Induction of cortical reorganisation for rehabilitation in stroke.

Stroke is a cerebrovascular injury to the brain leading to neural tissue death and is the leading cause of long-tenn disability in the world today. My primary goal in this study was to examine the possibility that reorganisation in the stroke-affected brain could be made in a manner that supported improved motor function. To achieve this, I induced reorganisation of the motor cortex by stimulating peripheral afferents, in both normal subjects and stroke-affected patients. I also carried out a series of experiments examining the reliability of the test methods used to evaluate cortical function, and to induce functional changes in the motur cortex. Reorganisation is possible in the neural networks of the adult nervous system following alteration of afferent inputs brought about by conditions such as motor leaming or by injury. This concept of dynamic functional plasticity in the nervous system provides the foundation for the development of learning and memory throughout life and offers a potential for repair and recovery in pathological conditions. The strOke-injured brain is capable of reorganisation; hence, rehabilitation techniques should be aimed at enhancing possible mechanisms for the brain to compensate for the lesion through reorganisation or brain plasticity. I used the technique of transcranial magnetic stimulation (TMS) to examine corticomotor function, and a series of functional tests to examine motor perfonnance. My first series of experiments in this thesis investigated the stability of TMS map parameters over time in healthy individuals. The areas of the scalp from which responses were evoked from corticospinal cells projecting to three intrinsic hand muscles were systematically mapped with TMS at intervals of 24 hours, one week and two weeks from eight nonnal subjects. The area, volume and centre of gravity of these maps did not change significantly over this period. I concluded that the conventional method for mapping the cortical representational areas of individual hand muscles gives maps that are stable over periods of up to two weeks. This validates the use of such maps for the investigation of both short-term and long-term effects of interventions that may modify the cortical representation of muscles. I induced prolonged changes in the excitability of the motor cortex in a group of stroke patients nsing the technique of dual stimulation. This combines a central stimulus (TMS) with electrical stimulation of afferent nerves. The experiments described in Chapters 4 and 5 aimed to determine the effect of dual stimulation on cortical reorganisation and motor function in a group of stroke patients. Chapter 4 describes the results of my intervention on stroke-affected lower limbs and chapter 5 on upper limbs. Neurophysiological and functional changes were seen in the affected upper and lower limb muscles. Some stroke-affected individuals showed marked neurophysiological and functional changes. Furthermore, stroke-affected subjects who had the largest changes in neurophysiological measures were also the ones with the largest change in functional measures. However, the effect of the intervention was highly variable and the overall changes in the group scores were not statistically significant. The final series of experiments described in this thesis (Chapter 6) investigated the effects of a short period of anodal direct current (DC) stimulation and peripheral nerve stimulation on corticospinal excitability. The effect of this combined DC stimulation and peripheral nerve stimulation was contrasted with peripheral nerve stimulation alone. It demonstrated that the effects of peripheral nerve stimulation on cortical excitability could be potentiated by a preceding period of DC stimulation.Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 200

The evidence for services to avoid or delay residential aged care admission: A systematic review

Background Interventions that enable people to remain in their own home as they age are of interest to stakeholders, yet detailed information on effective interventions is scarce. Our objective was to systematically search and synthesise evidence for the effectiveness of community-based, aged care interventions in delaying or avoiding admission to residential aged care. Method Nine databases were searched from January 2000 to February 2018 for English publications. Reference lists of relevant publications were searched. The databases yielded 55,221 citations and 50 citations were gleaned from other sources. Where there was sufficient homogeneity of study design, population, intervention and measures, meta-analyses were performed. Studies were grouped by the type of intervention: complex multifactorial interventions, minimal/single focus interventions, restorative programs, or by the target population (e.g. participants with dementia). Results Data from 31 randomised controlled trials (32 articles) that met our inclusion criteria were extracted and analysed. Compared to controls, complex multifactorial interventions in community aged care significantly improved older adults’ ability to remain living at home (risk difference − 0.02; 95% CI -0.03, − 0.00; p = 0.04). Commonalities in the 13 studies with complex interventions were the use of comprehensive assessment, regular reviews, case management, care planning, referrals to additional services, individualised interventions, frequent client contact if required, and liaison with General Practitioners. Complex interventions did not have a significantly different effect on mortality. Single focus interventions did not show a significant effect in reducing residential aged care admissions (risk difference 0, 95% CI -0.01, 0.01; p = 0.71), nor for mortality or quality of life. Subgroup analysis of complex interventions for people with dementia showed significant risk reduction for residential aged care admissions (RD -0.05; 95% CI -0.09, -0.01; p = 0.02). Compared to controls, only interventions targeting participants with dementia had a significant effect on improving quality of life (SMD 3.38, 95% CI 3.02, 3.74; p \u3c 0.000001). Conclusions Where the goal is to avoid residential aged care admission for people with or without dementia, there is evidence for multifactorial, individualised community programs. The evidence suggests these interventions do not result in greater mortality and hence are safe. Minimal, single focus interventions will not achieve the targeted outcomes. Trial registration PROSPERO Registration CRD42016050086

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

A systems study on the high rise modular production of Modular Fusion Inc.

Modular Fusion, Inc. (MFI) was established on August 2009 to produce modular kitchen and closet cabinets. The study has specifically focused on the production of high-rise modular furniture of MFI. Based on the present system and the SWOT Analysis, it was found out that the high-rise modular production section is unable to produce 4.08% of the production schedule on time. Due to this, the company has been incurring an average of Php 543, 125.00 worth of penalty costs per month due to late production. To address the said problem, an Ishikawa Diagram was used to analyze the causes of the problem inside the high-rise modular furniture production section of MFI. It was found out that modules are not produced on time because of poor production scheduling, batching(which accounts to one-fourth of total processing time), lack of 2 workers for ideal production, absenteeism due to fatigue, insufficient machine capacity, and poor stockroom layout. With the use of Kepner-Tregoe Decision Analysis, the solutions generated to address the causes of the problems are hiring of 2 additional workers, application of smaller transfer batches in production, implementation of 5S by installing racks in the inventory stockroom, and integrated production scheduling. After implementing the said alternative solutions, the company was able to have a average monthly savings of Php199,618.75 or Php 2,395,425.00 per year. As for the production side, application of smaller transfer batches would have monthly savings of Php 271, 562.50, without incurring any monthly penalty costs, at the same time decreasing the absenteeism rate from 12.12% to 9.70%

Legumes as Functional Food for Cardiovascular Disease

Legumes are an essential food source worldwide. Their high-quality proteins, complex carbohydrates, dietary fiber, and relatively low-fat content make these an important functional food. Known to possess a multitude of health benefits, legume consumption is associated with the prevention and treatment of cardiovascular diseases (CVD). Legume crude protein isolates and purified peptides possess many cardiopreventive properties. Here, we review selected economically valued legumes, their taxonomy and distribution, biochemical composition, and their protein components and the mechanism(s) of action associated with cardiovascular health. Most of the legume protein studies had shown upregulation of low-density lipoprotein (LDL) receptor leading to increased binding and uptake, in effect significantly reducing total lipid levels in the blood serum and liver. This is followed by decreased biosynthesis of cholesterol and fatty acids. To understand the relationship of identified genes from legume studies, we performed gene network analysis, pathway, and gene ontology (GO) enrichment. Results showed that the genes were functionally interrelated while enrichment and pathway analysis revealed involvement in lipid transport, fatty acid and triglyceride metabolic processes, and regulatory processes. This review is the first attempt to collate all known mechanisms of action of legume proteins associated with cardiovascular health. This also provides a snapshot of possible targets leading to systems-level approaches to further investigate the cardiometabolic potentials of legumes

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society