A Systematic Review Investigating the Presence of Inflammatory Synovitis in Hip and Knee Joint Replacement Surgery.

Synovial tissue can display an inflammatory response in the presence of OA. There is increasing interest to better understand the role of inflammation in OA, particularly with regard to those who require joint replacement. A systematic review of inflammatory synovitis in OA of literature databases was undertaken from their inception until October 14, 2014. Independent critical appraisal of each study was undertaken using the CASP appraisal tool. From a total of sixty-six identified citations, twenty-three studies were deemed eligible for review. The studies presented moderate to strong methodological quality. Strong correlation was identified between histological and imaging synovitis severity. Correlation was weaker between clinical symptoms and imaging and/or histological synovitis severity. There was little consensus, with regard to expressed cytokines and chemokines at the different stages of OA disease progression. Few studies investigated the influence of inflammatory synovitis on the outcome of major joint replacement. Research into inflammatory synovitis in OA is an emerging field. Longitudinal studies applying proven imaging modalities, histological analysis, and longer follow-up are required in order to further define our understanding of the role of synovitis in the pathogenesis of OA and its effects on outcomes following major joint replacement

Efficacy of Probiotic in Improving Welfare and Mitigating Overcrowding Stress in Broilers

This study was conducted to investigate the efficacy of probiotic in improving welfare of broilers reared under low stocking density (LSD) and mitigating high stocking density (HSD) stress. A total number of 240 chicks were sub divided into four groups with three replicates for each. Two groups were reared under LSD (10 bird/m2).; 48 chicks (16 bird/ replicate) for each and another 2 groups were reared under HSD (15 bird/m2); 72 chicks (24 bird/ replicate). At each density, one group was supplemented with Protexin® and the other was not supplemented. Blood corticosterone (CS) level was measured and behavior of broilers was recorded weekly. At the end of the growing cycle, behavioral welfare fear response test (time of first attempt to stand, number of attempts to stand and tonic immobility duration) was performed and brain monoamines (serotonin, norepinephrine and dopamine) concentrations were measured. As a result, HSD stress increased the time birds spent to perform the first attempt to stand and prolonged TI duration. However, Protexin® supplementation only reduced the time of first attempt to stand at higher density without alteration of the number of attempts required to induce TI. No significant improvement in fear response in LSD birds supplied with Protexin®. Furthermore, HSD stress decreased feeding, drinking and walking duration. However, Protexin® supplementation improved feeding, drinking and walking behaviors at LSD and did not improve behaviors of birds at HSD. Moreover, HSD increased CS levels at the 4th, 5th and 6th week of the growing cycle. However, Protexin® supplementation had a decreasing effect on CS levels in the birds reared at HD at the last two weeks of the growing cycle. In addition, brain serotonin concentration was increased in birds reared at HD without Protexin® supplementation and showed no alteration in that supplemented with the probiotic at LSD and HSD. Data suggests that, Protexin® supplementation may be beneficial in improving welfare (behavior al indicator) of broilers reared at LSD and alleviate some effects of HSD stress on birds

Effects of Probiotic on Comfort and Body Care Behaviors of Broilers Reared at Different Stocking Densities

This study was conducted to investigate the effect of probiotic on comfort and body care behaviors of broilers reared at two different densities. Two hundred and forty chicks were subdivided into four groups, two groups were reared under low stocking density (LSD); 10 bird/m2 and another 2 groups were reared under high stocking density (HSD); 15 bird/m2. In each density, one group was supplemented with probiotic in the drinking water and the other was not supplemented. Normal behavior of birds was recorded throughout the growing cycle twice a week, using video camera (Sony, Japan). Then after, comfort (standing, lying and sleeping), body care (preening, dust bathing, wing/leg stretching and head scratching) and aggressive behaviors of birds were analyzed. HSD reduced comfort behavior compared to low density without probiotic group. Standing frequency was significantly increased at the 6th week of the growing cycle. In addition, interrupted lying bouts frequency was increased and the non-interrupted lying bouts (frequency and duration) were decreased significantly. Moreover, preening frequency was decreased. However, aggressive behavior was not observed in all groups. Probiotic supplementation didn’t alter comfort, aggressive and body care behaviors of broilers at both densities in comparison to low density without probiotic group. However, birds stocked at high stocking density and supplemented with probiotic showed no alterations in all behavioral patterns compared to HSD group without probiotic supplementation. Data suggested that the used probiotic in this study was unable to improve comfort and body care behaviors of broilers reared at low stocking density and failed to alleviate impacts of high density stress on these behaviors

Ethnicity, consanguinity, and genetic architecture of hypertrophic cardiomyopathy

AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by phenotypic heterogeneity that is partly explained by the diversity of genetic variants contributing to disease. Accurate interpretation of these variants constitutes a major challenge for diagnosis and implementing precision medicine, especially in understudied populations. The aim is to define the genetic architecture of HCM in North African cohorts with high consanguinity using ancestry-matched cases and controls. METHODS AND RESULTS: Prospective Egyptian patients (n = 514) and controls (n = 400) underwent clinical phenotyping and genetic testing. Rare variants in 13 validated HCM genes were classified according to standard clinical guidelines and compared with a prospective HCM cohort of majority European ancestry (n = 684). A higher prevalence of homozygous variants was observed in Egyptian patients (4.1% vs. 0.1%, P = 2 × 10-7), with variants in the minor HCM genes MYL2, MYL3, and CSRP3 more likely to present in homozygosity than the major genes, suggesting these variants are less penetrant in heterozygosity. Biallelic variants in the recessive HCM gene TRIM63 were detected in 2.1% of patients (five-fold greater than European patients), highlighting the importance of recessive inheritance in consanguineous populations. Finally, rare variants in Egyptian HCM patients were less likely to be classified as (likely) pathogenic compared with Europeans (40.8% vs. 61.6%, P = 1.6 × 10-5) due to the underrepresentation of Middle Eastern populations in current reference resources. This proportion increased to 53.3% after incorporating methods that leverage new ancestry-matched controls presented here. CONCLUSION: Studying consanguineous populations reveals novel insights with relevance to genetic testing and our understanding of the genetic architecture of HCM

Multi-scale modeling and mechanical performance characterization of stingray skeleton-inspired tessellations

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordSharks and rays have distinctive skeletons among vertebrate animals, consisting primarily of unmineralized cartilage wrapped in a surface tessellation of minute polygonal tiles called tesserae, linked by unmineralized collagenous fibers. The discrete combination of hard and soft tissues is hypothesized to enhance the mechanical performance of tessellated cartilage (which performs many of the same functional roles as bone) by providing either rigidity or flexibility, depending on the nature of the applied load. These mechanisms and the effect of tesserae ultrastructure on cartilage mechanics, however, have never been demonstrated in the actual tissue, nor in bio-accurate models. Here, we develop bio-inspired three-dimensional tesserae computer models, incorporating material properties and ultrastructural features from natural tessellated cartilage. The geometries of ultrastructural features were varied parametrically, and the effective modulus of whole tesserae was evaluated using finite element analysis (FEA) to determine the roles of ultrastructural features in mechanics. Whereas altering some structural features had no effect on the macroscopic in-plane modulus of tesserae, a three-fold increase in the contact surface area between two adjacent tesserae increased the effective modulus of tesserae by 6%. Modeled stress distributions suggest that tesseral ‘spokes’ (distinct hypermineralized features in tesserae) bear maximum stresses in the skeleton and serve to funnel stresses to particular populations of cells in tesserae, while spokes’ lamellated structure likely helps dissipate crack energy, making tesserae more damage-tolerant. Simulations of multi-tesseral arrays showed that maximum stresses in tension and compression are borne by different tissues, supporting hypotheses of multi-functional properties of tessellated cartilage. Further, tesseral array models showed that minor alterations to tesserae/joint shape and/or material properties can be used to tune the mechanical behavior of the whole tiled composite. Our models provide the first functional understanding of the distinct morphologies of spokes and of ‘stellate’ tesserae (a tesseral shape observed first over 150 years ago), while also being useful drivers for hypotheses of growth, mechanics, load management, and the prevention and ‘directing’ of cracks in tessellated cartilage, as well as other biological composites. Additionally, these results establish guidelines and design principles for bio-inspired, tunable tiled materials

MIA-Prognosis: A Deep Learning Framework to Predict Therapy Response

Predicting clinical outcome is remarkably important but challenging. Research efforts have been paid on seeking significant biomarkers associated with the therapy response or/and patient survival. However, these biomarkers are generally costly and invasive, and possibly dissatifactory for novel therapy. On the other hand, multi-modal, heterogeneous, unaligned temporal data is continuously generated in clinical practice. This paper aims at a unified deep learning approach to predict patient prognosis and therapy response, with easily accessible data, e.g., radiographics, laboratory and clinical information. Prior arts focus on modeling single data modality, or ignore the temporal changes. Importantly, the clinical time series is asynchronous in practice, i.e., recorded with irregular intervals. In this study, we formalize the prognosis modeling as a multi-modal asynchronous time series classification task, and propose a MIA-Prognosis framework with Measurement, Intervention and Assessment (MIA) information to predict therapy response, where a Simple Temporal Attention (SimTA) module is developed to process the asynchronous time series. Experiments on synthetic dataset validate the superiory of SimTA over standard RNN-based approaches. Furthermore, we experiment the proposed method on an in-house, retrospective dataset of real-world non-small cell lung cancer patients under anti-PD-1 immunotherapy. The proposed method achieves promising performance on predicting the immunotherapy response. Notably, our predictive model could further stratify low-risk and high-risk patients in terms of long-term survival.Comment: MICCAI 2020 (Early Accepted; Student Travel Award