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Objective: The cardioprotective enzyme paraoxonase-1 (PON1) suffers an important influence from genetic polymorphisms and nutritional factors. The aim of this study was to investigate the influence of diet, nutritional status, and the C(-107)T polymorphism on PON1 arylesterase activity in children. Methods: This was a cross-sectional study with 97 children, aged between 5 and 8 years, of both genders, from a pediatric outpatient clinic in southern Brazil. A sociodemographic, behavioral, and food consumption questionnaire was applied, and anthropometric measurements and laboratory blood samples were taken. PON1 arylesterase activity was measured by phenol extinction (U/mL), and DNA extraction and analysis of the PON1 C(-107)T polymorphism were performed. The Hardy-Weinberg equilibrium was tested with the chi-squared test and linear regression was used to estimate PON1 activity according to four adjustment models, with an acceptable error of 5%. Results: In the sample, the male gender accounted for 50.5%, 39.2% were 6 years of age, 54.5% had normal weight, and 51.5% had PON1 activity below the median (90.0, 15-30 U/mL). Genotype frequency was 54.6% (53/97), 31.0% (30/97), and 14.4% (14/97), respectively, for CT, CC, and TT, consistent with the Hardy-Weinberg equilibrium (p = 0.22). In the regression analysis, the model that included sociodemographic variables as well as frequency of consumption of fruits, vegetables, legumes, dairy products, and beans estimated a variability of 14.8% in PON1 activity combined with the PON1 C(-107)T polymorphism. Conclusions: During childhood, a good-quality diet with greater inclusion of healthy foods was important to predict the activity of the cardioprotective enzyme PON1 combined with the C(-107)T polymorphism of the PON1 gene. Resumo Objetivo: A enzima cardioprotetora Paraoxonase 1 (PON1) sofre importante influência de polimorfismos genéticos e fatores nutricionais. O objetivo deste estudo foi investigar a influência da alimentação, do estado nutricional e do polimorfismo C(-107)T sobre a atividade arilesterase da PON1 em crianças. Métodos: Estudo transversal com 97 crianças entre 5 e 8 anos, de ambos os sexos, de um ambulatório de pediatria no sul do Brasil. Realizou-se questionário sociodemográfico, de comportamento e de consumo alimentar, medidas antropométricas e coleta de sangue em laboratório. A atividade arilesterase da PON1 foi mensurada pela extinção de fenol (U/mL), realizada extração do DNA e análise do polimorfismo PON1 C(-107)T. O equilíbrio de Hardy-Weinberg foi testado com qui-quadrado e usada regressão linear para estimar a atividade da PON1 segundo quatro modelos de ajuste, erro aceitável de 5%. Resultados: Na amostra o sexo masculino representou 50,5%, 39,2% tinham 6 anos, 54,5% eram eutróficos e 51,5% tinha atividade da PON1 inferior à mediana (90,0;15-30 U/ml). A frequência dos genótipos foi 54,6% (53/97), 31,0% (30/97) e 14,4% (14/97), respectivamente, para CT, CC e TT, estiveram em equilíbrio de Hardy-Weinberg (p = 0,22). Na análise de regressão o modelo que incluiu variáveis sociodemográficas, de frequência do consumo de frutas, verduras, legumes, laticínios e feijões estimou uma variabilidade de 14,8% na atividade da PON1 combinada ao polimorfismo PON1 C(-107)T. Conclusões: Na infância uma alimentação de boa qualidade, com maior participação de alimentos saudáveis foi importante para predizer a atividade da enzima cardioprotetora PON1 combinada ao polimorfismo C(-107)T do gene da PON1.

Affective disorders (i.e. anxiety and depression) are commonly observed in patients with epilepsy and induce seizure aggravation. Animal models of epilepsy that exhibit affective disorder features are essential in developing new neuromodulatory treatments. GEAS-W rats (Generalized Epilepsy with Absence Seizures, Wistar background) are an inbred model of generalized epilepsy showing spontaneous spike-wave discharges concomitant with immobility. Transcranial Direct Current Stimulation (tDCS) is a safe non-invasive neuromodulatory therapy used to modulate dysfunctional circuitries frequently and successfully applied in affective disorders for symptom alleviation. Here we investigated anxiolytic and antidepressant effects of tDCS in GEAS-W rats and the role of corticosterone as a possible mechanism of action. GEAS-W and Wistar rats were randomly divided into control, sham-tDCS and active-tDCS groups. Both tDCS groups received 15 sessions of sham or active-tDCS (1mA, cathode). Behavioural tests included the Open Field and Forced Swimming tests followed by corticosterone analysis. We observed a main effect of treatment and a significant treatment by strain interaction on anxiety-like and depressive-like behaviours, with active-tDCS GEAS-W rats entering the center of the open field more often and showing less immobility in the forced swimming test. Furthermore, there was a main effect of treatment on corticosterone with active-tDCS animals showing marked reduction in plasmatic levels. This study described preclinical evidence to support tDCS treatment of affective disorders in epilepsy and highlights corticosterone as a possible mechanism of action.

We present an adaptation of Bemis & Pylkkänen’s (2011) two-word, composition-list paradigm to study elementary composition in Spanish using electroencephalography. Our main objective is to determine if EEG is sensitive enough to detect a composition-related activity and to evaluate whether the expectancy of participants to compose contributes to this signal. Although we found relevant activity at the expected channels and times, we also found putative composition-related activity before the second word onset. Using a threshold-free cluster permutation analysis combined with linear models we show a task progression effect for the composition task that is not present for the list task. In a second experiment we evaluate two-word composition while avoiding differential expectancy effects across stimuli by incorporating all conditions to a single task. In this case, we failed to find any significant composition-related activity. We suggest that the composition-related activity measured with EEG may be at least in part carried by expectancy processes arising from the block design of the experiment. We conclude that for this paradigm it is important to complement the block based experiments with those controlling for expectancy, and to use powerful data-driven techniques to analyze the data.

Periprosthetic fractures of the upper and lower extremities not only represent a challenge for surgeons but also for the rehabilitation team. The sometimes multimorbid patients have often undergone several surgical operations and need special planning and cooperation between an interdisciplinary team in order to achieve the best possible functional result and social reintegration. A structured rehabilitation planning after surgical treatment is a prerequisite for the patient to return to life as normal as possible. The aim is always rapid mobilization to achieve independence in activities of daily living. Special attention should be paid to postoperative immobilization and weight bearing.

We present a neural network model that can execute some of the procedures used in the information sciences literature. In particular we offer a simplified notion of topic and how to implement it using neural networks that use the Kronecker tensor product. We show that the topic detecting mechanism is related to Naive Bayes statistical classifiers, and that it is able to disambiguate the meaning of polysemous words. We evaluate our network in a text categorization task, resulting in performance levels comparable to Naive Bayes classifiers, as expected. Hence, we propose a simple scalable neural model capable of dealing with machine learning tasks, while retaining biological plausibility and probabilistic transparency.

Background Paraoxonase 1 (PON1) is an enzyme that possesses anti-atherogenic and anti-inflammatory properties with serum levels determined by genetic and exogenous factors. Lower serum PON1 arylesterase activity is associated to metabolic alterations related to childhood overweight and onset and/or development of diabetes and CVD later in life. However, data on the relationship between genetic PON1 polymorphisms and nutritional status as well as lipid profile in children are limited. To investigate the distribution of the C(−107)T PON1 gene polymorphism and its relation with serum PON1 enzyme activity, nutritional status and lipid profile in children. Methods A cross-sectional study was performed including 73 children aged 5 to 7 years who attended public pediatric clinics. PON1 C(−107)T, arylesterase activity, body mass index for the age, and serum lipid profile were evaluated. Results PON1 activity was higher in overweight children compared to the normal weight ones (p = 0.02). The genotypic frequency did not differ between the two groups (p > 0.05). Carriers of CC genotype had higher enzyme activity than T allele carriers, and this difference was greater among normal weight children. HDL levels were higher among normal weight children carrying CC genotype, compared to those carrying the T allele (p Conclusion The PON1 C(−107)T polymorphism is associated with higher serum enzyme activity in children, as observed previously in adults. In addition, this polymorphism also shows association to higher high density lipoprotein (HDL) levels and serum PON1 arylesterase activity in the normal weight children studied.

OBJECTIVES: This prospective, randomized, experimental study with rats aimed to investigate the influence of general treatment strategies on the motor recovery of Wistar rats with moderate contusive spinal cord injury. METHODS: A total of 51 Wistar rats were randomized into five groups: control, maze, ramp, runway, and sham (laminectomy only). The rats underwent spinal cord injury at the T9-T10 levels using the NYU-Impactor. Each group was trained for 12 minutes twice a week for two weeks before and five weeks after the spinal cord injury, except for the control group. Functional motor recovery was assessed with the Basso, Beattie, and Bresnahan Scale on the first postoperative day and then once a week for five weeks. The animals were euthanized, and the spinal cords were collected for histological analysis. RESULTS: Ramp and maze groups showed an earlier and greater functional improvement effect than the control and runway groups. However, over time, unexpectedly, all of the groups showed similar effects as the control group, with spontaneous recovery. There were no histological differences in the injured area between the trained and control groups. CONCLUSION: Short-term benefits can be associated with a specific training regime; however, the same training was ineffective at maintaining superior long-term recovery. These results might support new considerations before hospital discharge of patients with spinal cord injuries.

Graph-theoretical methods have recently been used to analyze certain properties of natural and social networks. In this work, we have investigated the early stages in the growth of a Uruguayan academic network, the Biology Area of the Programme for the Development of Basic Science (PEDECIBA). This transparent social network is a territory for the exploration of the reliability of clustering methods that can potentially be used when we are confronted with opaque natural systems that provide us with a limited spectrum of observables (happens in research on the relations between brain, thought and language). From our social net, we constructed two different graph representations based on the relationships among researchers revealed by their co-participation in Master’s thesis committees. We studied these networks at different times and found that they achieve connectedness early in their evolution and exhibit the small-world property (i.e. high clustering with short path lengths). The data seem compatible with power law distributions of connectivity, clustering coefficients and betweenness centrality. Evidence of preferential attachment of new nodes and of new links between old nodes was also found in both representations. These results suggest that there are topological properties observed throughout the growth of the network that do not depend on the representations we have chosen but reflect intrinsic properties of the academic collective under study. Researchers in PEDECIBA are classified according to their specialties. We analysed the community structure detected by a standard algorithm in both representations. We found that much of the pre-specified structure is recovered and part of the mismatches can be attributed to convergent interests between scientists from different sub-disciplines. This result shows the potentiality of some clustering methods for the analysis of partially known natural systems.

▪ Abstract Objective: To investigate whether active anodal transcranial direct current stimulation (tDCS) (of dorsolateral prefrontal cortex [DLPFC] and primary motor cortex [M1]) as compared to sham treatment is associated with changes in sleep structure in fibromyalgia. Methods: Thirty-two patients were randomized to receive sham stimulation or active tDCS with the anode centered over M1 or DLPFC (2 mA, 20 minutes for five consecutive days). A blinded evaluator rated the clinical symptoms of fibromyalgia. All-night polysomnography was performed before and after five consecutive sessions of tDCS. Results: Anodal tDCS had an effect on sleep and pain that was specific to the site of stimulation: such as that M1 and DLPFC treatments induced opposite effects on sleep and pain, whereas sham stimulation induced no significant sleep or pain changes. Specifically, whereas M1 treatment increased sleep efficiency (by 11.8%, P = 0.004) and decreased arousals (by 35.0%, P = 0.001), DLPFC stimulation was associated with a decrease in sleep efficiency (by 7.5%, P = 0.02), an increase in rapid eye movement (REM) and sleep latency (by 47.7%, P = 0.0002, and 133.4%, P = 0.02, respectively). In addition, a decrease in REM latency and increase in sleep efficiency were associated with an improvement in fibromyalgia symptoms (as indexed by the Fibromyalgia Impact Questionnaire). Finally, patients with higher body mass index had the worse sleep outcome as indexed by sleep efficiency changes after M1 stimulation. Interpretation: Our findings suggest that one possible mechanism to explain the therapeutic effects of tDCS in fibromyalgia is via sleep modulation that is specific to modulation of primary M1 activity. ▪

This analysis is focused on the comparison of costs of allergic rhinitis (R) alone or with allergic asthma (R + A) in grass pollen allergy, for subjects treated with sublingual immunotherapy (SLIT) and symptomatic drugs, versus standard care controls.The SIMAP (Sublingual IMmunotherapy in Allergic Patients) study is a longitudinal observational database operated by a network of Allergy centers. Patients suffering from grass pollen allergy were included in this analysis and assigned to SLIT (plus drugs as needed) or to treatment with drugs alone. Outcome measures included use of medications, SLIT, visits and tests. Costs were assessed from the perspective of the Italian National Health Service; unit costs were obtained from published sources to produce an average cost/patient for the first year after enrolment.One hundred and two patients were analyzed. Demographics were comparable in the two groups. Overall per patient yearly cost of treatment was higher in SLIT patients, both in the whole sample (euro311 vs. euro180/patient), in the R (euro288 vs. euro116) and R + A (euro362 vs. euro230) subpopulations, with R + A patients generating more costs than R patients in both groups. Nevertheless considerable savings were obtained in the cost of symptomatic drugs (-22% for R; -34% for R + A) in SLIT patients.Other studies have shown that SLIT can reduce the use of drugs for asthma and rhinitis, but this is the first time this outcome has been demonstrated in a routine care population (in the medical practice environment of an observational study) within the first year of treatment.

Possible interactions between the sleep-wakefulness cycle and a new kind of spontaneous epilepsy, expressed as absence-like seizures and spike-wave bursts in FMUSP rats, are evaluated. The electro-oscillograms of some cortical and subcortical regions of the brain were recorded, as well as head, rostrum/vibrissae and eye movements. Recordings were performed uninterruptedly during 24 hours. The seizures were mostly concentrated in the wakefulness state but they could occur in any other phase, including paradoxical sleep. After the seizure, the rats usually returned to the same phase that was interrupted, although they often returned to wakefulness. There was an intense fragmentation of the sleep-wakefulness cycle. The incidence of each cycle phase was significantly reduced, except S III of synchronized sleep and paradoxical sleep, thus maintaining the overall duration and architecture of the sleep-wakefulness cycle. The fragmentation of the cycle seems to be due to an impairment of the very processes that generate sleep and wakefulness. Electrophysiological and behavioral profiles of the FMUSP rats recommend accurate and comprehensive study of the animal model owing to its resemblance to seizures in humans and also to discrepancies with existing genetic or experimental epilepsy models.

Objective. Recent evidence suggests that fibromyalgia is a disorder characterized by dysfunctional brain activity. Because transcranial direct current stimulation (tDCS) can modulate brain activity noninvasively and can decrease pain in patients with refractory central pain, we hypothesized that tDCS treatment would result in pain relief in patients with fibromyalgia. Methods. Thirty-two patients were randomized to receive sham stimulation or real tDCS with the anode centered over the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC) (2 mA for 20 minutes on 5 consecutive days). A blinded evaluator rated the patient’s pain, using the visual analog scale for pain, the clinician’s global impression, the patient’s global assessment, and the number of tender points. Other symptoms of fibromyalgia were evaluated using the Fibromyalgia Impact Questionnaire and the Short Form 36 Health Survey. Safety was assessed with a battery of neuropsychological tests. To assess potential confounders, we measured mood and anxiety changes throughout the trial. Results. Anodal tDCS of the primary motor cortex induced significantly greater pain improvement compared with sham stimulation and stimulation of the DLPFC (P < 0.0001). Although this effect decreased after treatment ended, it was still significant after 3 weeks of followup (P 0.004). A small positive impact on quality of life was observed among patients who received anodal M1 stimulation. This treatment was associated with a few mild adverse events, but the frequency of these events in the active-treatment groups was similar to that in the sham group. Cognitive changes were similar in all 3 treatment groups. Conclusion. Our findings provide initial evidence of a beneficial effect of tDCS in fibromyalgia, thus encouraging further trials.

The development of neural network models has greatly enhanced the comprehension of cognitive phenomena. Here, we show that models using multiplicative processing of inputs are both powerful and simple to train and understand. We believe they are valuable tools for cognitive explorations. Our model can be viewed as a subclass of networks built on sigma-pi units and we show how to derive the Kronecker product representation from the classical sigma-pi unit. We also show how the connectivity requirements of the Kronecker product can be relaxed considering statistical arguments. We use the multiplicative network to implement what we call an Elman topology, that is, a simple recurrent network (SRN) that supports aspects of language processing. As an application, we model the appearance of hallucinated voices after network damage, and show that we can reproduce results previously obtained with SRNs concerning the pathology of schizophrenia.

Grande variedade de modelos experimentais foram estabelecidos em neuro-oncologia durante as últimas décadas, a fim de estudar a biologia tumoral e a eficiciência de novas drogas e novos tratamentos em gliomas malignos humanos. Embora estes modelos estejam bem caracterizados e sejam facilmente reproduzíveis e aplicáveis, há limitações quanto ao seu uso e à resposta obtida, principalmente quando utilizados para monitorização de tratamentos. A proposta deste estudo é padronizar modelo de tumor cerebral glial experimental e detectar variáveis que possam influenciar o seu desenvolvimento. Células 9L foram inoculadas na substância branca do cérebro em 48 ratos machos Sprague-Dawley; destes, 25 animais receberam eletrodos corticais para realização de eletroencefalografia. Os animais eram avaliados diariamente por observação neurológica. Vinte e quatro ratos desenvolveram tumor - 10 animais morreram ou no pós-operatório imediato ou durante a evolução; 14 animais não desenvolveram tumor. Macroscopicamente, o tumor parecia bem delimitado; características de malignidade e extensa infiltração foram observadas à microscopia de luz; o diagnóstico foi o de astrocitoma maligno. A utilização de técnica estereotáxica e a infusão de pequeno volume de suspensão celular por um tempo longo de infusão foram considerados importantes para o bom desenvolvimento do tumor. Procedimentos que merecem atenção são: contagem precisa das células na câmara de Neubauer, agitação constante da suspensão de células a serem inoculadas e fixação precisa da profundidade de inoculação. O modelo experimental desenvolvido no presente trabalho mostrou ser de execução relativamente fácil, com custo razoável e reprodutível. A number of experimental models have been established during the last decades in order to study tumor biology and the effects of treatment or manipulation of the microenvironment of malignant glial tumors. Even though those models have been well characterised and are, to a certain extent, easily reproducible, there are limitations as to their use and to the interpretation of the results. The aim of this study is to standardize a model of a malignant glial tumor and detect possible events able to modify its development. 9L cells were inoculated intracerebrally in 48 Sprague-Dawley rats; from these, 25 animals were also implanted with a device containing electrodes for the registration of the electroencephalogramm. Animals were daily evaluated by neurologic examination. Twenty four animals developed tumor - 10 animals died either in the immediate pos-operatory period or during evolution; 14 animals did not develop tumor. Macroscopically the tumor was well demarcated from the adjacent brain; by light microscopy the tumor exhibited malignant characteristics as well as extensive infiltration of the brain parenchyma. Diagnosis was that of a malignant astrocytoma. The use of the stereotaxic frame and care to infuse a small volume of liquid containing cells during a period of 120 seconds were the most important procedures to obtain sucess in the model. Additional care should be taken in counting cells in the Neubauer camera and in maintaining cells in constant agitation before injecting the tumor-containing solution. The model here developed was efficient besides being of low cost and of relatively easy execution.

A primary consideration and concern in development and implementation of risk assessment and management based hurricane and earthquake criteria for design and requalification of platforms in the Bay of Campeche criteria is the reliability characteristics of the pile foundations that support the platforms. Analyses of the ultimate limit state (ULS) performance characteristics of the platform pile foundations are summarized. These analyses indicated that in many cases when the capacities of the piles were based on American Petroleum Institute “static” pile capacity analysis methods, the piles were the most likely to fail elements in the platforms. Results from these analyses were in dramatic contrast with the performance of pile foundations supporting more than 250 platforms during the 100-year hurricane Roxanne (1995). Detailed analytical and field studies were performed to determine the ULS performance characteristics of pile foundations subjected to hurricane induced lateral and axial loadings. This stud...

A 39-year-old man presenting with pulmonary infiltrations and hemolytic anemia was diagnosed as having primary sclerosing cholangitis (PSC) without evidence of ulcerative colitis. This constellation of associations is unique to the best of our knowledge. Autoimmune hemolytic anemia has been reported to be associated with PSC on only a few occasions, and pulmonary infiltrations in association with PSC are also quite unusual. Genetic and immunologic mechanisms are major factors in the pathogenesis of these disorders.

Polysensitization is quite frequent in allergic children and may cause difficulties for the allergist in prescribing allergen-specific immunotherapy. This study aimed at evaluating the clinical effectiveness of 1 year of sublingual immunotherapy (SLIT) in a cohort of Italian allergic children with polysensitization. This open study was performed on 51 polysensitized children (34 boys; mean age, 11.8 years; range, 5.2-17.7 years) with allergic rhinitis and/or mild to moderate asthma. All of them were treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, the type of diagnosis, the severity of symptoms, and the use of drugs were evaluated at baseline and after 1 year. The adverse events to SLIT were also evaluated. Forty-two children were treated with a single extract, four with two different extracts and three with a mix of allergens. SLIT treatment induced a significant reduction in the number of sensitizations (p = 0.018); significant improvement of allergic rhinitis classification and severity; significant reduction of ocular, nasal, and bronchial symptoms (p < 0.01 for all); and drugs use (p < 0.01 for all drugs). No systemic reactions to SLIT were observed. This open study provides evidence that polysensitization is not an obstacle for prescribing SLIT in polysensitized children. Indeed, SLIT efficacy on clinical parameters is significant after 1 year and the therapy is safe.

A randomized, controlled parallel-group trial has assessed 14 days' use of a new ankle support (Malleotrain, Bauerfeind, Aldershot, UK) in 220 patients (118 Malleotrain, 102 control group) with acute ankle injuries. Self-assessed pain levels were significantly lower in the group using Malleotrain at the end of the trial (P less than 0.05), as were median times taken for reduction of symptom scores to 10% (P less than 0.05) and total analgesic consumption during the trial (P less than 0.05). Overall clinical assessment scores were significantly superior in the Malleotrain group (P less than 0.02). Of those patients who received Malleotrain, 112 of 116 patients who commented (95% of all Malleotrain-treated patients) did so positively and only one patient stopped wearing the support during the trial. Malleotrain is acceptable to patients with acute ankle injuries and its use increases the rate of alleviation of symptoms. Its use should therefore be considered in the management of all such patients.

The relationship between sleep and epilepsy is both complex and clinically significant. Temporal lobe epilepsy (TLE) influences sleep architecture, while sleep plays an important role in facilitating and/or inhibiting possible epileptic seizures. The pilocarpine experimental model reproduces several features of human temporal lobe epilepsy and is one of the most widely used models in basic research. The aim of the present study was to characterize, behaviorally and electrophysiologically, the phases of sleep–wake cycles (SWC) in male rats with pilocarpine-induced epilepsy. Epileptic rats presented spikes in all phases of the SWC as well as atypical cortical synchronization during attentive wakefulness and paradoxical sleep. The architecture of the sleep–wake phases was altered in epileptic rats, as was the integrity of the SWC. Because our findings reproduce many relevant features observed in patients with epilepsy, this model is suitable to study sleep dysfunction in epilepsy.

Cognitive functions rely on the extensive use of information stored in the brain, and the searching for the relevant information for solving some problem is a very complex task. Human cognition largely uses biological search engines, and we assume that to study cognitive function we need to understand the way these brain search engines work. The approach we favor is to study multi-modular network models, able to solve particular problems that involve searching for information. The building blocks of these multimodular networks are the context dependent memory models we have been using for almost 20 years. These models work by associating an output to the Kronecker product of an input and a context. Input, context and output are vectors that represent cognitive variables. Our models constitute a natural extension of the traditional linear associator. We show that coding the information in vectors that are processed through association matrices, allows for a direct contact between these memory models and some procedures that are now classical in the Information Retrieval field. One essential feature of context-dependent models is that they are based on the thematic packing of information, whereby each context points to a particular set of related concepts. The thematic packing can be extended to multimodular networks involving input-output contexts, in order to accomplish more complex tasks. Contexts act as passwords that elicit the appropriate memory to deal with a query. We also show toy versions of several ‘neuromimetic’ devices that solve cognitive tasks as diverse as decision making or word sense disambiguation. The functioning of these multimodular networks can be described as dynamical systems at the level of cognitive variables.

Background and Purpose— It has been recently shown that a single session of repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can improve motor function in stroke patients; however, this improvement is short-lasting. We therefore conducted a randomized, sham-controlled, phase II trial to evaluate whether five sessions of low-frequency rTMS can increase the magnitude and duration of these effects and whether this approach is safe. Methods— Fifteen patients with chronic stroke were randomized to receive active or sham rTMS of the unaffected hemisphere. A blinded rater assessed motor function and corticospinal excitability at baseline, during and after 2 weeks of treatment. Safety was assessed using a neuropsychologic battery and electroencephalogram. Results— Active rTMS resulted in a significant improvement of the motor function performance in the affected hand that lasted for 2 weeks. These effects were not observed in the sham rTMS group (affected and unaffected hand) and in the unaffected hand in the active rTMS group. Corticospinal excitability decreased in the stimulated, unaffected hemisphere and increased in the affected hemisphere. There was a significant correlation between motor function improvement and corticospinal excitability change in the affected hemisphere. Cognitive performance and electroencephalogram were not changed significantly throughout the trial in both groups of treatment. Conclusions— These results support and extend the findings of previous studies on rTMS in stroke patients because five consecutive sessions of rTMS increased the magnitude and duration of the motor effects. Furthermore, this increased dose of rTMS is not associated with cognitive adverse effects and/or epileptogenic activity.

New theoretical instruments, as goal-directed neural networks models and geometric representations based on semantic graphs, open new approaches for our understanding of the schizophrenic speech. The neuropathologic disorders of the schizophrenia can be simulated using neural models, and these models can eventually explain the origin of goal confusion and incoherence in the schizophrenic discourse trajectory. Moreover, these models are useful to evaluate the different hypothesis about the pathogenic mechanisms of the disease. At the same time, a geometric representation of the trajectory of the speech can be obtained from real data. Our conjecture is that a context-dependent graph can be constructed in order to explore if, when the disease became more severe, a transition from a quasi ordered graph to a nearly completely random graph occurs. Plausibly, there exists a wide region where the graph has the properties of a "small-world". This kind of analyses could be potentially carried out using data coming from the spontaneous speech of schizophrenic patients, and can help to evaluate the progress of the disease. At the same time, these geometrical representations could help to evaluate the effect of treatments.

Current investigation describes the behavioral and electrographic characteristics of spontaneous absence-like seizures identified in Wistar rats (referred to here as FMUSP-rats, after the Faculty of Medicine, University of Sao Paulo, Sao Paulo State, Brazil), and characterized by spike-wave discharges (SWDs) in the neocortex and the hippocampus. After consanguineous crossing directed to an increased incidence of seizures, the latter were observed in almost all F9 offspring. FMUSP-rat seizures are expressed as immobility and concomitant SWDs, oscillating between 7.5 and 12 Hz in the frontoparietal cortex and the hippocampus. Behaviorally, they are mainly associated with clonic movements of the eyes, rostrum and vibrissae, the latter ranging between 1 and 70 seconds and occur at a rate of up to 229 per hour. Systemic injections of ethosuximide (0, 25, 50, 100, 250 mg kg -1 ) and of diazepam (15 mg kg -1 ) increased the latency for the first seizure and reduced both the hourly incidence of SWD bursts and their mean duration. Carbamazepine (30 mg kg -1 ) injections increased both the incidence and duration of the SWDs, leaving the latency for the first seizure unchanged. Comparisons between FMUSP-rats and well-established genetic models of absence seizures data indicated that the animals described herein might contribute towards studies on the neurological condition under analysis.

In this study we compared infrared tympanic thermometry with rectal mercury thermometry and digital rectal thermometry in patients admitted to a medical department. We found that infrared tympanic thermometry has a low sensitivity for detecting fever. Digital rectal thermometry is a good alternative to rectal mercury thermometry.

Colorectal cancer (CRC) is the third most common cancer in both men and women. There were 148,810 new cases and 49,960 deaths anticipated in 2008. The 1-year and 5-year relative survival for CRC patients is 82% and 64% respectively. When CRC is detected early, at a localized stage, the 5-year survival is 90%. However only 39% of CRC are diagnosed at this stage, as only 44% of US adults over 50 undergo the recommended screening. Our aim is to develop rapid, easy-to-use and cost-effective serum-based immunoassays for CRC surveillance and recurrence monitoring. We have developed proprietary approaches to the discovery of biomarkers (Bm) using an in-house generated library of monoclonal antibodies (mAb), a large collection of clinical samples from patients with major cancers, and a proprietary multiplex screening platform, known as Matrix Protein Array Technology (MPAT). The MPAT enables us to screen a large number of clinical samples with a large number of antibodies. Briefly, a protein matrix comprising samples from cancer patients, benign and normal controls, is replica printed on the MPAT solid support. Each sample matrix is simultaneously interrogated with a different mAb. mAb-Bm reaction is detected using fluorescence-based Odyssey imaging system (Li-Cor), followed by spot quantification and statistical analysis to select mAb against Bm that are significantly and differentially expressed in cases versus controls. We have used this approach to identify CRC specific Bm and mAb. We further validated Bm expression by MPAT, using the mAb on tissue protein extracts derived from patients with CRC (173), benign and inflammatory conditions of the colon (23), and normal controls (240). The clinical sample set used also included breast, lung, and ovary cases and controls, amounting to a total of 1329 samples. Some mAb-based Bm showed excellent discriminatory power between cancer and control, with up to 90% sensitivity at 90% specificity, as determined by ROC curves using statistical package GB-STAT (Dynamic Microsystems). Then, immunohistochemistry on in-house and commercial tissue microarrays (75 cases) confirmed cancer specificity, and mAb specifically stained CRC tissues, with membrane, nuclear and cytoplasmic localization. Finally, some candidate Bm appeared to be secreted and overexpressed in CRC patient serum, when tested by Western blot. From the pool of serum-based Bm, we have developed a pair of capture-detection mAb in an ELISA sandwich assay, and compared performance to a carcinoembryonic antigen (CEA) standard assay. This serum-based immunodiagnostic assay would have tremendous applications in CRC monitoring, whether alone or in combination with CEA. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2683.

Background Several strategies and devices have been designed to protect health care providers from acquiring transmissible respiratory diseases while providing care. In modulating the physical characteristics of the respiratory secretions to minimize the aerosolization that facilitates transmission of airborne diseases, a fundamental premise is that the prototype drugs have no adverse effect on the first line of respiratory defense, clearance of mucus by ciliary action. Methods To assess and demonstrate the primary mechanism of our mucomodulators (XLs), we have built our evidence moving from basic laboratory studies to an ex-vivo model and then to an in-vivo large animal model. We exposed anesthetized dogs without hypersecretion to different dose concentrations of aerosolized XL "B", XL "D" and XL "S". We assessed: cardio-respiratory pattern, tracheal mucus clearance, airway patency, and mucus viscoelastic changes. Results Exposure of frog palate mucus to XLs did not affect the clearance of mucus by ciliary action. Dogs maintained normal cardio-respiratory pattern with XL administration. Tracheal mucociliary clearance in anesthetized dogs indicated a sustained 40% mean increase. Tracheal mucus showed increased filance, and there was no mucus retention in the airways. Conclusion The ex-vivo frog palate and the in-vivo mammalian models used in this study, appear to be appropriate and complement each other to better assess the effects that our mucomodulators exert on the mucociliary clearance defence mechanism. The physiological function of the mucociliary apparatus was not negatively affected in any of the two epithelial models. Airway mucus crosslinked by mucomodulators is better cleared from an intact airway and normally functioning respiratory system, either due to enhanced interaction with cilia or airflow-dependent mechanisms. Data obtained in this study allow us to assure that we have complied with the fundamental requirement criteria established in the initial phase of developing the concept of mucomodulation: Can we modulate the physical characteristics of the respiratory secretions to reduce aerosolization without affecting normal mucociliary clearance function, or even better improving it?

Introduccion. La angiografia cerebral (AC) es la tecnica de referencia en el diagnostico de aneurismas intracraneales; no obstante, la angiografia por resonancia magnetica (angio-RM) se utiliza con gran efectividad para la deteccion de aneurismas en pacientes que no han presentado hemorragia subaracnoidea (HSA). Por lo tanto, algunos autores han propuesto que la angio-RM puede suplantar a la AC, incluso en el tratamiento de aneurismas rotos. Objetivos. Valorar la utilidad de la angio-RM comparada con la AC y la observacion quirurgica en el diagnostico de aneurismas intracraneales rotos, ademas de determinar la seguridad del tratamiento quirurgico con angio-RM como unico metodo diagnostico. Pacientes y metodos. Se estudiaron prospectivamente 52 pacientes con HSA aguda por ruptura de aneurisma en los hospitales Teodoro Maldonado Carbo y Alcivar Guayaquil, de la ciudad de Guayaquil, Ecuador, en un periodo de 5 anos. Comparamos los resultados de la angio-RM con la AC y los hallazgos quirurgicos en el diagnostico y caracterizacion de aneurismas intracraneales. Resultados. Diagnosticamos el 100% de 54 aneurismas intracraneales con angio-RM, mientras que con la AC, el 98%. Los hallazgos quirurgicos fueron similares a lo mostrado en la angio-RM. Conclusiones. La angio-RM es un metodo no invasivo y libre de contraste nefrotoxico optimo en el diagnostico de aneurismas intracerebrales rotos y puede reemplazar a la AC en casos seleccionados.

9736 Background: Evaluation of prostate specific antigen (PSA) is the current screening method for early detection of prostate cancer. PSA is more prostate specific than cancer specific, and elevat...

We report a case of a male patient with Hodgkin's lymphoma and severe acne-like lesions associated with taking amineptine, a tricyclic antidepressant. The lesions appeared after self-administration of high doses of the drug, up to 4000 mg/day. The relationship between the acne-like lesions, drug intake and lymphoma are discussed. The severity of these cutaneous lesions seems to be correlated with the degree of overdose. A high concentration of lactam metabolites found in the lesions may explain their persistence. Drug addiction and alcoholism seem to be adjunctive risk factors for amineptine side-effects. The effect of amineptine may be facilitated by the presence of Hodgkin's disease.

INTRODUCTION Many patients with multiple sclerosis (MS) develop tremors that may involve one or both lower and/or upper extremities, head and/or voice. In the last few years, chronic high frequency deep brain stimulation of the ventral intermedious (Vim) thalamic nucleus (Vim-DBS, deep brain stimulation) seems to be gradually replacing Vim-thalamotomy in surgical treatment of tremor. The thalamotomy is a destructive procedure of the whole neural components, whereas Vim-DBS has shown to be a selective neurophysiological procedure to block a specific group of neural components, in particular large, fast and low threshold ones. MS is a disease of uncertain etiology characterized by demyelinating plaques in central nervous system. The neurophysiological intraoperative targeting applied to this pathology identifies demyelinated plaques and the functional state of Vim, reduces pitfalls and increases accuracy. Methods included spontaneous and induced multiunit activity recording, semimicroelectrode and tetraelectrode thalamic evoked potentials recording and micro/macro stimulation techniques.

1 Forty-four clinically anxious patients entered a comparative double-blind trial of clobazam 20 mg, clobazam 30 mg and dipotassium clorazepate 15 mg, all drugs given as a single dose at night. 2 Assessment by the Hamilton Anxiety Scale, Morbid Anxiety Inventory (Salkind) and a Visual Analogue Scale showed a statistically significant improvement for all treatment groups after 2 weeks, with continued improvement after a further 2 weeks. 3 Daytime drowsiness was the commonest side-effect in all treatment groups but there was a tendency for a lower incidence in patients on clobazam. There was no evidence of a dose-related incidence of drowsiness in the clobazam 20 mg and 30 mg groups. Other side-effects were few and non-specific. 4 Clobazam is a 1,5-benzodiazepine with an elimination half-life of 18 hours. When given in single doses of 20-30 mg at night it has an equivalent effect to dipotassium clorazepate 15 mg.

A double-blind two-group comparison of fluphenazine/nortriptyline (F/N) with amitriptyline in 72 patients aged 65 or over suffering from mixed states of anxiety and depression, each treated for four weeks, showed F/N to be significantly superior to amitriptyline by Day 7 in terms of patients' self-ratings and clinicians' ratings. Patients' preference for F/N was even more pronounced by Day 28 (P less than 0.001), when the improvement in symptoms relating to depression was rated by the clinicians as significantly greater for the patients receiving F/N (P less than 0.025). The incidence of drowsiness was significantly greater (P less than 0.05) in the amitriptyline group than the F/N group. The implications of these results for the treatment of emotional disturbances in the elderly are discussed.

Ten acute attacks were managed in nine patients with hereditary angioedema by means of the infusion of a C1 INH concentrate produced on large scale. No side effects were observed.

C1-inhibitor is an acid glycoprotein, isoelectric point 3.5-3.6. Plasma of some patients with a variant form of hereditary angioedema contains high levels of functionless C1-inhibitor-albumin complex with an isoelectric point at 4.5-4.6. Therapy with Danazol, which increases C1-inhibitor levels, does not modify the isoelectric focusing pattern of such protein in patients with hereditary angioedema.

Administration of pilocarpine causes epilepsy in rats if status epilepticus (SE) is induced at an early age. To determine in detail the electrophysiological patterns of the epileptogenic activity in these animals, 46 Wistar rats, 7-17 days old, were subjected to SE induced by pilocarpine and electro-oscillograms from the cortex, hippocampus, amygdala, thalamus and hypothalamus, as well as head, rostrum and vibrissa, eye, ear and forelimb movements, were recorded 120 days later. Six control animals of the same age range did not show any signs of epilepsy. In all the rats subjected to SE, iterative spike-wave complexes (8.1 ± 0.5 Hz in frequency, 18.9 ± 9.1 s in duration) were recorded from the frontal cortex during absence fits. However, similar spike-wave discharges were always found also in the hippocampus and, less frequently, in the amygdala and in thalamic nuclei. Repetitive or single spikes were also detected in these same central structures. Clonic movements and single jerks were recorded from all the rats, either concomitantly with or independently of the spike-wave complexes and spikes. We conclude that rats made epileptic with pilocarpine develop absence seizures also occurring during paradoxical sleep, showing the characteristic spike-wave bursts in neocortical areas and also in the hippocampus. This is in contrast to the well-accepted statement that one of the main characteristics of absence-like fits in the rat is that spike-wave discharges are never recorded from the hippocampal fields. Universidade de São Paulo Faculdade de Medicina Laboratório de Neurocirurgia Funcional Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Laboratório de Neurologia Experimental UNIFESP, EPM, Laboratório de Neurologia Experimental SciELO

The natural history of allergic rhinitis (AR) is commonly characterized by worsening of symptom severity, frequent comorbidity with asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts in early childhood. AR classification has been recently revised, and some studies investigated the new types: intermittent (IAR) and persistent (PER) AR. However, no study has been carried out on children regarding this issue. This preliminary study was performed on a large cohort of children with allergic rhinitis to evaluate the type and severity of rhinitis and its possible association with asthma, including severity grade. One hundred and thirty-nine children (86 males, 53 females, mean age 11.8 years, range 3.5–17.7 years) with allergic rhinitis were prospectively and consecutively evaluated. Seventy-one children had rhinitis alone and 68 had rhinitis associated with asthma. Forty children had IAR, 30 of whom with moderate-severe grade. Ninety-nine children had PER, 65 of whom had moderate-severe grade. The severity of AR was not associated with asthma presence (Fisher χ2 = 0.5765; Prob.=0.9018). Regarding asthma severity, 30 children had the intermittent form, whereas 38 had the persistent form: 15 mild, 22 moderate, and 1 severe. This study provides the first evidence concerning the ARIA classification in children, partially confirming findings obtained in adulthood.