How Useful Are Monogenic Rodent Models for the Study of Human Non-Alcoholic Fatty Liver Disease?

Improving understanding of the genetic basis of human non-alcoholic fatty liver disease (NAFLD) has the potential to facilitate risk stratification of affected patients, permit personalized treatment, and inform development of new therapeutic strategies. Animal models have been widely used to interrogate the pathophysiology of, and genetic predisposition to, NAFLD. Nevertheless, considerable interspecies differences in intermediary metabolism potentially limit the extent to which results can be extrapolated to humans. For example, human genome-wide association studies have identified polymorphisms in PNPLA3 and TM6SF2 as the two most prevalent determinants of susceptibility to NAFLD and its inflammatory component (NASH), but animal models of these mutations have had only variable success in recapitulating this link. In this review, we critically appraise selected murine monogenic models of NAFLD, NASH, and hepatocellular carcinoma (HCC) with a focus on how closely they mirror human disease.RS is supported by the Wellcome Trust (grant number WT098498)

Exploring the performance of molecular rectifiers: Limitations and factors affecting molecular rectification

There has been significant work investigating the use of molecules as nanoscale rectifiers in so-called "molecular electronics". However, less attention has been paid to optimizing the design parameters of molecular rectifiers or to their inherent limitations. Here we use a barrier tunneling model to examine the degree of rectification that can be achieved and to provide insight for the design and development of molecules with optimum rectification responses. © 2007 American Chemical Society

Outcomes of the NuroSleeve and Occupational Therapy on Upper Limb Function of an Individual with Chronic Hemiparesis Following a Stroke: A Case Report

Background: Upper limb neuromuscular impairments can adversely impact function. This case report investigates the process and outcomes of occupational therapy (OT) for training in the use of the NuroSleeve, a novel research-grade exoskeletal powered orthosis, with a participant with chronic right hemiparesis following a stroke. Method: The participant engaged in 24 OT sessions using the NuroSleeve over 10 weeks. Therapeutic interventions included neuromuscular reeducation, device management, and engagement in occupation-based activities with training to use the NuroSleeve. The Canadian Occupational Performance Measure (COPM), ABILHAND, Patient Reported Outcomes Measurement Information System Upper Extremity Short Form 7a (PROMIS UE SF), Action Research Arm Test (ARAT), and Manual Muscle Testing (MMT) were administered before and after the 24 sessions. Results: With the NuroSleeve, there were clinically important increases in COPM performance and satisfaction for 6/8 and 7/8 goals, respectively; ABILHAND showed a clinically important increase of 4.959 logits; and there was an 11-point increase on the ARAT, indicating a clinically important difference. T-score on the PROMIS UE SF was 33.7 (SD = 2) compared to 23 (SD = 2.8) without the device. MMT remain unchanged. Conclusion: The data suggest that the NuroSleeve was the primary source of increased function and that incorporating OT with the NuroSleeve has benefits

Roles of Education and IQ in Cognitive Reserve in Parkinson's Disease-Mild Cognitive Impairment.

Background/aimsThe role of cognitive reserve in Parkinson's disease (PD)-mild cognitive impairment (MCI) is incompletely understood.MethodsThe relationships between PD-MCI, years of education, and estimated premorbid IQ were examined in 119 consecutive non-demented PD patients using logistic regression models.ResultsHigher education and IQ were associated with reduced odds of PD-MCI in univariate analysis. In multivariable analysis, a higher IQ was associated with a significantly decreased odds of PD-MCI, but education was not.ConclusionThe association of higher IQ and decreased odds of PD-MCI supports a role for cognitive reserve in PD, but further studies are needed to clarify the interaction of IQ and education and the impact of other contributors such as employment and hobbies

Effectiveness of bridge V.A.C. dressings in the treatment of diabetic foot ulcers

Objectives: This is a prospective study of the clinical efficacy of the V.A.C. Granufoam Bridge Dressing for the treatment of diabetic foot ulcers. Materials and methods: Five consecutive patients with diabetic foot ulcers were treated with V.A.C. Granufoam Bridge Dressings and studied over a period of 22–48 days. The indications for treatment included diabetic patients with open ray amputation wounds and wounds post-drainage for abscess with exposed deep structures. Clinical outcome was measured in terms of reduction in wound dimensions, presence of wound granulation, microbial clearance, and development of wound complications. Results: Our results showed that with V.A.C. therapy, wound healing occurred in all patients. The number of dressings required ranged from 8 to 10. The baseline average wound size was 23.1 cm2. Wound areas shrunk by 18.4–41.7%. All subjects achieved 100% wound bed granulation with an average length of treatment of 33 days. Microbial clearance was achieved in all cases. All wounds healed by secondary intention in one case and four cases required split-thickness skin grafting. Conclusion: The V.A.C. Granufoam Bridge Dressing is effective in the treatment of diabetic foot ulcers. It promotes reduction of wound area, wound bed granulation, and microbial clearance. By allowing placement of the suction pad outside the foot, it allowed patients to wear protective shoes and to walk non-weight bearing with crutches during V.A.C. therapy

Proposed New Antiproton Experiments at Fermilab

Fermilab operates the world's most intense source of antiprotons. Recently various experiments have been proposed that can use those antiprotons either parasitically during Tevatron Collider running or after the Tevatron Collider finishes in about 2010. We discuss the physics goals and prospects of the proposed experiments.Comment: 6 pages, 2 figures, to appear in Proceedings of IXth International Conference on Low Energy Antiproton Physics (LEAP'08), Vienna, Austria, September 16 to 19, 200

Sociodemographic Trends in National Ambulatory Care Visits for Hepatitis C Virus Infection

Poor and non-white patients are disproportionately infected with the hepatitis C virus (HCV). The objective of this research is to determine sociodemographic patterns of HCV-related ambulatory care visits over time. Data from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey-Outpatient (NHAMCS-OPD) for the years 1997–2005 were analyzed in 3-year intervals. Demographic and other variables were compared for each period, and multivariable logistic regression was performed to examine whether the likelihood of a visit being HCV-related (versus non-HCV) was independently associated with (1) race and/or (2) Medicaid status over time. The total number of HCV-related ambulatory visits more than doubled from 3,583,585 during the years 1997–1999 to 8,027,166 during 2003–2005. During this time, the proportion of non-whites and Medicaid recipients presenting for HCV-related visits approximately doubled (non-whites: 16% vs. 33%, P = 0.04; Medicaid recipients: 10% vs. 25%, P = 0.07). In 2003–2005, HCV-related visits were more than twice as likely to occur among non-white patients vs. white patients (OR = 2.49; 95% CI: 1.60–3.86) and patients on Medicaid vs. non-Medicaid (3.49; 1.79–6.80). Our results show that HCV-associated ambulatory care visits are increasing, with a greater proportion of visits occurring among non-white patients and Medicaid recipients

The effectiveness of digital interventions for increasing physical activity in individuals of low socioeconomic status: a systematic review and meta-analysis.

This is the final version. Available from Springer via the DOI in this record. All data and code to replicate our analysis are freely available at https://github.com/MarkKelson/REPAIDBACKGROUND: Digital technologies such as wearables, websites and mobile applications are increasingly used in interventions targeting physical activity (PA). Increasing access to such technologies makes an attractive prospect for helping individuals of low socioeconomic status (SES) in becoming more active and healthier. However, little is known about their effectiveness in such populations. The aim of this systematic review was to explore whether digital interventions were effective in promoting PA in low SES populations, whether interventions are of equal benefit to higher SES individuals and whether the number or type of behaviour change techniques (BCTs) used in digital PA interventions was associated with intervention effects. METHODS: A systematic search strategy was used to identify eligible studies from MEDLINE, Embase, PsycINFO, Web of Science, Scopus and The Cochrane Library, published between January 1990 and March 2020. Randomised controlled trials, using digital technology as the primary intervention tool, and a control group that did not receive any digital technology-based intervention were included, provided they had a measure of PA as an outcome. Lastly, studies that did not have any measure of SES were excluded from the review. Risk of Bias was assessed using the Cochrane Risk of Bias tool version 2. RESULTS: Of the 14,589 records initially identified, 19 studies were included in the final meta-analysis. Using random-effects models, in low SES there was a standardised mean difference (SMD (95%CI)) in PA between intervention and control groups of 0.06 (- 0.08,0.20). In high SES the SMD was 0.34 (0.22,0.45). Heterogeneity was modest in both low (I2 = 0.18) and high (I2 = 0) SES groups. The studies used a range of digital technologies and BCTs in their interventions, but the main findings were consistent across all of the sub-group analyses (digital interventions with a PA only focus, country, chronic disease, and duration of intervention) and there was no association with the number or type of BCTs. DISCUSSION: Digital interventions targeting PA do not show equivalent efficacy for people of low and high SES. For people of low SES, there is no evidence that digital PA interventions are effective, irrespective of the behaviour change techniques used. In contrast, the same interventions in high SES participants do indicate effectiveness. To reduce inequalities and improve effectiveness, future development of digital interventions aimed at improving PA must make more effort to meet the needs of low SES people within the target population.Engineering and Physical Sciences Research CouncilHealth and Care Research Wales Health Fellowship AwardGW4 AllianceUK Centre for Ageing BetterElizabeth Blackwell InstituteMedical Research CouncilUniversity of BristolCentre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer)Alan Turing Institut

Approximate Analytical Model for the Squeeze-Film Lubrication of the Human Ankle Joint with Synovial Fluid Filtrated by Articular Cartilage

The aim of this article is to propose an analytical approximate squeeze-film lubrication model of the human ankle joint for a quick assessment of the synovial pressure field and the load carrying due to the squeeze motion. The model starts from the theory of boosted lubrication for the human articular joints lubrication (Walker et al., Rheum Dis 27:512–520, 1968; Maroudas, Lubrication and wear in joints. Sector, London, 1969) and takes into account the fluid transport across the articular cartilage using Darcy’s equation to depict the synovial fluid motion through a porous cartilage matrix. The human ankle joint is assumed to be cylindrical enabling motion in the sagittal plane only. The proposed model is based on a modified Reynolds equation; its integration allows to obtain a quick assessment on the synovial pressure field showing a good agreement with those obtained numerically (Hlavacek, J Biomech 33:1415–1422, 2000). The analytical integration allows the closed form description of the synovial fluid film force and the calculation of the unsteady gap thickness