How to gain evidence in neurorehabilitation: a personal view

Neurorehabilitation is an emerging field driven by developments in neuroscience and biomedical engineering. Most patients that require neurorehabilitation have had a stroke, but other diseases of the brain, spinal cord, or nerves can also be alleviated. Modern therapies in neurorehabilitation focus on reducing impairment and improving function in daily life. As compared with acute care medicine, the clinical evidence for most neurorehabilitative treatments (modern or conventional) is sparse. Clinical trials support constraint-induced movement therapy for the arm and aerobic treadmill training for walking, both high-intensity interventions requiring therapist time (i.e., cost) and patient motivation. Promising approaches for the future include robotic training, telerehabilitation at the patient's home, and supportive therapies that promote motivation and compliance. It is argued that a better understanding of the neuroscience of recovery together with results from small-scale and well-focused clinical experiments are necessary to design optimal interventions for specific target groups of patient

Role of walking-exercise therapy after stroke

Stroke commonly leads to reduced mobility, which leads to deconditioning and a worsening of vascular risk factors, such as diabetes. The worsened risk profile leads to further strokes and disability--a vicious cycle for the stroke survivor. Exercise (walking) therapy may break this cycle by providing adequate stimuli for improving gait through plastic adaptation in the brain and through increasing fitness. Randomized, controlled data demonstrate the efficacy for gains in fitness and walking speed, the latter being related to lasting changes in activation patterns of the brainstem and cerebellum. Diabetes and muscle inflammation can also be improved by aerobic exercise training. The scope of this review summarizes these data and identifies unresolved issues related to optimization, intensity and maintenance of therapy effects. Exercise should be an integral part of every rehabilitation program

Inhibition of Trophoblast-Induced Spiral Artery Remodeling Reduces Placental Perfusion in Rat Pregnancy.

Rats harboring the human angiotensinogen and human renin genes develop preeclamptic features in pregnancy. The preeclamptic rats exhibit a deeper trophoblast invasion associated with a reduced resistance index by uterine Doppler. Doxycycline inhibits matrix metalloproteinase activity. We tested the hypothesis that matrix metalloproteinase inhibition reduces trophoblast invasion with subsequent changes in placental perfusion. Preeclamptic and pregnant control Sprague-Dawley rats were treated with doxycycline (30 mg/kg of body weight orally) from gestational day 12 until day 18. Placental perfusion was assessed using a micromarker contrast agent. The animals were euthanized on day 18 of pregnancy; biometric data were acquired, and trophoblast invasion was analyzed. Doxycycline resulted in intrauterine growth retardation and lighter placentas in both groups. Maternal body weight was not affected. As shown earlier, preeclamptic rats exhibited a deeper endovascular trophoblast invasion. However, doxycycline treatment reduced trophoblast invasion in the preeclamptic rats. The physiological spiral artery remodeling, as assessed by the deposition of fibrinoid and α-actin in the spiral artery contour, was significantly reduced by doxycycline. The vascularity index, as assessed by perfusion measurement of the placenta, was reduced after doxycycline treatment in preeclamptic rats. Thus, matrix metalloproteinase inhibition with doxycycline leads to reduced trophoblast invasion and associated reduced placental perfusion. These studies are the first to show that reducing trophoblast-induced vascular remodeling decreases subsequent placental perfusion. Our model allows the study of dysregulated trophoblast invasion and vascular remodeling in vivo to gain important insights into preeclampsia-related mechanisms

Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy.

The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration

The repertory of bone marrow progenitor cells associated with lymphogenic metastasis in patients with invasive carcinoma of no special type

The high mortality of patients with breast cancer is determined by metastatic disease. It is thought that the metastatic disease development associated with the repertory of bone marrow progenitor cells in breast cancer patients. In our study the correlation between the bone marrow progenitor cells presences in the tumor and blood of patients and the lymphogenic metastasis development was studied. The main clinical and pathological parameters of 24 patients with invasive breast carcinoma of non-specific type were analyzed. Endothelial progenitor cells, mesenchymal stem cells, macrophage precursors, hematopoietic progenitor cells were detected with specific antibodies against CD34, CD133, CD90, VEGFR1, CD11b, CD45, CD202 in the cell-rich fluid from frozen tumor. The amount of MCP-1 in the patients blood serum was assessed by enzymelinked immunosorbent assay (ELISA), at a wavelength of 450 nm. The cytokines concentration was calculated from the calibration plot. The program package Statistica 10.0. was used for statistical data processing. The high risk of lymphogenic metastasis in patients who didn't complete a neoadjuvant chemotherapy course was associated with the number of HPC, EPC and MSC in tumor and MCP-1 in blood

Coherent states on the circle

We present a possible construction of coherent states on the unit circle as configuration space. In our approach the phase space is the product Z x S^1. Because of the duality of canonical coordinates and momenta, i.e. the angular variable and the integers, this formulation can also be interpreted as coherent states over an infinite periodic chain. For the construction we use the analogy with our quantization over a finite periodic chain where the phase space was Z_M x Z_M. Properties of the coherent states constructed in this way are studied and the coherent states are shown to satisfy the resolution of unity.Comment: 7 pages, presented at GROUP28 - "28th International Colloquium on Group Theoretical Methods in Physics", Newcastle upon Tyne, July 2010. Accepted in Journal of Physics Conference Serie

Monitoring and Pay: An Experiment on Employee Performance under Endogenous Supervision

We present an experimental test of a shirking model where monitoring intensity is endogenous and effort a continuous variable. Wage level, monitoring intensity and consequently the desired enforceable effort level are jointly determined by the maximization problem of the firm. As a result, monitoring and pay should be complements. In our experiment, between and within treatment variation is qualitatively in line with the normative predictions of the model under standard assumptions. Yet, we also find evidence for reciprocal behavior. Our data analysis shows, however, that it does not pay for the employer to solely rely on the reciprocity of employees

No Impact of Body Mass Index on Outcome in Stroke Patients Treated with IV Thrombolysis BMI and IV Thrombolysis Outcome.

The impact of excess body weight on prognosis after stroke is controversial. Many studies report higher survival rates in obese patients ("obesity paradox"). Recently, obesity has been linked to worse outcomes after intravenous (IV) thrombolysis, but the number and sample size of these studies were small. Here, we aimed to assess the relationship between body weight and stroke outcome after IV thrombolysis in a large cohort study. In a prospective observational multicenter study, we analyzed baseline and outcome data of 896 ischemic stroke patients who underwent IV thrombolysis. Patients were categorized according to body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obese (30-34.9 kg/m2) or severely obese (>35 kg/m2). Using uni- and multivariate modeling, we assessed the relationship of BMI with favorable outcome (defined as modified Rankin Scale 0 or 1) and mortality 3 months after stroke as well as the occurrence of symptomatic intracerebral hemorrhages (sICH). We also measured the incidence of patients that had an early neurological improvement of >40% on the National Institutes of Health Stroke Scale (NIHSS) after 24 hours. Among 896 patients, 321 were normal weight (35.8%), 22 underweight (2.5%), 378 overweight (42.2%), 123 obese (13.7%) and 52 severely obese (5.8%). Three-month mortality was comparable in obese vs. non-obese patients (8.1% vs. 8.3%) and did not differ significantly among different BMI groups. This was also true for favorable clinical outcome, risk of sICH and early neurological improvement on NIHSS at 24 hours. These results remained unchanged after adjusting for potential confounding factors in the multivariate analyses. BMI was not related to clinical outcomes in stroke patients treated with IVT. Our data suggest that the current weight-adapted dosage scheme of IV alteplase is appropriate for different body weight groups, and challenge the existence of the obesity paradox after stroke

Mortality among World Trade Center rescue and recovery workers, 2002-2011

BACKGROUND: Rescue and recovery workers responding to the 2001 collapse of the World Trade Center (WTC) sustained exposures to toxic chemicals and have elevated rates of multiple morbidities. METHODS: Using data from the World Trade Center Health Program and the National Death Index for 2002-2011, we examined standardized mortality ratios (SMR) and proportional cancer mortality ratios (PCMR) with indirect standardization for age, sex, race, and calendar year to the U.S. general population, as well as associations between WTC-related environmental exposures and all-cause mortality. RESULTS: We identified 330 deaths among 28,918 responders (SMR 0.43, 95%CI 0.39-0.48). No cause-specific SMRs were meaningfully elevated. PCMRs were elevated for neoplasms of lymphatic and hematopoietic tissue (PCMR 1.76, 95%CI 1.06-2.75). Mortality hazard ratios showed no linear trend with exposure. CONCLUSIONS: Consistent with a healthy worker effect, all-cause mortality among responders was not elevated. There was no clear association between intensity and duration of exposure and mortality. Surveillance is needed to monitor the proportionally higher cancer mortality attributed to lymphatic/hematopoietic neoplasms

Закономерности изменения физико-механических свойств сплава Zr-1%Nb при комплексном ионно-плазменном модифицировании поверхности и наводороживании

В работе были изучены особенности изменения морфологии, структуры и физико-механических свойств циркониевого сплава Zr-1%Nb, подвергнутого комплексному ионно-плазменному модифицированию поверхности методами плазменно-иммерсионной ионной имплантации титана и осаждения покрытий нитрида титана. Показана высокая эффективность защиты сформированных структур от проникновения водорода в циркониевый сплав. Изучены механизмы сорбции и захвата водорода в титансодержащем модифицированном слое.In the present work, the features of the change in the morphology, structure, and physico-mechanical properties of zirconium alloy Zr-1%Nb subjected to complex ion-plasma surface modification by the methods of plasma-immersion titanium ion implantation and deposition of titanium nitride coatings were studied. The high protective properties of the formed structures against hydrogen permeation into the zirconium alloy is shown. Mechanisms of sorption and capture of hydrogen in a titanium-doped modified layer are studied