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The neuropathological feature of multiple system atrophy (MSA), a fatal adult-onset disorder without effective therapy, is the accumulation of pathological α-synuclein (α-Syn) in the central nervous system (CNS). Here we show that pathological α-Syn exists in nerve terminals in detrusor and external urethral sphincter (EUS) of patients with MSA. Furthermore, α-Syn-preformed fibrils (PFFs) injected in the EUS or detrusor in TgM83+/- mice initiated the transmission of pathological α-Syn from the urogenital tract to brain via micturition reflex pathways, and these mice developed widespread phosphorylated α-Syn inclusion pathology together with phenotypes. In addition, urinary dysfunction and denervation-reinnervation of external anal sphincter were detected earlier in the mouse models with α-Syn PFFs inoculation before the behavioral manifestations. These results suggest that pathological α-Syn spreading through the micturition reflex pathways retrogradely from the urogenital tract to CNS may lead to urinary dysfunction in patients with MSA, which is different from the etiology of idiopathic Parkinson disease.Purpose Handgrip strength used to identify sarcopenia is not representative of overall strength, especially as greater muscle volume and consequent autonomy-mobility are concentrated in the lower limbs. While absolute strength or relative to body mass is used to define sarcopenia, this relationship is not always linear. The aim of this study was to establish allometrically adjusted cut-off points of lower limb (quadriceps) muscle strength to identify sarcopenia risk in older adults. Methods ninety-four physically independent individuals over the age of 60 were measured by DXA and sarcopenia was identified. The one-repetition maximum (1RM) test of knee extension strength was estimated using the extensor chair by the submaximal repetition protocol. The six-minute walk test performance was recorded. 1RM values were scaled by body mass (1RM/body mass) and allometrically adjusted (1RM/body massb). Cut-off points for sarcopenia from 1RM were defined with ROC curve and Youden index with functional limitation (walking distance0.70). The cut-off points for women and men were respectively, 38.1 and 56.1 kg for 1RM, 0.53 and 0.85 for 1RM/body mass, 1.48 and 1.00 for 1RM/body massb. Conclusions 1RM of knee extension scaled by body mass or allometrically adjusted is an effective parameter to identify sarcopenia in older adults. The proposed cut-off points could be used to monitor sarcopenia risk in geriatrics.Background Litigation and disciplinary action taken by the Nursing and Midwifery Council (NMC) against nurses' remains a concern with costs of claims against the NHS increasing by 72% over the five years up to 2015/16 with almost £1.5 billion spent in one year alone. Additionally, 5476 referrals regarding registrants' fitness to practice were made to the NMC in 2016-2017. The aims of this paper are to discuss how a pair of scenario based IPE sessions focussed on healthcare law and ethical topics were introduced as an addition to the existing nursing and midwifery curricula and to report the evaluation of these sessions. Methods Two scenario based sessions attended by nursing, midwifery and law students were delivered as an addition to existing nursing, midwifery and law curricula. The scenarios were based on real life cases and students collaborated to identify means of managing legal and ethical issues arising from the scenarios. These sessions were facilitated by lecturers from the schools of law, midwifery and nursing. Temsirolimus manufacturer Findings All attending students completed an evaluation questionnaire. Student evaluations indicated that the experience of working through the scenarios with their colleagues from other disciplines had enabled them to gain further knowledge and understanding around healthcare law and ethics. Student evaluations indicated a high level of engagement and interest in the subject and also drew attention to the supportive structure of the IPE sessions. Conclusion Nurses and midwives continue to be called to account by both their professional body and in law for issues related to their practice. A way to enable students to consider this and aid their preparation for clinical and professional practice is through the use of clinically and professionally relevant healthcare law and ethics scenarios in IPE sessions.Crime scene investigation protocols and procedures are well established when concerning terrestrial environments, but are limited when associated with aquatic environments. In aquatic contexts, the soil, sediments and microscopic algae (e.g. diatoms) may all be used as sources of trace evidence for criminal investigations. Diatoms are one such source that can be used to support the diagnosis of death by drowning and can be used to verify contact between a suspect and a specific water body. For the latter, diatoms can be collected from clothing and shoes for forensic comparisons. Over the years, there have been several methods proposed for the extraction of diatoms from clothing, however, a best practice method is yet to be established and is still open to debate. The present research represents the first investigation that evaluates four different methods for the extraction of native and common Australian diatom species from four different types of fabrics. Diatoms of two different species and shape (pennate extraction rates; c) H treatment had the highest extraction rate of diatoms; d) the application of centrifugal force on the RE method significantly improved the extraction of diatoms; e) DA is a potential method for the extraction of pennate-shaped diatoms from all of the tested fabrics, however, does have a tendency to induce modifications of the morphological structure of the diatoms. Overall, the application of different extraction methods is suggested to maximise the extraction of diatoms that would closely reflect their natural assemblage in the water body under investigation.The ability to visualize enzyme activity in a cell, tissue, or living organism can greatly enhance our understanding of the biological roles of that enzyme. While many aspects of cellular signaling are controlled by reversible protein phosphorylation, our understanding of the biological roles of the protein phosphatases involved is limited. Here, we provide an overview of progress toward the development of fluorescent probes that can be used to visualize the activity of protein phosphatases. Significant advances include the development of probes with visible and near-infrared (near-IR) excitation and emission profiles, which provides greater tissue and whole-animal imaging capabilities. In addition, the development of peptide-based probes has provided some selectivity for a phosphatase of interest. Key challenges involve the difficulty of achieving sufficient selectivity for an individual member of a phosphatase enzyme family and the necessity of fully validating the best probes before they can be adopted widely.

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