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Abstract Mitral regurgitation (MR) is associated with morphological and functional alterations of left atrium (LA) and ventricle (LV), possibly inducing LA–LV misalignment. We aimed to: (1) characterize angulation between LA and mitral annulus from conventional cine MRI data and feature-tracking (FT) contours, (2) assess their associations with functional capacity in MR patients, as assessed by oxygen consumption (peak-VO2) and minute ventilation to carbon dioxide production (VE/VCO2) slope, in comparison with MRI LA/LV strain indices. Thirty-two asymptomatic primary MR patients (56 [40; 66] years, 12 women) underwent cardiac MRI resulting in LA/LV conventional FT-derived strain indices. Then, end-diastolic angles were derived from FT LA contours: (1) α, centered on the LA centre of mass and defined by mitral valve extremities, (2) γ, centered on the mitral ring anterior/lateral side, and defined by LA centre and the other extremity of the mitral ring. Cardiopulmonary exercise testing with simultaneous echocardiography were also performed; peak-VO2 and VE/VCO2 slope were measured. While peak-VO2 and VE/VCO2 slope were not correlated to LA/LV strains, they were significantly associated with angles (α: r = 0.50, p = 0.003 and r = − 0.52, p = 0.003; γ: r = − 0.53, p = 0.002 and r = 0.52, p = 0.003; respectively), independently of age and gender (R2 ≥ 0.29, p ≤ 0.03). In primary MR, the new LA/mitral annulus angles, computed directly from standard-of-care MRI, are better correlated to exercise tolerance than conventional LA/LV strain.

Abstract Background The EURO-NMD Registry collects data from all neuromuscular patients seen at EURO-NMD's expert centres. In-kind contributions from three patient organisations have ensured that the registry is patient-centred, meaningful, and impactful. The consenting process covers other uses, such as research, cohort finding and trial readiness. Results The registry has three-layered datasets, with European Commission-mandated data elements (EU-CDEs), a set of cross-neuromuscular data elements (NMD-CDEs) and a dataset of disease-specific data elements that function modularly (DS-DEs). The registry captures clinical, neuromuscular imaging, neuromuscular histopathology, biological and genetic data and patient-reported outcomes in a computer-interpretable format using selected ontologies and classifications. The EURO-NMD registry is connected to the EURO-NMD Registry Hub through an interoperability layer. The Hub provides an entry point to other neuromuscular registries that follow the FAIR data stewardship principles and enable GDPR-compliant information exchange. Four national or disease-specific patient registries are interoperable with the EURO-NMD Registry, allowing for federated analysis across these different resources. Conclusions Collectively, the Registry Hub brings together data that are currently siloed and fragmented to improve healthcare and advance research for neuromuscular diseases.

Abstract BackgroundOpioid and substance misuse has become a widespread problem in the United States, leading to the “opioid crisis.” The relationship between substance misuse and mental health has been extensively studied, with one possible relationship being that substance misuse causes poor mental health. However, the lack of evidence on the relationship has resulted in opioids being largely inaccessible through legal means. ObjectivesThis study aims to analyze social media posts related to substance use and opioids being sold through cryptomarket listings. The study aims to use state-of-the-art deep learning models to generate sentiment and emotion from social media posts to understand users’ perceptions of social media. The study also aims to investigate questions such as which synthetic opioids people are optimistic, neutral, or negative about; what kind of drugs induced fear and sorrow; what kind of drugs people love or are thankful about; which drugs people think negatively about; and which opioids cause little to no sentimental reaction. MethodsThe study used the drug abuse ontology and state-of-the-art deep learning models, including knowledge-aware Bidirectional Encoder Representations From Transformers–based models, to generate sentiment and emotion from social media posts related to substance use and opioids being sold through cryptomarket listings. The study crawled cryptomarket data and extracted posts for fentanyl, fentanyl analogs, and other novel synthetic opioids. The study performed topic analysis associated with the generated sentiments and emotions to understand which topics correlate with people’s responses to various drugs. Additionally, the study analyzed time-aware neural models built on these features while considering historical sentiment and emotional activity of posts related to a drug. ResultsThe study found that the most effective model performed well (statistically significant, with a macro–F1 ConclusionsThe study provides insight into users’ perceptions of synthetic opioids based on sentiment and emotion expressed in social media posts. The study’s findings can be used to inform interventions and policies aimed at reducing substance misuse and addressing the opioid crisis. The study demonstrates the potential of deep learning models for analyzing social media data to gain insights into public health issues.

Abstract The role of dietary patterns in the development of osteoporosis is unclear. The heel quantitative ultrasound (QUS) is a potential alternative to Dual X-Ray Absorptiometry. Nutrients, foods, dietary patterns and compliance to dietary guidelines were compared between the lowest and the highest tertiles of QUS parameters [Broadband Ultrasound Attenuation (BUA), Speed of Sound (SOS), Stiffness Index (SI)], using data from the OsteoLaus cohort. Participants in the highest tertiles of QUS parameters (385 for BUA, 397 for SOS, 386 for SI) were younger, of higher body weight, and had less major osteoporotic fractures. Women in the highest tertiles of SI and BUA consumed more fat (35.1 ± 0.4 vs 33.9 ± 0.4 and 34.9 ± 0.4 vs 33.8 ± 0.4 gr/day for SI and BUA, respectively, p

Abstract There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21–28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P

Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very poor prognosis, characterized by incidence rates very close to death rates. Despite the efforts of the scientific community, preclinical models that faithfully recreate the PDAC tumor microenvironment remain limited. Currently, the use of 3D bio-printing is an emerging and promising method for the development of cancer tumor models with reproducible heterogeneity and a precisely controlled structure. This study presents the development of a model using the extrusion 3D bio-printing technique. Initially, a model combining pancreatic cancer cells (Panc-1) and cancer-associated fibroblasts (CAFs) encapsulated in a sodium alginate and gelatin-based hydrogel to mimic the metastatic stage of PDAC was developed and comprehensively characterized. Subsequently, efforts were made to vascularize this model. This study demonstrates that the resulting tumors can maintain viability and proliferate, with cells self-organizing into aggregates with a heterogeneous composition. The utilization of 3D bio-printing in creating this tumor model opens avenues for reproducing tumor complexity in the future, offering a versatile platform for improving anti-cancer therapy models.

Introduction Despite international efforts, the number of individuals struggling with obesity is still increasing. An important aspect of obesity prevention relates to identifying individuals at risk at early stage, allowing for timely risk stratification and initiation of countermeasures. However, obesity is complex and multifactorial by nature, and one isolated (bio)marker is unlikely to enable an optimal risk stratification and prognosis for the individual; rather, a combined set is required. Such a multicomponent interpretation would integrate biomarkers from various domains, such as classical markers (eg, anthropometrics, blood lipids), multiomics (eg, genetics, proteomics, metabolomics), lifestyle and behavioural attributes (eg, diet, physical activity, sleep patterns), psychological traits (mental health status such as depression) and additional host factors (eg, gut microbiota diversity), also by means of advanced interpretation tools such as machine learning. In this paper, we will present a protocol that will be employed for a scoping review that attempts to summarise and map the state-of-the-art in the area of multicomponent (bio)markers related to obesity, focusing on the usability and effectiveness of such biomarkers.Methods and analysis PubMed, Scopus, CINAHL and Embase databases will be searched using predefined key terms to identify peer-reviewed articles published in English until January 2024. Once downloaded into EndNote for deduplication, CADIMA will be employed to review and select abstracts and full-text articles in a two-step procedure, by two independent reviewers. Data extraction will then be carried out by several independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and Peer Review of Electronic Search Strategies guidelines will be followed. Combinations employing at least two biomarkers from different domains will be mapped and discussed.Ethics and dissemination Ethical approval is not required; data will rely on published articles. Findings will be published open access in an international peer-reviewed journal. This review will allow guiding future directions for research and public health strategies on obesity prevention, paving the way towards multicomponent interventions.

Background This study took place at the height of the fifth wave of COVID-19 in France, coinciding with stigmatizing communication toward the unvaccinated. We hypothesized that adherence to this communication would facilitate or inhibit the effects of priming on vaccination intention, depending on whether the priming included a dimension of connection to others. Participants and procedure In a convenience online French sample (N = 1800, M age = 26.30), vaccination intention was asked after love priming, no love/prejudice priming, materialism priming, or a control condition. Participants also reported their adherence to restrictive measures, i.e., media control, vaccination pass, and mandatory vaccination. Results Vaccination intention was higher in the no love/prejudice and materialism conditions than in the love and control condi-tions. Adherence to restrictive measures mediated the effect of prejudice or materialism priming on intention to get vaccinated. Conclusions Implications of these results are discussed in light of the socially situated cognition perspective and the congruence of (a) a societal context of communication toward the vaccine and the unvaccinated, (b) the participant’s degree of adherence to that communication, (c) the theme of priming, whether or not related to feeling connected to others. Implications of mate-rialism priming are discussed, and the effect of commitment on intention to get vaccinated.

Abstract The present study aims to assess the effects of thermal and chemical inactivating procedures, that can be used for SARS-CoV-2 inactivation, on different salivary analytes. SDS–Polyacrylamide Gel Electrophoresis (SDS-PAGE) protein profile and a panel of 25 specific biomarkers of oxidative status, stress, metabolism and tissue damage were evaluated in samples subjected to different treatments: thermal (65 °C or 92 °C) and chemical with detergents [sodium dodecyl sulphate (SDS), Triton X-100 or NP-40]. Salivary SDS-PAGE profile was most affected by heating at 92 °C, with three and two protein bands decreasing and increasing their expression levels, respectively. This treatment also affected the results of several enzymes, with some of them being also affected by heating at 65 °C and incubation with SDS. The use of Triton X-100 or NP-40 resulted in increased values of cortisol, triglycerides and glucose, not affecting the other tested biomarkers. The present results will help researchers and clinicians to select the best protocols to work in safe conditions with saliva, taking into account the target analyte planned to be measured.

Introduction Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies.Methods and analysis This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites.Ethics and dissemination The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code ‘2021-778 f-A’) and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal.Trial registration number NCT05126303.

Abstract Phospholipases are esterases involved in lipid catabolism. In pathogenic micro-organisms (bacteria, fungi, parasites) they often play a critical role in virulence and pathogenicity. A few phospholipases (PL) have been characterised so far at the gene and protein level in unicellular parasites including African trypanosomes (AT). They could play a role in different processes such as host–pathogen interaction, antigenic variation, intermediary metabolism. By mining the genome database of AT we found putative new phospholipase candidate genes and here we provided biochemical evidence that one of these has lipolytic activity. This protein has a unique non-canonical glycosome targeting signal responsible for its dual localisation in the cytosol and the peroxisomes-related organelles named glycosomes. We also show that this new phospholipase is excreted by these pathogens and that antibodies directed against this protein are generated during an experimental infection with T. brucei gambiense, a subspecies responsible for infection in humans. This feature makes this protein a possible tool for diagnosis.

Abstract The important pharmacological actions of Crotoxin (CTX) on macrophages, the main toxin in the venom of Crotalus durissus terrificus, and its important participation in the control of different pathophysiological processes, have been demonstrated. The biological activities performed by macrophages are related to signaling mediated by receptors expressed on the membrane surface of these cells or opening and closing of ion channels, generation of membrane curvature and pore formation. In the present work, the interaction of the CTX complex with the cell membrane of macrophages is studied, both using biological cells and synthetic lipid membranes to monitor structural alterations induced by the protein. Here we show that CTX can penetrate THP-1 cells and induce pores only in anionic lipid model membranes, suggesting that a possible access pathway for CTX to the cell is via lipids with anionic polar heads. Considering that the selectivity of the lipid composition varies in different tissues and organs of the human body, the thermostructural studies presented here are extremely important to open new investigations on the biological activities of CTX in different biological systems.

Abstract Increasing evidence has uncovered associations between the cognition of abstract schemas and spatial perception. Here we examine such associations for Western musical syntax, tonality. Spatial metaphors are ubiquitous when describing tonality: stable, closural tones are considered to be spatially central and, as gravitational foci, spatially lower. We investigated whether listeners, musicians and nonmusicians, indeed associate tonal relationships with visuospatial dimensions, including spatial height, centrality, laterality, and size, implicitly or explicitly, and whether such mappings are consistent with established metaphors. In the explicit paradigm, participants heard a tonality-establishing prime followed by a probe tone and coupled each probe with a subjectively appropriate location (Exp.1) or size (Exp.4). The implicit paradigm used a version of the Implicit Association Test to examine associations of tonal stability with vertical position (Exp.2), lateral position (Exp3) and size (Exp.5). Tonal stability was indeed associated with perceived physical space: the spatial distances between the locations associated with different scale-degrees significantly correlated with the tonal stability differences between these scale-degrees. However, inconsistently with musical discourse, stable tones were associated with leftward (instead of central) and higher (instead of lower) spatial positions. We speculate that these mappings are influenced by emotion, embodying the “good is up” metaphor, and by the spatial structure of music keyboards. Taken together, the results demonstrate a new type of cross-modal correspondence and a hitherto under-researched connotative function of musical structure. Importantly, the results suggest that the spatial mappings of an abstract domain may be independent of the spatial metaphors used to describe that domain.

Introduction In France, despite fear-based communication by the authorities and the media, vaccination against COVID-19 has received little support from the population. For a young population often convinced that severe forms of the disease affect older people, we hypothesized that communication based on the idea of love would be more effective than communication based on fear of vaccination. Material and methods In a convenience online French sample (N = 480, M age = 19.4), vaccination intention was asked after fear priming, love priming, no love/prejudice priming, or a control condition. Participants also reported their fear of vaccination against COVID-19, and the recommendation they would make regarding vaccination of a loved/unloved person. Results Vaccination intention was higher in the love condition than in the fear and no love/prejudice conditions. Surprisingly, fear of vaccination was lower in participants who were presented with fear-inducing questions. Conclusions Implications of these results are discussed in relation to the fear of vaccination and the transpersonal value of the idea of love. The results suggest that COVID-19 is experienced as a threat both to oneself and to those one loves most. Therefore, calls for fear in the media and on social networks seem less likely to motivate a young population to vaccinate than the reminder of intense emotional ties to loved ones.

Objetivo: avaliar a assistência prestada às crianças pela Atenção Primária à Saúde na terceira etapa do método canguru. Métodos: estudo transversal realizado com as mães, com o uso de questionário estruturado contendo variáveis sócio-demográficas, clínicas e variáveis relacionadas à assistência prestada na atenção primária à saúde. Resultados: participaram 156 crianças, das quais 54,5% tinham idade acima de seis meses, 50,6% pesaram ao nascer entre 1500 a 1999g considerados de muito baixo peso, 9,6% nasceram extremos, peso inferior a 1000 g, 62,2% nasceram com idade gestacional entre 28 a 33 semanas e 12,2%, idade gestacional inferior a 28 semanas. Quanto à assistência prestada: 59,6% não receberam visita domiciliar, 74,4% não fizeram consulta na Unidade Básica de Saúde, 55% das mães desconheciam os sinais de risco da criança e 58,8% não receberam essa orientação. Conclusão: a assistência na terceira etapa do método canguru prestada pela Atenção Primária à Saúde apresenta fragilidades.

Abstract Biodiversity is changing at an accelerating rate at both local and regional scales. Beta diversity, which quantifies species turnover between these two scales, is emerging as a key driver of ecosystem function that can inform spatial conservation. Yet measuring biodiversity remains a major challenge, especially in aquatic ecosystems. Decoding environmental DNA (eDNA) left behind by organisms offers the possibility of detecting species sans direct observation, a Rosetta Stone for biodiversity. While eDNA has proven useful to illuminate diversity in aquatic ecosystems, its utility for measuring beta diversity over spatial scales small enough to be relevant to conservation purposes is poorly known. Here we tested how eDNA performs relative to underwater visual census (UVC) to evaluate beta diversity of marine communities. We paired UVC with 12S eDNA metabarcoding and used a spatially structured hierarchical sampling design to assess key spatial metrics of fish communities on temperate rocky reefs in southern California. eDNA provided a more-detailed picture of the main sources of spatial variation in both taxonomic richness and community turnover, which primarily arose due to strong species filtering within and among rocky reefs. As expected, eDNA detected more taxa at the regional scale (69 vs. 38) which accumulated quickly with space and plateaued at only ~ 11 samples. Conversely, the discovery rate of new taxa was slower with no sign of saturation for UVC. Based on historical records in the region (2000–2018) we found that 6.9 times more UVC samples would be required to detect 50 taxa compared to eDNA. Our results show that eDNA metabarcoding can outperform diver counts to capture the spatial patterns in biodiversity at fine scales with less field effort and more power than traditional methods, supporting the notion that eDNA is a critical scientific tool for detecting biodiversity changes in aquatic ecosystems.

Abstract Large protein complexes carry out some of the most complex activities in biology1,2. Such structures are often assembled spontaneously through the process of self-assembly and have characteristic chemical or biological assets in the cellular mechanisms3. Gold-based nanomaterials have attracted much attention in many areas of chemistry, physics and biosciences because of their size- and shape-dependent optic, electric, and catalytic properties. Here we report for the first time a one step synthesis in which Manganese Superoxide Dismutase protein plays a key role in the reduction of gold salts via the use of a Good's buffer (HEPES) to produce gold nanoparticles, compared to other proteins as catalase (CAT) and bovine serum albumin (BSA).We prove that this effect is directly related with the biological activities of the proteins that have an effect on the gold reduction mechanisms. Such synthesis route also induces the integration of proteins directly in the AuNPs that are intrinsically safe by design using a one-step production method. This is an important finding that will have uses in various applications, particularly in the green synthesis of novel nanomaterials.

Abstract: A trend towards increasing birth weight has been shown, but factors that explain these trends have not been elucidated. The objectives of this study were to evaluate changes in mean birth weight of term newborns and to identify factors associated with them. All cohorts are population-based studies in which random samples of births (Ribeirão Preto, São Paulo State in 1978/1979, 1994 and 2010; Pelotas, Rio Grande do Sul State in 1982, 1993 and 2004; and São Luís, Maranhão State in 1997/1998 and 2010, Brazil). A total of 32,147 full-term, singleton live births were included. Mean birth weight reduced in the first study period (-89.1g in Ribeirão Preto from 1978/1979 to 1994, and -27.7g in Pelotas from 1982 to 1993) and increased +30.2g in Ribeirão Preto from 1994 to 2010 and +24.7g in São Luís from 1997 to 2010. In the first period, in Ribeirão Preto, mean birth weight reduction was steeper among mothers with high school education and among those born 39-41 weeks. In the second period, the increase in mean birth weight was steeper among mothers with low schooling in Ribeirão Preto and São Luís, females and those born 37-38 weeks in Ribeirão Preto and cesarean section in São Luís. Birth weight decreased in the first study period then increased thereafter. The variables that seem to have been able to explain these changes varied over time.

BackgroundImmune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity.MethodsWe identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis.ResultsOf the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of -9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at -12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = -0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = -0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment.ConclusionIn patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.

Abstract: The aim of this study was to analyze the association between birth by cesarean section and central adiposity in adolescents in São Luís, Maranhão State, Brazil. This was a cohort study that included 601 participants evaluated at birth and at 18-19 years. At birth we assessed type of delivery, maternal education, family income, maternal marital status, maternal body mass index before pregnancy, prenatal care, maternal smoking habit, gestational age at delivery and intrauterine growth restriction. In the adolescents, we evaluated central adiposity using the dual X-ray energy absorptiometry method. The indicators of central fat used were the trunk-to-total fat mass ratio (T/T), the android-to-gynoid fat mass ratio (A/G), the trunk-to-limb fat mass ratio (T/Lb), and the trunk-to-leg fat mass ratio (T/Lg). A theoretical model for the study of associations was developed using directed acyclic graphs, which allowed selecting the variables that required minimum adjustment for inclusion in the predictive model of exposure to cesarean delivery. The data were analyzed with marginal structural models weighted by the inverse of the probability of selection. A total of 38.6% of the adolescents studied were delivered by cesarean section. There was no significant difference in the central adiposity of adolescents delivered by cesarean section according to the indicators used: T/T ( coefficient = -0.003; 95%CI: -0.013; 0.007), A/G (coefficient = 0.001; 95%CI: -0.015; 0.018); T/Lb (coefficient = -0.016; 95%CI: -0.048; 0.016); T/Lg (coefficient = 0.014; 95%CI: -0.060; 0.030). In conclusion, there was no association between cesarean section delivery and greater central adiposity in the studied adolescents.

Osteoporosis is the most common chronic metabolic bone disease, known to be underdiagnosed and undertreated in parts of the Swiss population. Due to expected rise in new fragility fractures, adequate awareness of associated risk factors and diagnostic and therapeutic options will be essential for the management of osteoporosis. We therefore explored these aspects in a nationwide survey of Swiss specialists and their patients. A total of 262 physician questionnaires and 9065 patient questionnaires were analyzed, mainly from general practitioners (64.9%), followed by rheumatologists (16.8%), gynecologists (12.2%), and endocrinologists (6.1%). Around 20% of patients were under medication and/or had a medical condition increasing the risk of osteoporosis. Further risk factors, such as low consumption of calcium-rich foods, smoking, elevated alcohol intake, and insufficient physical activity, were present across regions and medical fields. 53.9% of patients did not take calcium/vitamin D supplements; 3.5% reported having fragility fractures, and 7.3% received treatment for osteoporosis. Only 38.5% of surveyed patients knew of the chronic nature of osteoporosis, indicating rather low awareness in this population. Despite generally perceived relevance of osteoporosis for daily practice, aspects of its prevention and management varied across regions and medical fields. Raising awareness among patients and physicians will be vital for addressing osteoporosis on a national scale.

We report the early growth and neurologic findings of 48 infants in Brazil diagnosed with probable congenital Zika virus syndrome and followed to age 1–8 months. Most of these infants had microcephaly (86.7%) and craniofacial disproportion (95.8%). The clinical pattern included poor head growth with increasingly negative z-scores, pyramidal/extrapyramidal symptoms, and epilepsy.

Resumo: O objetivo deste estudo foi compreender como as mães interpretam e explicam a morte de seus filhos no período neonatal. Trata-se de uma pesquisa de abordagem qualitativa. Foram utilizadas entrevistas semiestruturadas com 15 mulheres residentes no Município de São Luís, Maranhão, Brasil, cujos recém-nascidos morreram no período de julho de 2012 a julho de 2014. A coleta de dados foi realizada entre 1º de abril e 29 de agosto de 2014. As entrevistas incluíram perguntas acerca do trabalho de parto, parto, nascimento e puerpério. Foi realizada análise de conteúdo na modalidade temática. A partir da fala das entrevistadas, foram evidenciadas fragilidades na rede de assistência. Para muitas, o atendimento recebido esteve relacionado a eventos que levaram à morte dos filhos. Foram identificados como núcleos de sentido a demora no atendimento e a negligência na maternidade, que evidenciaram um contexto de violência obstétrica sofrida pelas mulheres. Fica evidente a importância de criação de estratégias para promover e assegurar o cuidado humanizado no atendimento ao parto e nascimento. Deve-se buscar o fortalecimento de políticas públicas integralizadas que contemplem as demandas de atenção à saúde da mulher e da criança.

The genetic diagnostics of inherited neuromuscular diseases (NMDs) is challenging due to their clinical and genetic heterogeneity. We launched an online survey within the EURO-NMD European Reference Network (ERN) to collect information about the availability/distribution of genetic testing across 61 ERN health care providers (HCPs). A 17 items questionnaire was designed to address methods used, the number of genetic tests available, the clinical pathway to access genetic testing, the use of next-generation sequencing (NGS) and participation to quality assessment schemes (QAs). A remarkable number of HCPs (49%) offers ≥ 500 genetic tests per year, 43,6% offers 100–500 genetic tests per year, and 7,2% ≤ 100 per year. NGS is used by 94% of centres, Sanger sequencing by 84%, MLPA by 66% and Southern blotting by 36%. The majority of centres (60%) offer NGS for all patients that fulfil criteria for NMD of genetic origin. Pipelines for NGS vary amongst centres, even within the same national system. Referral of patients to genetic laboratories by specialists was frequently reported (58%), and 65% of centres participates in genetic testing QAs. We specifically evaluated how many centres cover SMA, DMD, Pompe, LGMDs, and TTR genes/diseases genetic diagnosis, since these rare diseases benefit from personalised therapies. We used the Orphanet EUGT numbers, provided by 82% of HCPs. SMA, DMD, LGMD, TTR and GAA genes are covered by EUGTs although with different numbers and modalities. The number of genetic tests for NMDs offered across HCPs National Health systems is quite high, including routine techniques and NGS. The number and type of tests offered and the clinical practices differ among centres. We provided evidence that survey tools might be useful to learn about the state-of-the-art of ERN health-related activities and to foster harmonisation and standardisation of the complex care for the rare disease patients in the EU.

Resumo: Este artigo tem como objetivo compreender como os pais de crianças com microcefalia receberam a comunicação do diagnóstico. Trata-se de um estudo qualitativo, realizado no Centro de Referência Estadual em Neurodesenvolvimento, Assistência e Reabilitação de Crianças (NINAR), em São Luís, Maranhão, Brasil, no período de abril de 2017 a fevereiro de 2018. Participaram do estudo os responsáveis de crianças com microcefalia. As técnicas de coleta de dados foram entrevistas estruturadas e semiestruturadas com 3 casais, 16 mães e 1 bisavó, totalizando 20 entrevistas. A amostra foi definida pelo critério de saturação, e foi realizada análise de conteúdo na modalidade temática. Para 18 entrevistados, a forma da comunicação foi considerada inadequada e traumática, algumas vezes atrelada ao sentido de “fim da vida” e dissociada de orientações sobre as formas de enfrentar a situação e cuidar do filho. Em 15 dos 20 casos, o diagnóstico de microcefalia foi dado por médicos e, em 3 casos, por enfermeira, por sogra (que soube pelo médico) e por uma funcionária da Secretaria de Saúde. Os dois outros não receberam diagnóstico: um casal soube da microcefalia pela Declaração de Nascido Vivo e outro associou o problema do filho a informações veiculadas na mídia. Foram três os eixos temáticos analisados: omissão do diagnóstico, processo de comunicação do diagnóstico e antecipação de prognóstico. As formas de comunicação do diagnóstico da microcefalia aos familiares influenciaram nos modos de aceitação e enfrentamento da situação.

Abstract Objective To assess the prevalence and clinical significance of incidental findings identified during computed tomography imaging of coronary artery bypass grafts. Results This prospective study includes 144 patients undergoing coronary graft patency assessment using computed tomography. Incidental findings were classified as significant if they were considered to need an immediate action or treatment, short-term work-up or follow-up, or minor. A total of 211 incidental findings were present in 109 (75.7%) patients. Seventy-one incidental findings (33.6%) were cardiac and 140 (66.4%) were extracardiac. Most common cardiac incidental findings were atrial dilatation [39 patients, 48 incidental findings (67.6%)] and aortic valve calcifications (7 patients, 9.9%). Among the 140 extracardiac incidental findings, the most common were lung nodules (51 patients, 54 nodules, 38.6%), and emphysema (21 patients, 15%). Thirty-six (25.7%) extracardiac incidental findings were significant and notably, 23 (63.9%) were lung nodules. Follow-up was recommended in 37 cases, among which all patients with significant lung nodules (23 patients, 62.2%). In conclusion, most common computed tomography incidental findings in patients with coronary grafts were lung nodules and emphysema.

Abstract DCC, a NETRIN-1 receptor, is considered as a cell-autonomous regulator for midline guidance of many commissural populations in the central nervous system. The corticospinal tract (CST), the principal motor pathway for voluntary movements, crosses the anatomic midline at the pyramidal decussation. CST fails to cross the midline in Kanga mice expressing a truncated DCC protein. Humans with heterozygous DCC mutations have congenital mirror movements (CMM). As CMM has been associated, in some cases, with malformations of the pyramidal decussation, DCC might also be involved in this process in human. Here, we investigated the role of DCC in CST midline crossing both in human and mice. First, we demonstrate by multimodal approaches, that patients with CMM due to DCC mutations have an increased proportion of ipsilateral CST projections. Second, we show that in contrast to Kanga mice, the anatomy of the CST is not altered in mice with a deletion of DCC in the CST. Altogether, these results indicate that DCC controls CST midline crossing in both humans and mice, and that this process is non cell-autonomous in mice. Our data unravel a new level of complexity in the role of DCC in CST guidance at the midline.

The objective of this study was to analyze changes in perinatal health in two birth cohorts started in 1997/1998 and 2010, respectively, in São Luís, Maranhão State, Brazil. A total of 2,493 live born infants were included in 1997/1998 and 5,166 in 2010. Low birth weight (LBW) rate did not change (8.5% in 1997/1998 and 8.6% in 2010). Preterm birth (PTB) rate also remained stable (13.2% in 1997/1998 and 13% in 2010). Teenage deliveries and births to single mothers decreased. Maternal schooling and prenatal care coverage increased. Intrauterine growth restriction (IUGR) decreased from 13.3% to 10.6% (p < 0.001). The perinatal mortality rate decreased from 36.6 to 20.7 per 1,000 (p < 0.001) and the infant mortality rate (IMR) dropped from 28.5 to 12.8 per 1,000 (p < 0.001). The cesarean rate increased from 34.1% to 47.5% (p < 0.001). In conclusion, despite favorable changes in socio-demographic, behavioral, and health service factors and decreasing rates of IUGR and perinatal and infant mortality, LBW and PTB remained stable, while the cesarean rate increased.

IntroductionGolden retrievers are over-represented in cases of taurine-deficient dilated cardiomyopathy and recently a surge in cases has prompted further investigation.ObjectiveTo describe the clinical, dietary, and echocardiographic features in golden retrievers diagnosed with taurine deficiency and dilated cardiomyopathy, and to determine specific dietary associations. A second aim was to determine the whole blood taurine concentrations in a representative sample of healthy golden retrievers.AnimalsTwenty-four client-owned golden retrievers with documented taurine deficiency and dilated cardiomyopathy and 52 healthy client-owned golden retrievers.MethodsIn this multicenter prospective observational study, baseline and follow-up echocardiographic data, complete diet and medical histories, and whole blood, plasma, or serum taurine concentrations were obtained. Baseline and follow-up echocardiographic data were compared. Associations were evaluated between specific diets and taurine deficiency or congestive heart failure. The prevalence of low whole blood taurine concentrations in the healthy golden retrievers was calculated.ResultsTwenty-three of 24 dogs diagnosed with taurine deficiency and dilated cardiomyopathy were fed diets that were either grain-free, legume-rich, or a combination of these factors. None of these diets were feeding trial tested using Association of American Feed Control Officials (AAFCO) procedures. Twenty-three of 24 dogs had significant improvement in their echocardiographic parameters and normalization of taurine concentrations following diet change and taurine supplementation. Nine of 11 dogs diagnosed with congestive heart failure (CHF) had resolution of their congestion at follow-up with five no longer requiring diuretic therapy and four tolerating diuretic dose reduction by >50%.ConclusionsCertain diets and diet characteristics were associated with the development of taurine deficiency. Taurine deficiency and dilated cardiomyopathy in golden retrievers is likely multifactorial, including a combination of dietary, metabolic, and genetic factors.

INTRODUCTION:Magnetic resonance imaging (MRI) shows slight spatial variations in brain white matter (WM). We used quantitative multi-parametric MRI to evaluate in what respect these inhomogeneities could correspond to WM subtypes with specific characteristics and spatial distribution. MATERIALS AND METHODS:Twenty-six controls (12 women, 38 ±9 Y) took part in a 60-min session on a 3T scanner measuring 7 parameters: R1 and R2, diffusion tensor imaging which allowed to measure Axial and Radial Diffusivity (AD, RD), magnetization transfer imaging which enabled to compute the Macromolecular Proton Fraction (MPF), and a susceptibility-weighted sequence which permitted to quantify R2* and magnetic susceptibility (χm). Spatial independent component analysis was used to identify WM subtypes with specific combination of quantitative parameters values. RESULTS:Three subtypes could be identified. t-WM (track) mostly mapped on well-formed projection and commissural tracts and came with high AD values (all p < 10(-18)). The two other subtypes were located in subcortical WM and overlapped with association fibers: f-WM (frontal) was mostly anterior in the frontal lobe whereas c-WM (central) was underneath the central cortex. f-WM and c-WM had higher MPF values, indicating a higher myelin content (all p < 1.7 10(-6)). This was compatible with their larger χm and R2, as iron is essentially stored in oligodendrocytes (all p < 0.01). Although R1 essentially showed the same, its higher value in t-WM relative to c-WM might be related to its higher cholesterol concentration. CONCLUSIONS:Thus, f- and c-WMs were less structured, but more myelinated and probably more metabolically active regarding to their iron content than WM related to fasciculi (t-WM). As known WM bundles passed though different WM subtypes, myelination might not be uniform along the axons but rather follow a spatially consistent regional variability. Future studies might examine the reproducibility of this decomposition and how development and pathology differently affect each subtype.

Many virulence factors have been described for opportunistic pathogens within the genus Aeromonas. Polymerase Chain Reactions (PCRs) are commonly used in population studies of aeromonads to detect virulence-associated genes in order to better understand the epidemiology and emergence of Aeromonas from the environment to host, but their performances have never been thoroughly evaluated. We aimed to determine diagnostic sensitivity and specificity of PCR assays for the detection of virulence-associated genes in a collection of Aeromonas isolates representative for the genetic diversity in the genus. Thirty-nine Aeromonas strains belonging to 27 recognized species were screened by published PCR assays for virulence-associated genes (act, aerA, aexT, alt, ascFG, ascV, ast, lafA, lip, ser, stx1, stx2A). In parallel, homologues of the 12 putative virulence genes were searched from the genomes of the 39 strains. Of the 12 published PCR assays for virulence factors, the comparison of PCR results and genome analysis estimated diagnostic sensitivities ranging from 34% to 100% and diagnostic specificities ranged from 71% to 100% depending upon the gene. To improve the detection of virulence-associated genes in aeromonads, we have designed new primer pairs for aerA/act, ser, lafA, ascFG and ascV, which showed excellent diagnostic sensitivity and specificity. Altogether, the analysis of high quality genomic data, which are more and more easy to obtain, provides significant improvements in the genetic detection of virulence factors in bacterial strains.