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    Monitoring gait in multiple sclerosis with novel wearable motion sensors

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    Mobility impairment is common in people with multiple sclerosis (PwMS) and there is a need to assess mobility in remote settings. Here, we apply a novel wireless, skin-mounted, and conformal inertial sensor (BioStampRC, MC10 Inc.) to examine gait characteristics of PwMS under controlled conditions. We determine the accuracy and precision of BioStampRC in measuring gait kinematics by comparing to contemporary research-grade measurement devices.A total of 45 PwMS, who presented with diverse walking impairment (Mild MS = 15, Moderate MS = 15, Severe MS = 15), and 15 healthy control subjects participated in the study. Participants completed a series of clinical walking tests. During the tests participants were instrumented with BioStampRC and MTx (Xsens, Inc.) sensors on their shanks, as well as an activity monitor GT3X (Actigraph, Inc.) on their non-dominant hip. Shank angular velocity was simultaneously measured with the inertial sensors. Step number and temporal gait parameters were calculated from the data recorded by each sensor. Visual inspection and the MTx served as the reference standards for computing the step number and temporal parameters, respectively. Accuracy (error) and precision (variance of error) was assessed based on absolute and relative metrics. Temporal parameters were compared across groups using ANOVA.Mean accuracy±precision for the BioStampRC was 2±2 steps error for step number, 6±9ms error for stride time and 6±7ms error for step time (0.6–2.6% relative error). Swing time had the least accuracy±precision (25±19ms error, 5±4% relative error) among the parameters. GT3X had the least accuracy±precision (8±14% relative error) in step number estimate among the devices. Both MTx and BioStampRC detected significantly distinct gait characteristics between PwMS with different disability levels (p<0.01).BioStampRC sensors accurately and precisely measure gait parameters in PwMS across diverse walking impairment levels and detected differences in gait characteristics by disability level in PwMS. This technology has the potential to provide granular monitoring of gait both inside and outside the clinic

    Innovative exercise device for the abdominal trunk muscles: An early validation study

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    Exercise is one of the few treatments that provide significant improvements in chronic low back pain (CLBP). We developed an innovative exercise device for abdominal trunk muscles. This device can be used in a sitting or standing position and contains a built-in system to measure abdominal trunk muscle strength. We examined whether subjects can adequately use the device to perform the exercises and measure their abdominal trunk muscle strength.F-fluorodeoxyglucose (FDG). PET-computed tomography images were obtained 60 minutes after FDG injection in each study. We compared the skeletal muscle metabolism of the participants in both studies using the standardized uptake value.The muscle strength measured by the device and the 30-second sit-up frequency were correlated. FDG accumulation within the diaphragm and abdominal rectus muscles was significantly higher in the exercise study.Our innovative exercise device facilitates a coordinated contraction of the abdominal trunk muscles at the anterior aspect and the roof of the core, and enables subjects to measure the strength of these muscles

    PUMA and NF-kB Are Cell Signaling Predictors of Reovirus Oncolysis of Breast Cancer

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    Reovirus is a ubiquitous RNA virus that exploits aberrant signaling pathways for its replication. The oncolytic potential of reovirus against numerous cancers under pre-clinical/clinical conditions has been documented by us and others. Despite its proven clinical activity, the underlying mechanisms of reovirus oncolysis is still not well elucidated. If reovirus therapy is to be optimized for cancer, including breast cancer patients, it is imperative to understand the mechanisms of reovirus oncolysis, especially in treatment of resistant tumour.In the present study global gene expression profiling was utilized as a preliminary roadmap to tease-out pivotal molecules involved in reovirus induced apoptosis in breast cancer. Reovirus treated HTB133 and MCF7 breast cancer cells revealed transcriptional alteration of a defined subset of apoptotic genes and members of the nuclear factor-kappa B (NF-kB) family and p53 upregulated modulator of apoptosis (PUMA) were prominent. Since NF-kB can paradoxically suppress or promote apoptosis in cancer, the significance of NF-kB in reovirus oncolysis of breast cancer was investigated. Real time PCR analysis indicated a 2.9–4.3 fold increase in NF-kB p65 message levels following reovirus infection of MCF7 and HTB133, respectively. Nuclear translocation of NF-kB p65 protein was also dramatically augmented post reovirus treatment and correlated with enhanced DNA binding. Pharmacologic inhibition of NF-kB lead to oncolytic protection and significant down regulation of PUMA message levels. PUMA down regulation using siRNA suppressed reovirus oncolysis via significantly repressed apoptosis in p53 mutant HTB133 cells.This study demonstrates for the first time that a prominent pathway of reovirus oncolysis of breast cancer is mediated through NF-kB and that PUMA upregulation is dependent on NF-kB activation. These findings represent potential therapeutic indicators of reovirus treatment in future clinical trials

    Fecal Fat Analyses in Chronic Pancreatitis Importance of Fat Ingestion before Stool Collection

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    Quantitative determination of fecal fat still is the gold standard for measuring malabsorption. We evaluated the importance of standardized food intake before and under the collection of feces.In a project, evaluating patients with suspected chronic pancreatitis (CP) and healthy volunteers (HC), stools were collected for 72 hours coupled to registration of nutritional intake over five consecutive days. Patient groups were created by a modified Layer score, which includes imaging findings, clinical parameters and pancreas function testing.We found 12 patients with CP, 11 patients without CP and 13 healthy individuals in our database. Median fecal fat in CP patients was 12 g/day, in non-CP patients 5 g/day and in healthy controls 5 g/day. Median fat absorption coefficient was 81% in those with chronic pancreatitis, 92% in those without CP and 92% in healthy controls. Corresponding median fat intake was 65 g/day, 68 g/day and 81 g/day in the respective groups. Spearman Rank Order Correlation between fecal fat (g/d) and fat absorption coefficient in all study subjects (n = 36) was good (-0.88 (p<0.001)). When we stratified groups according to fat intake, correlation between fecal fat and fat absorption was also good (-0.86 to -0.95).In the diagnoses of fat malabsorption, calculating the ratio of fat absorption did not give additional information compared to fecal fat

    GDM-Induced Macrosomia Is Reversed by Cav-1 via AMPK-Mediated Fatty Acid Transport and GLUT1-Mediated Glucose Transport in Placenta

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    To investigate if the role of Cav-1 in GDM-induced macrosomia is through regulating AMPK signaling pathway in placenta.We used diagnostic criteria of gestational diabetes mellitus (GDM) and macrosomia to separate and compare placental protein and mRNA levels from GDM with macrosomia group (GDMM), GDM with normal birth weight group (GDMN) and normal glucose tolerance (NGT) with normal birth weight group (CON). Western blotting was performed to examine differentially expressed proteins of caveolin-1 (Cav-1) and Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway related proteins, including phosphorylated-AMPKα(Thr172), AMPKα, phosphorylated-Acetyl-CoA carboxylase(Ser79) (p-ACC(Ser79)), ACC and glucose transporter 1 (GLUT1) in placenta between the three groups. The mRNA levels of Cav-1, AMPKα, ACC and GLUT1 in placenta were measured by real time-PCR.In the GDMM placenta group, both protein and mRNA levels of Cav-1 were down-regulated, while GLUT1 was up-regulated; the phosphorylation and mRNA levels of ACC and AMPKα were decreased, but total ACC protein levels were increased compared to both the GDMN (p<0.05) and CON groups (p<0.05). In GDMM placenta group, there was a significant negative correlation observed between neonatal birth weight (NBW) and protein expression levels of Cav-1, p-ACC(Ser79) and p-AMPKα(Thr172) (p<0.05), while positive relationship with ACC and GLUT1 protein levels. Besides, in GDMM group placental mRNA levels, NBW had a positive correlation with GLUT1 (p<0.05), while negative with Cav-1, AMPKα and ACC expression (p<0.05). Cav-1 protein expression was positively associated with p-AMPK and p-ACC (p<0.05), and negatively associated with GLUT1 (p<0.05). Interestingly, p-AMPK protein expression was closely related to p-ACC (p<0.05), but not with GLUT1.GDM-induced macrosomias have more severe inhibition of Cav-1 expression in placenta. Cav-1 is associated with placental glucose and fatty acid transport via the induction of AMPK signaling pathway and the reduction of GLUT1 signaling pathway to reverse GDM-induced macrosomia

    Association of the Endothelial Nitric Oxide Synthase Gene T786C Polymorphism with In-Stent Restenosis in Chinese Han Patients with Coronary Artery Disease Treated with Drug-Eluting Stent

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    Many studies have reported that genetic variants correlate with higher risk for coronary artery disease (CAD) or in-stent restenosis (ISR) after bare metal stent (BMS) implantation. However, there is limited data assessing the impact of these variants on ISR in patients treated with drug-eluting stent (DES). The purpose of this study was to investigate the effects of genetic risk factors on ISR in Chinese Han patients treated with DES.F). Quantitative coronary angiography (QCA) was performed during the follow-up period to detect ISR. Logistic regression models were used to test for association. was significantly higher in the ISR group (22.2%) compared to the non-ISR group (12.7%) (p<0.01). In the ISR group, the frequency of the TT, TC, and CC genotypes was 61.1%, 33.3%, and 5.6%, respectively, and in the non-ISR group, the frequencies were 76.8%, 21.0%, and 2.2%, respectively. The multivariable analysis adjusted for potential confounders and revealed that the T786C polymorphism increased the risk of ISR in both additive and dominant models with odds ratios of 1.870 (95% confidence interval [CI]: 1.079–3.240, p = 0.03) and 2.045 (95% CI: 1.056–3.958, p = 0.03), respectively. T786C polymorphism was associated with ISR in Chinese Han patients treated with DES. Genotyping may be helpful to identify patients with higher risks of ISR after DES implantation

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