Citations

AbstractBicuspid aortic valve is the most prevalent cardiac valvular malformation. It is associated with a high rate of long‐term morbidity including development of calcific aortic valve disease, aortic regurgitation and concomitant thoracic aortic aneurysm and dissection. Recently, basic and translational studies have identified some key processes involved in the development of bicuspid aortic valve and its morbidity. The development of aortic valve disease and thoracic aortic aneurysm and dissection is the result of complex interactions between genotypes, environmental risk factors and specific haemodynamic conditions created by bicuspid aortic valve anatomy. Herein, we review the pathobiology of bicuspid aortic valve with a special emphasis on translational aspects of these basic findings. Important but unresolved problems in the pathology of bicuspid aortic valve and thoracic aortic aneurysm and dissection are discussed, along with the molecular processes involved.

Abstract Summary: Structural variations (SVs) are large genomic rearrangements that vary significantly in size, making them challenging to detect with the relatively short reads from next-generation sequencing (NGS). Different SV detection methods have been developed; however, each is limited to specific kinds of SVs with varying accuracy and resolution. Previous works have attempted to combine different methods, but they still suffer from poor accuracy particularly for insertions. We propose MetaSV, an integrated SV caller which leverages multiple orthogonal SV signals for high accuracy and resolution. MetaSV proceeds by merging SVs from multiple tools for all types of SVs. It also analyzes soft-clipped reads from alignment to detect insertions accurately since existing tools underestimate insertion SVs. Local assembly in combination with dynamic programming is used to improve breakpoint resolution. Paired-end and coverage information is used to predict SV genotypes. Using simulation and experimental data, we demonstrate the effectiveness of MetaSV across various SV types and sizes. Availability and implementation: Code in Python is at http://bioinform.github.io/metasv/. Contact: rd@bina.com Supplementary information: Supplementary data are available at Bioinformatics online.

ABSTRACTHuman and dog and rabbit skin blood vessel strips give contractile responses to catecholamines, serotonin, and angiotensin II. Alpha receptors for catecholamine can be demonstrated. Species and organ variations occur in the small vessel tissue response to bradykinin (dog), histamine (rabbit) and acetylcholine (lung). A prostaglandin‐contractile activity could be demonstrated on cutaneous vessels. This activity was most marked in dog paw vessels and rarely occurred in human skin. Potentiation of catecholamine by prostaglandin E‐, A‐ and F‐ contractions could be demonstrated. The prostaglandin receptor was not blocked by alpha or beta blocking agents. The prostaglandin response was related to calcium concentration and was unrelated to exogenous or endogenous cyclic AMP.

ABSTRACTDynamics of structures within the carpal tunnel may alter in carpal tunnel syndrome (CTS) due to fibrotic changes and increased carpal tunnel pressure. Ultrasound can visualize these potential changes, making ultrasound potentially an accurate diagnostic tool. To study this, we imaged the carpal tunnel of 113 patients and 42 controls. CTS severity was classified according to validated clinical and nerve conduction study (NCS) classifications. Transversal and longitudinal displacement and shape (changes) were calculated for the median nerve, tendons and surrounding tissue. To predict diagnostic value binary logistic regression modeling was applied. Reduced longitudinal nerve displacement (p≤ 0.019), increased nerve cross‐sectional area (p≤ 0.006) and perimeter (p≤ 0.007), and a trend of relatively changed tendon displacements were seen in patients. Changes were more convincing when CTS was classified as more severe. Binary logistic modeling to diagnose CTS using ultrasound showed a sensitivity of 70–71% and specificity of 80–84%. In conclusion, CTS patients have altered dynamics of structures within the carpal tunnel. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1332–1340, 2015.

ABSTRACTAchilles tendon is one of the most commonly injured tendons. Mechanical force is regarded as a major causative factor. However, the biomechanics of Achilles tendon and mechanical mechanism of the injuries are unclear. Lubricin expresses at regions exposed to sliding motion and shear force in a number of tissues. This study investigated the distribution and concentration of lubricin in human Achilles tendons for better understanding the biomechanics of Achilles tendon. Achilles tendons were harvested from nine cadavers. Lubricin was extracted from various locations proximal to the calcaneal insertion and quantified with ELISA. The distribution of lubricin was investigated with immunohistochemistry. Lubricin was mainly identified at the interfaces of tendon fascicles, especially in the mid‐portion of the tendon. The concentration of lubricin in Achilles tendons varied by individual and the distance from its calcaneal insertion. The distal portion of the tendon had a higher concentration of lubricin than the proximal regions of the tendon. This study suggests the presence of intratendinous sliding motion of fascicles and shear force at interfaces of fascicles in human Achilles tendon. Shear force could be an important mechanical factor for the development of Achilles tendinopathy and rupture. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:932–937, 2015.