Dietary protein restriction inhibits tumor growth in human xenograft models of prostate and breast cancer

Purpose: Data from epidemiological and experimental studies suggest that dietary protein intake may play a role in inhibiting prostate and breast cancer by modulating the IGF/AKT/mTOR pathway. In this study we investigated the effects of diets with different protein content or quality on prostate and breast cancer. Experimental Design: To test our hypothesis we assessed the inhibitory effect of protein diet restriction on prostate and breast cancer growth, serum PSA and IGF-1 concentrations, mTOR activity and epigenetic markers, by using human xenograft cancer models. Results: Our results showed a 70% inhibition of tumor growth in the castrate-resistant LuCaP23.1 prostate cancer model and a 56% inhibition in the WHIM16 breast cancer model fed with a 7% protein diet when compared to an isocaloric 21% protein diet. Inhibition of tumor growth correlated, in the LuCaP23.1 model, with decreased serum PSA and IGF-1 levels, down-regulation of mTORC1 activity, decreased cell proliferation as indicated by Ki67 staining, and reduction in epigenetic markers of prostate cancer progression, including the histone methyltransferase EZH2 and the associated histone mark H3K27me3. In addition, we observed that modifications of dietary protein quality, independently of protein quantity, decreased tumor growth. A diet containing 20% plant protein inhibited tumor weight by 37% as compared to a 20% animal dairy protein diet. Conclusions: Our findings suggest that a reduction in dietary protein intake is highly effective in inhibiting tumor growth in human xenograft prostate and breast cancer models, possibly through the inhibition of the IGF/AKT/mTOR pathway and epigenetic modifications

Colonização micorrízica de videiras cultivadas em sistemas orgânico e convencional no estado de Santa Catarina

Microbiological indicators are used to assess soil quality and to compare management forms in agricultural production systems. The objective of this study was to evaluate the grapevines mycorrhizal colonization in production systems under organic and conventional management in Tangará and Videira counties, Santa Catarina State. Mycorrhizal colonization rates and arbuscular mycorrhizal fungi spores density in soil were evaluated. In the organic systems, compared to conventional systems, increases in mycorrhizal colonization rate and density of arbuscular mycorrhizal fungi spores in soil were observed. The results suggest that variables associated with mycorrhizal colonization can be used as microbiological indicators for assessing soil quality in vineyards.Resumo – Indicadores microbiológicos são utilizados para avaliação da qualidade do solo e comparação de formas de manejoem sistemas de produção agrícolas. O objetivo do trabalho foi avaliar colonização micorrízica de videiras em sistemas deprodução com manejo orgânico e convencional nos municípios de Tangará e Videira, SC. Foram avaliadas taxas de colonizaçãomicorrízica e densidade de esporos de fungos micorrízicos no solo. Nos sistemas orgânicos, em relação aos sistemas convencionais,foram constatados aumentos na taxa de micorrização do córtex radicular e na densidade de esporos de fungos micorrízicosarbusculares no solo. Os resultados sugerem que variáveis associadas à colonização micorrízica podem ser utilizadas comoindicadores microbiológicos para avaliação da qualidade do solo em vinhedos.

Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations

Spastic ataxias are rare neurogenetic disorders involving spinocerebellar and pyramidal tracts. Many genes are involved. Among them, CAPN1, when mutated, is responsible for a complex inherited form of spastic paraplegia (SPG76). We report the largest published series of 21 novel patients with nine new CAPN1 disease-causing variants and their clinical characteristics from two European university hospitals (Paris and Stockholm). After a formal clinical examination, causative variants were identified by next-generation sequencing and confirmed by Sanger sequencing. CAPN1 variants are a rare cause (~ 1.4%) of young-adult-onset spastic ataxia; however, together with all published cases, they allowed us to better describe the clinical and genetic spectra of this form. Truncating variants are the most frequent, and missense variants lead to earlier age at onset in favor of an additional deleterious effect. Cerebellar ataxia with cerebellar atrophy, dysarthria and lower limb weakness are often associated with spasticity. We also suggest that cognitive impairment and depression should be assessed specifically in the follow-up of SPG76 cases.Identification of new causative genes in spinocerebellar degenerations by combination of whole genome scan, next-generation sequencing and biological validation in vitro and in vivoInfrastructure de Recherche Translationnelle pour les Biothérapies en NeurosciencesEuropean Union’s Horizon 2020 research and innovation programm

Comparison of different estimators of SARS-CoV-2 pandemic activity on geographical and temporal levels

International audienceBackground: Studies began investigating occupational exposures as a source of contamination to SARS-CoV-2, yet few considered the variation in SARS-Cov2 pandemic activity for these exposures. Several indicators were built to assess SARS-Cov2 activity though they usually serve a specific purpose and have limitations. The aim was to compare qualitatively different estimators of the SARS-CoV-2 pandemic activity and to create an estimator of pandemic activity level based on daily hospital admissions for job-exposure matrices (JEM) usage. Methods: From publicly available French databases, we retrieved all data from March 19, 2020 (first day available) to March 25, 2021 (day of data collection) on four different estimators: percentage of intensive care bed occupied, reproductive number, tests' positive rate and number positive tests. An indicator based on new daily hospital admissions was created for a COVID JEM. Due to the heterogeneity of the estimators, a qualitative comparison was carried out. Results: During the study period, three major outbreaks took place. Though the number of positive tests was the first indicator to worsen during the 2nd outbreak, it failed to identify variation during the outbreak. Though each indicators behaved differently during the study period, the indicator based on new daily hospital admissions and the positive rate seemed to be the closest to one another. Conclusion: This study highlights the heterogeneity of the indicators used during the first and second SARS-Cov2 outbreaks in France. An indicator based on new daily hospital admissions seems to be a good candidate for estimating SARS-CoV-2 epidemic activity for COVID JEMs and is easily available in countries where usual indicators are not commonly accessible. Copyrigh

Usefulness of a job-exposure matrix 'MADE' as a decision tool for compensation of work-related musculoskeletal disorders

International audienceWe aimed to assess the predictivity of the biomechanical job-exposure matrix 'MADE' using compensation data from the National Health Insurance for work-related disorders. Data were obtained from 2013 to 2015, area under curves (AUC), sensitivity, specificity and predictive values were calculated using compensation results as reference. We collected 163 128 cases data. AUC ranged from 0.64 for shoulders disorder to 0.82 for knee disorders. If two thresholds were considered, 28.7% of the sample fit under or over those. The matrix showed a fair predictivity. Such matrix cannot replace expertise but might be a tool used for improving compensation process

Influence of severe knee pain, meniscus surgery and knee arthroplasty on physical ability an observational study of 114 949 adults in the CONSTANCES cohort

International audienceBackground - The knee is one of the major sites of musculoskeletal pain, yet few large-scale studies have evaluated the impact of knee disorders on physical limitations. Our objective was to describe this impact in a large-scale population study. Methods - We included subjects of working age from the CONSTANCES cohort, from its inception. Four groups were distinguished according to their medical history: whether they had knee arthroplasty (KA), meniscus surgery, severe knee pain, or none of these. Outcomes assessed for physical limitations were self-reported limitations in the last 6 months due to health problems, limitation on carrying 5 kg on 10 m and a 3-metre length rapid gait speed test (for participants aged >45). Associations between knee groups and patients' characteristics and physical limitations were analysed using logistic regression. Robust associations were deemed relevant if their ORs were higher than 2 and their p value lower than 0.0001. Results - Of the 114 949 individuals, 99 052 (86.2%) were in the 'no pain and no surgery' group, 14 740 (12.8%) were in the severe knee pain group, 1019 (0.89%) had meniscus surgery and 138 (0.12%) had KA. Severe knee pain and KA groups showed a similar profile (they were less at work, reported more deterioration in their health and had more limitations).Conclusion - Almost 14% of the sample had knee disorders. Subjects reporting severe knee pain or who had KA reported more important physical limitations then subjects who reported neither severe knee pain nor knee surgery

Table_1_Comparison of different estimators of SARS-CoV-2 pandemic activity on geographical and temporal levels.XLSX

BackgroundStudies began investigating occupational exposures as a source of contamination to SARS-CoV-2, yet few considered the variation in SARS-Cov2 pandemic activity for these exposures. Several indicators were built to assess SARS-Cov2 activity though they usually serve a specific purpose and have limitations. The aim was to compare qualitatively different estimators of the SARS-CoV-2 pandemic activity and to create an estimator of pandemic activity level based on daily hospital admissions for job-exposure matrices (JEM) usage.MethodsFrom publicly available French databases, we retrieved all data from March 19, 2020 (first day available) to March 25, 2021 (day of data collection) on four different estimators: percentage of intensive care bed occupied, reproductive number, tests' positive rate and number positive tests. An indicator based on new daily hospital admissions was created for a COVID JEM. Due to the heterogeneity of the estimators, a qualitative comparison was carried out.ResultsDuring the study period, three major outbreaks took place. Though the number of positive tests was the first indicator to worsen during the 2nd outbreak, it failed to identify variation during the outbreak. Though each indicators behaved differently during the study period, the indicator based on new daily hospital admissions and the positive rate seemed to be the closest to one another.ConclusionThis study highlights the heterogeneity of the indicators used during the first and second SARS-Cov2 outbreaks in France. An indicator based on new daily hospital admissions seems to be a good candidate for estimating SARS-CoV-2 epidemic activity for COVID JEMs and is easily available in countries where usual indicators are not commonly accessible.</p

Should We Quantify Valvular Calcifications on Cardiac CT in Patients with Infective Endocarditis?

Background: Evaluate the impact of valvular calcifications measured on cardiac computed tomography (CCT) in patients with infective endocarditis (IE). Methods: Seventy patients with native IE (36 aortic IE, 31 mitral IE, 3 bivalvular IE) were included and explored with CCT between January 2016 and April 2018. Mitral and aortic valvular calcium score (VCS) were measured on unenhanced calcium scoring images, and correlated with clinical, surgical data, and 1-year death rate. Results: VCS of patients with mitral IE and no peripheral embolism was higher than those with peripheral embolism (868 (25–1725) vs. 6 (0–95), p &lt; 0.05). Patients with high calcified mitral IE (mitral VCS &gt; 100; n = 15) had a lower rate of surgery (40.0% vs.78.9%; p = 0.03) and a higher 1-year-death risk (53.3% vs. 10.5%, p = 0.04; OR = 8.5 (2.75–16.40) than patients with low mitral VCS (n = 19). Patients with aortic IE and high aortic calcifications (aortic VCS &gt; 100; n = 18) present more frequently atypical bacteria on blood cultures (33.3% vs. 4.8%; p = 0.03) than patients with low aortic VCS (n = 21). Conclusion: The amount of valvular calcifications on CT was associated with embolism risk, rate of surgery and 1-year risk of death in patients with mitral IE, and germ’s type in aortic IE raising the question of their systematic quantification in native IE

A Protocol for the Use of Case Reports/Studies and Case Series in Systematic Reviews for Clinical Toxicology

International audienceIntroduction: Systematic reviews are routinely used to synthesize current science and evaluate the evidential strength and quality of resulting recommendations. For specific events, such as rare acute poisonings or preliminary reports of new drugs, we posit that case reports/studies and case series (human subjects research with no control group) may provide important evidence for systematic reviews. Our aim, therefore, is to present a protocol that uses rigorous selection criteria, to distinguish high quality case reports/studies and case series for inclusion in systematic reviews. Methods: This protocol will adapt the existing Navigation Guide methodology for specific inclusion of case studies. The usual procedure for systematic reviews will be followed. Case reports/studies and case series will be specified in the search strategy and included in separate sections. Data from these sources will be extracted and where possible, quantitatively synthesized. Criteria for integrating cases reports/studies and case series into the overall body of evidence are that these studies will need to be well-documented, scientifically rigorous, and follow ethical practices. The instructions and standards for evaluating risk of bias will be based on the Navigation Guide. The risk of bias, quality of evidence and the strength of recommendations will be assessed by two independent review teams that are blinded to each other. Conclusion: This is a protocol specified for systematic reviews that use case reports/studies and case series to evaluate the quality of evidence and strength of recommendations in disciplines like clinical toxicology, where case reports/studies are the norm

Pathogenic Variants in ABHD16A Cause a Novel Psychomotor Developmental Disorder With Spastic Paraplegia

International audienceIntroduction: Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurological entity that includes more than 80 disorders which share lower limb spasticity as a common feature. Abnormalities in multiple cellular processes are implicated in their pathogenesis, including lipid metabolism; but still 40% of the patients are undiagnosed. Our goal was to identify the disease-causing variants in Sudanese families excluded for known genetic causes and describe a novel clinico-genetic entity.Methods: We studied four patients from two unrelated consanguineous Sudanese families who manifested a neurological phenotype characterized by spasticity, psychomotor developmental delay and/or regression, and intellectual impairment. We applied next-generation sequencing, bioinformatics analysis, and Sanger sequencing to identify the genetic culprit. We then explored the consequences of the identified variants in patients-derived fibroblasts using targeted-lipidomics strategies.Results and Discussion: Two homozygous variants in ABHD16A segregated with the disease in the two studied families. ABHD16A encodes the main brain phosphatidylserine hydrolase. In vitro, we confirmed that ABHD16A loss of function reduces the levels of certain long-chain lysophosphatidylserine species while increases the levels of multiple phosphatidylserine species in patient's fibroblasts.Conclusion: ABHD16A loss of function is implicated in the pathogenesis of a novel form of complex hereditary spastic paraplegia