A multimodal approach to understanding motor impairment and disability after stroke

Many different measures have been found to be related to behavioral outcome after stroke. Preclinical studies emphasize the importance of brain injury and neural function. However, the measures most important to human outcomes remain uncertain, in part because studies often examine one measure at a time or enroll only mildly impaired patients. The current study addressed this by performing multimodal evaluation in a heterogeneous population. Patients (n = 36) with stable arm paresis 3-6 months post-stroke were assessed across 6 categories of measures related to stroke outcome: demographics/medical history, cognitive/mood status, genetics, neurophysiology, brain injury, and cortical function. Multivariate modeling identified measures independently related to an impairment-based outcome (arm Fugl-Meyer motor score). Analyses were repeated (1) identifying measures related to disability (modified Rankin Scale score), describing independence in daily functions and (2) using only patients with mild deficits. Across patients, greater impairment was related to measures of injury (reduced corticospinal tract integrity) and neurophysiology (absence of motor evoked potential). In contrast, (1) greater disability was related to greater injury and poorer cognitive status (MMSE score) and (2) among patients with mild deficits, greater impairment was related to cortical function (greater contralesional motor/premotor cortex activation). Impairment after stroke is most related to injury and neurophysiology, consistent with preclinical studies. These relationships vary according to the patient subgroup or the behavioral endpoint studied. One potential implication of these results is that choice of biomarker or stratifying variable in a clinical stroke study might vary according to patient characteristics. © 2014 Springer-Verlag Berlin Heidelberg

Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

Potential for airborne transmission of infection in the waiting areas of healthcare premises: stochastic analysis using a Monte Carlo model

BACKGROUND: Although many infections that are transmissible from person to person are acquired through direct contact between individuals, a minority, notably pulmonary tuberculosis (TB), measles and influenza are known to be spread by the airborne route. Airborne infections pose a particular threat to susceptible individuals whenever they are placed together with the index case in confined spaces. With this in mind, waiting areas of healthcare facilities present a particular challenge, since large numbers of people, some of whom may have underlying conditions which predispose them to infection, congregate in such spaces and can be exposed to an individual who may be shedding potentially pathogenic microorganisms. It is therefore important to understand the risks posed by infectious individuals in waiting areas, so that interventions can be developed to minimise the spread of airborne infections. METHOD: A stochastic Monte Carlo model was constructed to analyse the transmission of airborne infection in a hypothetical 132 m3 hospital waiting area in which occupancy levels, waiting times and ventilation rate can all be varied. In the model the Gammaitoni-Nucci equation was utilized to predict probability of susceptible individuals becoming infected. The model was used to assess the risk of transmission of three infectious diseases, TB, influenza and measles. In order to allow for stochasticity a random number generator was applied to the variables in the model and a total of 10000 individual simulations were undertaken. The mean quanta production rates used in the study were 12.7, 100 and 570 per hour for TB, influenza and measles, respectively. RESULTS: The results of the study revealed the mean probability of acquiring a TB infection during a 30-minute stay in the waiting area to be negligible (i.e. 0.0034), while that for influenza was an order of magnitude higher at 0.0262. By comparison the mean probability of acquiring a measles infection during the same period was 0.1349. If the duration of the stay was increased to 60 minutes then these values increased to 0.0087, 0.0662 and 0.3094, respectively. CONCLUSION: Under normal circumstances the risk of acquiring a TB infection during a visit to a hospital waiting area is minimal. Likewise the risks associated with the transmission of influenza, although an order of magnitude greater than those for TB, are relatively small. By comparison, the risks associated with measles are high. While the installation of air disinfection may be beneficial, when seeking to prevent the transmission of airborne viral infection it is important to first minimize waiting times and the number of susceptible individuals present before turning to expensive technological solutions

Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy

Clinical implications of having reduced mid forced expiratory flow rates (FEF25-75), independently of FEV1, in adult patients with asthma

INTRODUCTION:FEF25-75 is one of the standard results provided in spirometry reports; however, in adult asthmatics there is limited information on how this physiological measure relates to clinical or biological outcomes independently of the FEV1 or the FEV1/FVC ratio. PURPOSE:To determine the association between Hankinson's percent-predicted FEF25-75 (FEF25-75%) levels with changes in healthcare utilization, respiratory symptom frequency, and biomarkers of distal airway inflammation. METHODS:In participants enrolled in the Severe Asthma Research Program 1-2, we compared outcomes across FEF25-75% quartiles. Multivariable analyses were done to avoid confounding by demographic characteristics, FEV1, and the FEV1/FVC ratio. In a sensitivity analysis, we also compared outcomes across participants with FEF25-75% below the lower limit of normal (LLN) and FEV1/FVC above LLN. RESULTS:Subjects in the lowest FEF25-75% quartile had greater rates of healthcare utilization and higher exhaled nitric oxide and sputum eosinophils. In multivariable analysis, being in the lowest FEF25-75% quartile remained significantly associated with nocturnal symptoms (OR 3.0 [95%CI 1.3-6.9]), persistent symptoms (OR 3.3 [95%CI 1-11], ICU admission for asthma (3.7 [1.3-10.8]) and blood eosinophil % (0.18 [0.07, 0.29]). In the sensitivity analysis, those with FEF25-75% <LLN had significantly more nocturnal and persistent symptoms, emergency room visits, higher serum eosinophil levels and increased methacholine responsiveness. CONCLUSIONS:After controlling for demographic variables, FEV1 and FEV1/FVC, a reduced FEF25-75% is independently associated with previous ICU admission, persistent symptoms, nocturnal symptoms, blood eosinophilia and bronchial hyperreactivity. This suggests that in some asthmatics, a reduced FEF25-75% is an independent biomarker for more severe asthma

Initiating undergraduate medical students into communities of research practise: what do supervisors recommend?

Abstract Background Much has been written in the educational literature on the value of communities of practise in enhancing student learning. Here, we take the experience of senior undergraduate medical students involved in short-term research as a member of a team as a paradigm for learning in a community of practise. Based on feedback from experienced supervisors, we offer recommendations for initiating students into the research culture of their team. In so doing, we endeavour to create a bridge between theory and practise through disseminating advice on good supervisory practise, where the supervisor is perceived as an educator responsible for designing the research process to optimize student learning. Methods Using the questionnaire design tool SurveyMonkey and comprehensive lists of contact details of staff who had supervised research projects at the University of Edinburgh during 1995 - 2008, current and previous supervisors were invited to recommend procedures which they had found successful in initiating students into the research culture of a team. Text responses were then coded in the form of derivative recommendations and categorized under general themes and sub-themes. Results Using the chi-square tests of linear trend and association, evidence was found for a positive trend towards more experienced supervisors offering responses (χ2 = 16.833, p 2 = 0.482, p = 0.487, n = 203), respectively. A total of 126 codes were extracted from the text responses of 65 respondents. These codes were simplified to form a complete list of 52 recommendations, which were in turn categorized under seven derivative overarching themes, the most highly represented themes being Connecting the student with others and Cultivating self-efficacy in research competence. Conclusions Through the design of a coding frame for supervisor responses, a wealth of ideas has been captured to make communities of research practise effective mediums for undergraduate student learning. The majority of these recommendations are underpinned by educational theory and have the potential to take the learner beyond the stage of initiation to that of integration within their community of research practise.</p

Perception of limb orientation in the vertical plane depends on center of mass rather than inertial eigenvectors

We performed two experiments to test the hypothesis that the perception of limb orientation depends on inertial eigenvectors (

A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study

Background: A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention. Methods an design: There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and precancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division. Discussion: This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function

Classifying gait alterations using an instrumented smart sock and deep learning

This paper presents a non-invasive method of classifying gait patterns associated with various movement disorders and/or neurological conditions, utilising unobtrusive, instrumented socks and a deep learning network. Seamless instrumented socks were fabricated using three accelerometer embedded yarns, positioned at the toe (hallux), above the heel and on the lateral malleolus. Human trials were conducted on 12 able-bodied participants, an instrumented sock was worn on each foot. Participants were asked to complete seven trials consisting of their typical gait and six different gait types that mimicked the typical movement patterns associated with various movement disorders and neurological conditions. Four Neural Networks and an SVM were tested to ascertain the most effective method of automatic data classification. The Bi-LSTM generated the most accurate results and illustrates that the use of three accelerometers per foot increased classification accuracy compared to a single accelerometer per foot by 11.4%. When only a single accelerometer was utilised for classification, the ankle accelerometer generated the most accurate results in comparison to the other two. The network was able to correctly classify five different gait types: stomp (100%), shuffle (66.8%), diplegic (66.6%), hemiplegic (66.6%) and “normal walking” (58.0%). The network was incapable of correctly differentiating foot slap (21.2%) and steppage gait (4.8%). This work demonstrates that instrumented textile socks incorporating three accelerometer yarns were capable of generating sufficient data to allow a neural network to distinguish between specific gait patterns. This may enable clinicians and therapists to remotely classify gait alterations and observe changes in gait during rehabilitation