Pain Relief and Functional Recovery in Patients with Complex Regional Pain Syndrome after Motor Cortex Stimulation

In addition to pain and neurovegetative symptoms, patients with severe forms of complex regional pain syndrome (CRPS) develop a broad range of symptoms, including sensory disturbances, motor impairment and dystonic posturing. While most patients respond to medical therapy, some are considered refractory and become surgical candidates. To date, the most commonly used surgical procedure for CRPS has been spinal cord stimulation. This therapy often leads to important analgesic effects, but no sensory or motor improvements. We report on 2 patients with pain related to CRPS and severe functional deficits treated with motor cortex stimulation (MCS) who not only had significant analgesic effects, but also improvements in sensory and motor symptoms. In the long term (27 and 36 months after surgery), visual analog scale pain scores were improved by 60-70% as compared to baseline. There was also a significant increase in the range of motion in the joints of the affected limbs and an improvement in allodynia, hyperpathia and hypoesthesia. Positron emission tomography scan in both subjects revealed that MCS influenced regions involved in the circuitry of pain. Copyright (C) 2011 S. Karger AG, Basel

alpha-Melanocyte Stimulating Hormone Analogue AP214 Protects Against Ischemia Induced Acute Kidney Injury in a Porcine Surgical Model

Purpose: alpha-Melanocyte stimulating hormone protects kidneys against ischemia and sepsis induced acute kidney injury in rodents. We examined the efficacy of a-melanocyte stimulating hormone analogue AP214 to protect against acute kidney injury in higher vertebrates. Materials and Methods: We performed a prospective, blinded, randomized, placebo controlled study in 26 pigs. Laparoscopic technique was used for left nephrectomy and to induce complete warm ischemia in the right kidney for 120 minutes. AP214 (200 mu g/kg intravenously) was administered daily on the day of surgery and for 5 days thereafter. Kidney function was measured for 9 days. We measured changes in serum creatinine, estimated glomerular filtration rate, serum C-reactive protein and urine interleukin-18. Results: In the placebo control and AP214 groups mean peak serum creatinine was 10.2 vs 3.92 mg/dl and the estimated glomerular filtration rate nadir was 22.9 vs 62.6 ml per minute per kg (each p = 0.001). Functional nadir occurred at 72 vs 24 hours in the control vs AP214 groups. Estimated glomerular filtration rate outcome on postoperative day 9 was 118 vs 156 ml per minute per kg in the control vs AP214 groups (p = 0.04). Conclusions: We noted a robust renoprotective effect of AP214. A similar AP214 effect may be observed in humans. Future research includes mechanistic studies in pigs and a phase II human clinical trial of AP214 in kidney transplant and partial nephrectomy populations.

Is the Sciatic Functional Index always reliable and reproducible?

The Sciatic Functional Index (SFI) is a quite useful tool for the evaluation of functional recovery of the sciatic nerve of rats in a number of experimental injuries and treatments. Although it is an objective method, it depends on the examiner`s ability to adequately recognize and mark the previously established footprint key points, which is an entirely subjective step, thus potentially interfering with the calculations according to the mathematical formulae proposed by different authors. Thus, an interpersonal evaluation of the reproducibility of an SFI computer-aided method was carried out here to study data variability. A severe crush injury was produced on a 5 mm-long segment of the right sciatic nerve of 20 Wistar rats (a 5000 g load directly applied for 10 min) and the SH was measured by four different examiners (an experienced one and three newcomers) preoperatively and at weekly intervals from the 1st to the 8th postoperative week. Three measurements were made for each print and the average was calculated and used for statistical analysis. The results showed that interpersonal correlation was high (0.82) in the 3rd, 4th, 5th, 7th and 8th weeks, with an unexpected but significant (p < 0.01) drop in the 6th week. There was virtually no interpersonal correlation (correlation index close to 0) on the 1st and 2nd weeks, a period during which the variability between animals and examiners (p =0.24 and 0.32, respectively) was similar, certainly due to a poor definition of the footprints. The authors conclude that the SFI method studied here is only reliable from the 3rd week on after a severe lesion of the sciatic nerve of rats. (C) 2008 Elsevier B.V. All rights reserved.

Experimental model for study of anorectal sphincter musculature by manometry and computerized tomography in piglets

There seems to be controversy on the anorectal sphincter presentation and anatomical division, as well as on its functional representation. Evaluation of the anorectal sphincter musculature has been achieved through several methods, including anorectal manometry and computerized tomography, but to date there is no experimental model allowing a detailed manometric study of this muscle complex. In this work, we have developed such a model, which should enable the manometric and radiographic study of the anatomical features and functional mechanisms of sphincteric injuries, as well as the assessment of drug effects on the anorectal musculature upon incontinence and constipation. Twenty-two piglets (aged 25-30 days, weighing 5-7 kg) were studied by anorectal manometry (rectoanal inhibitory reflex and vector volume) and computerized tomography (anorectal angle and anal canal length). The data obtained for the rectoanal inhibitory reflex, represented here as the average and standard deviation, were the following: relaxation duration = 14.75 +/- 3.62 s, sphincter basal pressure = 41.58 +/- 8.20 mmHg, relaxation index = 87.26 +/- 11.52%, speed of relaxation = 5.90 +/- 2.10 mm/s, and speed of relaxation recovery = 4.03 +/- 1.78 mm/s. As for the vector volume, results were as follows: vector volume = 2692.32 +/- 1298.12 mmHg(2) cm, sphincter length = 11.82 +/- 2.74 mm, high pressure zone length = 5.09 +/- 1.34 mm, maximum pressure = 61.50 +/- 20.58 mmHg, and asymmetry index = 43.50 +/- 10.03%. Radiographic evaluation led to the following results: anal canal length = 9.61 +/- 2.14 mm and anorectal angle = 137.91 +/- 7.75 degrees. The experimental model designed here allows both anorectal manometry and computerized tomography to be carried out in the same way it is performed in human beings, as long as animal sedation is strictly controlled.

Functional characterization of the hypothalamic-pituitary-adrenal axis of the Wistar Audiogenic Rat (WAR) strain

The Wistar Audiogenic Rat (WAR) strain is a genetic model of sound-induced reflex epilepsy which was selected starting from audiogenic seizures susceptible Wistar rats. Wistar resistant rats were used as WAR`s control in this study. In the acute situation, audiogenic seizures (AS) in WARs mimic tonic-clonic seizures and, in the chronic protocol, mimic temporal lobe epilepsy. AS have been shown to evoke neuroendocrine responses; however, the hypothalamic-pituitary-adrenal activity in the WAR has not been established. The aim of this study was to evaluate the hypothalamic-pituitary-adrenal axis (HPA) responses to exogenous ACTH stimulation (8 ng/rat), fifteen minute restraint stress and circadian variation (8 am and 8 pm) under rest conditions in these animals through plasma measurements of ACTH and corticosterone concentrations. We also measured the body weight from birth to the 9th week of life and determined adrenal gland weight. We found that WARs are smaller than Wistar and presented a higher adrenal gland weight with a higher level of corticosterone release after intravenous ACTH injection. They also showed altered HPA axis circadian rhythms and responses to restraint stress. Our data indicate that, despite the lower body weight, WARs have increased adrenal gland weight associated with enhanced pituitary and adrenal responsiveness after HPA axis stimulation. Thus, we propose WARs as a model to study stress-epilepsy interactions and epilepsy-neuropsychiatry comorbidities. (C) 2011 Elsevier B.V. All rights reserved.

The Stability of the Blood Oxygenation Level-Dependent Functional MRI Response to Motor Tasks Is Altered in Patients With Chronic Ischemic Stroke

Background and Purpose-Functional MRI is a powerful tool to investigate recovery of brain function in patients with stroke. An inherent assumption in functional MRI data analysis is that the blood oxygenation level-dependent (BOLD) signal is stable over the course of the examination. In this study, we evaluated the validity of such assumption in patients with chronic stroke. Methods-Fifteen patients performed a simple motor task with repeated epochs using the paretic and the unaffected hand in separate runs. The corresponding BOLD signal time courses were extracted from the primary and supplementary motor areas of both hemispheres. Statistical maps were obtained by the conventional General Linear Model and by a parametric General Linear Model. Results-Stable BOLD amplitude was observed when the task was executed with the unaffected hand. Conversely, the BOLD signal amplitude in both primary and supplementary motor areas was progressively attenuated in every patient when the task was executed with the paretic hand. The conventional General Linear Model analysis failed to detect brain activation during movement of the paretic hand. However, the proposed parametric General Linear Model corrected the misdetection problem and showed robust activation in both primary and supplementary motor areas. Conclusions-The use of data analysis tools that are built on the premise of a stable BOLD signal may lead to misdetection of functional regions and underestimation of brain activity in patients with stroke. The present data urge the use of caution when relying on the BOLD response as a marker of brain reorganization in patients with stroke. (Stroke. 2010; 41:1921-1926.)

Spironolactone and hydrochlorothiazide exert antioxidant effects and reduce vascular matrix metalloproteinase-2 activity and expression in a model of renovascular hypertension

Background and purpose: Increased oxidative stress and up-regulation of matrix metalloproteinases (MMPs) may cause structural and functional vascular changes in renovascular hypertension. We examined whether treatment with spironolactone (SPRL), hydrochlorothiazide (HCTZ) or both drugs together modified hypertension-induced changes in arterial blood pressure, aortic remodelling, vascular reactivity, oxidative stress and MMP levels and activity, in a model of renovascular hypertension. Experimental approach: We used the two-kidney,one-clip (2K1C) model of hypertension in Wistar rats. Sham-operated or hypertensive rats were treated with vehicle, SPRL (25 mg center dot kg-1 center dot day-1), HCTZ (20 mg center dot kg-1 center dot day-1) or a combination for 8 weeks. Systolic blood pressure was monitored weekly. Aortic rings were isolated to assess endothelium-dependent and -independent relaxations. Morphometry of the vascular wall was carried out in sections of aorta. Aortic NADPH oxidase activity and superoxide production were evaluated. Formation of reactive oxygen species was measured in plasma as thiobarbituric acid-reactive substances. Aortic MMP-2 levels and activity were determined by gelatin and in situ zymography, fluorimetry and immunohistochemistry. Key results: Treatment with SPRL, HCTZ or the combination attenuated 2K1C-induced hypertension, and reversed the endothelial dysfunction in 2K1C rats. Both drugs or the combination reversed vascular aortic remodelling induced by hypertension, attenuated hypertension-induced increases in oxidative stress and reduced MMP-2 levels and activity. Conclusions and implications: SPRL or HCTZ, alone or combined, exerted antioxidant effects, and decreased renovascular hypertension-induced MMP-2 up-regulation, thus improving the vascular dysfunction and remodelling found in this model of hypertension.

Color constancy and the functional significance of McCollough effects

A central problem in visual perception concerns how humans perceive stable and uniform object colors despite variable lighting conditions (i.e. color constancy). One solution is to 'discount' variations in lighting across object surfaces by encoding color contrasts, and utilize this information to 'fill in' properties of the entire object surface. Implicit in this solution is the caveat that the color contrasts defining object boundaries must be distinguished from the spurious color fringes that occur naturally along luminance-defined edges in the retinal image (i.e. optical chromatic aberration). In the present paper, we propose that the neural machinery underlying color constancy is complemented by an 'error-correction' procedure which compensates for chromatic aberration, and suggest that error-correction may be linked functionally to the experimentally induced illusory colored aftereffects known as McCollough effects (MEs). To test these proposals, we develop a neural network model which incorporates many of the receptive-field (RF) profiles of neurons in primate color vision. The model is composed of two parallel processing streams which encode complementary sets of stimulus features: one stream encodes color contrasts to facilitate filling-in and color constancy; the other stream selectively encodes (spurious) color fringes at luminance boundaries, and learns to inhibit the filling-in of these colors within the first stream. Computer simulations of the model illustrate how complementary color-spatial interactions between error-correction and filling-in operations (a) facilitate color constancy, (b) reveal functional links between color constancy and the ME, and (c) reconcile previously reported anomalies in the local (edge) and global (spreading) properties of the ME. We discuss the broader implications of these findings by considering the complementary functional roles performed by RFs mediating color-spatial interactions in the primate visual system. (C) 2002 Elsevier Science Ltd. All rights reserved.

Close packed transitions in slit-shaped pores: Density functional theory study of methane adsorption capacity in carbon

An important feature of improving lattice gas models and classical isotherms is the incorporation of a pore size dependent capacity, which has hitherto been overlooked. In this paper, we develop a model for predicting the temperature dependent variation in capacity with pore size. The model is based on the analysis of a lattice gas model using a density functional theory approach at the close packed limit. Fluid-fluid and solid-fluid interactions are modeled by the Lennard-Jones 12-6 potential and Steele's 10-4-3, potential respectively. The capacity of methane in a slit-shaped carbon pore is calculated from the characteristic parameters of the unit cell, which are extracted by minimizing the grand potential of the unit cell. The capacities predicted by the proposed model are in good agreement with those obtained from grand canonical Monte Carlo simulation, for pores that can accommodate up to three adsorbed layers. Single particle and pair distributions exhibit characteristic features that correspond to the sequence of buckling and rhombic transitions that occur as the slit pore width is increased. The model provides a useful tool to model continuous variation in the microstructure of an adsorbed phase, namely buckling and rhombic transitions, with increasing pore width. (C) 2002 American Institute of Physics.

Density functional theory analysis of the influence of pore wall heterogeneity on adsorption in carbons

Density functional theory for adsorption in carbons is adapted here to incorporate a random distribution of pore wall thickness in the solid, and it is shown that the mean pore wall thickness is intimately related to the pore size distribution characteristics. For typical carbons the pore walls are estimated to comprise only about two graphene layers, and application of the modified density functional theory approach shows that the commonly used assumption of infinitely thick walls can severely affect the results for adsorption in small pores under both supercritical and subcritical conditions. Under supercritical conditions the Henry's law coefficient is overpredicted by as much as a factor of 2, while under subcritical conditions pore wall heterogeneity appears to modify transitions in small pores into a sequence of smaller ones corresponding to pores with different wall thicknesses. The results suggest the need to improve current pore size distrubution analysis methods to allow for pore wall heterogeneity. The density functional theory is further extended here to allow for interpore adsorbate interactions, and it appears that these interaction are negligible for small molecules such as nitrogen but significant for more strongly interacting heavier molecules such as butane, for which the traditional independent pore model may not be adequate.

The structural and functional diversity of naturally occurring antimicrobial peptides

Antimicrobial peptides occur in a diverse range of organisms from microorganisms to insects, plants and animals. Although they all have the common function of inhibiting or killing invading microorganisms they achieve this function using an extremely diverse range of structural motifs. Their sizes range from approximately 10-90 amino acids. Most carry an overall positive charge, reflecting a preferred mode of electrostatic interaction with negatively charged microbial membranes. This article describes the structural diversity of a representative set of antimicrobial peptides divided into five structural classes: those with agr-helical structure, those with bgr-sheet structure, those with mixed helical / bgr- sheet structure, those with irregular structure, and those incorporating a macrocyclic structure. There is a significant diversity in both the size and charge of molecules within each of these classes and between the classes. The common feature of their three-dimensional structures is, however, that they have a degree of amphipathic character in which there is separate localisation of hydrophobic regions and positively charged regions. An emerging trend amongst antimicrobial proteins is the discovery of more macrocyclic analogues. Cyclisation appears to impart an additional degree of stability on these molecules and minimizes proteolytic cleavage. In conclusion, there appear to be a number of promising opportunities for the development of novel clinically useful antimicrobial peptides based on knowledge of the structures of naturally occurring antimicrobial molecules.

Motor and functional skills of children with developmental coordination disorder: A pilot investigation of measurement issues

This paper reports on the motor and functional outcomes of 20 children with developmental coordination disorder (DCD) aged 4-8 years consecutively referred to a pediatric physiotherapy service. Children with a Movement ABC (M-ABC) score less than the 15th percentile, and with no concurrent medical, sensory, physical, intellectual or neurological impairments, were recruited. The Motor Assessment Outcomes Model (MAOM) [Coster and Haley, Infants and Young Children 4 (1992) 11] provided the theoretical base for measurement selection, and preliminary findings at the activities and participation levels of the model are reported in this article. Children with DCD performed at the lower end of the normal range on the Pea-body Developmental Motor Scales (fine motor total score) (M = 85.65, SD = 12.23). Performance on the Visual Motor Integration Test (VMI) standard scores was within the average range (M = 96.15, SD = 10.69). Videotaped observations of the children's writing and cutting indicated that 29% were left-handed and that a large proportion of all children (31%) utilized unusual pencil grasp patterns and immature prehension of scissors. Measurement at the participation level involved use of the Pictorial Scale of Perceived Competence and Social Acceptance (PCSA) and Pediatric Evaluation of Disability Inventory (PEDI). Overall, these young children rated themselves towards the more competent and accepted end of the PCSA over the dimensions of physical and cognitive competence and peer and maternal acceptance. The PEDI revealed generally average performance on social (M = 49.98, SD = 16.62) and mobility function (M = 54.71, SD = 3.99), however, self-care function was below the average range for age (M = 38.01, SD = 12.19). The utility of the MAOM as a framework for comprehensive measurement of functional and motor outcomes of DCD in young children is discussed. (C) 2003 Elsevier B.V. All rights reserved.

Combining Formal Methods and Functional Strategies Regarding the Reverse Engineering of Interactive Applications

Abstract. Graphical user interfaces (GUIs) make software easy to use by providing the user with visual controls. Therefore, correctness of GUI’s code is essential to the correct execution of the overall software. Models can help in the evaluation of interactive applications by allowing designers to concentrate on its more important aspects. This paper describes our approach to reverse engineer an abstract model of a user interface directly from the GUI’s legacy code. We also present results from a case study. These results are encouraging and give evidence that the goal of reverse engineering user interfaces can be met with more work on this technique.

Studies in search of a suitable experimental insect model for xenodiagnosis of hosts with Chagas' disease: 4 - The reflection of parasite stock in the responsiveness of different vector species to chronic infection with different Trypanosoma cruzi stocks

Previous studies (1982,1987) have emphasized the superiority of sylvatic vector species over domestic species as xenodiagnostic agents in testing hosts with acute or chronic infections by T. cruzi "Y" stock. The present study, which is unique in that it contains data on both infectivity rates produced by the same stock in 11 different vector species and also the reaction of the same vector species to seven different parasite stocks, establishes the general validity of linking efficiency of xenodiagnosis to the biotope of its agent. For example, infectivity rates produced by "São Felipe" stock varied from 82.5% to 98.3% in sylvatic vectors but decreased to 42.5% to 71.3% in domestic species. "Colombiana" stock produced in the same sylvatic vectors infectivity rates ranging from 12.5% to 45%. These shrank to 5%-22.5% in domestic bugs. The functional role of the biotope in the vector-parasite interaction has not been eluddated. But since this phenomenon has been observed to be stable and easy to reproduce, it leads us to believe that the results obtained are valid. Data presented also provide increasing evidence that the infectivity rates exhibited by bugs from xenodiagnosis in chronic hosts, are parasite stock specific. For example, infectivity rates produced by "Berenice", "Y", "FL" and "CL" varied in R. neglectus from 26.3% to 75%; in P. megistus from 56.3% to 83.8%; in T. sordida from 28.8% to 58.8% in T. pseudomaculata from 41.3% to 66.3% and in T. rubrovaria from 48.8% to 85%. Data from xenodiagnosis in the same hosts, carrying acute infections by the same parasite stocks, gave the five sylvatic vectors a positive rating of approximately 100%, thus suggesting that the heavy loads of parasites circulating in the acute hosts obscured the characteristic interspecific differences for the parasite stock. Nonetheless these latter were revealed in the same hosts with chronic infections stimulated by very low numbers of the same parasite stocks. Certain observations here described lead us to speculate as to the possibility of further results from other parasite stocks, allowing the association of the infectivity rates produced in bugs by different parasite stocks with the isoenzymic patterns revealed by these stocks.

MDAI: Model based Design in Automobile Industry

It is proposed a new approach based on a methodology, assisted by a tool, to create new products in the automobile industry based on previous defined processes and experiences inspired on a set of best practices or principles: it is based on high-level models or specifications; it is component-based architecture centric; it is based on generative programming techniques. This approach follows in essence the MDA (Model Driven Architecture) philosophy with some specific characteristics. We propose a repository that keeps related information, such as models, applications, design information, generated artifacts and even information concerning the development process itself (e.g., generation steps, tests and integration milestones). Generically, this methodology receives the users' requirements to a new product (e.g., functional, non-functional, product specification) as its main inputs and produces a set of artifacts (e.g., design parts, process validation output) as its main output, that will be integrated in the engineer design tool (e.g. CAD system) facilitating the work.