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Myeloperoxidase (MPO) activity has been associated with the metabolic syndrome, cardiovascular and liver disease. Here, we evaluate the therapeutic potential of MPO inhibition on nonalcoholic steatohepatitis (NASH) and NASH-induced fibrosis, the main determinant of outcomes. MPO plasma levels were elevated in patients with nonalcoholic fatty liver disease (NAFLD) compared with healthy controls. In a second cohort, hepatic MPO messenger RNA expression correlated with higher body mass index and hemoglobin A1c, both being risk factors for NAFLD. We could establish by immunohistochemistry that MPO-positive cells were recruited to the liver in various mouse models of fibrogenic liver injury, including bile duct ligation, carbon tetrachloride (CCl 4 ) treatment, spontaneous liver fibrogenesis in multidrug resistance 2 knockout (MDR2 KO) mice, and NASH-inducing diet. Comparison of MPO-deficient mice and their wild-type littermates exposed to a high-caloric diet revealed that MPO deficiency protects against NASH-related liver injury and fibrosis. In line with this, hepatic gene expression analysis demonstrated a MPO-dependent activation of pathways relevant for wound healing, inflammation, and cell death in NASH. MPO deficiency did not affect NAFLD-independent liver injury and fibrosis in MDR2 KO or CCl 4 -treated mice. Finally, we treated wild-type mice exposed to NASH-inducing diet with an oral MPO inhibitor. Pharmacological MPO inhibition not only reduced markers of MPO-mediated liver damage, serum alanine aminotransferase levels, and hepatic steatosis, but also significantly decreased NASH-induced liver fibrosis. MPO inhibitor treatment, but not MPO deficiency, significantly altered gut microbiota including a significant expansion of Akkermansia muciniphila . Conclusions: MPO specifically promotes NASH-induced liver fibrosis. Pharmacological MPO inhibition attenuates NASH progression and NASH-induced liver fibrosis in mice and is associated with beneficial changes of intestinal microbiota., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background & Aims: Refractory ascites is the main reason for the implantation of a transjugular intrahepatic portosystemic shunt (TIPS) in liver cirrhosis, but ascites control by TIPS fails in a relevant proportion of cases. Here, we investigated whether routine parameters pre-TIPS can predict persistent ascites after TIPS implantation and whether persistent ascites predicts long-term clinical outcome., Methods: A detailed retrospective analysis of 128 patients receiving expanded polytetrafluoroethylene-covered stents for the treatment of refractory ascites was performed. Persistent ascites post-TIPS was defined as the prolonged need for paracentesis >3 months after TIPS. The influence of demographics, laboratory results, pre-TIPS heart and liver ultrasound results, and invasive hemodynamic parameters on persistent ascites was evaluated by univariable and multivariable logistic regression. Predictors of the composite endpoint liver transplantation/death were analyzed using a multivariable Cox regression., Results: Ascites control post-TIPS was achieved in 95/128 patients (74%), whereas ascites remained persistent in 33/128 cases (26%). On multivariable analysis, a lower paracentesis frequency pre-TIPS (odds ratio 1.672; 95% CI 1.253-2.355) and lower baseline creatinine levels (odds ratio 2.640; CI 1.201-6.607) were associated with ascites control. Patients with persistent ascites post-TIPS had and impaired transplant-free survival (median 10.0 vs. 25.8 months), for which persistent ascites was the only independent predictor (hazard ratio 5.654; CI 3.019-10.59)., Conclusion: TIPS-placement in patients with lower paracentesis frequency and creatinine levels is associated with superior ascites control. Thus, TIPS implantation should be considered in moderate decompensation and not as a last resort. Persistent ascites post-TIPS seems to be the only predictor of liver transplantation and death., Lay Summary: The insertion of a transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory ascites should be considered in patients with moderate decompensation and not as a last resort, as lower paracentesis frequency and creatinine levels pre-TIPS are associated with superior ascites control. In turn, failure to control ascites seems to be the only predictor of liver transplantation and death., (© 2019 The Authors.)

Background: The majority of stroke patients are inactive outside formal therapy sessions. Tailored activity feedback via a smartwatch has the potential to increase inpatient activity. The aim of the study was to identify the challenges and support needed by ward staff and researchers and to examine the feasibility of conducting a randomised controlled trial (RCT) using smartwatch activity monitors in research-naive rehabilitation wards. Objectives (Phase 1 and 2) were to report any challenges and support needed and determine the recruitment and retention rate, completion of outcome measures, smartwatch adherence rate, (Phase 2 only) readiness to randomise, adherence to protocol (intervention fidelity) and potential for effect., Methods: First admission, stroke patients (onset < 4 months) aged 40-75, able to walk 10 m prior to stroke and follow a two-stage command with sufficient cognition and vision (clinically judged) were recruited within the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine. Phase 1: a non-randomised observation phase (to allow practice of protocol)-patients received no activity feedback. Phase 2: a parallel single-blind pilot RCT. Patients were randomised into one of two groups: to receive daily activity feedback over a 9-h period or to receive no activity feedback. EQ-5D-5L, WHODAS and RMI were conducted at baseline, discharge and 3 months post-discharge. Descriptive statistics were performed on recruitment, retention, completion and activity counts as well as adherence to protocol., Results: Out of 470 ward admissions, 11% were recruited across the two phases, over a 30-week period. Retention rate at 3 months post-discharge was 48%. Twenty-two percent of patients dropped out post-baseline assessment, 78% completed baseline and discharge admissions, from which 62% were assessed 3 months post-discharge. Smartwatch data were received from all patients. Patients were correctly randomised into each RCT group. RCT adherence rate to wearing the smartwatch was 80%. Baseline activity was exceeded for 65% of days in the feedback group compared to 55% of days in the no feedback group., Conclusions: Delivery of a smartwatch RCT is feasible in a research-naive rehabilitation ward. However, frequent support and guidance of research-naive staff are required to ensure completeness of clinical assessment data and protocol adherence., Trials Registration: ClinicalTrials.gov Identifier, NCT02587585-30th September 2015., Competing Interests: The study was approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT-20150034), West China Hospital, Sichuan University, 37 Guoxuexiang, Chengdu, Sichuan, China. All research was in compliance with the Helsinki Declarations and the Research Governance Framework for Health and Social Care. Informed written consent was obtained by a recruiting doctor based on the wards whereby sufficient mental capacity (based on clinical judgement) and understanding of anonymity and the inclusion of their data was ensured.Not applicable.The gait measurement system and the smartwatch software were developed by the research team (HD, PE and DW) and (CJ and JA) respectively, and both systems are in the process of being commercialised by the universities concerned.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Practicing activities improves recovery after stroke, but many people in hospital do little activity. Feedback on activity using an accelerometer is a potential method to increase activity in hospital inpatients. This study's goal is to investigate the effect of feedback, enabled by a Smart watch, on daily physical activity levels during inpatient stroke rehabilitation and the short-term effects on simple functional activities, primarily mobility., Methods/design: A randomized controlled trial will be undertaken within the stroke rehabilitation wards of the Second Affiliated hospital of Anhui University of Traditional Chinese Medicine, Hefei, China. The study participants will be stroke survivors who meet inclusion criteria for the study, primarily: able to participate, no more than 4 months after stroke and walking independently before stroke. Participants will all receive standard local rehabilitation and will be randomly assigned either to receive regular feedback about activity levels, relative to a daily goal tailored by the smart watch over five time periods throughout a working day, or to no feedback, but still wearing the Smart watch. The intervention will last up to 3 weeks, ending sooner if discharged. The data to be collected in all participants include measures of daily activity (Smart watch measure); mobility (Rivermead Mobility Index and 10-metre walking time); independence in personal care (Barthel Activities of Daily Living (ADL) Index); overall activities (the World Health Organization (WHO) Disability Assessment Scale, 12-item version); and quality of life (the Euro-Qol 5L5D). Data will be collected by assessors blinded to allocation of the intervention at baseline, 3 weeks or at discharge (whichever is the sooner); and a reduced data set will be collected at 12 weeks by telephone interview. The primary outcome will be change in daily accelerometer activity scores. Secondary outcomes are compliance and adherence to wearing the watch, and changes in mobility, independence in personal care activities, and health-related quality of life., Discussion: This project is being implemented in a large city hospital with limited resources and limited research experience. There has been a pilot feasibility study using the Smart watch, which highlighted some areas needing change and these are incorporated in this protocol., Trial Registration: ClinicalTrials.gov, NCT02587585 . Registered on 30 September 2015. Chinese Clinical Trial Registry, ChiCTR-IOR-15007179 . Registered on 8 August 2015.

This study explored the potential utility of gait analysis using a single sensor unit (inertial measurement unit [IMU]) as a simple tool to detect peripheral neuropathy in people with diabetes. Seventeen people (14 men) aged 63±9 years (mean±SD) with diabetic peripheral neuropathy performed a 10-m walk test instrumented with an IMU on the lower back. Compared to a reference healthy control data set (matched by gender, age, and body mass index) both spatiotemporal and gait control variables were different between groups, with walking speed, step time, and SDa (gait control parameter) demonstrating good discriminatory power (receiver operating characteristic area under the curve >0.8). These results provide a proof of principle of this relatively simple approach which, when applied in clinical practice, can detect a signal from those with known diabetes peripheral neuropathy. The technology has the potential to be used both routinely in the clinic and for tele-health applications. Further research should focus on investigating its efficacy as an early indicator of or effectiveness of the management of peripheral neuropathy. This could support the development of interventions to prevent complications such as foot ulceration or Charcot's foot., Competing Interests: Oxford Brookes University hold UK, EU, and USA Patent (PCT/GB2009/051767) on the methods used to transpose and integrate data inertial data. Patrick Esser, Johnny Collett, and Helen Dawes are inventors on patent., (Copyright © 2018 Korean Diabetes Association.)

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is upregulated during hepatic fibrogenesis and considered to promote fibrosis in the injured liver by inhibition of matrix metalloproteases (MMP) and degradation of extracellular matrix. Moreover, TIMP-1 displays anti-apoptotic properties, in patients with hepatocellular carcinoma (HCC) TIMP-1 serum levels are elevated and high TIMP-1 expression levels in HCC are associated with a poor prognosis. Therefore, TIMP-1 could functionally link fibrogenesis and carcinogenesis in the liver. The aim of our study was to characterize the role of TIMP-1 in hepatic fibrogenesis and carcinogenesis. Experimental hepatic fibrogenesis as well as diethylnitrosamine (DEN) -induced hepatocarcinogenesis were studied in TIMP-1-deficient mice and wild type littermates. Hepatic TIMP-1 expression was upregulated following induction of liver fibrosis by bile duct ligation (BDL) or by carbon tetrachloride (CCl 4 ). Unexpectedly, in comparison to wild type littermates, TIMP-1-deficient mice were not protected from liver fibrosis induced by BDL or CCl 4 . TIMP-1 expression was significantly higher in HCC nodules than in surrounding liver tissue. However, experimental hepatic carcinogenesis was similar in TIMP-1-deficient mice and wild type littermates following DEN-treatment or combined treatment with DEN and CCl 4 . Therefore we concluded that TIMP-1 is not essential for hepatic fibrogenesis and carcinogenesis in mice.

The purpose of this study was to establish and cross-validate a method for analyzing gait patterns determined by the center of mass (COM) through inertial sensors embedded in smart devices. The method employed an extended Kalman filter in conjunction with a quaternion rotation matrix approach to transform accelerations from the object onto the global frame. Derived by double integration, peak-to-trough changes in vertical COM position captured by a motion capture system, inertial measurement unit, and smart device were compared in terms of averaged and individual steps. The inter-rater reliability and levels of agreement for systems were discerned through intraclass correlation coefficients (ICC) and Bland-Altman plots. ICCs corresponding to inter-rater reliability were good-to-excellent for position data (ICCs,.80-.95) and acceleration data (ICCs,.54-.81). Levels of agreements were moderate for position data (LOA, 3.1-19.3%) and poor for acceleration data (LOA, 6.8%-17.8%). The Bland-Altman plots, however, revealed a small systematic error, in which peak-to-trough changes in vertical COM position were underestimated by 2.2mm; the Kalman filter׳s accuracy requires further investigation to minimize this oversight. More importantly, however, the study׳s preliminary results indicate that the smart device allows for reliable COM measurements, opening up a cost-effective, user-friendly, and popular solution for remotely monitoring movement. The long-term impact of the smart device method on patient rehabilitation and therapy cannot be underestimated: not only could healthcare expenditures be curbed (smart devices being more affordable than today's motion sensors), but a more refined grasp of individual functioning, activity, and participation within everyday life could be attained., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Integrating rehabilitation services through wearable systems has the potential to accurately assess the type, intensity, duration, and quality of movement necessary for procuring key outcome measures., Objectives: This review aims to explore wearable accelerometry-based technology (ABT) capable of assessing mobility-related functional activities intended for rehabilitation purposes in community settings for neurological populations. In this review, we focus on the accuracy of ABT-based methods, types of outcome measures, and the implementation of ABT in non-clinical settings for rehabilitation purposes., Data Sources: Cochrane, PubMed, Web of Knowledge, EMBASE, and IEEE Xplore. The search strategy covered three main areas, namely wearable technology, rehabilitation, and setting., Study Selection: Potentially relevant studies were categorized as systems either evaluating methods or outcome parameters., Methods: Methodological qualities of studies were assessed by two customized checklists, depending on their categorization and rated independently by three blinded reviewers., Results: Twelve studies involving ABT met the eligibility criteria, of which three studies were identified as having implemented ABT for rehabilitation purposes in non-clinical settings. From the twelve studies, seven studies achieved high methodological quality scores. These studies were not only capable of assessing the type, quantity, and quality measures of functional activities, but could also distinguish healthy from non-healthy subjects and/or address disease severity levels., Conclusion: While many studies support ABT's potential for telerehabilitation, few actually utilized it to assess mobility-related functional activities outside laboratory settings. To generate more appropriate outcome measures, there is a clear need to translate research findings and novel methods into practice.