Oncocytic carcinoma of the thyroid: Conclusions from a 20-year patient cohort.

BACKGROUND: Oncocytic carcinoma (OCA) was recently reclassified as a distinct differentiated thyroid carcinoma (DTC). Given its rarity, OCA studies are limited. This study describes the characteristics of OCA in a 20-year cohort. METHODS: Retrospective analysis of patients with OCA at a single tertiary care hospital from 2000 to 2021. RESULTS: Fifty-one OCA patients (22M:29F) were identified. The mean age at diagnosis was 60.3 years; 90% presented as palpable mass; 24% had a family history of thyroid cancer. None had vocal fold paresis. On ultrasound, most tumors were solid and hypoechoic. FNA (n = 14) showed Bethesda-4 lesions in 93%. All were treated surgically. Histologically, 63% demonstrated angioinvasion, 35% had lymphovascular invasion, and 15% had extrathyroidal extension. Radioactive iodine was used as adjunct therapy in 77%. CONCLUSION: OCA has distinct features that distinguish it from other DTCs, and additional focused studies will help clarify the aggressive nature, treatment options, and prognosis of the disease.

Pelvic floor tissue damping during running using an intra-vaginal accelerometry approach.

BACKGROUND: While cumulative loading of the pelvic floor during exercise appears to increase the risk of developing pelvic floor disorders, the pathophysiologic role of pelvic floor loading is poorly understood. The aim of this exploratory study was to present a method for evaluating vibrational frequency damping of the female pelvic floor and to investigate the potential utility of this approach in a preliminary evaluation. METHODS: Female participants were instrumented with an intravaginal accelerometer and a hip-mounted accelerometer, then ran on a treadmill at 7 km/h and 10 km/h both before and after a 30-min self-selected pace. Displacement of the pelvic floor relative to the bony pelvis was calculated using double integration of the accelerometer data. Vibrational damping coefficients were calculated using a wavelet-based approach to determine the effect of continence status, parity, running speed and time on vibrational damping. FINDINGS: Seventeen women (n = 10 reported regularly leaking urine while exercising, while n = 7 reported not leaking) completed the running protocol. No differences in vibrational damping were detected between continent and incontinent women when all frequency bands were evaluated together, however significant effects of parity, time, running speed and continence status were found within specific frequency bands. Parous women demonstrated less damping in the 25-40 Hz band compared to nulliparae, damping in the 13-16 Hz band was lower after the 30-min run, and incontinent women demonstrated lower damping in the 4.5-5.5 Hz band than continent women when running at 7 km/h. INTERPRETATION: Intra-vaginal vibrational damping may be useful in detecting biomechanical mechanisms associated with pelvic floor disorders experienced by females during exercise.

Design and validation of an automated dual-arm instrumented intravaginal dynamometer.

AIMS: (1) To present the design of a novel intravaginal dynamometer (IVD) capable of measuring vaginal closure force on both the anterior and posterior arms, (2) to use bench testing to validate the force, speed of arm opening, and positional accuracy of load measurement along the IVD arms, and (3) to present in vivo force measurements made with this device, comparing forces measured by the anterior and posterior arms. METHODS: IVD load measurements were validated against an Instron® Universal Tester, arm opening speeds were validated using video analysis, and position-load accuracy was validated against calibration weights. In vivo IVD data were acquired from female volunteers during passive opening and pelvic floor muscle contraction tasks. Anterior and posterior IVD arm force outcomes were compared. RESULTS: Forces measured by the IVD and Instron® exhibited a strong linear relationship with excellent model fit. The speed control system was valid when tested under physiological loading conditions, however smaller antero-posterior opening diameters (25 and 30 mm) exhibited some error. The loading position along the IVD arms had no effect on force outcomes. In vivo data exhibited differences between force outcomes measured at the anterior and posterior aspects of the vagina during active contraction and passive elongation of the pelvic floor muscles. CONCLUSIONS: This IVD design demonstrates valid load measurement and speed control during bench testing. Active and passive forces measured are consistent with the literature. With dual instrumented arms, this device allows for further investigation into the source of measured vaginal closure forces.

The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization.

Lamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear envelope transmembrane protein 39 (Net39) is a muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression, and metabolism. These abnormalities resemble those of Emery-Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings highlight the role of Net39 at the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and its potential contribution to the molecular etiology of EDMD.