To determine effects of bite depth for placement of an epitendinous suture on the biomechanical strength and gap formation of repaired canine tendons.
48 superficial digital flexor tendons (SDFTs) ...obtained from 24 canine cadavers.
Tendons were assigned to 3 groups (16 tendons/group). Each SDFT was transected and then repaired with a continuous epitendinous suture placed with a bite depth of 1, 2, or 3 mm for groups 1, 2, and 3, respectively. Specimens were loaded to failure. Failure mode, gap formation, yield force, peak force, and failure force were analyzed.
Yield, peak, and failure forces differed significantly between groups 1 and 3 and groups 2 and 3 but not between groups 1 and 2. Comparison of the force resisted at 1 and 3 mm of gapping revealed a significant difference between groups 1 and 3 and groups 2 and 3 but not between groups 1 and 2. Failure mode did not differ among groups; suture pull-through occurred in 43 of 48 (89.6%) specimens.
Increasing bite depth of an epitendinous suture toward the center of the tendon substance increased repair site strength and decreased the incidence of gap formation. Repair of tendon injuries in dogs by use of an epitendinous suture with bites made deep into the tendon should result in a stronger repair, which potentially would allow loading and rehabilitation to begin sooner after surgery. Suture techniques should be investigated in vivo to determine effects on tendinous healing and blood supply before clinical implementation.
Here, with the example of common copy number variation (CNV) in the TSPAN8 gene, we present an important piece of work in the field of CNV detection, that is, CNV association with complex human ...traits such as 1H NMR metabolomic phenotypes and an example of functional characterization of CNVs among human induced pluripotent stem cells (HipSci). We report TSPAN8 exon 11 (ENSE00003720745) as a pleiotropic locus associated with metabolomic regulation and show that its biology is associated with several metabolic diseases such as type 2 diabetes (T2D) and cancer. Our results further demonstrate the power of multivariate association models over univariate methods and define metabolomic signatures for variants in TSPAN8.
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•We demonstrate neuro-exocrine axis for type 2 diabetes and metabolic regulation•Human induced pluripotent stem cells was successfully applied for disease modeling•We note germline CNV deletions are reversed to somatic amplifications•We characterizedgene variants associated with obesity with greater odds ratio than FTO SNPs
Biological sciences; Genetics and physiology; Molecular biology; Endocrinology ; Cancer systems biology
Human disease phenotypes are driven primarily by alterations in protein expression and/or function. To date, relatively little is known about the variability of the human proteome in populations and ...how this relates to variability in mRNA expression and to disease loci. Here, we present the first comprehensive proteomic analysis of human induced pluripotent stem cells (iPSC), a key cell type for disease modelling, analysing 202 iPSC lines derived from 151 donors, with integrated transcriptome and genomic sequence data from the same lines. We characterised the major genetic and non-genetic determinants of proteome variation across iPSC lines and assessed key regulatory mechanisms affecting variation in protein abundance. We identified 654 protein quantitative trait loci (pQTLs) in iPSCs, including disease-linked variants in protein-coding sequences and variants with
regulatory effects. These include pQTL linked to GWAS variants that cannot be detected at the mRNA level, highlighting the utility of dissecting pQTL at peptide level resolution.
The article Niacin‑mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system, written by Khalil S. Rawji, Adam M.H. Young, Tanay Ghosh, Nathan J. ...Michaels, Reza Mirzaei, Janson Kappen, Kathleen L. Kolehmainen, Nima Alaeiilkhchi, Brian Lozinski, Manoj K. Mishra, Annie Pu, Weiwen Tang, Salma Zein, Deepak K. Kaushik, Michael B. Keough, Jason R. Plemel, Fiona Calvert, Andrew J. Knights, Daniel J. Gaffney, Wolfram Tetzlaff, Robin J. M. Franklin and V. Wee Yong, was originally published electronically on the publisher’s internet.
For some individuals with autism spectrum disorder, driving apprehension may interfere with the acquisition and application of driving privileges. The Driving Attitude Scale Parent-Report provides an ...indication of novice drivers’ positive and negative attitudes toward driving. Responses were compared for parents of 66 autism spectrum disorder and 166 neuro-typical novice drivers. After the autism spectrum disorder drivers completed 3 months of driver training, 60 parents repeated the Driving Attitude Scale Parent-Report. Parents reported autism spectrum disorder drivers to have less positive and more negative attitudes toward driving than parents of neuro-typical drivers. Parents of autism spectrum disorder drivers who received driving training in a safe/low-threat virtual reality driving simulator demonstrated a significant increase in positive attitudes and reduction in negative attitudes, compared to parents of autism spectrum disorder drivers undergoing routine driver training. The reports of parents of autism spectrum disorder drivers suggest potential problems with learning to drive that can go beyond general abilities and include driving apprehension.
Recent work has suggested that there are many more selectively constrained, functional noncoding than coding sites in mammalian genomes. However, little is known about how selective constraint varies ...amongst different classes of noncoding DNA. We estimated the magnitude of selective constraint on a large dataset of mouse-rat gene orthologs and their surrounding noncoding DNA. Our analysis indicates that there are more than three times as many selectively constrained, nonrepetitive sites within noncoding DNA as in coding DNA in murids. The majority of these constrained noncoding sites appear to be located within intergenic regions, at distances greater than 5 kilobases from known genes. Our study also shows that in murids, intron length and mean intronic selective constraint are negatively correlated with intron ordinal number. Our results therefore suggest that functional intronic sites tend to accumulate toward the 5' end of murid genes. Our analysis also reveals that mean number of selectively constrained noncoding sites varies substantially with the function of the adjacent gene. We find that, among others, developmental and neuronal genes are associated with the greatest numbers of putatively functional noncoding sites compared with genes involved in electron transport and a variety of metabolic processes. Combining our estimates of the total number of constrained coding and noncoding bases we calculate that over twice as many deleterious mutations have occurred in intergenic regions as in known genic sequence and that the total genomic deleterious point mutation rate is 0.91 per diploid genome, per generation. This estimated rate is over twice as large as a previous estimate in murids.
ObjectiveWe examined whether measures of vitamin D were associated with transitioning to systemic lupus erythematosus (SLE) in individuals at risk for SLE.Methods436 individuals who reported having a ...relative with SLE but who did not have SLE themselves were evaluated at baseline and again an average of 6.3 (±3.9) years later. Fifty-six individuals transitioned to SLE (≥4 cumulative American College of Rheumatology criteria). 25-Hydroxyvitamin D (25OHD) levels were measured by ELISA. Six single-nucleotide polymorphisms in four vitamin D genes were genotyped. Generalised estimating equations, adjusting for correlation within families, were used to test associations between the vitamin D variables and the outcome of transitioning to SLE.ResultsMean baseline 25OHD levels (p=0.42) and vitamin D supplementation (p=0.65) were not different between those who did and did not transition to SLE. Vitamin D deficiency (25OHD <20 ng/mL) was greater in those who transitioned compared with those who did not transition to SLE (46% vs 33%, p=0.05). The association between 25OHD and SLE was modified by CYP24A1 rs4809959, where for each additional minor allele increased 25OHD was associated with decreased SLE risk: zero minor alleles (adjusted OR: 1.03, CI 0.98 to 1.09), one minor allele (adjusted OR: 1.01, CI 0.97 to 1.05) and two minor alleles (adjusted OR: 0.91, CI 0.84 to 0.98). Similarly, vitamin D deficiency significantly increased the risk of transitioning to SLE in those with two minor alleles at rs4809959 (adjusted OR: 4.90, CI 1.33 to 18.04).ConclusionsVitamin D status and CYP24A1 may have a combined role in the transition to SLE in individuals at increased genetic risk for SLE.
Both the Institute of Medicine and the Agency for Healthcare Research and Quality suggest patient safety can be enhanced by implementing aviation Crew Resource Management (CRM) in health care. CRM ...emphasizes six key areas: managing fatigue, creating and managing teams, recognizing adverse situations (red flags), cross-checking and communication, decision making, and performance feedback. This study evaluates participant reactions and attitudes to CRM training.
From April 22, 2003, to December 11, 2003, clinical teams from the trauma unit, emergency department, operative services, cardiac catheterization laboratory, and administration underwent an 8-hour training course. Participants completed an 11-question End-of-Course Critique (ECC), designed to assess the perceived need for training and usefulness of CRM skill sets. The Human Factors Attitude Survey contains 23 items and is administered on the same day both pre- and posttraining. It measures attitudinal shifts toward the six training modules and CRM.
Of the 489 participants undergoing CRM training during the study period, 463 (95%) completed the ECC and 338 (69%) completed the Human Factors Attitude Survey. The demographics of the group included 288 (59%) nurses and technicians, 104 (21%) physicians, and 97 (20%) administrative personnel. Responses to the ECC were very positive for all questions, and 95% of respondents agreed or strongly agreed CRM training would reduce errors in their practice. Responses to the Human Factors Attitude Survey indicated that the training had a positive impact on 20 of the 23 items (p < 0.01).
CRM training improves attitudes toward fatigue management, team building, communication, recognizing adverse events, team decision making, and performance feedback. Participants agreed that CRM training will reduce errors and improve patient safety.
Selection against deleterious mutations imposes a mutation load on populations because individuals die or fail to reproduce. In vertebrates, estimates of genomic rates of deleterious mutations in ...protein-coding genes imply the existence of a substantial mutation load, but many functionally important regions of the genome are thought to reside in noncoding DNA, and the contribution of noncoding DNA to the mutation load has been unresolved. Here, we infer the frequency of deleterious mutations in noncoding DNA of rodents by comparing rates of substitution at noncoding nucleotides with rates of substitution at the fastest evolving intronic sites of adjacent genes sampled from the whole genome sequences of mouse and rat. We show that the major elements of selectively constrained noncoding DNA are within 2,500 bp upstream and downstream of coding sequences and in first introns. Our estimate of the genomic deleterious point mutation rate for noncoding DNA (0.22 per diploid per generation) is similar to that for coding DNA. Mammalian populations therefore experience a substantial genetic load associated with selection against deleterious mutations in noncoding DNA. Deleterious mutations in noncoding DNA have predominantly quantitative effects and could be an important source of the burden of complex genetic disease variation in human populations.
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