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No well-established staging system exists for bladder leiomyosarcoma (LMS), and the current staging system does not include tumor size, a thoroughly validated prognostic parameter for sarcomas. Uterine and extremity/trunk LMS are more common than those in the bladder and have well-established staging systems incorporating tumor size. We aim to improve the understanding of LMS of the urinary bladder by assessing cancer-specific survival (CSS) and comparing LMS at this unusual anatomic site to those arising at other sites using the Surveillance, Epidemiology, and End Results (SEER) database. The SEER database (1973-2013) was queried for bladder, uterus, and trunk/extremity LMS. Multivariable Cox proportional hazard regression was performed to identify predictors of CSS for each anatomic location and used to compare outcomes at different sites. We identified 165 bladder, 4987 uterus, and 2536 extremity/trunk LMS cases. Five-year CSS was 52% for uterus, 73% for bladder, and 82% for extremity/trunk LMS. For LMS at all sites, uterine location (HR = 2.14, P less then 0.001) and increasing tumor size (HR = 1.05, P less then 0.001) were significant predictors of worse CSS on multivariate analysis. For bladder LMS, increasing tumor size (HR = 1.18, P = 0.003) was an independent prognostic factor and the conventional staging cut-off threshold of 5 cm for sarcomas outside the head/neck showed statistical significance in stratifying patient risk of cancer-related death. Bladder LMS appears to have clinical behavior intermediate between those of the extremities/trunk and uterus. We suggest that the conventional sarcoma staging protocols based on tumor size be applied to LMS of the urinary bladder.
Embryonal tumor with multilayered rosettes (ETMR) are a heterogenous group clinically, pathologically and topographically. Due to limited cases, data regarding its molecular genetics, pathology and prognostic factors is evolving. We retrospectively analysed our cohort of ETMR over last decade in order to study their clinicopathological characteristics and outcome.
Our cohort consisted of patients diagnosed with Embryonal tumor with abundant neuropil and true rosettes (ETANTR)/Ependymoblastoma (EBL)/ Medulloepithelioma (MEPL) over the past decade. Clinical details, including outcome and imaging data was retrieved. Histological analysis including immunohistochemical work-up was performed.
Cohort included 15 patients with age range between 1 and 28years and MF ratio of 1.51. Supratentorial location predominated in comparison to tumors arising in posterior fossa. Cobimetinib datasheet ETANTR and EBL patterns were equally distributed (40% each), followed by one case each of mixed pattern (EBL+ETANTR), MEPL and embryonal tumor, unology. Prognosis of ETMR remains dismal despite multimodal therapy.We aimed to quantitatively characterize progressive brain network disruption in Amyotrophic Lateral Sclerosis (ALS) during cognition using the mismatch negativity (MMN), an electrophysiological index of attention switching. We measured the MMN using 128-channel EEG longitudinally (2-5 timepoints) in 60 ALS patients and cross-sectionally in 62 healthy controls. Using dipole fitting and linearly constrained minimum variance beamforming we investigated cortical source activity changes over time. In ALS, the inferior frontal gyri (IFG) show significantly lower baseline activity compared to controls. The right IFG and both superior temporal gyri (STG) become progressively hyperactive longitudinally. By contrast, the left motor and dorsolateral prefrontal cortices are initially hyperactive, declining progressively. Baseline motor hyperactivity correlates with cognitive disinhibition, and lower baseline IFG activities correlate with motor decline rate, while left dorsolateral prefrontal activity predicted cognitive and behavioural impairment. Shorter survival correlates with reduced baseline IFG and STG activity and later STG hyperactivation. Source-resolved EEG facilitates quantitative characterization of symptom-associated and symptom-preceding motor and cognitive-behavioral cortical network decline in ALS.Late-onset Alzheimer's disease (AD) disproportionately affects women compared to men. Episodic memory decline is one of the earliest and most pronounced deficits observed in AD. However, it remains unclear whether sex influences episodic memory-related brain function in cognitively intact older adults at risk of developing AD. Here we used task-based multivariate partial least squares analysis to examine sex differences in episodic memory-related brain activity and brain activity-behavior correlations in a matched sample of cognitively intact older women and men with a family history of AD from the PREVENT-AD cohort study in Montreal, Canada (Mage=63.03±3.78; Meducation=15.41±3.40). We observed sex differences in task-related brain activity and brain activity-behavior correlations during the encoding of object-location associative memories and object-only item memory, and the retrieval of object only item memories. Our findings suggest a generalization of episodic memory-related brain activation and performance in women compared to men. Follow up analyses should test for sex differences in the relationship between brain activity patterns and performance longitudinally, in association with risk factors for AD development. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https//www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.Sarcopenia, or age-related loss of muscle mass and strength, is an important contributor to loss of physical function in older adults. The pathogenesis of sarcopenia is likely multifactorial, but recently the role of neurological degeneration, such as motor unit loss, has received increased attention. Here, we investigated the longitudinal effects of muscle hypertrophy (via overexpression of human follistatin, a myostatin antagonist) on neuromuscular integrity in C57BL/6J mice between the ages of 24 and 27 months. Following follistatin overexpression (delivered via self-complementary adeno-associated virus subtype 9 injection), muscle weight and torque production were significantly improved. Follistatin treatment resulted in improvements of neuromuscular junction innervation and transmission but had no impact on age-related losses of motor units. These studies demonstrate that follistatin overexpression-induced muscle hypertrophy not only increased muscle weight and torque production but also countered age-related degeneration at the neuromuscular junction in mice.
Homepage: https://www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html
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