Semi-automated stereoradiographic upper limb 3D reconstructions using a combined parametric and statistical model: a preliminary study

PURPOSE: Quantitative assessment of 3D clinical indices may be crucial for elbow surgery planning. 3D parametric modeling from bi-planar radiographs was successfully proposed for spine and lower limb clinical investigation as an alternative for CT-scan. The aim of this study was to adapt this method to the upper limb with a preliminary validation. METHODS: CT-scan 3D models of humerus, radius and ulna were obtained from 20 cadaveric upper limbs and yielded parametric models made of geometric primitives. Primitives were defined by descriptor parameters (diameters, angles...) and correlations between these descriptors were found. Using these correlations, a semi-automated reconstruction method of humerus using bi-planar radiographs was achieved: a 3D personalized parametric model was built, from which clinical parameters were computed [orientation and projections on bone surface of trochlea sulcus to capitulum (CTS) axis, trochlea sulcus anterior offset and width of distal humeral epiphysis]. This method was evaluated by accuracy compared to CT-scan and reproducibility. RESULTS: Points-to-surface mean distance was 0.9 mm (2 RMS = 2.5 mm). For clinical parameters, mean differences were 0.4-1.9 mm and from 1.7° to 2.3°. All parameters except from angle formed by CTS axis and bi-epicondylar axis in transverse plane were reproducible. Reconstruction time was about 5 min. CONCLUSIONS: The presented method provides access to morphological upper limb parameters with very low level of radiation. Preliminary in vitro validation for humerus showed that it is fast and accurate enough to be used in clinical daily practice as an alternative to CT-scan for total elbow arthroplasty pre operative evaluation

Overcoming feudal constraints on educational research in Spain: the impact of the CIMIE conference

Feudal structures and power relationships that Spanish universities inherited from Franco's dictatorship have damaged the quality of educational research. However, the emergence of initiatives aimed to address these limitations have been identified. In this article, we analyze the impact of the Multidisciplinary International Conference on Educational Research (CIMIE). Specifically, we analyze how CIMIE is contributing to overcome some of the feudal constraints affecting educational research in Spain, such as fragmentation of areas of knowledge, limited international research efforts, and precarious and unstable employment situations of many researchers. Grounded in the communicative methodology of research and using mixed methods, we have conducted a longitudinal study of this research initiative (2012-2016), comprising interviews and communicative observations, analysis of documentation and quantitative data. The results show that participants understand that their involvement in CIMIE is contributing to make them feel released from the constraints of university feudalism by building solidarity networks and egalitarian relationships, and by rethinking research

Genetic, parental and lifestyle factors influence telomere length

The average length of telomere repeats (TL) declines with age and is considered to be a marker of biological ageing. Here, we measured TL in six blood cell types from 1046 individuals using the clinically validated Flow-FISH method. We identified remarkable cell-type-specific variations in TL. Host genetics, environmental, parental and intrinsic factors such as sex, parental age, and smoking are associated to variations in TL. By analysing the genome-wide methylation patterns, we identified that the association of maternal, but not paternal, age to TL is mediated by epigenetics. Single-cell RNA-sequencing data for 62 participants revealed differential gene expression in T-cells. Genes negatively associated with TL were enriched for pathways related to translation and nonsense-mediated decay. Altogether, this study addresses cell-type-specific differences in telomere biology and its relation to cell-type-specific gene expression and highlights how perinatal factors play a role in determining TL, on top of genetics and lifestyle.We thank J. Dekens for management, A. Maatman and M. Platteel for technical support and K. Mc Intyre for English editing. This project was funded by the BBMRI grant for measuring telomere length and by a Rosalind Franklin Fellowship to A.Z. The researchers participated in this project are supported by Netherlands Heart Foundation (IN-CONTROL CVON grants 2012-03 and 2018-27); the Netherlands Organization for Scientific Research (NWO) Gravitation Netherlands Organ-on-Chip Initiative to J.F. and C.W.; NWO Gravitation Exposome-NL (024.004.017) to J.F., A.K. and A.Z.; NWO-VIDI (864.13.013) and NWO-VICI (VI.C.202.022) to J.F.; NWO-VIDI (016.178.056) to A.Z.; NWO-VIDI (917.14.374) to L.F.; NWO-VENI (194.006) to D.V.Z.; NWO-VENI (192.029) to M.W.; NWO Spinoza Prize SPI 92–266 to C.W.; the European Research Council (ERC) (FP7/2007–2013/ERC Advanced Grant 2012-322698) to C.W.; ERC Starting grant 637640 to L.F.; ERC Starting Grant 715772 to A.Z.; ERC Consolidator Grant (grant agreement No. 101001678) to J.F.; and RuG Investment Agenda Grant Personalized Health to C.W. MM work is supported by RYC- 2017-22249 and PID2019-107937GA-I00 grants. T.S. holds scholarships from the Junior Scientific Masterclass, University of Groningen[grant no. 17–34]. AR is funded by a Formación Personal Investigador (FPI) grant [grant no. PRE2019-090193]. The Lifelines Biobank initiative has been made possible by a subsidy from the Dutch Ministry of Health, Welfare and Sport; the Dutch Ministry of Economic Affairs; the University Medical Centre Groningen (UMCG, the Netherlands); the University of Groningen and the Northern Provinces of the Netherlands. The authors wish to acknowledge the services of the Lifelines Cohort Study, the contributing research centres delivering data to Lifelines and all the study participants. Finally, we would like to acknowledge the Genomics Coordination Centre (GCC) at the University Medical College Groningen for the HPC support and the MOLGENIS team for the cloud storage of the data associated with this work.Peer Reviewed"Article signat per 16 autors/es: Sergio Andreu-Sánchez, Geraldine Aubert, Aida Ripoll-Cladellas, Sandra Henkelman, Daria V. Zhernakova, Trishla Sinha, Alexander Kurilshikov, Maria Carmen Cenit, Marc Jan Bonder, Lude Franke, Cisca Wijmenga, Jingyuan Fu, Monique G. P. van der Wijst, Marta Melé, Peter Lansdorp & Alexandra Zhernakova"Postprint (published version

Association between the indole pathway of tryptophan metabolism and subclinical depressive symptoms in obesity: a preliminary study

12partially_openInternationalInternational coauthor/editorConverging data support the role of chronic low-grade inflammation in depressive symptomatology in obesity. One mechanism likely to be involved relies on the effects of inflammation on tryptophan (TRP) metabolism. While recent data document alterations in the indole pathway of TRP metabolism in obesity, the relevance of this mechanism to obesity-related depressive symptoms has not been investigated. The aim of this preliminary study was to assess the association between plasma levels of TRP and indole metabolites and depressive symptoms in 44 subjects with severe or morbid obesity, free of clinically relevant neuropsychiatric disorders. The interaction effect of inflammation, reflected in serum high-sensitive C-reactive protein (hsCRP) levels, and indoles on depressive symptoms was also determined. Higher serum levels of hsCRP and lower concentrations of TRP and indoles, particularly indole-3-carboxaldehyde (IAld), correlated with more severe depressive symptoms. Interestingly, the effect of high hsCRP levels in predicting greater depressive symptoms was potentiated by low IAld levels. These results comfort the link between inflammation, the indole pathway of TRP metabolism, and obesity-related depressive symptomsmixedDelgado, Inês; Cussotto, Sofia; Anesi, Andrea; Dexpert, Sandra; Aubert, Agnès; Aouizerate, Bruno; Beau, Cédric; Forestier, Damien; Ledaguenel, Patrick; Magne, Eric; Mattivi, Fulvio; Capuron, LucileDelgado, I.; Cussotto, S.; Anesi, A.; Dexpert, S.; Aubert, A.; Aouizerate, B.; Beau, C.; Forestier, D.; Ledaguenel, P.; Magne, E.; Mattivi, F.; Capuron, L

Tryptophan metabolic pathways are altered in obesity and are associated with systemic inflammation

Background: Obesity is a condition with a complex pathophysiology characterized by both chronic low-grade inflammation and changes in the gut microbial ecosystem. These alterations can affect the metabolism of tryptophan (TRP), an essential amino acid and precursor of serotonin (5-HT), kynurenine (KYN), and indoles. This study aimed to investigate alterations in KYN and microbiota-mediated indole routes of TRP metabolism in obese subjects relatively to non-obese controls and to determine their relationship with systemic inflammation. Methods: Eighty-five obese adults (avg. BMI = 40.48) and 42 non-obese control individuals (avg. BMI = 24.03) were recruited. Plasma levels of TRP catabolites were assessed using Ultra High Performance Liquid Chromatography-ElectroSpray-Ionization-Tandem Mass Spectrometry. High-sensitive C-reactive protein (hsCRP) and high-sensitive interleukin 6 (hsIL-6) were measured in the serum as markers of systemic inflammation using enzyme-linked immunosorbent assay. Results: Both KYN and microbiota-mediated indole routes of TRP metabolism were altered in obese subjects, as reflected in higher KYN/TRP ratio and lower 5-HT and indoles levels, relatively to non-obese controls. HsIL-6 and hsCRP were increased in obesity and were overall associated with TRP metabolic pathways alterations. Conclusion: These results indicate for the first time that KYN and indole TRP metabolic pathways are concomitantly altered in obese subjects and highlight their respective associations with obesity-related systemic inflammation.A Menu for Brain Responses Opposing Stress-Induced Alterations in CognitionMetabolic HEALTH through nutrition, microbiota and tryptophan bioMARKer

Statistical methodology for the analysis of dye-switch microarray experiments

<p>Abstract</p> <p>Background</p> <p>In individually dye-balanced microarray designs, each biological sample is hybridized on two different slides, once with <it>Cy3 </it>and once with <it>Cy5</it>. While this strategy ensures an automatic correction of the gene-specific labelling bias, it also induces dependencies between log-ratio measurements that must be taken into account in the statistical analysis.</p> <p>Results</p> <p>We present two original statistical procedures for the statistical analysis of individually balanced designs. These procedures are compared with the usual ML and REML mixed model procedures proposed in most statistical toolboxes, on both simulated and real data.</p> <p>Conclusion</p> <p>The UP procedure we propose as an alternative to usual mixed model procedures is more efficient and significantly faster to compute. This result provides some useful guidelines for the analysis of complex designs.</p

Distinct Changes in cAMP and Extracellular Signal-Regulated Protein Kinase Signalling in L-DOPA-Induced Dyskinesia

Background: In rodents, the development of dyskinesia produced by L-DOPA in the dopamine-depleted striatum occurs in response to increased dopamine D1 receptor-mediated activation of the cAMP- protein kinase A and of the Rasextracellular signal-regulated kinase (ERK) signalling pathways. However, very little is known, in non-human primates, about the regulation of these signalling cascades and their association with the induction, manifestation and/or maintenance of dyskinesia. Methodology/Results: We here studied, in the gold-standard non-human primate model of Parkinson’s disease, the changes in PKA-dependent phosphorylation of DARPP-32 and GluR1 AMPA receptor, as well as in ERK and ribosomal protein S6 (S6) phosphorylation, associated to acute and chronic administration of L-DOPA. Increased phosphorylation of DARPP-32 and GluR1 was observed in both L-DOPA first-ever exposed and chronically-treated dyskinetic parkinsonian monkeys. In contrast, phosphorylation of ERK and S6 was enhanced preferentially after acute L-DOPA administration and decreased during the course of chronic treatment. Conclusion: Dysregulation of cAMP signalling is maintained during the course of chronic L-DOPA administration, while abnormal ERK signalling peaks during the initial phase of L-DOPA treatment and decreases following prolonged exposure

Fat metabolism is associated with telomere length in six population-based studies

Telomeres are repetitive DNA sequences located at the end of chromosomes, which are associated to biological aging, cardiovascular disease, cancer and mortality. Lipid and fatty acid metabolism have been associated with telomere shortening. We have conducted an in-depth study investigating the association of metabolic biomarkers with telomere length (LTL). We performed an association analysis of 226 metabolic biomarkers with LTL using data from 11 775 individuals from six independent population-based cohorts (BBMRI-NL consortium). Metabolic biomarkers include lipoprotein lipids and subclasses, fatty acids, amino acids, glycolysis measures and ketone bodies. LTL was measured by quantitative polymerase chain reaction or FlowFISH. Linear regression analysis was performed adjusting for age, sex, lipid-lowering medication and cohort-specific covariates (model 1) and additionally for body mass index (BMI) and smoking (model 2), followed by inverse variance-weighted meta-analyses (significance threshold Pmeta = 6.5 × 10-4). We identified four metabolic biomarkers positively associated with LTL, including two cholesterol to lipid ratios in small VLDL (S-VLDL-C % and S-VLDL-CE %) and two omega-6 fatty acid ratios (FAw6/FA and LA/FA). After additionally adjusting for BMI and smoking, these metabolic biomarkers remained associated with LTL with similar effect estimates. In addition, cholesterol esters in very small VLDL (XS-VLDL-CE) became significantly associated with LTL (P = 3.6 × 10-4). We replicated the association of FAw6/FA with LTL in an independent dataset of 7845 individuals (P = 1.9 × 10-4). To conclude, we identified multiple metabolic biomarkers involved in lipid and fatty acid metabolism that may be involved in LTL biology. Longitudinal studies are needed to exclude reversed causation