Comparison of Direct Digital to Conventional Film-Screen Radiography in Detection of Experimentally Created Osseous Lesions of the Equine Third Metacarpal Bone

Veterinary Pathobiolog

Survey of equine veterinarians regarding primary equine back pain in the United States

Back pain is a common complaint, clinical finding and performance limiting factor in sport horses. This study sought to gather current veterinary trends in the diagnosis, treatment and management of primary equine back pain in the United States. A 22 question survey was distributed electronically to equine practitioners through AAEP and ACVSMR listservs and through closed social media groups. The survey was open from April 20, 2022 to July 5, 2022. Responses were analyzed using Microsoft excel pivot tables. Ninety-seven survey responses were obtained and analyzed. Respondents reported the clinical signs most frequently relayed to them by the owner/rider/trainer of horses diagnosed with primary back pain were behavioral issues and poor performance. Most common diagnostic tests reported were radiography of the spinous processes, thoraco-lumbar vertebral bodies, and transcutaneous ultrasound of the thoraco-lumbar region. Most common pathologies reported were impinging dorsal spinous processes, degenerative sacro-iliac joint disease, and osteoarthritis in lumbar or thoracic articular process joints. In regards to impinging spinous process (“kissing spine”) treatments, 72.2% of respondents recommended surgery only after non-surgical treatments failed, and 14.6% of respondents never recommended surgery. The majority (82%) of respondents reported some level of improvement in clinical signs of primary back pain with rehabilitation alone. To date, there has been no consensus or discussion about common abnormalities, diagnostic tests, treatments or management options for primary equine back pain in the United States. Results of this survey are a starting point showing current trends in diagnosis, treatment and management of primary equine back pain among equine practitioners in the United States showing 82% of practitioners using rehabilitation as a component of treatment

Identification of novel epithelial ovarian cancer loci in women of African ancestry.

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10-6 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2) and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of follistatin [FST]), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry

ESR1/SYNE1 Polymorphism and Invasive Epithelial Ovarian Cancer Risk: An Ovarian Cancer Association Consortium Study

We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) region in three population-based case-control studies of epithelial ovarian cancer conducted in the United States, comprising a total of 1,128 and 1,866 non-Hispanic white invasive cases and controls, respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 (95% confidence interval (CI), 1.06–1.44, p=0.006). rs2295190 is a non-synonymous coding SNP in a neighboring gene called spectrin repeat containing, nuclear envelope 1 (SYNE1) which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be downregulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 studies through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02–1.17, p=0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n=3,545; OR=1.09, 95% CI, 1.01–1.18, p=0.025), and our findings were strongest for the mucinous subtype (n=447; OR=1.32, 95% CI, 1.11–1.58, p=0.002). No association was observed for the endometrioid subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190 was not associated with risk. These data provide suggestive evidence that the rs2295190 T allele, or another allele in linkage disequilibrium with it, may be associated with increased risk of invasive ovarian cancer

Consortium analysis of 7 candidate SNPs for ovarian cancer

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5′ flanking CDKN2A, rs523349 in the 3′ UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach

Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium

We previously reported risks of ovarian carcinoma for common polymorphisms in one-carbon (1-C) transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990 and TYMS rs495139 with risk of ovarian carcinoma overall, and to utilize the large sample of assembled cases to investigate associations by histological type

Polymorphism in the IL18 Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women

Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNPs) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (p=0.002) with a <25% chance of being a false positive finding (q-value=0.240). Using a multivariate model search algorithm over eleven IL18 tagging SNPs, we found the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (OR=1.24, 95% CI: 1.06, 1.45). In a replication stage, twelve independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (OR=0.99, 95% CI: 0.94, 1.05) when data from the twelve OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial NCO data. This analysis demonstrates the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes

Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.Includes NIHR and CRUK

Use of the inertial measurement unit to assess normal and abnormal equine hoof kinematics

2013 Spring.Includes bibliographical references.Lameness is a major medical concern and results in a large economic impact for both horse owners and the equine industry. In addition, subtle to mild lameness can result in poor performance, which can result in decreased competition winnings. While the subjective lameness examination is the most common tool for lameness evaluation, its sensitivity and repeatability have been shown to be poor, especially for subtle and mild lameness. This has led to the development of objective methods to supplement the subjective lameness examination, including stationary force platform analysis, optical kinematics, and horse-based inertial sensor systems. Several of these methods have been shown to be sensitive in identifying lameness. However, stationary force platform and optical kinematics are largely confined to experimental settings, are expensive and time-consuming, and require expertise for collecting and analyzing data. Horse-based systems have become widely investigated, as the components are small, light-weight, telemetric, and can be more easily used in a clinical setting. One specific system with poll and pelvis-mounted sensors, allows for real-time identification of asymmetry, which objectively supplements the subjective lameness examination. While this inertial-sensor system has been shown to be sensitive enough to detect subtle lameness at the trot, it cannot accurately detect bilateral forelimb lameness at the trot and has not been investigated for use evaluating other gaits. As previous optical methods have shown that distal limb kinematics are altered with moderate lameness and the hoof is an ideal place to rigidly mount a small sensor, the kinematics of the hoof should also be investigated to determine if mild lameness can also be detected in this manner. Inertial measurement units (IMU) combine a three-dimensional accelerometer, three-dimensional rate gyroscope, three-dimensional magnetometer, and thermostat. By the integration of these signals, these sensors allow determination of linear and angular kinematics in a global coordinate system. IMUs have been investigated for their use in assessing equine locomotion, by attaching them to the body of a horse. However, an IMU has not been previously utilized on the hoof of the horse. As emerging IMUs are small, light-weight, and often wireless, they have appropriate characteristics to measure hoof kinematics and may be a useful method of also objectively determining abnormal hoof kinematics associated with lameness. As optical methods are currently the gold standard for assessing distal limb kinematics, we used these as a standard to which to compare both linear and angular kinematics determined by an IMU. In the first experiment, optical methods were used to validate the IMU in five clinically normal horses. Walk and trot data were collected on a single forelimb and hind-limb, as the horse was led over-ground, and three-dimensional linear and angular kinematics were compared between the two systems. In the second experiment, three grades of lameness were induced in a single forelimb in six clinically normal horses, and following the most severe lameness, peri-neural anesthesia of the medial and lateral palmar nerves was performed to alleviate the lameness. Using optical kinematics, intra- and inter-limb comparisons were made at the walk and trot at baseline, and following lameness and peri-neural anesthesia. Linear variables were assessed in the cranial-caudal and vertical directions, as well as sagittal plane orientation (Θ). Intra-limb changes to three-dimensional orientation were assessed in the lame forelimb with the IMU. In the first study, the IMU was found to produce similar, yet not identical, kinematics to the optical system. While the IMU produced highly correlated data in the sagittal plane, the linear and angular profiles in the other planes showed similar trends to the optical system. In the second set of experiments, multiple linear and angular variables of the hoof were altered following induction of lameness, using both kinematic methods. The optical and IMU systems both identified significant changes in sagittal plane (Θ) orientation with lameness. In addition, hoof kinematics were significantly altered in mild lameness at the trot and when no lameness could be visually assessed at the walk. The IMU also detected significant changes in the frontal and transverse planes of rotation following lameness. After peri-neural anesthesia, the IMU detected a significant increase in variance in Θ orientation. Overall, it was demonstrated that the IMU can be mounted on the hoof to measure both normal kinematics and detect significant orientation changes following both lameness and peri-neural anesthesia. The IMU appeared to be a sensitive device to evaluate hoof kinematics even when lameness is mild or undetectable to the human eye. While its usefulness on clinical lameness has yet to be determined, the IMU should be further investigated for its use in a non-research setting