Transcatheter aortic valve implantation (TAVI) is often undertaken in the oldest frailest cohort of patients undergoing cardiac interventions. We plan to investigate the potential benefit of cardiac rehabilitation (CR) in this vulnerable population.

Cerebral palsy (CP) is the most frequent movement disorder of childhood affecting 1 in 500 live births in developed countries. We previously identified likely pathogenic de novo or inherited single nucleotide variants (SNV) in 14% (14/98) of trios by exome sequencing and a further 5% (9/182) from evidence of outlier gene expression using RNA sequencing. Here, we detected copy number variants (CNV) from exomes of 186 unrelated individuals with CP (including our original 98 trios) using the CoNIFER algorithm. CNV were validated with Illumina 850 K SNP arrays and compared with RNA-Seq outlier gene expression analysis from lymphoblastoid cell lines (LCL). Gene expression was highly correlated with gene dosage effect. We resolved an additional 3.7% (7/186) of this cohort with pathogenic or likely pathogenic CNV while a further 7.7% (14/186) had CNV of uncertain significance. We identified recurrent genomic rearrangements previously associated with CP due to 2p25.3 deletion, 22q11.2 deletions and duplications and Xp monosomy. We also discovered a deletion of a single gene, PDCD6IP, and performed additional zebrafish model studies to support its single allele loss in CP aetiology. Combined SNV and CNV analysis revealed pathogenic and likely pathogenic variants in 22.7% of unselected individuals with CP.

EXamining everolimus In a Study of Tuberous sclerosis 3 (EXIST-3) demonstrated significantly reduced seizure frequency (SF) with everolimus vs placebo. In this study, we evaluate the long-term efficacy and safety of everolimus for tuberous sclerosis complex (TSC)-associated treatment-refractory seizures.

To establish a robust workflow for combined mass spectrometry-based analysis of metabolites and proteins in tear fluid with regard to clinical applicability.

To evaluate retinal toxicity of ziv-aflibercept, a drug that had been approved for use for patients with colon cancer.

Pineapple is one of the most economically important tropical or subtropical fruit trees. However, few studies focus on the development of its unique collective fruit. In this study, we generated a genome-wide developmental transcriptomic profile of 14 different tissues of the collective fruit of the pineapple covering each of the three major fruit developmental stages. In total, 273 tissue-specific and 1,051 constitutively expressed genes were detected. We also performed gene co-expression analysis and 18 gene modules were classified. Among these, we found three interesting gene modules; one was preferentially expressed in bracts and sepals and was likely involved in plant defense; one was highly expressed at the beginning of fruit expansion and faded afterward and was probably involved in endocytosis; Another gene module increased expression level with pineapple fruit development and was involved in terpenoid and polyketide metabolism. In addition, we built a pineapple electronic fluorescent pictograph (eFP) browser to facilitate exploration of gene expression during pineapple fruit development. With this tool, users can visualize expression data in this study in an intuitive way. Together, the transcriptome profile generated in this work and the corresponding eFP browser will facilitate further study of fruit development in pineapple.

We explored the genetic background of social interactions in two breeding metapopulations of the pied flycatcher (Ficedula hypoleuca) in Western Siberia. In 2005, we sampled blood from birds breeding in study areas located in the city of Tomsk and in a natural forest 13 km southward of Tomsk (Western Siberia, Russia). We sampled 30 males, 46 females, 268 nestlings (46 nests) in the urban settlement of pied flycatcher, and 232 males, 250 females, 1,485 nestlings (250 nests) in the woodland plot. DNA fingerprinting was carried out using eight microsatellite loci, which were amplified by two multiplex-PCRs and analyzed by capillary electrophoresis. About 50-58% of all couples were socially and genetically monogamous in both study plots. However, almost all possible social and genetic interactions were detected for non-monogamous couples: polygamy, polyandry, helping, adoption, and egg dumping. Differences in the rate of polygyny and the rate of extra-pair paternity between both study sites could be explained by differences in environmental heterogeneity and breeding density. Our findings suggest that egg dumping, adoption, polygamy, extra pair copulation, and other types of social-genetic interactions are modifications of the monogamous social system caused by patchy environment, breeding density, and birds' breeding status.

Mesenchymal stem/stromal cells (MSCs) are a promising tool for cell-based therapies in the treatment of tissue injury. The stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis plays a significant role in directing MSC homing to sites of injury. However in vivo MSC distribution following intravenous transplantation remains poorly understood, potentially hampering the precise prediction and evaluation of therapeutic efficacy.

Introduction: To examined survival outcome by histological subtypes in de novo stage IV epithelial ovarian cancer (EOC). Methods: Between 2004 and 2015, patients with stage IV EOC were included using the Surveillance, Epidemiology, and End Results program. The effects of histological subtypes on overall survival (OS) were assessed using Kaplan-Meier and multivariable Cox regression analyses. Results: We identified 5,953 patients including 5,351 (89.9%), 249 (4.2%), 145 (2.4%), and 208 (3.4%) patients with high-grade serous, endometrioid, mucinous, and clear cell subtypes, respectively. The 5-year OS rates were 28.1, 38.6, 14.2, and 18.8% in patients with high-grade serous, endometrioid, mucinous, and 18.8% clear cell subtypes, respectively, (p < 0.001). Multivariate analyses indicated that histological subtype was an independent predictor of OS. Using the high-grade serous subtype as a reference, OS was comparable for the endometrioid subtype (hazard ratio (HR) 0.915, 95% confidence interval) (CI 0.772-1.085, p = 0.305), but significantly lower for mucinous (HR 3.292, 95% CI 2.701-4.011, p < 0.001) and clear cell subtypes (HR 1.820, 95% CI 1.546-2.141, p < 0.001). Patients with no residual tumor had better OS in the high-grade serous and endometrioid subtypes compared to patients with residual tumors. However, the residual tumor size was not a prognostic factor for OS in mucinous and clear cell carcinoma. Conclusions: Our study suggest a markedly mortality rate in patients with stage IV mucinous and clear cell carcinoma, but better survival in patients with high-grade serous and endometrioid subtypes. Aggressive radical surgery to leave no residual disease would improve survival for high-grade serous and endometrioid carcinoma. More studies are needed to assess the value of aggressive radical surgery in patients with mucinous and clear cell subtypes.

Osteoarticular brucellosis is the most common localization of human active disease. Osteoblasts are specialized mesenchymal-derived cells involved in bone formation and are considered as professional mineralizing cells. Autophagy has been involved in osteoblast metabolism. The present study demonstrates that Brucella abortus infection induces the activation of the autophagic pathway in osteoblast cells. Autophagy was revealed by upregulation of LC3II/LC3I ratio and Beclin-1 expression as well as inhibition of p62 expression in infected cells. Induction of autophagy was also corroborated by using the pharmacological inhibitors wortmannin, a PI 3-kinase inhibitor, and leupeptin plus E64 (inhibitors of lysosomal proteases). Autophagy induction create a microenvironment that modifies osteoblast metabolism by the inhibition of the deposition of organic and mineral matrix, the induction of matrix metalloproteinase (MMP)-2, osteopontin, and RANKL secretion leading to bone loss. Accordingly, autophagy is also involved in the down-modulation of the master transcription factor in bone formation osterix during B. abortus infection. Taking together our results indicate that B. abortus induces the activation of autophagy pathway in osteoblast cells and this activation is involved in the modulation of osteoblast function and bone formation.

The efficacy of Vernonia amygdalina against chemical toxicity has attracted attention. The aim of this study was to evaluate the protective potentials of Vernonia amygdalina methanol extract (BLME) against petroleum toxicity. Thirty six male albino rats (Rattus norvegicus) were redistributed randomly into six groups of six rats each and fed with growers feed for a period of 30 days according to the following description: Group A = Feed; Group B = Feed + 100 mg kg-1 body weight of BLME; Group C = Feed + 200 mg kg-1 body weight of BLME; Group D = Feed (100 g Feed + 4 mL crude petroleum); Group E = Feed (100 g Feed + 4 mL crude petroleum) + 100 mg kg-1 body weight of BLME; Group F = Feed (100 g Feed + 4 mL crude petroleum) + 200 mg kg-1 body weight of BLME. Animals were sacrificed at the end of the experimental period and the serum and kidney were harvested for biochemical and histological analysis following standard procedures. The data generated were subjected to analysis of variance (ANOVA). The study revealed that crude petroleum stimulated alterations in kidney dysfunction makers: urea, creatinine and serum electrolytes which were significantly (P < 0.05) ameliorated by BLME administration relative to control. Oxidative stress markers, lipid peroxidation and enzymatic and non-enzymatic antioxidant profiles (MDA levels, GSH, Vitamin C. FRAP, CAT, SOD, GPx, GSTs) as well as oxidase enzymes (AO, SO, MO and XO) induced changes by crude petroleum were positively modulated by BLME administration. The study concluded that crude petroleum contaminated diets are injurious to animal health and BLME is able to prevent the renal dysfunction induced by crude petroleum contaminated diets.

The aims of this study were to evaluate the activity of Lactococcus garvieae of dairy origin against pathogenic bacteria during cheese manufacture and its suitability and safety as a probiotic on Nile tilapia (Oreochromis niloticus). For these purposes, Lactococcus garvieae isolated from raw cow milk was tested to control the growth of Staphylococcus aureus in artificially contaminated cheese during storage under refrigeration. Also a feeding experiment was conducted on 120 Oreochromis niloticus using a diet containing Lactococcus garvieae as a probiotic bacteria against pathogenic S. aureus. The findings of this study showed that Lactococcus garvieae of dairy origin produced inhibitory substances against pathogenic microorganisms. The selected strain had a good inhibitory activity against Staphylococcus aureus in artificially contaminated cheese during refrigerated storage. Concerning fish experiment, it showed no evidence of disease in fish that were fed a diet containing Lactococcus garvieae, and showed a higher survival rate than others. Further investigations for purification of the produced inhibitory substance and confirming that is a bacteriocin-like substance are needed. Nonetheless, it is the first report of using L. garvieae of dairy origin as a probiotic for controlling the pathogenic Staphylococcus aureus in Oreochromis niloticus.

Parasitism is of great concern to the production, reproduction and performance of man and animals. The present study evaluated the parasitic conditions of rabbits brought for medical attention in the major Veterinary hospitals in Osun State, Southwestern Nigeria during ten years (2006-2015). A total of 444 rabbits were brought during the study period, out of which 312 (70.27%) was diagnosed for mange, 126 (28.38%) for helminthoses, 60 (13.51%) for coccidiosis and 6 (1.35%) for flea infestation. There was no defined pattern in the yearly and monthly prevalence of these parasitic diseases. Age, sex and season were the statistically significant (P < 0.05) risk factors associated with the prevalence of helminthoses, while age and season were associated with mange at P < 0.05. There was a significant negative correlation in the co-infection of helminthoses and coccidiosis, helminthoses and mange, coccidiosis and mange, while the co-infection of helminthoses with flea infestation, coccidiosis with flea infestation and mange with flea infestation was not statistically significant. These findings could be useful for surveillance, monitoring and designing of appropriate interventions for diseases control in Osun State and Nigeria at large. The proper management, prevention, control and eradication of these disease conditions will improve the production and reproduction of rabbits for better profitability for farmers and increased availability of protein sources for consumers.

The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials.

To investigate the characteristics of atherosclerotic plaques in stroke-related vascular beds and their relationship with stroke using three-dimensional magnetic resonance (MR) vessel wall imaging.

Timely recognition and referral of patients with spondyloarthritis (SpA) is challenging due to the frequent unawareness of the clinical picture.

Dihydrofolate reductase (DHFR) catalyzes the stereospecific reduction of 7,8-dihydrofolate (FH2) to (6s)-5,6,7,8-tetrahydrofolate (FH4) via hydride transfer from NADPH. The consensus Escherichia coli DHFR mechanism involves conformational changes between closed and occluded states occurring during the rate-limiting product release step. Although the Protein Data Bank (PDB) contains over 250 DHFR structures, the FH4 complex structure responsible for rate-limiting product release is unknown. We report to our knowledge the first crystal structure of an E. coli. DHFR:FH4 complex at 1.03 Å resolution showing distinct stabilizing interactions absent in FH2 or related (6R)-5,10-dideaza-FH4 complexes. We discover the time course of decay of the co-purified endogenous FH4 during crystal growth, with conversion from FH4 to FH2 occurring in 2-3 days. We also determine another occluded complex structure of E. coli DHFR with a slow-onset nanomolar inhibitor that contrasts with the methotrexate complex, suggesting a plausible strategy for designing DHFR antibiotics by targeting FH4 product conformations.

Reactive locomotor adaptations are crucial for safe mobility, but remain relatively unexplored. Here we assess reactive gait adaptations, and their retention, savings and interlimb transfer. Using new methods to normalise walking speed and perturbation magnitude, we expose eighteen healthy adults to ten unexpected treadmill belt accelerations during walking (the first and last perturbing the right leg, the others perturbing the left leg) on two days, one month apart. Analysis of the margins of stability using kinematic data reveals that humans reactively adapt gait, improving stability and taking fewer recovery steps, and fully retain these adaptations over time. On re-exposure, retention and savings lead to further improvements in stability. Currently, the role of interlimb transfer is unclear. Our findings show that humans utilise retention and savings in reactive gait adaptations to benefit stability, but that interlimb transfer may not be exclusively responsible for improvements following perturbations to the untrained limb.

This study investigated the effects of xylanase supplementations with cereal-based diets on nutrient digestibility and gut microbiota of growing pigs. A total of 96 individually penned pigs (initial BW = 22.7 ± 0.65 kg) were allotted to 12 treatments and subjected to a completely randomized block design experiment. Pigs in each treatment were fed an isocaloric wheat-based or corn-based diet with or without 1 of 5 types of xylanase supplements (XA, XB, XC, XD, XE). On d 42, all piglets were euthanized to obtain ileal and cecal digesta for microbial analysis, which involved high-throughput sequencing of the V1 - V3 regions of 16S rRNA gene. Corn- and wheat-based diets differed (P < 0.05) in digestion characteristics. Dietary treatments affected the alpha- and beta-diversities of microbiota in the cecum but not in the ileum. The wheat-based diet increased (P < 0.05) alpha-diversity and clustered separately (P < 0.05) compared with the corn-based diet. Wheat-based diet also promoted the relative abundance of genus (g.) Succinivibrio while corn-based diet promoted the proportion of family (f.) Veillonellaceae in the community. Among xylanases, only XC within the wheat-based diet altered (P < 0.05) the beta-diversity of the cecal microbiota compared with control. For each cereal-based diet and compared with the controls, xylanase treatments affected (P < 0.05) the proportions of 5 bacterial taxa in the ileum (f. Peptostreptococcaceae, order [o.] Streptophyta, f. Clostridiaceae, g. Clostridium and g. Streptococcus) and 8 in the cecum (g. Lactobacillus, g. Streptococcus, class [c.] Clostridia, f. Clostridiaceae, g. Megasphaera, g. Prevotella, g. Roseburia and f. Ruminococcaceae). Network analysis showed that across diets under control treatments, Bacteroidetes was the most influential phylum promoting cooperative relationships among members of the ileum and cecum microbiota. Xylanase treatment, however, reduced the influence of Bacteroidetes and promoted a large number of hub taxa majority of which belonged to the Firmicutes phylum. To maximize the efficiency of xylanase supplementation, our data suggest that xylanase C originated from Bacillus subtilis was more effective when applied to wheat-based diets, while xylanase A originated from Fusarium verticillioides was more beneficial when applied to corn-based diets.

Corn distillers dried grains with solubles (DDGS) is a co-product of the fuel ethanol industry that is an excellent source of energy, digestible amino acids, and digestible phosphorus. However, the antioxidant capacity and phytochemical content of DDGS and how it is influenced by production parameters is unknown. Therefore, 16 DDGS samples obtained from different ethanol production plants in the U.S. were characterized for antioxidant capacity, vitamin E, xanthophylls, and ferulic acid content and compared with corn. The antioxidant capacity of DDGS samples, measured using the 2,2-diphenyl-l-picrylhydrazyl (DPPH) assay, varied almost 2 folds among samples, but in all cases was more than 3 times that of corn. All DDGS samples had a considerably greater concentration of tocopherols and tocotrienols (lipid-soluble antioxidants) than corn. However, the relative concentrations among the tocopherols and tocotrienols tended to be similar to corn. The xanthophyll lutein was present in all DDGS samples and in all cases exceeded the content in corn. Zeaxanthin was detected in most samples. The total ferulic acid content of the DDGS samples was almost 3-fold greater than corn, but, as in corn, almost all was present in a bound form. However, the concentration of unbound (free) ferulic acid was more than 3 times the concentration found in the corn sample. Thus, DDGS is a rich source of phytochemical compounds and may provide antioxidant and health benefits beyond its macronutrient composition. However, differences in processing can greatly influence the phytochemical content and quality of DDGS. In particular, thermal abuse due to excessive heat used in drying may lead to lipid oxidation products that may have deleterious effects when incorporated into feeds.