Analyses bactériologiques et cellulaires des échantillons de lait chez des chèvres après sélection divergente sur la résistance aux mammites

La concentration des cellules somatiques (CCS) est un critère très utilisé pour évaluer le statut infectieux de la mamelle chez la chèvre. Grace à l’analyse en cytométrie en flux, celle-ci a été décomposée en concentrations de neutrophiles (vivants et morts), lymphocytes, macrophages dans le but d’étudier la réponse inflammatoire locale chez deux lignées de chèvres génétiquement divergentes sur le critère de la CCS. L’objectif de cette étude était de décrire l’évolution au cours de la lactation de la CCS en fonction du statut bactériologique. Les infections mammaires chez les chèvres de la lignée résistante sont moins fréquentes et avec des titres bactériens plus faibles d’après les données acquises par les méthodes conventionnelle et moléculaire. De plus, leurs réponses inflammatoire et immunitaire locales semblent plus efficaces lors d’infection

Posterior condylar offset changes and its effect on clinical outcomes after posterior-substituting, fixed-bearing total knee arthroplasty: anterior versus posterior referencing

Background We sought to determine whether there was a difference in the posterior condylar offset (PCO), posterior condylar offset ratio (PCOR) and clinical outcomes following total knee arthroplasty (TKA) with anterior referencing (AR) or posterior referencing (PR) systems. We also assessed whether the PCO and PCOR changes, as well as patient factors were related to range of motion (ROM) in each referencing system. Methods This retrospective study included 130 consecutive patients (184 knees) with osteoarthritis who underwent primary posterior cruciate ligament (PCL)-substituting fixed-bearing TKA. The difference between preoperative and postoperative PCO and PCOR values were calculated. Clinical outcomes including ROM and Western Ontario and McMaster University (WOMAC) scores were evaluated. Furthermore, multiple linear regression analysis was performed to determine the factors related to postoperative ROM in each referencing system. Results The postoperative PCO was greater in the AR group (28.4 mm) than in the PR group (27.4 mm), whereas the PCO was more consistently preserved in the PR group. The mean postoperative ROM after TKA was greater in the AR group (129°) than in the PR group (122°), whereas improvement in WOMAC score did not differ between the two groups. Preoperative ROM was the only factor related to postoperative ROM in both groups. Conclusions There was no difference in postoperative PCO in AR and PR group and the PCO was not associated with postoperative ROM. PCO was more consistently preserved after surgery in the PR group. The postoperative PCO and PCOR changes did not affect the postoperative ROM. Furthermore, similar clinical outcomes were achieved in the AR and PR groups. Trial registration Retrospectively registered (Trial registration number: 06-2010-110).This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2017M3A9D8063538)

Sociodemographic and Smoking Behavioral Predictors Associated with Smoking Cessation According to Follow-up Periods: A Randomized, Double-blind, Placebo-controlled Trial of Transdermal Nicotine Patches

This study investigated sociodemographic and smoking behavioral factors associated with smoking cessation according to follow-up periods. In this randomized, double-blind, placebo-controlled trial of transdermal nicotine patches, subjects were a total of 118 adult male smokers, who were followed up for 12 months. Univariable logistic regression analysis and stepwise multiple logistic regression analyses were performed to identify the predictors of smoking cessation. The overall self-reported point prevalence rates of abstinence were 20% (24/118) at 12 months follow-up, and there was no significant difference in abstinence rates between placebo and nicotine patch groups. In the univariable logistic regression analysis, predictors of successful smoking cessation were the low consumption of cigarettes per day and the low Fagerstrom Test for Nicotine Dependence (FTND) scores (p<0.05) at 3, 6, and 12 months follow-up. In the stepwise multiple logistic regression analyses, predictors of successful smoking cessation, which were different according to the follow-up periods, were found to be the low consumption of cigarettes per day at the short-term and midterm follow-up (≤6 months), older age, and the low consumption of cigarettes per day at the long-term follow-up (12 months)

Roles of Exosome-Like Vesicles Released from Inflammatory C2C12 Myotubes: Regulation of Myocyte Differentiation and Myokine Expression

Background/Aims: The complicated differentiation processes of cells in skeletal muscle against inflammation that induce muscle atrophy are not fully elucidated. Given that skeletal muscle is a secretory organ, we evaluated the effects of inflammation on myogenic signals and myokine expression, and the roles of inflammatory exosomes released by myotubes in myogenic differentiation. Methods: Inflammation was induced by treatment of fully differentiated C2C12 myotubes with a cytokine mixture of TNF-α and INF-γ. Exosome-like vesicles (ELVs) were isolated from conditioned media of control or inflamed myotubes and incubated with myoblasts. The expression of molecular switches that contribute to myogenic differentiation, including several kinases, their downstream targets, and myokines, were evaluated using immunoblot analysis in inflamed myotubes and in myoblasts treated with ELVs. Results: Inflammation activated molecular mechanisms contributing to muscle atrophy, including AMPK, p-38 MAPK and JNK, while inhibiting Akt-mediated myogenic signals. In addition, inflammation induced myostatin expression with suppression of a myostatin-counteracting myokine, decorin. Well-characterized ELVs released from inflamed myotubes induced myoblast inflammation and inhibited myogenic mechanisms while stimulating atrophic signals. Conclusion: Inflammation of skeletal muscle induces muscle atrophy via multiple mechanisms, including the regulation of myokines and kinases. Inflammatory ELVs are likely to contribute to inflammation-induced muscle atrophy

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Enrichment of Exosome-Like Extracellular Vesicles from Plasma Suitable for Clinical Vesicular miRNA Biomarker Research

Exosome-like extracellular vesicles (ELVs) contain biomolecules that have potential as diagnostic biomarkers, such as proteins, micro-RNAs (miRNAs), and lipids. However, it is difficult to enrich ELVs consistently with high yield and purity from clinical samples, which hampers the development of ELV biomarkers. This is particularly true for miRNAs in protein-rich plasma. Hence, we modified ELV isolation protocols of three commercially available polymer-precipitation-based kits using proteinase K (PK) treatment to quantify ELV-associated miRNAs in human plasma. We compared the yield, purity, and characteristics of enriched plasma ELVs, and measured the relative quantity of three selected miRNAs (miR-30c, miR-126, and miR-192) in ELVs using six human plasma samples. Compared with the original protocols, we demonstrated that ELVs can be isolated with PK treatment with high purity (i.e., lack of non-exosomal proteins and homogeneous size of vesicles) and yield (i.e., abundancy of exosomal markers), which were dependent on kits. Using the kit with the highest purity and yield with PK treatment, we successfully quantified ELV miRNAs (levels of 45%–65% in total plasma) with acceptable variability. Collectively, ELV enrichment using the modified easy-to-use method appears suitable for the analysis of miRNAs, although its clinical applicability needs to be confirmed in larger clinical studies

TRANSFORMATION OF 2D PLANES INTO 3D SOFT STRUCTURES WITH ELECTRICAL FUNCTIONS

3-dimensional (3D) structures composed of flexible and soft materials have been in demand for bio-integrated devices. However, the fabrication of 3D structures using micro electro mechanical systems (MEMS) techniques has limitations in terms of commonly used inorganic materials and the microscale of resulted structures. Here, we developed a novel technique to selectively bond polydimethylsiloxane (PDMS) and parylene C by plasma treatment, with which 2D structures fabricated using conventional MEMS techniques are transformed into 3D structures by the inflation of selectively non-bonded patterns. We demonstrated various soft and flexible 3D devices with embedded electrical functions for biomedical applications. © 2021 IEEE