Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk

Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P < 5.0 × 10 (−) (7)). One of the most significant signals (P(all histologies )=( )1.01 × 10 (−) (13);P(serous )=( )3.54 × 10 (−) (14)) occurred at 3q25.31 for rs62273959, a missense variant mapping to the LEKR1 gene that is in LD (r(2 )=( )0.90) with a previously identified ‘best hit’ (rs7651446) mapping to an intron of TIPARP. Suggestive associations (5.0 × 10 (−) (5 )>( )P≥5.0 ×10 (−) (7)) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (P(AML )=( )3.23 × 10 (−) (5); P(SKAT-o )=( )9.23 × 10 (−) (4)) and KRT13 (P(AML )=( )1.67 × 10 (−) (4); P(SKAT-o )=( )1.07 × 10 (−) (5)), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed to further unravel the unexplained heritability and biology of this disease

condylar chamfer cuts in total knee arthroplasty

Orthopedic surgeons remove more bone from the posteromedial femoral condyle than the posterolateral condyle to achieve the desired femoral component rotation. Here, the correlation between the asymmetry of chamfer cuts and femoral component rotation in total knee arthroplasty was determined.A model was built to simulate anterior chamfer cuts performed during total knee arthroplasty to measure posterior condylar offset. Right knee axial magnetic resonance imaging slices were examined from 280 consecutive patients (142 men, 138 women; mean age 31.4 +/- A 6.6 years). The anatomic and surgical transepicondylar axes, as well as the posterior condylar joint line, were drawn. Differences in the posteromedial and posterolateral offsets and the femoral rotation angles relative to the posterior joint line were measured.The mean surgical femoral rotation angle was 4.8A degrees A A +/- A 1.2A degrees, and the mean posterior condylar offset difference was 4.4 +/- A 1 mm, with a strong correlation (p < 0.0001; r = 0.803). There was no statistically significant difference between genders. Linear regression analyses revealed that a 0.8-mm difference between the anteroposterior dimensions of the medial and lateral posterior condylar offsets corresponded to 1A degrees of femoral external rotation (p < 0.0001, R (2) = 0.645).The accuracy of the applied technique intra-operatively can be verified by correlating the asymmetry of posterior chamfer cuts with the achieved femoral component rotation, as determined by measuring the thicknesses of posterior chamfer cuts with a caliper. Technical errors can also be minimized by confirming the association between the femoral component rotation-as predicted by the posterior condylar offset difference-and the preoperatively measured femoral rotation angle

Strain Ratio Measurements of Patellar and Achilles Tendons With Different Reference Regions in Healthy Volunteers.

Strain ratio measurements of tendons vary because of the reference tissue selection. The main purpose of this study is to highlight, in detail, the numeric variability attributable to the use of various reference materials on strain ratio measurements of patellar and Achilles tendons. Measurements were performed at the proximal, middle and distal thirds of the patellar and Achilles tendons on the dominant site of healthy volunteers. A total of 3 references were used: the Hoffa's fat pad for the patellar tendon, the Kager's fat pad for the Achilles tendon, subcutaneous tissue and Aquaflex gel pads (Parker Laboratories, Fairfield, NJ, USA) for both tendons. Although the same methods were used by the same physician for each tendon site on repeated measurements, strain ratio values had numeric variability with various reference materials in each measurement. Therefore, comparison of numeric strain ratio results of various studies with various reference materials could confuse the clinical interpretations of these numeric data, and, using a reference material with standard stiffness like Aquaflex ultrasound gel pads, should be considered by verifying these results with further studies

Thickness in Children with Subclinical Hypothyroidism

Background: Subclinical hypothyroidism (SH) is defined as elevated serum thyroid-stimulating hormone (TSH) concentration associated with normal serum-free thyroxine levels. Effects of hypothyroidism on hemorheology had widely attracted the attention of researchers during the last decade. Objective: The purpose of this study is to determine alterations in hemorheological parameters and carotid intima-media thickness (CIMT) in children with SH. Methods: Fifty-three SH children and 31 healthy controls were enrolled. Erythrocyte deformability and aggregation were determined by an ektacytometer and plasma viscosity (PV) by a cone-plate rotational viscometer. CIMT was evaluated sonographically. Results: Erythrocyte deformability of the SH group measured at 0.53 and 1.69-30 Pa was lower than that of the control group. The erythrocyte aggregation index, aggregation half time and PV were not different between the groups. However, the aggregation amplitude and mean corpuscular hemoglobin concentration were significantly higher in SH compared to the control group. There was a negative correlation between TSH and deformability values measured at 5.33-30.0 Pa. CIMT in patients with SH was significantly higher than in the control group (p = 0.001; SH = 0.48 +/- 0.04 mm, control group = 0.43 +/- 0.03 mm). Conclusion: Impaired hemorheology and increased CIMT are well-known risk factors for developing cardiovascular pathologies. The results of the current study suggest the treatment of children with SH in order to avoid early circulatory problems. (C) 2016 S. Karger AG, Base