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Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation is an important diagnostic tool for tumor diagnosis and prognosis; however, its role in glioma development, and its impact on response to therapy, is not fully understood. We developed a murine model of proneural IDH1R132H-mutated glioma that shows elevated production of 2-hydroxyglutarate (2-HG) and increased trimethylation of lysine residue K27 on histone H3 (H3K27me3) compared to IDH1 wild-type tumors. We found that using Tazemetostat to inhibit the methyltransferase for H3K27, Enhancer of Zeste 2 (EZH2), reduced H3K27me3 levels and increased acetylation on H3K27. We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.

Abstract Multiple Sclerosis (MS) is a heterogeneous inflammatory and neurodegenerative disease with an unpredictable course towards progressive disability. Treating progressive MS is challenging due to limited insights into the underlying mechanisms. We examined the molecular changes associated with primary progressive MS (PPMS) using a cross-tissue (blood and post-mortem brain) and multilayered data (genetic, epigenetic, transcriptomic) from independent cohorts. In PPMS, we found hypermethylation of the 1q21.1 locus, controlled by PPMS-specific genetic variations and influencing the expression of proximal genes (CHD1L, PRKAB2) in the brain. Evidence from reporter assay and CRISPR/dCas9 experiments supports a causal link between methylation and expression and correlation network analysis further implicates these genes in PPMS brain processes. Knock-down of CHD1L in human iPSC-derived neurons and knock-out of chd1l in zebrafish led to developmental and functional deficits of neurons. Thus, several lines of evidence suggest a distinct genetic-epigenetic-transcriptional interplay in the 1q21.1 locus potentially contributing to PPMS pathogenesis.

Proneural gliomas are brain tumors characterized by enrichment of oligodendrocyte progenitor cell (OPC) transcripts and genetic alterations. In this study we sought to identify transcriptional and epigenetic differences between OPCs with Trp53 deletion and PDGF-BB overexpression (BB-p53n) and those carrying only p53 deletion (p53n). In culture, the BB-p53n OPCs display growth characteristics more similar to glioma cells than p53n OPCs. When injected in mouse brains, BB-p53n OPC form tumors, while the p53n OPCs do not. Unbiased histone proteomics and transcriptomic analysis on these OPC populations identified higher levels of the histone H3K27me3 mark and lower levels of the histone H4K20me3. The transcriptome of the BB-p53n OPCs was characterized by higher levels of transcripts related to proliferation and cell adhesion compared to p53n OPCs. Pharmacological inhibition of the enzyme responsible for histone H3K27 trimethylation (EZH2i) in BB-p53n OPCs, reduced cell cycle transcripts and increased the expression of differentiation markers, but was not sufficient to restore their growth characteristics. This suggests that PDGF-BB overexpression in p53n OPCs favors the early stages of transformation, by promoting proliferation and halting differentiation in a H3K27me3-dependent pathway, and favoring growth characteristics in a H3K27me3 independent manner

Abstract Background Triatoma garciabesi, a potential vector of the parasitic protozoan Trypanosoma cruzi, which is the causative agent of Chagas disease, is common in peridomestic and wild environments and found throughout northwestern and central Argentina, western Paraguay and the Bolivian Chaco. Genetic differentiation of a species across its range can help to understand dispersal patterns and connectivity between habitats. Dispersal by flight is considered to be the main active dispersal strategy used by triatomines. In particular, the morphological structure of the hemelytra is associated with their function. The aim of this study was to understand how genetic diversity is structured, how morphological variation of dispersal-related traits varies with genetic diversity and how the morphological characteristics of dispersal-related traits may explain the current distribution of genetic lineages in this species. Methods Males from 24 populations of T. garciabesi across its distribution range were examined. The cytochrome c oxidase I gene (coI) was used for genetic diversity analyses. A geometric morphometric method based on landmarks was used for morpho-functional analysis of the hemelytra. Centroid size (CS) and shape of the forewing, and contour of both parts of the forewing, the head and the pronotum were characterised. Length and area of the forewing were measured to estimate the aspect ratio. Results The morphometric and phylogenetic analysis identified two distinct lineages, namely the Eastern and Western lineages, which coincide with different ecological regions. The Eastern lineage is found exclusively in the eastern region of Argentina (Chaco and Formosa provinces), whereas the Western lineage is prevalent in the rest of the geographical range of the species. CS, shape and aspect ratio of the hemelytra differed between lineages. The stiff portion of the forewing was more developed in the Eastern lineage. The shape of both portions of the hemelytra were significantly different between lineages, and the shape of the head and pronotum differed between lineages. Conclusions The results provide preliminary insights into the evolution and diversification of T. garciabesi. Variation in the forewing, pronotum and head is congruent with genetic divergence. Consistent with genetic divergence, morphometry variation was clustered according to lineages, with congruent variation in the size and shape of the forewing, pronotum and head. Graphical Abstract

In this paper we describe the validation of a focus reduction neutralization test (FRNT) to quantitate human SARS-CoV-2 neutralizing antibodies by using the CTL Immunospot S6 Universal Analyzer. We employed a previously published protocol and compared its performances to a well-established and traditional serum-neutralization assay (SN). To assess diagnostic sensitivity, a total number of 201 human sera positive by SN for SARS-CoV-2 NAbs were processed: 196/201 tested positive by FRNT50 (97.51 %). A diagnostic specificity of 100 % was obtained by evaluating 206 negative serum samples. Repeatability of the test was evaluated by determining the intra and inter-assay coefficient of variation (CV). A standard deviation of 0.83 and a CV of 13 % were evidenced demonstrating an acceptable reproducibility of the assay. Moreover, a Cohen's Kappa of 0.975 was obtained proving an extremely high level of agreement between the FRNT protocol and the SN. Despite an acceptable correlation between methods (p

IntroductionWith a decreasing workforce of carers and a transition from care homes to home care, people with dementia (PwD) increasingly rely on informal caregivers (ICs) and assistive technologies (ATs). There is growing evidence that ATs in the home environment can reduce workload for formal carers (FCs) and ICs, reduce care costs, and can have a positive influence on quality of life (QoL) for PwD and their caregivers. In practice, using multiple ATs still often implies using different separate point solutions and applications. However, the integral, combined use of the data generated using various applications can potentially enhance the insight into the health and wellbeing status of PwD and can provide decision support for carers. The purpose of the current study was to evaluate the use of a DSS that integrated multiple ATs into one dashboard through a small-scale field study.MethodsThe current study presents the formative evaluation of a Decision Support System (DSS) connected to multiple ATs. This DSS has been developed by means of co-creation during an international project. The DSS provides an insight into the physical and cognitive status of a PwD, as well as an insight into sleep activity and general wellbeing. Semi-structured interview sessions were held in three countries (Netherlands, Italy, and Taiwan) with 41 participants to gain insight into the experiences of formal and informal carers and PwD with both the ATs and the DSS Alpha prototype dashboard.ResultsThe results showed that participants using the DSS were satisfied and perceived added value and a fit with certain care demands from the PwD. In general, ICs and FCs have limited insight into the status of PwD living independently at home, and in these moments, the DSS dashboard and AT bundle can provide valuable insights. Participants experienced the DSS dashboard as well-organized and easy to navigate. The accuracy of the data displayed in the dashboard is important, the context, and (perceived) privacy issues should be tackled according to all users. Furthermore, based in the insight gained during the evaluation a set of design improvements was composed which can be used to further improve the DSS for the Beta evaluation.Discussion and conclusionThe current paper evaluates a possible solution for excess AT usage and how the use of a DSS which integrated multiple AT into one single technology could support caregivers in providing care for PwD. The formative evaluation scrutinized the integration of the developed DSS and the composed bundle of ATs across diverse cultural contexts. Insights from multi-center observations shed light on user experiences, encompassing overall usability, navigational efficacy, and attitudes toward the system. FCs and ICs expressed positivity toward the DSS dashboard's design and functionalities, highlighting its utility in remote monitoring, tracking changes in the person's abilities, and managing urgent situations. There is a need for personalized solutions and the findings contribute to a nuanced understanding of DSS and AT integration, providing insights for future developments and research in the field of DSS for the care of PwD.

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease affecting 30% of the world’s population and is often associated with metabolic disorders such as metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease. This review is an update of the Brazilian Diabetes Society (Sociedade Brasileira de Diabetes [SBD]) evidence-based guideline for the management of MASLD in clinical practice. Methods The methodology was published previously and was defined by the internal institutional steering committee. The SBD Metabolic Syndrome and Prediabetes Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed with the MeSH terms [diabetes] and [fatty liver]. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to MASLD. Results and conclusions The SBD Metabolic Syndrome and Prediabetes Department formulated 9 recommendations for the management of MASLD in people with prediabetes or T2D. Screening for the risk of advanced fibrosis associated with MASLD is recommended in all adults with prediabetes or T2D. Lifestyle modification (LSM) focusing on a reduction in body weight of at least 5% is recommended as the first choice for these patients. In situations where LSMs are insufficient to achieve weight loss, the use of anti-obesity medications is recommended for those with a body mass index (BMI) ≥ 27 kg/m2. Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) monotherapy are the first-line pharmacological treatments for steatohepatitis in people with T2D, and sodium–glucose cotransporter-2 (SGLT2) inhibitors may be considered in this context. The combination of these agents may be considered in the treatment of steatohepatitis and/or fibrosis, and bariatric surgery should be considered in patients with a BMI ≥ 35 kg/m2, in which the combination of LSM and pharmacotherapy has not been shown to be effective in improving MASLD.

Background Chronic kidney disease (CKD) affects around 10% of the global population and has been estimated to affect around 50% of individuals with type 2 diabetes and 50% of those with heart failure. The guideline-recommended approach is to manage with disease-modifying therapies, but real-world data suggest that prescribing rates do not reflect this in practice.Objective To develop a cross-specialty consensus on optimal management of the patient with CKD using a modified Delphi method.Design An international steering group of experts specialising in internal medicine, endocrinology/diabetology, nephrology and primary care medicine developed 42 statements on aspects of CKD management including identification and screening, risk factors, holistic management, guidelines, cross-specialty alignment and education. Consensus was determined by agreement using an online survey.Participants The survey was distributed to cardiologists, nephrologists, endocrinologists and primary care physicians across 11 countries.Main outcomes and measures The threshold for consensus agreement was established a priori by the steering group at 75%. Stopping criteria were defined as a target of 25 responses from each country (N=275), and a 4-week survey period.Results 274 responses were received in December 2022, 25 responses from Argentina, Australia, Brazil, Guatemala, Mexico, Singapore, South Korea, Taiwan, Thailand, Turkey and 24 responses from Egypt. 53 responses were received from cardiologists, 52 from nephrologists, 55 from endocrinologists and 114 from primary care physicians. 37 statements attained very high agreement (≥90%) and 5 attained high agreement (≥75% and

Abstract Background Indocyanine Green (ICG) fluorescence-guided surgery is widely used for intraoperative visualization of lymphatic structures. To date, there are no reports indicating this dye being used in lymph node biopsies for suspected or relapsed lymphoma. Methods Between October 2021 and June 2022, 12 patients underwent a fluorescence-guided laparoscopic lymph node biopsy (FGLLB) using ICG. The following was retrospectively evaluated: the dosage of ICG, the injection site, the number of patients where fluorescence was obtained after ICG administration, and additionally, the parameters indicating the outcome of the surgical procedure. Results The median duration of the surgery was 90 min. A laparotomy conversion was required in one case due to bleeding. Fluorescence was obtained in 10/12 (83.3%) patients by means of subcutaneous/perilesional injection in six of the patients, and intravenously in the other four. Hospitalization had a mean duration of three days. There were no major postoperative complications. FGLLB was used in seven patients to follow lymphoproliferative disease progression, and in five patients to establish a diagnosis. In all cases, FGLLB provided the information necessary for the correct diagnosis. Conclusions Fluorescence with ICG offers a simple and safe method for detecting pathological lymph nodes. FGLLB in suspected intra-abdominal lymphoma can largely benefit from this new opportunity which has not yet been tested to date. Further studies with large case series are needed to confirm its efficacy.

The complexity of affected brain regions and cell types is a challenge for Huntington's disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes. The data implicates glucose and lipid metabolism in abnormal cell maturation and identify PRKCE and Thiamine Pyrophosphokinase 1 (TPK1) as central genes. Thiamine/biotin treatment of R6/1 HD mice to compensate for TPK1 dysregulation restores OL maturation and rescues neuronal pathology. Our insights into HD OL pathology spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.

Abstract Background The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. Methods The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Abstract Background Triatoma guasayana is considered an emerging vector of Chagas disease in the Southern Cone of South America. The presence of a triatomine population with brachypterous individuals, in which both wings are reduced, has recently been reported for this species. The aim of the present study was to determine if flight-related traits varied across populations, if these traits could explain differences in flight capacity across populations and if flight-related traits are associated with geographic and/or climatic variation. Methods The study involved 66 male T. guasayana specimens from 10 triatomine populations. Digital images of wing, head and pronotum were used to estimate linear and geometric morphometric variables. Variations in size and shape were analysed using one-way analysis of variance and canonical variate analysis (CVA), respectively. Mantel tests were applied to analyse the relationship between morphometric and geographic distances, and the association between size measurements was analysed using Pearson’s correlation. We explored covariation between size and shape variables using partial least square analyses (PLS). The association of geographic and climatic variables with size measurements was tested using linear regression analyses. We performed PLS analyses for shape measurements. Results Wing size differed significantly across triatomine populations. The CVA showed that wing shape of the brachypterous population is well discriminated from that of the other populations. The Mantel test showed a positive and significant association between wing shape and geographic distances. The heads of the brachypterous population were significantly larger than those of the other populations. Similar to wing shape, the head shape of the brachypterous population was well discriminated from those of the other populations. Pronotum width did not show significant differences across populations. Geographic and climatic factors were associated with size and shape of both the wing and head, but not with pronotum width. Conclusions Most of the traits related to flight dispersal varied across populations. Wing shape and head shape were found to be better markers for differentiated morphological variation across populations. Head measurements also varied in accordance with this condition. Geographic and climatic variables were associated with most of the flight-related traits. Graphical Abstract

Abstract Introduction For individuals diagnosed with diabetes mellitus, the practice of properly oriented physical exercises brings significant benefits to the individual's health and is considered an indispensable tool for metabolic management. The individualization of exercise routines is an essential aspect for therapeutic success, despite the need to consider some general recommendations. This review is an authorized literal translation of the Brazilian Society of Diabetes (SBD) Guidelines 2021–2022, which is based on scientific evidence and provides guidance on physical activities and exercises aimed at individuals with type 1 and 2 diabetes. Methods SBD designated 9 specialists from its “Department of Diabetes, Exercise & Sports” to author chapters on physical activities and exercises directed to individuals with type 1 and 2 diabetes. The aim of these chapters was to highlight recommendations in accordance with Evidence Levels, based on what is described in the literature. These chapters were analyzed by the SBD Central Committee, which is also responsible for the SBD 2021–2022 guidelines. Main clinical inquiries were selected to perform a narrated review by using MEDLINE via PubMed. Top available evidence, such as high-quality clinical trials, large observational studies and meta-analyses related to physical activity and exercise advisory, were analyzed. The adopted MeSh terms were [diabetes], [type 1 diabetes], [type 2 diabetes], [physical activity] [physical exercise]. Results 17 recommendations were defined by the members. For this review, it was considered different Evidence Levels, as well as different Classes of Recommendations. As to Evidence Levels, the following levels were contemplated: Level A) More than one randomized clinical trial or a randomized clinical trial meta-analysis with low heterogeneity. Level B) Meta analysis with observational studies, one randomized clinical trial, sizeable observational studies and sub-groups analysis. Level C) Small non-randomized studies, cross-sectional studies, case control studies, guidelines or experts’ opinions. In respect to Recommendation Classes, the following criteria were adopted: I. “Recommended”: Meaning there was a consent of more than 90% of the panel; IIa. “Must be considered”: meaning there is a general preference of the panel which 70–90% agrees; IIb. “Can be considered”. 50–70% agrees; III Not recommended: There is a consensus that the intervention should not be performed. Conclusion Physical exercise aids on the glycemic control of type 2 diabetes individuals while also decreasing cardiovascular risk in individuals with type 1 and 2 diabetes. Individuals diagnosed with diabetes should perform combined aerobic and resistance exercises in order to manage the disease. In addition, exercises focusing on flexibility and balance should be specially addressed on elderly individuals. Diabetes individuals using insulin as therapeutic treatment should properly monitor glycemia levels before, during and after exercise sessions to minimize health incidents, such as hypoglycemia.

Here the authors evaluate single cell gene expression from mouse and human Huntington’s disease brains, finding incomplete oligodendrocyte maturation and pathways involved. Treating mice with thiamine/biotin ameliorates molecular pathology.

Abstract Background Insulin therapy regimens for people with type 1 diabetes (PWT1D) should mimic the physiological insulin secretion that occurs in individuals without diabetes. Intensive insulin therapy, whether by multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII), constitutes the fundamental therapy from the initial stages of type 1 diabetes (T1D), at all ages. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021–2022. This evidence-based guideline supplies guidance on insulin therapy in T1D. Methods The methods were published elsewhere in earlier SBD guidelines and was approved by the Internal Institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated fourteen experts to constitute the Central Committee, designed to regulate the method review of the manuscripts, and judge the degrees of recommendations and levels of evidence. SBD Type 1 Diabetes Department drafted the manuscript selecting key clinical questions to do a narrative review using MEDLINE via PubMed, with the best evidence available, including high-quality clinical trials, metanalysis, and large observational studies related to insulin therapy in T1D, by using the Mesh terms [type 1 diabetes] and [insulin]. Results Based on extensive literature review the Central Committee defined ten recommendations. Three levels of evidence were considered: A. Data from more than one randomised clinical trial (RCT) or one metanalysis of RCTs with low heterogeneity (I2

Summary: Oligodendrocytes are specialized cells that insulate and support axons with their myelin membrane, allowing proper brain function. Here, we identify lamin A/C (LMNA/C) as essential for transcriptional and functional stability of myelinating oligodendrocytes. We show that LMNA/C levels increase with differentiation of progenitors and that loss of Lmna in differentiated oligodendrocytes profoundly alters their chromatin accessibility and transcriptional signature. Lmna deletion in myelinating glia is compatible with normal developmental myelination. However, altered chromatin accessibility is detected in fully differentiated oligodendrocytes together with increased expression of progenitor genes and decreased levels of lipid-related transcription factors and inner mitochondrial membrane transcripts. These changes are accompanied by altered brain metabolism, lower levels of myelin-related lipids, and altered mitochondrial structure in oligodendrocytes, thereby resulting in myelin thinning and the development of a progressively worsening motor phenotype. Overall, our data identify LMNA/C as essential for maintaining the transcriptional and functional stability of myelinating oligodendrocytes.

ABSTRACT Recent data from meta-analyses of randomized clinical trials (RCTs) suggest that dietary intake of coconut oil, rich in saturated fatty acids, does not result in cardiometabolic benefits, nor in improvements in anthropometric, lipid, glycemic, and subclinical inflammation parameters. Nevertheless, its consumption has surged in recent years all over the world, a phenomenon which can possibly be explained by an increasing belief among health professionals that this oil is as healthy as, or perhaps even healthier than, other oils, in addition to social network misinformation spread. The objective of this review is to present nutritional and epidemiological aspects related to coconut oil, its relationship with metabolic and cardiovascular health, as well as possible hypotheses to explain its high rate of consumption, in spite of the most recent data regarding its actual effects.

[This corrects the article DOI: 10.1371/journal.pntd.0011003.].

Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation is an important diagnostic tool for tumor diagnosis and prognosis; however, its role in glioma development, and its impact on response to therapy, is not fully understood. We developed a murine model of proneural IDH1R132H-mutated glioma that shows elevated production of 2-hydroxyglutarate (2-HG) and increased trimethylation of lysine residue K27 on histone H3 (H3K27me3) compared to IDH1 wild-type tumors. We found that using Tazemetostat to inhibit the methyltransferase for H3K27, Enhancer of Zeste 2 (EZH2), reduced H3K27me3 levels and increased acetylation on H3K27. We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.

With a substantial rise in life expectancy throughout the last century, society faces the imperative of seeking inventive approaches to foster active aging and provide adequate aging care. The e-VITA initiative, jointly funded by the European Union and Japan, centers on an advanced virtual coaching methodology designed to target essential aspects of promoting active and healthy aging. This paper describes the technical framework underlying the e-VITA virtual coaching system platform and presents preliminary feedback on its use. At its core is the e-VITA Manager, a pivotal component responsible for harmonizing the seamless integration of various specialized devices and modules. These modules include the Dialogue Manager, Data Fusion, and Emotional Detection, each making distinct contributions to enhance the platform’s functionalities. The platform’s design incorporates a multitude of devices and software components from Europe and Japan, each built upon diverse technologies and standards. This versatile platform facilitates communication and seamless integration among smart devices such as sensors and robots while efficiently managing data to provide comprehensive coaching functionalities.

In Italy, many people aged over 65 cannot live independently, causing an overall decrease in their quality of life and a need for social and health care. Due to the lack of both formal and informal caregivers, technological solutions become of paramount importance in this scenario. This article describes the user-centered development of the GUARDIAN ecosystem, consisting of a social robot integrated with two mobile applications which aim to monitor, coach, and keep the older user company in order to prolong his/her independence at home. In particular, the advancements from the alpha to the beta prototype of the ecosystem are described, achieved through the feedback collected from 41 end users—older people and their carers—that have tested the system for 6 weeks. By enhancing human–robot interaction, a positive improvement in terms of usability and acceptability of the system was retrieved. However, to increase the perceived usefulness and the impact on older users’ lives, it is necessary to make the entire system more customizable, and more capable in providing support for daily activities.

Objective:To determine the effects of the disease-modifying therapies, glatiramer acetate (GA) and dimethyl fumarate (DMF), on the gut microbiota in patients with MS. Methods:Participants with relapsing MS who were either treatment-naive or treated with GA or DMF were recruited. Peripheral blood mononuclear cells were immunophenotyped. Bacterial DNA was extracted from stool, and amplicons targeting the V4 region of the bacterial/archaeal 16S rRNA gene were sequenced (Illumina MiSeq). Raw reads were clustered into Operational Taxonomic Units using the GreenGenes database. Differential abundance analysis was performed using linear discriminant analysis effect size. Phylogenetic investigation of communities by reconstruction of unobserved states was used to investigate changes to functional pathways resulting from differential taxon abundance. Results:One hundred sixty-eight participants were included (treatment-naive n = 75, DMF n = 33, and GA n = 60). Disease-modifying therapies were associated with changes in the fecal microbiota composition. Both therapies were associated with decreased relative abundance of the Lachnospiraceae and Veillonellaceae families. In addition, DMF was associated with decreased relative abundance of the phyla Firmicutes and Fusobacteria and the order Clostridiales and an increase in the phylum Bacteroidetes. Despite the different changes in bacterial taxa, there was an overlap between functional pathways affected by both therapies. Interpretation:Administration of GA or DMF is associated with differences in gut microbial composition in patients with MS. Because those changes affect critical metabolic pathways, we hypothesize that our findings may highlight mechanisms of pathophysiology and potential therapeutic intervention requiring further investigation.

Abstract Background Interleukin-6 (IL-6) is an inflammation-related cytokine associated with an elevated risk of cardiovascular events. In a previous study, we demonstrated that increased IL-6 was predictive of sub-clinical atherosclerotic coronary disease in intermediate-risk patients undergoing coronary angiography. In the present study, we investigated whether increased serum IL-6 is predictive of cardiovascular events in high-risk patients. Methods In this observational study, consecutive patients referred for elective coronary angiography due to stable chest pain/myocardial ischemia had IL-6 measured immediately before the procedure. Long-term follow-up was performed by phone call or e-mail, and their clinical registries were revised. The primary outcome was a composite of new myocardial infarction, new ischemic stroke, hospitalization due to heart failure, new coronary revascularization, cardiovascular death, and death due to all causes. Results From 141 patients submitted to coronary angiography and IL-6 analysis, 100 had complete follow-up data for a mean of 5.7 years. The median age was 61.1 years, 44% were men, and 61% had type-2 diabetes. The median overall time-to-event for the primary outcome was 297 weeks (95% confidence interval [CI] 266.95–327.16). A receiver operator characteristic curve defined the best cut-off value of baseline serum IL-6 (0.44 pg/mL) with sensitivity (84.37%) and specificity (38.24%) to define two groups. High (> 0.44 pg/mL) IL-6 levels were predictive of cardiovascular events. (p for interaction = 0.015) (hazard ratio = 2.81; 95% CI 1.38–5.72, p = 0.01). Subgroup analysis did not find interactions between patients with or without diabetes, obesity, or hypertension. Conclusion In conclusion, an interleukin-6 level higher than 0.44 pg/mL, obtained just before elective coronary angiography, was associated with a poorer prognosis after a mean of 5,7-year. A pre-procedure IL-6 below 0.44 pg/mL, on the other hand, has a very good negative predictive value, suggesting a good prognosis, and may be useful to better indicate coronary angiography in high-risk patients. .

Abstract Background Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021–2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. Methods The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. Results The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2

Management of pediatric Primary Spontaneous Pneumothorax (PSP) is controversial and based on guidelines on adults. Therapeutic strategies include: observation, needle aspiration, chest drain, or surgery. We aimed to assess: i) differences in the management of PSP in pediatric vs. adult departments; ii) risk of recurrence associated to each therapeutic choice; iii) management of “large” pneumothorax (i.e. >3cm at the apex on chest X-Ray); iv) role of CT scan in addressing the treatment. We reviewed all PSP treated at Pediatric Surgery Unit (PSU) and Thoracic Surgery Unit for adults (TSU) in a 10-year period (2011 to 2020). We included a total of 42 PSP: 30/42 1st episodes and 12/42 recurrences. Among the 30/42 1st episodes, 15/30 were managed in the PSU and 15/30 in the TSU. Observation was significantly most common among PSU patients (9/15, 60%) vs. TSU cases (1/15, 6.7%; p=0.005]. Chest drain placement was reduced in PSU (3/15, 20%) vs. TSU (12/15, 80%; p=0.002). Observational was associated with a reduced risk of recurrence (0/10, 0%) compared to chest drain (7/15, 46.7%; p=0.01). Management of 20/42 “large” pneumothorax was: 4/20 (20%) observation, 10/20 (50%) chest drain, 2/20 (10%) needle aspiration, 4/20 (20%) surgery. Twentythree/ 29 PSP (79.3%) underwent CT-scan after the first episode. Bullae were detected in 17/23 patients and 5/17 (29.4%) had seven episodes of recurrence. PSP patients treated by PSU were more likely to receive clinical observation. Those managed by TSU were mostly treated by chest drain. Observation seems an effective choice for clinically stable PSP, with low risk of recurrence at a mid-term follow-up. CT-scan seems not to detect those patients at higher risk of recurrence.

Abstract Existing risk prediction scores based on clinical and laboratory variables have been considered inaccurate in patients with Type 2 Diabetes Mellitus (T2DM). Circulating concentrations of natriuretic peptides have been used to aid in the diagnosis and to predict outcomes in heart failure. However, there is a growing body of evidence for the use of natriuretic peptides measurements, mainly N-terminal pro-B-type natriuretic peptide (NT-proBNP), as a tool in risk stratification for individuals with T2DM. Studies have demonstrated the ability of NT-proBNP to improve outcomes prediction when incorporated into multivariate models. More recently, evidence has emerged of the discriminatory power of NT-proBNP, demonstrating, as a single variable, a similar and even superior ability to multivariate risk models for the prediction of death and cardiovascular events in individuals with T2DM. Natriuretic peptides are synthesized and released from the myocardium as a counter-regulatory response to increased cardiac wall stress, sympathetic tone, and vasoconstriction, acting on various systems and affecting different biological processes. In this article, we present a review of the accumulated knowledge about these biomarkers, underscoring the strength of the evidence of their predictive ability for fatal and non-fatal outcomes. It is likely that, by influencing the functioning of many organs, these biomarkers integrate information from different systems. Although not yet recommended by guidelines, measurement of natriuretic peptides, and particularly NT-proBNP, should be strongly considered in the risk stratification of individuals with T2DM.

A measurement setup for localising people in indoor environment based on a system characterized by acquisition of audio files and images implemented on a sensorised social robot is proposed. The audio signal processing for human voice identification applies the segmentation methodology for the direction of arrival (DOA) estimation. The audio signal analysis evaluates the performance of beamforming algorithms and of Covariance Matrix Fitting (CMF) when optimization in beamforming algorithm and alternative microphones’ configurations have been evaluated by simulations. Tests shows an accuracy in people detection of the optimized beamforming algorithm comparable to CMF method (96.5% and 96.6% respectively) with a lower computational cost. An image acquisition procedure has been then activated on the robot and the localisation of the people is performed using YOLO-v3 algorithm. Monte Carlo method applied to evaluate the propagation of uncertainty of the whole processing system presents a global accuracy of 98.2 ± 0.8%.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune system dysregulation. Recent work has revealed moderate alteration of gut microbial communities in subjects with MS and in experimental, induced models. However, a mechanistic understanding linking the observed changes in the microbiota and the presence of the disease is still missing. Chloroform-resistant, spore-forming bacteria, which primarily belong to the classes Bacilli and Clostridia in the phylum Firmicutes, have been shown to exhibit immunomodulatory properties in vitro and in vivo, but they have not yet been characterized in the context of human disease. This study addresses the community composition and immune function of this bacterial fraction in MS. We identify MS-associated spore-forming taxa (primarily in the class Clostridia) and show that their presence correlates with impaired differentiation of IL-10-secreting, regulatory T lymphocytes in vitro. Colonization of antibiotic-treated mice with spore-forming bacteria allowed us to identify some bacterial taxa favoring IL-10+ lymphocyte differentiation and others inducing differentiation of proinflammatory, IFN-γ+ T lymphocytes. However, when fed into antibiotic-treated mice, both MS and control-derived spore-forming bacteria were able to induce similar IL-10-expressing Treg immunoregulatory responses, thus ameliorating symptoms of experimental allergic encephalomyelitis (EAE). Our analysis also identified Akkermansia muciniphila as a key organism that may interact either directly or indirectly with spore-forming bacteria to exacerbate the inflammatory effects of MS-associated gut microbiota. Thus, changes in the spore-forming fraction may influence T lymphocyte-mediated inflammation in MS. This experimental approach of isolating a subset of microbiota based on its functional characteristics may be useful to investigate other microbial fractions at greater depth. IMPORTANCE To address the impact of microbiome on disease development, it is essential to go beyond a descriptive study and evaluate the physiological importance of microbiome changes. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of spore-forming microbial communities, revealing novel functional correlations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform-resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is correlated with impaired immunomodulatory responses in vitro.

BackgroundChagas is a complex and multidimensional socio-environmental health phenomenon, in which different components converge and interact. Historically, this disease was associated with insect vectors found in the rural environment. However, in the Americas, we are currently facing a new paradigm, in which different scenarios allow maintaining the vectorial transmission of the parasite through triatomine populations that either occasionally enter the dwellings or colonize urban environments.Methodology/principal findingsRecords of scientific reports available in the PubMed and LILACS search engines were retrieved, using three criteria according to the main triatomine genera of epidemiological importance and to the general scientific production on Chagas disease in urban contexts. Results showed that records on the occurrence of vectors in urban dwellings began to increase in the last three decades. Results also showed that the main species of triatomines collected inside dwellings (18 in total) belong mainly to the genera Triatoma and Panstrongylus, with most species (16/18, 88.8%) infected with the parasite, and that infestation of triatomine species occurs in all types of cities (small, medium and large, including megalopolises), from Argentina to the USA.Conclusions/significanceUrban Chagas represents a new challenge that adds a different dimension to the problem of Chagas disease due to the particular characteristics of the lifestyle in urban agglomerates. The new scenario will require adaptations of the programs of control of vector to this shift from rural to urban settlements.

This work illustrates an innovative localisation sensor network that uses multiple PIR and ultrasonic sensors installed on a mobile social robot to localise occupants in indoor environments. The system presented aims to measure movement direction and distance to reconstruct the movement of a person in an indoor environment by using sensor activation strategies and data processing techniques. The data collected are then analysed using both a supervised (Decision Tree) and an unsupervised (K-Means) machine learning algorithm to extract the direction and distance of occupant movement from the measurement system, respectively. Tests in a controlled environment have been conducted to assess the accuracy of the methodology when multiple PIR and ultrasonic sensor systems are used. In addition, a qualitative evaluation of the system’s ability to reconstruct the movement of the occupant has been performed. The system proposed can reconstruct the direction of an occupant with an accuracy of 70.7% and uncertainty in distance measurement of 6.7%.