Citations

Calf muscles and Achilles tendon play important roles in functional activities. However, it is not clear how biomechanical properties of the uniarticular soleus (SOL) and biarticular gastrocnemius muscle and Achilles tendon, including the fascicle length, pennation angle, and stiffness, change concurrently post stroke. Biomechanical properties of the medial gastrocnemius (GM) and soleus muscles were evaluated bilaterally in 10 hemiparetic stroke survivors using combined ultrasonography-biomechanical measurements. Biomechanical properties of the Achilles tendon including the length, cross-sectional area (CSA), stiffness, and Young's modulus were evaluated, together with calf muscle biomechanical properties. Gastrocnemius and SOL contributions were separated using flexed and extended knee positions. The impaired side showed decreased fascicle length (GM: 6%, P = 0.002 and SOL: 9%, P = 0.03, at full knee extension and 0° ankle dorsiflexion) and increased fascicular stiffness (GM: 64%, P = 0.005 and SOL: 19%, P = 0.012, at a common 50 N force level). In contrast, Achilles tendon on the impaired side showed changes in the opposite direction as the muscle fascicles with increased tendon length (5%, P < 0.001), decreased tendon CSA (5%, P = 0.04), decreased tendon stiffness (42%, P < 0.001) and Young's modulus (30%, P < 0.001) compared with the unimpaired side. The fascicle and tendon stiffness changes were correlated negatively to the corresponding fascicle and tendon length changes, and decrease in Achilles tendon stiffness was correlated to the increases of SOL and GM fascicular stiffness ( P < 0.05). Characterizations of calf muscle fascicles and Achilles tendon biomechanical properties help us better understand concurrent changes of fascicles and tendon as part of the calf muscle-tendon unit and facilitate development of more effective treatments.

Key Points CLL stereotyped subset #2 (IGHV3-21/IGLV3-21) is uniformly aggressive independently of somatic hypermutation status. The prognosis for non–subset #2/IGHV3-21 CLL resembles that of the remaining CLL cases with similar somatic hypermutation status.

Context and Objective:Oncocytic thyroid carcinoma, also known as Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation, and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management.Design and Patients:Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line, and five Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in the multiple endocrine neoplasia I (MEN1) gene.Results:Here we report the identification of MEN1 loss-of-function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumors.Conclusion:Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of MEN1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis, and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain‐only donations and currently has banked more than 1600 brains. More than 430 whole‐body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0‐hour median post‐mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant‐funded projects.