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Because of the small sample size existing of online self-help group members, results should be taken with caution.Tau protein accumulation is a common denominator of major dementias, but this process is inhomogeneous, even when triggered by the same germline mutation. We considered stochastic misfolding of human tau conformers followed by templated conversion of native monomers as an underlying mechanism and derived sensitive conformational assays to test this concept. Assessments of brains from aged TgTauP301L transgenic mice revealed a prodromal state and three distinct signatures for misfolded tau. Frontotemporal lobar degeneration (FTLD)-MAPT-P301L patients with different clinical phenotypes also displayed three signatures, two resembling those found in TgTauP301L mice. As physicochemical and cell bioassays confirmed diverse tau strains in the mouse and human brain series, we conclude that evolution of diverse tau conformers is intrinsic to the pathogenesis of this uni-allelic form of tauopathy. In turn, effective therapeutic interventions in FTLD will need to address evolving repertoires of misfolded tau species rather than singular, static molecular targets.Primary sarcoma of the liver (PSL) is a rare entity accounting for less than 1% of all liver cancers, with unknown aetiology. Several subtypes have been recognized, with histology playing an essential role in patient tailoring and management. We are about to report a case of an unusual PSL, with peculiar morphologic and immunohistochemical properties. A 65-year-old female with a multicystic hepatic lesion underwent surgery due to spontaneous rupture. Pathology revealed dilated bile duct-like structures lined by benign cuboidal/columnar epithelium surrounded by neoplastic proliferation of spindle and epithelioid cells with interspersed osteoclast-like multinucleated giant cells, loosely arranged in a storiform pattern, positive for CD10. The conjugation of morphology and immunohistochemistry results provided the diagnosis of primary biliary adenosarcoma of the liver, biliary type. The patient experienced tumour relapse and died of disease 2 years and 7 months later.OBJECTIVE To evaluate predictive factors of urinary incontinence (UI) after holmium laser enucleation of the prostate (HoLEP). Zilurgisertib fumarate datasheet METHODS Patients (n = 2346) were included in a retrospective multicentric study from April 2012 to November 2017. Patients' characteristics (age, BMI, percentage with diabetes), preoperative data (IPSS score, whole gland volume, urinary drainage), operative data (enucleation time, enucleation efficiency, tissue enucleated weight, total delivered energy) and postoperative data were recorded. Absence of UI was defined as no pads at 3 and 6 months. Surgeon experience was stratified in three categories beginners ( 40 cases). Multivariate logistic regression analysis was performed. RESULTS UI was observed in 14.5% of patients (340/2346) at 3 months (95%CI 13-16%) and in 4.2% (98/2346) at 6 months (95%CI 3-5%). On multivariate analysis at 3 months, increasing age (OR per SD = 1.3 [1.14-1.48]), elevated BMI (OR per SD = 1.23 [1.09-1.38]), preoperative urinary drainage (OR = 0.62 [0.45-0.85]), increasing enucleated tissue weight (OR per SD = 1.29 [1.16-1.45]) and experienced surgeon with at least 40 cases (OR = 0.56 [0.42-0.75]) were significantly associated with UI. At 6 months, increasing age (OR per SD = 1.25 [1.01-1.53]), elevated BMI (OR per SD = 1.25 [1.03-1.5]), increasing whole gland volume (OR per one SD log = 1.24 [1.01-1.53]) and diabetes disorder (OR = 1.7 [1.03-2.78]) were significantly associated with UI. CONCLUSION UI after HoLEP was observed in 14.5% of patients at 3 months and 4.2% at 6 months, with stress UI in half of the cases. Surgeon experience with at least 40 cases was the main predictive factor of 3 months UI after HoLEP and diabetes disorder of persistent UI at 6 months.We examined the circadian rhythms of locomotor activity in three spider species in the Family Theridiidae under light-dark cycles and constant darkness. Contrary to previous findings in other organisms, we found exceptionally high variability in endogenous circadian period both within and among species. Many individuals exhibited circadian periods much lower (19-22 h) or much higher (26-30 h) than the archetypal circadian period. These results suggest relaxed selection on circadian period as well as an ability to succeed in nature despite a lack of circadian resonance with the 24-h daily cycle. Although displaying similar entrainment waveforms under light-dark cycles, there were remarkable differences among the three species with respect to levels of apparent masking and dispersion of activity under constant dark conditions. These behavioral differences suggest an aspect of chronotype adapted to the particular ecologies of the different species.Heterochromatin in eukaryotic interphase cells frequently localizes to the nucleolar periphery (nucleolus-associated domains (NADs)) and the nuclear lamina (lamina-associated domains (LADs)). Gene expression in somatic cell NADs is generally low, but NADs have not been characterized in mammalian stem cells. Here, we generated the first genome-wide map of NADs in mouse embryonic stem cells (mESCs) via deep sequencing of chromatin associated with biochemically purified nucleoli. As we had observed in mouse embryonic fibroblasts (MEFs), the large type I subset of NADs overlaps with constitutive LADs and is enriched for features of constitutive heterochromatin, including late replication timing and low gene density and expression levels. Conversely, the type II NAD subset overlaps with loci that are not lamina-associated, but in mESCs, type II NADs are much less abundant than in MEFs. mESC NADs are also much less enriched in H3K27me3 modified regions than are NADs in MEFs. Additionally, comparision of MEF and mESC NADs revealed enrichment of developmentally regulated genes in cell-type-specific NADs. Together, these data indicate that NADs are a developmentally dynamic component of heterochromatin. These studies implicate association with the nucleolar periphery as a mechanism for developmentally regulated gene expression and will facilitate future studies of NADs during mESC differentiation.