdrawn from the plasma reactor after 10 min and compared with the positive and negative control test results. The best performance were achieved whit the NTP reactors working with the upper electrode in the gas phase using 1:1 air/Ar and air as plasma gas. The results are linked with the E. coli inactivation due to membrane rupture by the NTP discharge followed by the attack of the reactive species produced in the solution. The E. coli inactivation was only partial using argon as plasma gas and the direct barrier discharge reactors showed partial inactivation even when air was used as plasma gas., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Software tools that allow the visualization and analysis of protein interaction networks are essential for studies in systems biology. One of the most popular network visualization tools in biology is Cytoscape, which offers a great selection of plug-ins for the interpretation of network data. Chemical cross-linking coupled to mass spectrometry (XL-MS) is an increasingly important source for protein interaction data; however, to date, no Cytoscape tools are available to analyze XL-MS results. In light of the suitability of the Cytoscape platform and to expand its toolbox, here we introduce XlinkCyNET, an open-source Cytoscape Java plug-in for exploring large-scale XL-MS-based protein interaction networks. XlinkCyNET offers the rapid and easy visualization of intra- and interprotein cross-links in a rectangular-bar style as well as on the 3D structure, allowing the interrogation of protein interaction networks at the residue level. XlinkCyNET is freely available from the Cytoscape App Store (http://apps.cytoscape.org/apps/xlinkcynet) and at the Liu lab webpage (https://www.theliulab.com/software/xlinkcynet).

Objective: To evaluate the use of off-label and unlicensed medications in preterm infants hospitalized in a neonatal intensive care unit., Methods: This nonconcurrent cohort study included preterm infants admitted to 3 neonatal intensive care units in 2016 and 2017 who were followed up during the neonatal period. The type and number of medications used were recorded for the entire period and classified based on the Anatomical Therapeutic Chemical. Descriptive and bivariate data analyses were performed to assess associations between the number of drugs used (total, off-label and unlicensed) and the explanatory variables of interest., Results: Four hundred preterm infants received 16,143 prescriptions for 86 different pharmaceuticals; 51.9% of these medications were classified as off-label and 23.5% as unlicensed. The most prescribed drugs were gentamicin and ampicillin (17.5% and 15.5% among off-label, respectively) and caffeine (75.5% among unlicensed). The results indicated significant associations between the use of off-label drugs and lower gestational age, low birth weight, lower 5-minute Apgar score, advanced resuscitation maneuver in the delivery room and death. The prescription of unlicensed drugs was associated with lower gestational age, low birth weight and 5-minute Apgar score below 7., Conclusion: Neonates admitted to neonatal intensive care units are highly exposed to off-label and unlicensed medications. Further studies are needed to achieve greater safety and quality of drug therapy used in neonatology.

Introduction: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor ( MAX ) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals., Case Presentation: The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene., Conclusion: This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Duarte, Ferreira, Santos, Costa, Lima, Santos, Afonso, Teixeira, Carvalho and Cardoso.)

Objectives: The aim of this study was to determine sensitivity, specificity, and best cutoff point for adductor pollicis muscle thickness (APMT) for diagnosis of sarcopenia in elderly community centers., Methods: This was a cross-sectional study comprising 321 elderly individuals from four community centers in Cuiabá, Central-West region of Brazil. The main outcome variables were calf circumference (CC; cm) and the APMT (mm). A receiver operating characteristic curve was built to assess the accuracy of APMT having CC as a golden pattern for sarcopenia. The best cutoff point was defined by Youden's J statistic., Results: The area under curve of APMT was 0.70 (95% confidence interval [CI], 0.63-0.76; P < 0.001) for all individuals, 0.74 (95% CI, 0.67-0.81; P < 0.001) for women, and 0.71 (95% CI, 0.58-0.85; P =.01) for men. The best cutoff point defined by Youden's J statistic was 17.63 mm for all individuals, the same for women. and 18.51 mm for men., Conclusion: The APMT can be used for the diagnosis of sarcopenia. The optimal cutoff points for APMT are 17.63 mm for women and 18.51 mm for men in elderly communities in the Central-West Region of Brazil., (Copyright © 2020. Published by Elsevier Inc.)

The ACERTO project is a multimodal perioperative care protocol. Implemented in 2005, the project in the last 15 years has disseminated the idea of a modern perioperative care protocol, based on evidence and with interdisciplinary team work. Dozens of published studies, using the protocol, have shown benefits such as reduced hospital stay, postoperative complications and hospital costs. Disseminated in Brazil, the project is supported by the Brazilian College of Surgeons and the Brazilian Society of Parenteral and Enteral Nutrition, among others. This article compiles publications by the authors who belong to the CNPq research group "Acerto em Nutrição e Cirurgia", refers to the experience of other national authors in various surgical specialties, and finally outlines the evolution of the ACERTO project in the timeline.

Objective: To estimate the association between homicide and suicide rates in Brazilian municipalities over a period of 7 years., Design: We conducted a longitudinal ecological study using annual mortality data from 5507 Brazilian municipalities between 2008 and 2014. Multivariable negative binomial regression models were used to examine the relationship between homicide and suicide rates. Robustness of results was explored using sensitivity analyses to examine the influence of data quality, population size, age and sex on the relationship between homicide and suicide rates., Setting: A nationwide study of municipality-level data., Participants: Mortality data and corresponding population estimates for municipal populations aged 10 years and older., Primary and Secondary Outcome Measures: Age-standardised suicide rates per 100 000., Results: Municipal suicide rates were positively associated with municipal homicide rates; after adjusting for socioeconomic and demographic factors, a doubling of the homicide rate was associated with 22% increase in suicide rate (rate ratio=1.22, 95% CI: 1.13 to 1.33). A dose-response effect was observed with 4% increase in suicide rates at the third quintile, 9% at the fourth quintile and 12% at the highest quintile of homicide rates compared with the lowest quintile. The observed effect estimates were robust to sensitivity analyses., Conclusions: Municipalities with higher homicide rates have higher suicide rates and the relationship between homicide and suicide rates in Brazil exists independently of many sociodemographic and socioeconomic factors. Our results are in line with the hypothesis that changes in homicide rates lead to changes in suicide rates, although a causal association cannot be established from this study. Suicide and homicide rates have increased in Brazil despite increased community mental health support and incarceration, respectively; therefore, new avenues for intervention are needed. The identification of a positive relationship between homicide and suicide rates suggests that population-based interventions to reduce homicide rates may also reduce suicide rates in Brazil., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)