Does the addition of virtual reality training to a standard program of inpatient rehabilitation improve sitting balance ability and function after stroke? Protocol for a single-blind randomized controlled trial.

BACKGROUND: Sitting ability and function are commonly impaired after stroke. Balance training has been shown to be helpful, but abundant repetitions are required for optimal recovery and patients must be motivated to perform rehabilitation exercises repeatedly to maximize treatment intensity. Virtual reality training (VRT), which allows patients to interact with a virtual environment using computer software and hardware, is enjoyable and may encourage greater repetition of therapeutic exercises. However, the potential for VRT to promote sitting balance has not yet been explored. The objective of this study is to determine if supplemental VRT-based sitting balance exercises improve sitting balance ability and function in stroke rehabilitation inpatients. METHODS/DESIGN: This is a single-site, single-blind, parallel-group randomized control trial. Seventy six stroke rehabilitation inpatients who cannot stand independently for greater than one minute but can sit for at least 20 minutes (including at least one minute without support) are being recruited from a tertiary-care dedicated stroke rehabilitation unit. Participants are randomly allocated to experimental or control groups. Both participate in 10-12 sessions of 30-45 minutes of VRT performed in sitting administered by a single physiotherapist, in addition to their traditional therapy. The experimental group plays five games which challenge sitting balance while the control group plays five games which minimize trunk lean. Outcome measures of sitting balance ability (Function in Sitting Test, Ottawa Sitting Scale, quantitative measures of postural sway) and function (Reaching Performance Scale, Wolf Motor Function Test, quantitative measures of the limits of stability) are administered prior to, immediately following, and one month following the intervention by a second physiotherapist blind to the participant's group allocation. DISCUSSION: The treatment of sitting balance post-stroke with VRT has not yet been explored. Results from the current study will provide important evidence for the use of low-cost, accessible VRT as an adjunct intervention to increase sitting balance in lower-functioning patients receiving inpatient rehabilitation. The motivating and enjoyable attributes of VRT may increase exercise dosage, leading to improved function and optimal results from rehabilitation. TRIAL REGISTRATION: https://clinicaltrials.gov/; Identifier: NCT02285933. Registered 06 November 2014. Funded by the Heart & Stroke Foundation of Canada and a generous donation from Tony & Elizabeth Graham.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Correlation-based ultrasound imaging of strong reflectors with phase coherence filtering.

Two main metrics are usually employed to assess the quality of medical ultrasound (US) images, namely the contrast and the spatial resolution. A number of imaging algorithms have been proposed to improve one of those metrics, often at the expense of the other one. This paper presents the application of a correlation-based ultrasound imaging method, called Excitelet, to medical US imaging applications and the inclusion of a new Phase Coherence (PC) metric within its formalism. The main idea behind this algorithm, originally developed and validated for Non-Destructive Testing (NDT) applications, is to correlate a reference signal database with the measured signals acquired from a transducer array. In this paper, it is shown that improved lateral resolutions and a reduction of imaging artifacts are obtained over the Synthetic Aperture Focusing Technique (SAFT) when using Excitelet in conjunction with a PC filter. This novel method shows potential for the imaging of specular reflectors, such as invasive surgical tools. Numerical and experimental results presented in this paper demonstrate the benefit, in terms of contrast and resolution, of using the Excitelet method combined with PC for the imaging of strong reflectors.

Demyelinating sensorimotor polyneuropathy associated with the use of sirolimus: a case report.

Liver transplantation is associated with a number of neurological complications. We herein report a case of chronic inflammatory demyelinating polyneuropathy associated with the use of sirolimus-based immunosuppression. The patient was treated by converting the immunosuppression from sirolimus to cyclosporine and by a short course of oral steroids. Following this, we observed almost complete clinical and electrophysiologic resolution of this syndrome. We believe that this is the first described case of such a complication occurring in association with sirolimus. This immunosuppressive agent can, therefore, lead to neurological complications similar to the ones that have been observed with calcineurin inhibitors.

Cyclic AMP signaling functions as a bimodal switch in sympathoadrenal cell development in cultured primary neural crest cells.

Cells of the vertebrate neural crest (crest cells) are an invaluable model system to address cell fate specification. Crest cells are amenable to tissue culture, and they differentiate to a variety of neuronal and nonneuronal cell types. Earlier studies have determined that bone morphogenetic proteins (BMP-2, -4, and -7) and agents that elevate intracellular cyclic AMP (cAMP) stimulate the development of the sympathoadrenal (SA, adrenergic) lineage in neural crest cultures. To investigate whether interactive mechanisms between signaling pathways influence crest cell differentiation, we characterized the combinatorial effects of BMP-2 and cAMP-elevating agents on the development of quail trunk neural crest cells in primary culture. We report that the cAMP signaling pathway modulates both positive and negative signals influencing the development of SA cells. Specifically, we show that moderate activation of cAMP signaling promotes, in synergy with BMP-2, SA cell development and the expression of the SA lineage-determining gene Phox2a. By contrast, robust activation of cAMP signaling opposes, even in the presence of BMP-2, SA cell development and the expression of the SA lineage-determining ASH-1 and Phox2 genes. We conclude that cAMP signaling acts as a bimodal regulator of SA cell development in neural crest cultures.

The mitogen-activated protein kinase kinase/extracellular signal-regulated kinase cascade activation is a key signalling pathway involved in the regulation of G(1) phase progression in proliferating hepatocytes.

In this study, activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signalling pathway was analyzed in proliferating rat hepatocytes both in vivo after partial hepatectomy and in vitro following epidermal growth factor (EGF)-pyruvate stimulation. First, a biphasic MEK/ERK activation was evidenced in G(1) phase of hepatocytes from regenerating liver but not from sham-operated control animals. One occurred in early G(1) (30 min to 4 h), and the other occurred in mid-late G(1), peaking at around 10.5 h. Interestingly, the mid-late G(1) activation peak was located just before cyclin D1 induction in both in vivo and in vitro models. Second, the biological role of the MEK/ERK cascade activation in hepatocyte progression through the G(1)/S transition was assessed by adding a MEK inhibitor (PD 98059) to EGF-pyruvate-stimulated hepatocytes in primary culture. In the presence of MEK inhibitor, cyclin D1 mRNA accumulation was inhibited, DNA replication was totally abolished, and the MEK1 isoform was preferentially targeted by this inhibition. This effect was dose dependent and completely reversed by removing the MEK inhibitor. Furthermore, transient transfection of hepatocytes with activated MEK1 construct resulted in increased cyclin D1 mRNA accumulation. Third, a correlation between the mid-late G(1) MEK/ERK activation in hepatocytes in vivo after partial hepatectomy and the mitogen-independent proliferation capacity of these cells in vitro was established. Among hepatocytes isolated either 5, 7, 9, 12 or 15 h after partial hepatectomy, only those isolated from 12- and 15-h regenerating livers were able to replicate DNA without additional growth stimulation in vitro. In addition, PD 98059 intravenous administration in vivo, before MEK activation, was able to inhibit DNA replication in hepatocytes from regenerating livers. Taken together, these results show that (i) early induction of the MEK/ERK cascade is restricted to hepatocytes from hepatectomized animals, allowing an early distinction of primed hepatocytes from those returning to quiescence, and (ii) mid-late G(1) MEK/ERK activation is mainly associated with cyclin D1 accumulation which leads to mitogen-independent progression of hepatocytes to S phase. These results allow us to point to a growth factor dependency in mid-late G(1) phase of proliferating hepatocytes in vivo as observed in vitro in proliferating hepatocytes and argue for a crucial role of the MEK/ERK cascade signalling pathway.

Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease.

BACKGROUND: Bleeding is a recognized complication of abdominal paracentesis. Special concern has been raised when it is performed in patients with liver failure because of coagulation disorders and collaterals in the abdominal wall. AIM: To assess the clinical characteristics of patients who developed haemorrhagic complications after paracentesis. METHODS: We reviewed all cases of severe haemorrhage occurring after paracentesis in patients admitted to the Liver Unit of our institution between 1994 and 2004. RESULTS: Nine cases were identified among 4729 procedures. The occurrence of severe haemorrhage represented 0.19% of all procedures with a death rate of 0.016%. Bleeding was not related to operator experience, elevated international normalized ratio or low platelets. It occurred in patients with high model for end-stage liver disease and Child-Pugh scores. Furthermore, some degree of renal failure was present in all but one patient. CONCLUSION: Severe haemorrhage after abdominal paracentesis in patients with liver disease occurs in 0.2% of cases. It occurs in patients with severe liver failure and is often associated with significant pre-existing renal dysfunction.

Skp2 induction and phosphorylation is associated with the late G1 phase of proliferating rat hepatocytes.

The changes in phosphoproteins purified with the affinity peptide p9CKShs1 were analyzed from extracts of regenerating rat livers in order to define some G1 and G1/S regulations characteristic of mature hepatocytes stimulated to proliferate. We observed a 47 kDa phosphoprotein that occurred first at the end of G1 before peaking in the S phase. P47 was also found to be phosphorylated in late G1 in primary hepatocyte cultures stimulated with mitogens. P47 was still phosphorylated in extracts depleted of Cdc2, but to a lesser extent after Cdk2 depletion. This phosphoprotein was identified as Skp2. (i) P47 shared the same electrophoretic mobility than Skp2, a cell cycle protein essential for S phase entry in human fibroblasts; (ii) Skp2, like P47, started to be expressed and was highly phosphorylated during the G1/S transition of hepatocytes stimulated to proliferate in vivo and in vitro; (iii) P47 was specifically immunoprecipitated by an antibody directed against Skp2. In addition, cyclin A/Cdk2 complexes from regenerating liver clearly interacted with Skp2. This is the first demonstration that Skp2 is induced and phosphorylated in the late G1 and S phase of hepatocytes in vivo in regenerating liver as well as in vitro in mitogen-stimulated hepatocytes.

Modulation of chylomicron remnant metabolism by an hepatic hydroxymethylglutaryl coenzyme A reductase inhibitor.

This study was designed to test the hypothesis that in patients with elevated plasma low-density lipoprotein (LDL) apolipoprotein-apoB, chylomicron remnant clearance can be modulated by therapy with a hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitor. Accordingly, chylomicron triglyceride and remnant clearance were determined following a vitamin-A fat load in 12 such patients, before and after therapy with Lovastatin (Merck, Sharp & Dohme, Rahway, NJ). Such therapy had no significant overall effect on plasma triglyceride clearance, although there was a trend to lower levels of Sf greater than 400 triglycerides at the later time points. By contrast, retinol clearance in plasma and Sf greater than 400 lipoproteins was markedly increased (30% and 40%, respectively). The data indicate, therefore, that following therapy with Lovastatin in this group of patients, chylomicron plasma remnant clearance was significantly enhanced. The exact mechanisms responsible remain to be explicated.

Short-term immobilization has a minimal effect on the strength and fatigability of a human hand muscle.

The purpose of this study was to determine the association between reduced fatigability typically observed in disused muscle and an improved resistance to the impairment of neuromuscular propagation. Endurance time of an isometric contraction sustained at 35% of maximum voluntary contraction (MVC) force and the fatigue-induced change in the evoked compound muscle action potential (M wave) were measured in the first dorsal interosseus muscle of human subjects before, during, and after 3 (n = 9) or 5 wk (n = 2) of immobilization. The immobilization procedure caused a substantial decline in the chronic electromyographic (EMG) activity (to 4% of control value) of the first dorsal interosseus muscle. Endurance time was found to be significantly correlated to the maintenance of M-wave amplitude during the fatigue task. However, neither of these variables was significantly affected by immobilization. Also, immobilization had no significant effect on the prefatigue values of MVC force and EMG or twitch contraction time or on the postfatigue changes in MVC force and EMG, M wave duration, twitch amplitude, and contraction time. In the unfatigued muscle, immobilization did cause an increase in twitch force (153%) and a decrease in M-wave amplitude (67%). It appears, therefore, that a healthy first dorsal interosseus muscle is generally resistant to adaptation when its use has been reduced for 3-5 wk by immobilization.

Effect of aging on fatigue characteristics of elbow flexor muscles during sustained submaximal contraction.

The purpose of this study was to compare fatigue-related measures of central and peripheral mechanisms between young and elderly subjects for a task performed with elbow flexor muscles. Ten young and nine elderly subjects performed a sustained submaximal fatigue task at 35% of their maximum voluntary contraction torque. Measures of neuromuscular function, reflecting changes in neuromuscular propagation, voluntary activation, excitation-contraction-relaxation processes, and metabolite buildup, were taken before, during, and after the fatigue task. The main results were the absence of neuromuscular propagation failure in either young or elderly subjects, the presence of central fatigue at the end of the fatigue task in 7 of 9 elderly but only 3 of 10 young subjects, and lesser changes in twitch torque contraction-relaxation variables and electromyographic median frequency in elderly compared with young subjects. The lesser fatigue-related changes in twitch contraction speed and median frequency in elderly compared with young subjects could reflect the increase in type I-to-type II fiber area reported with old age. The presence of significant central fatigue can apparently minimize some of the potential differences present in peripheral fatigue sites.

Pain management knowledge, attitudes and clinical practice: the impact of nurses' characteristics and education.

This study examined the knowledge, attitudes, and clinical practice of registered nurses (N = 120) regarding pain management. Data were collected from nine varied clinical units in a large, university-affiliated, teaching hospital in an urban area of the Northeast. Demographic information was also collected to explore the relationship between nurses' characteristics, including previous pain education, clinical experience, area of clinical practice, and other variables, and knowledge, attitudes, and clinical practice. Three instruments were used in the study: (a) the Pain Management: Nurses' Knowledge and Attitude Survey; (b) a 12-item demographic questionnaire; and (c) a Pain Audit Tool (PAT) to gather data regarding pain assessment, documentation, and treatment practices from charts. Mean scores from the nursing knowledge and attitudes survey on pain revealed knowledge deficits and inconsistent responses in many areas related to pain management (mean, 62%; range, 41%-90%). The top two nurse-ranked barriers to pain management were related to patient reluctance to report pain and to take opioids for pain relief. Demographic data revealed that education about pain was most inadequate in the following areas: nonpharmacological interventions to relieve pain, the difference between acute and chronic pain, and the anatomy and physiology of pain. Chart audits with the Pain Audit Tool revealed that 76% of the charts (N = 82) lacked documentation of the use of a patient self-rating tool by nurses to assess pain, despite a high reported use (76%) of such a self-rating tool. Adjunct medications were ordered with some consistency, but appeared to be underutilized. This was especially true of nonsteroidal anti-inflammatory agents (mean use, 1%). Ninety percent of the charts had no documentation of the use of nonpharmacological interventions to relieve pain. Although this clinical setting has policies and resources in place regarding the management of pain, it would appear that they are not optimal. Practical recommendations are presented for increasing nurses' knowledge about pain management; improving the quality and the consistency of the assessment, documentation and treatment of pain; and disseminating pain management information.

Do enzymatic hydrolyzability and Simons' stain reflect the changes in the accessibility of lignocellulosic substrates to cellulase enzymes?

In an attempt to elucidate the impact of substrate accessibility to cellulases on the susceptibility of lignocellulosic substrates to enzymatic hydrolysis, a hydrogen peroxide treated, Douglas fir kraft pulp was dried using several methods with varying levels of intensity. Oven-drying at 50 and 100 degrees C, air-drying, and freeze-drying methods were employed to remove the interfibrillar water from the pulp samples. Subsequently, the never-dried and variably dried pulps were hydrolyzed using a commercial cellulase preparation supplemented with additional beta-glucosidase. Drying reduced the susceptibility of the substrates to enzymatic hydrolysis, which can be attributed to the hornifying effect that drying has on fibers. This effect was more pronounced for the fibers that were oven-dried at 100 degrees C (23% reduction) and 50 degrees C (15% reduction), and there was a good correlation between the Simons's stain results and the enzymatic digestibility of the dried pulps. These observations indicated that drying significantly reduced the population of larger pores and that the partial closure of larger pores created a large number of smaller pores that were not accessible to the displacement dye molecules (orange dye). The inaccessibility of the cellulose to the enzymes, due to the collapse or closure of the large pores, appears to be the primary reason for the lower susceptibility of the dried pulps to enzymatic hydrolysis.

Angiogenesis inhibitors--a review of the recent patent literature.

The development of a general appreciation for the central role of angiogenesis in cancer growth and metastasis and other disease states has led to a wide range of new therapeutic strategies. This paper reviews the patent applications that appeared over the 6-month period between April and September 2000 in the field of angiogenesis inhibition. The review focuses on those approaches that directly target angiogenesis. The majority of the review covers patents in the area of mechanism-based inhibitors in which most of the activity of this field is focused. Later sections will cover the patenting of endogenous inhibitors and small molecules of unknown target, where there is significant effort but less understanding of mechanisms.

Differential expression of sympathoadrenal lineage-determining genes and phenotypic markers in cultured primary neural crest cells.

Bone morphogenetic protein-2 (BMP-2) promotes the development of primary neural crest cells grown in tissue culture to the sympathoadrenal (SA) lineage. Independent studies have characterized the expression patterns of SA-lineage genes in developing chicken embryo; however, studies using cultured primary neural crest cells have characterized only the expression patterns of the catecholaminergic markers, tyrosine hydroxylase (TH) and catecholamines (CAs). To further explore the molecular mechanisms that control SA-cell development using the in vitro model system, it is crucial to define the expression patterns of both the catecholaminergic markers and the genes regulating SA-lineage determination. Accordingly, we defined, in the absence and presence of BMP-2, the temporal expression patterns of TH and CA, the SA lineage-determining genes ASH-1, Phox2a, and Phox2b, the GATA-2 gene, and the pan-neuronal SCG10 gene. Comparison of these data with the reported temporal and spatial patterns of expression in vivo demonstrate that the inductive steps of SA-lineage determination, including the specification of neurotransmitter identity and neuronal fate, are recapitulated in the neural-crest culture system.

Use of clonidine as a component of the peribulbar block in patients undergoing cataract surgery.

BACKGROUND AND OBJECTIVES: This study was designed to determine whether administration of clonidine as a component of a peribulbar block enhanced analgesia increased sedation, improved akinesia, or decreased intraocular pressure. METHODS: A randomized, double-blinded study was undertaken at a University-affiliated tertiary care hospital. Forty outpatients undergoing unilateral cataract surgery by a single surgeon (J.P.) under peribulbar blockade were evaluated. Patients received either 100 microg (1 mL) clonidine or 1 mL preservative-free normal saline mixed with the local anesthetic (7 mL 1% preservative-free lidocaine). A Honan adapter was applied for 10 minutes after block placement. The outcome measures included sedation scores, intraocular pressure (IOP) before and after peribulbar block, need for supplemental block, 24-hour analgesic requirement, and patient satisfaction. RESULTS: There were no differences between groups with respect to pain, sedation, or satisfaction scores. There was no difference with respect to onset of akinesia. This study revealed no significant difference in baseline IOP and postperibulbar IOP. CONCLUSIONS: Clonidine did not alter, in any appreciable way, the perioperative course for patients undergoing cataract operations. We do not recommend clonidine as a component of a peribulbar block in patients undergoing cataract extraction operations.

Neuromuscular fatigue of elbow flexor muscles of dominant and non-dominant arms in healthy humans.

The purpose of this study was to assess differences in fatigue-related changes in variables related to structures within the neuromuscular system, between the dominant and non-dominant elbow flexor muscles of right-handed individuals. Two experimental sessions were performed on the right arm and one on the left arm. For each session, maximum voluntary torque, level of voluntary activation, M-wave amplitude, twitch/train or twitch/doublet torque ratio and EMG median frequency were obtained before and up to 20 min after a sustained maximum isometric fatigue task. Our main results were: 1) reproducible fatigue-induced changes in all variables of interest between the two sessions performed with the right arm, 2) significantly greater failure in voluntary activation and neuromuscular propagation with sustained activity for the non-dominant compared with dominant side, and 3) no effect of dominance on MVC torque, endurance time, and fatigue-induced changes in EMG median frequency and elicited torques. These results suggest that the preferential use of elbow flexor muscles with the dominant arm leads to more fatigue resistance in certain structures/mechanisms of the neuromuscular system, but not in others.

Normality and stationarity of EMG signals of elbow flexor muscles during ramp and step isometric contractions.

The purpose of this study was to test the stationarity and normality of electromyographic (EMG) signals obtained while exerting isometric contractions: (a) where a steady force level is maintained (step contractions); and (b) where the force level is increased linearly over time (ramp contractions). Ramp elbow flexions were performed from 0 to 100% of the maximum voluntary contraction (MVC) in a 5-s period. For the step contractions, four force levels (20, 40, 60 and 80% MVC) were maintained for a period of 3 s each. EMG signals of the biceps brachii (BB) and brachioradialis (BR) muscles of 16 subjects were recorded with surface electrodes and digitized at a sampling frequency of 2000 Hz. Tests of normality (Shapiro-Wilk test) and stationarity (reverse arrangement test) were performed locally on short finite time records (512-ms windows). Results show that, in general, EMG signals present a non-Gaussian amplitude distribution and are stationary. Furthermore, the amplitude distribution characteristics and the stationarity of the signal were not dependent on the muscle investigated, nor on the type of contraction or force level tested. The finding of local stationarity for both tasks is important, because it suggests that performing standard spectral analysis is applicable for both step and ramp contractions. It also allows a direct comparison between results obtained under both conditions.