A Flexible, Pooled CRISPR Library for Drug Development Screens.

Functional genomic screening with CRISPR has provided a powerful and precise new way to interrogate the phenotypic consequences of gene manipulation in high-throughput, unbiased analyses. However, some experimental paradigms prove especially challenging and require carefully and appropriately adapted screening approaches. In particular, negative selection (or sensitivity) screening, often the most experimentally desirable modality of screening, has remained a challenge in drug discovery.

Modeling of Bile Acid Processing by the Human Fecal Microbiota.

Bile acids, the products of concerted host and gut bacterial metabolism, have important signaling functions within the mammalian metabolic system and a key role in digestion. Given the complexity of the mega-variate bacterial community residing in the gastrointestinal tract, studying associations between individual bacterial genera and bile acid processing remains a challenge. Here, we present a novel approach to determine the bacterial genera associated with the metabolism of different primary bile acids and their potential to contribute to inter-individual variation in this processing.

Bikini versus traditional incision direct anterior approach: is there any difference in soft tissue damage?

Introduction: The direct anterior approach for total hip replacements has reported advantages of improved early function and muscle preservation. In an effort to improve healing and cosmesis, a change in the orientation of the incision has been proposed. Traditionally, the skin incision is in-line with the tensor fasciae latae muscle belly.

Lysophosphatidylcholines to phosphatidylcholines ratio predicts advanced knee osteoarthritis.

Objective: To identify novel biomarker(s) for predicting advanced knee OA.

Methods: Study participants were derived from the Newfoundland Osteoarthritis Study and the Tasmania Older Adult Cohort Study. All knee OA cases were patients who underwent total knee replacement (TKR) due to primary OA.

SMAD3 Is Upregulated in Human Osteoarthritic Cartilage Independent of the Promoter DNA Methylation.

Objective: To compare SMAD3 gene expression between human osteoarthritic and healthy cartilage and to examine whether expression is regulated by the promoter DNA methylation of the gene.

Methods: Human cartilage samples were collected from patients undergoing total hip/knee joint replacement surgery due to primary osteoarthritis (OA), and from patients with hip fractures as controls. DNA/RNA was extracted from the cartilage tissues.

Genome-wide DNA methylation study of hip and knee cartilage reveals embryonic organ and skeletal system morphogenesis as major pathways involved in osteoarthritis.

Background: Evidence suggests that epigenetics plays a role in osteoarthrits (OA). The aim of the study was to describe the genome wide DNA methylation changes in hip and knee OA and identify novel genes and pathways involved in OA by comparing the DNA methylome of the hip and knee osteoarthritic cartilage tissues with those of OA-free individuals.

Methods: Cartilage samples were collected from hip or knee joint replacement patients either due to primary OA or hip fractures as controls.

Overexpression of MMP13 in human osteoarthritic cartilage is associated with the SMAD-independent TGF-β signalling pathway.

Introduction: In vitro and animal model of osteoarthritis (OA) studies suggest that TGF-β signalling is involved in OA, but human data is limited. We undertook this study to elucidate the role of TGF-β signalling pathway in OA by comparing the expression levels of TGFB1 and BMP2 as ligands, SMAD3 as an intracellular mediator, and MMP13 as a targeted gene between human osteoarthritic and healthy cartilage.

Methods: Human cartilage samples were collected from patients undergoing total hip/knee joint replacement surgery due to primary OA or hip fractures as controls.

A cost analysis of single-stage bilateral versus two-stage direct anterior total hip arthroplasty.

Purpose: The potential cost savings of single-stage bilateral total hip arthroplasty (THA) are unclear, and the risks associated with it are not well defined. We sought to compare the costs and perioperative complications of single-stage bilateral THA via the direct anterior approach (DAA) to a two-stage bilateral protocol.

Methods: We retrospectively reviewed patients who underwent a single- stage bilateral DAA THA and compared them to a two-stage THA group.

Relationship between blood plasma and synovial fluid metabolite concentrations in patients with osteoarthritis.

Objective: To investigate the relationship between plasma and synovial fluid (SF) metabolite concentrations in patients with osteoarthritis (OA).

Methods: Blood plasma and SF samples were collected from patients with primary knee OA undergoing total knee arthroplasty. Metabolic profiling was performed by electrospray ionization tandem mass spectrometry using the AbsoluteIDQ kit.

Classification of osteoarthritis phenotypes by metabolomics analysis.

Objectives: To identify metabolic markers that can classify patients with osteoarthritis (OA) into subgroups.

Design: A case-only study design was utilised.

Participants: Patients were recruited from those who underwent total knee or hip replacement surgery due to primary OA between November 2011 and December 2013 in St.

SMAD3 is associated with the total burden of radiographic osteoarthritis: the Chingford study.

Background: A newly-described syndrome called Aneurysm-Osteoarthritis Syndrome (AOS) was recently reported. AOS presents with early onset osteoarthritis (OA) in multiple joints, together with aneurysms in major arteries, and is caused by rare mutations in SMAD3. Because of the similarity of AOS to idiopathic generalized OA (GOA), we hypothesized that SMAD3 is also associated with GOA and tested the hypothesis in a population-based cohort.

Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat.

Background: Probiotics are extensively used to promote gastrointestinal health, and emerging evidence suggests that their beneficial properties can extend beyond the local environment of the gut. Here, we determined whether oral probiotic administration can alter the progression of postinfarction heart failure.

Methods And Results: Rats were subjected to 6 weeks of sustained coronary artery occlusion and administered the probiotic Lactobacillus rhamnosus GR-1 or placebo in the drinking water ad libitum.

Long-term outcomes for Kienböck's disease.

Background: The precise etiology of Kienböck's disease is unclear. Controversy exists regarding the appropriate treatment modality. The present study sought to investigate and compare surgical and nonsurgical treatment outcomes of patients suffering from Kienböck's disease in the province of Newfoundland and Labrador (NL), Canada.

ReGAE 5: Can we improve the surgical journey for African-Caribbean patients undergoing glaucoma filtration surgery? Some preliminary findings.

Aim: To explore the experiences of African-Caribbean patients who had undergone filtration surgery for advanced glaucoma.

Methods: Semi-structured qualitative interviews were used to collect the data and an interview guide was developed. Participants recounted when they first became aware of a problem with their eyes and their feelings at the time.

Changes in the transcriptome of abdominal subcutaneous adipose tissue in response to short-term overfeeding in lean and obese men.

Background: Obesity is caused by the excessive accumulation of adipose tissue as a result of a chronic energy surplus. Little is known regarding the molecular mechanisms involved in the response to an energy surplus in human adipose tissue at the genomic level.

Objective: The objective was to investigate changes in the transcriptome of abdominal subcutaneous adipose tissue after a positive energy challenge induced by overfeeding in both lean and obese subjects to identify novel obesity candidate genes.

Lack of association of ghrelin precursor gene variants and percentage body fat or serum lipid profiles.

Ghrelin has been recognized for its involvement in food intake, control of energy homeostasis, and lipid metabolism. However, the roles of genetic variations in the ghrelin precursor gene (GHRL) on body compositions and serum lipids are not clear in humans. Our study investigated five single-nucleotide polymorphisms (SNPs) within GHRL to determine their relationship with body fat percentage (BF), trunk fat percentage (TF), lower body (legs) fat percentage (LF), and serum lipids in 1,464 subjects, which were recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada.

Altered calcium homeostasis is correlated with abnormalities of fasting serum glucose, insulin resistance, and beta-cell function in the Newfoundland population.

Alteration of extracellular calcium concentration may be involved in glucose metabolism in a number of pathways. The present study was designed to investigate the relationship between total serum calcium and 1) fasting serum glucose, 2) insulin, 3) insulin resistance, and 4) beta-cell function in 1,182 healthy subjects from the province of Newfoundland and Labrador, Canada. All variables were log10 transformed, and confounding factors including age, trunk fat percentage, serum phosphorus, magnesium, 25-OH vitamin D, and parathyroid hormone were adjusted before analyses.

Comparison of multifrequency bioelectrical impedance analysis with dual-energy X-ray absorptiometry for assessment of percentage body fat in a large, healthy population.

Background: Bioelectrical impedance analysis (BIA) is widely used in clinics and research to measure body composition. However, the results of BIA validation with reference methods are contradictory, and few data are available on the influence of adiposity on the measurement of body composition by BIA.

Objective: The goal was to determine the effects of sex and adiposity on the difference in percentage body fat (%BF) predicted by BIA compared with dual-energy X-ray absorptiometry (DXA).