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Context. In recent times, large organic molecules of exceptional complexity have been found in diverse regions of the interstellar medium. Aims. In this context, we aim to provide accurate frequencies of the ground vibrational state of two key aliphatic aldehydes, n-butanal and its branched-chain isomer, i-butanal, to enable their eventual detection in the interstellar medium. We also want to test the level of complexity that interstellar chemistry can reach in regions of star formation. Methods. We employ a frequency modulation millimeter-wave absorption spectrometer to measure the rotational features of n- and i-butanal. We analyze the assigned rotational transitions of each rotamer separately using the A-reduced semirigid-rotor Hamiltonian. We use the spectral line survey ReMoCA performed with the Atacama Large Millimeter/submillimeter Array to search for n- and i-butanal toward the star-forming region Sgr B2(N). We also search for both aldehydes toward the molecular cloud G+0.693−0.027 with IRAM 30 m and Yebes 40 m observations. The observational results are compared with computational results from a recent gas-grain astrochemical model. Results. Several thousand rotational transitions belonging to the lowest-energy conformers of two distinct linear and branched isomers have been assigned in the laboratory spectra up to 325 GHz. A precise set of the relevant rotational spectroscopic constants has been determined for each structure as a first step toward identifying both molecules in the interstellar medium. We report non-detections of n-and i-butanal toward both sources, Sgr B2(N1S) and G+0.693-0.027. We find that n- and i-butanal are at least 2-6 and 6-18 times less abundant than acetaldehyde toward Sgr B2(N1S), respectively, and that n-butanal is at least 63 times less abundant than acetaldehyde toward G+0.693−0.027. While propanal is not detected toward Sgr B2(N1S) either, with an abundance at least 5–11 lower than that of acetaldehyde, propanal is found to be 7 times less abundant than acetaldehyde in G+0.693−0.027. Comparison with astrochemical models indicates good agreement between observed and simulated abundances (where available). Grain-surface chemistry appears sufficient to reproduce aldehyde ratios in G+0.693−0.027; gas-phase production may play a more active role in Sgr B2(N1S). Model estimates for the larger aldehydes indicate that the observed upper limits may be close to the underlying values. Conclusions. Our astronomical results indicate that the family of interstellar aldehydes in the Galactic center region is characterized by a drop of one order of magnitude in abundance at each incrementation in the level of molecular complexity.

Introduction Premature ejaculation (PE) is a common, and under treated medical condition that affects men and their partners. Advances in clinical research in premature ejaculation (PE) over the last years have led to the development of a variety of new treatment options, including dietary supplements. Hypericum perforatum (HP), a natural supplement has demonstrated pharmacologic action to inhibit serotonin reuptake and that inhibits rat and human vas deferens contractility. These results might explain delayed ejaculation described in patients receiving HP. Quercetin is a naturally occurring bioflavonoid found in high concentrations in red wine, onions, and green tea. Therapy with the bioflavonoid quercetin provides significant symptomatic improvement in most men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Subjects with PE often show symptoms and signs compatible with CP/CPPS, as confirmed by many different studies, CP/CP are an organic risk factor for PE. Objective The purpose of the present investigation was to assess the safety and preliminary evidence of the effectiveness of a supplement that combined HP and quercetin for the treatment of PE. Methods A one-group pretest-posttest design was used in the current research. Main outcome measures were assessed using the mean stopwatch-measured Intravaginal Ejaculatory Latency Time (IELT) at baseline and after 12 weeks. The collected data were tabulated and analyzed using the Statistical Package for the Social Sciences version 22 (SPSS). Quantitative data are expressed as means ± standard deviations (SDs). For the comparison of paired variables the Wilcoxon test was used. Premature Ejaculation Diagnostic Tool (PEDT) was used for the diagnosis and as a secondary measure. The study inclusion criteria to be selected were as follows: Being over 18 years old, being in a heterosexual relationship for at least the last 6 months, having a score ≥ 11 in the PEDT and a mean self-reported IELT ≤ 2 minutes. Exclusion criteria included a history of alcohol abuse or dependence, having received medication or psychological treatment for PE in the last 6 months, suffering from diabetes or habitual use of recreational drugs. A total of 12 subjects, aged between 27 and 58 years of age (mean = 40.50 years, standard deviation (SD) = 8.31) were treated with 1 daily tablet of 650 mg of Myhixel Max®. Each tablet contained Hypereric dry extract 433.64mg, Sophora japonica L. (95% quercetin 72.27mg), 68.65mg quercetin and anti-caking agents (magnesium stearate and silico dioxide). Results In the present study, there was a significant improvement in mean IELT (mean pre = 69.6 seg (SD) = 37.8 mean post = 146.4 seg (SD) = 67.2, Wilcoxon test pre vs post p-value = 0.008). Conclusions Oral therapy with HP and quercetin was associated with a significant increase in mean IELT from baseline, with no adverse effects related to the treatment. We can conclude that this supplement in daily use has the potential to become an effective and safe treatment for patients suffering from PE, long-term durability of the response is yet to be determined. Future studies with, larger group of patients; larger follow-up and group control are needed. Disclosure Work supported by industry: yes, by New Wellness Concept S.L. A consultant, employee (part time or full time) or shareholder is among the authors (New Wellness Concept. S.L).

In recent decades, Cognitive Neuroscience has evolved from a rather arcane field trying to understand how the brain supports mental activities, to one that contributes to public policies. In this article, we focus on the contributions from Cognitive Neuroscience to Education. This line of research has produced a great deal of information that can potentially help in the transformation of Education, promoting interventions that help in several domains including literacy and math learning, social skills and science. The growth of the Neurosciences has also created a public demand for knowledge and a market for neuro-products to fulfill these demands, through books, booklets, courses, apps and websites. These products are not always based on scientific findings and coupled to the complexities of the scientific theories and evidence, have led to the propagation of misconceptions and the perpetuation of neuromyths. This is particularly harmful for educators because these misconceptions might make them abandon useful practices in favor of others not sustained by evidence. In order to bridge the gap between Education and Neuroscience, we have been conducting, since 2013, a set of activities that put educators and scientists to work together in research projects. The participation goes from discussing the research results of our projects to being part and deciding aspects of the field interventions. Another strategy consists of a course centered around the applications of Neuroscience to Education and their empirical and theoretical bases. These two strategies have to be compared to popularization efforts that just present Neuroscientific results. We show that the more the educators are involved in the discussion of the methodological bases of Neuroscientific knowledge, be it in the course or as part of a stay, the better they manage the underlying concepts. We argue that this is due to the understanding of scientific principles, which leads to a more profound comprehension of what the evidence can and cannot support, thus shielding teachers from the false allure of some commercial neuro-products. We discuss the three approaches and present our efforts to determine whether they lead to a strong understanding of the conceptual and empirical base of Neuroscience.

El presente artículo analiza la relación entre el potencial de implementación de redes inteligentes y el ciclo de energía en las ciudades, ciclo que comprende la extracción, producción, distribución y consumo final de la energía como garante de desarrollo. Este interés se desprende de la constatación de que uno de los principales retos de las ciudades es paliar la escasez energética mediante tecnologías eficientes, capaces de reducir las emisiones de CO2. En relación a este requerimiento, el estudio se propone demostrar, en base a experiencias internacionales, que la manera inteligente de aplicar la tecnología en nuestras ciudades como respuesta al consumo energético es la adopción de tecnologías apropiadas y compatibles con cada realidad específica.

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.

Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.

Background and aims Several epidemiological studies highlighted the association between folate and B-vitamins low intake and cardiovascular diseases (CVD) risk. Contrasting results were reported on the relationship between folate intake and DNA-methylation. Folate and B-vitamins may modulate DNA-methylation of specific enzymes which are included in the One-Carbon Metabolism (OCM) and in the homocysteine (Hcy) pathways. The aim of the study was to evaluate whether DNA-methylation profiles of OCM and Hcy genes could modulate the myocardial infarction (MI) risk conferred by a low B-vitamins intake. Methods and results Study sample (206 MI cases and 206 matched controls) is a case-control study nested in the prospective EPIC cohort. Methylation levels of 33 candidate genes where extracted by the whole epigenome analysis (Illumina-HumanMethylation450K-BeadChip). We identified three differentially methylated regions in males (TCN2 promoter, CBS 5′UTR, AMT gene-body) and two in females (PON1 gene-body, CBS 5′UTR), each of them characterized by an increased methylation in cases. Functional in silico analysis suggested a decreased expression in cases. A Recursively Partitioned Mixture Model cluster algorithm identified distinct methylation profiles associated to different MI risk: high-risk vs. low-risk methylation profile groups, OR = 3.49, p = 1.87 × 10 − 4 and OR = 3.94, p = 0.0317 in males and females respectively (multivariate logistic regression adjusted for classical CVD risk factors). Moreover, a general inverse relationship between B-vitamins intake and DNA-methylation of the candidate genes was observed. Conclusions Our findings support the hypothesis that DNA-methylation patterns in specific regions of OCM and Hcy pathways genes may modulate the CVD risk conferred by folate and B-vitamins low intake.

Phthalocyanine blue dye has been investigated as a carbon steel corrosion inhibitor in 0.5 M sulfuric acid by using polarization curves, electrochemical impedance spectroscopy, and gravimetric tests. Dye concentrations included 0, 100, 200, 400, 600, 800, and 1000 ppm, whereas testing temperatures were 25, 40, and 60°C. Results indicated that phtalocyanine blue is a good corrosion inhibitor with its efficiency increasing with the concentration up to 40°C, but it increases at 60°C. Inhibitor improves the passive film properties and it forms an adherent, compact, protective film, acting, therefore, as an anodic-type inhibitor. At 25 and 40°C the corrosion process was under charge transfer, whereas at 60°C the adsorption/desorption of some species from the metal surface controlled the corrosion process.

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.

Several psychiatric and neurological conditions affect the semantic organization and content of a patient's speech. Specifically, the discourse of patients with schizophrenia is frequently characterized as lacking coherence. The evaluation of disturbances in discourse is often used in diagnosis and in assessing treatment efficacy, and is an important factor in prognosis. Measuring these deviations, such as “loss of meaning” and incoherence, is difficult and requires substantial human effort. Computational procedures can be employed to characterize the nature of the anomalies in discourse. We present a set of new tools derived from network theory and information science that may assist in empirical and clinical studies of communication patterns in patients, and provide the foundation for future automatic procedures. First we review information science and complex network approaches to measuring semantic coherence, and then we introduce a representation of discourse that allows for the computation of measures of disorganization. Finally we apply these tools to speech transcriptions from patients and a healthy participant, illustrating the implications and potential of this novel framework.

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.

Epileptogenesis in the temporal lobe elicits regulation of gene expression and protein translation, leading to reorganization of neuronal networks. In this process, miRNAs were described as being regulated in a cell-specific manner, although mechanistics of miRNAs activity are poorly understood. The specificity of miRNAs on their target genes depends on their intracellular concentration, reflecting the balance of biosynthesis and degradation. Herein, we confirmed that pilocarpine application promptly (

In the present study, the list of alien marine macrophytes introduced into Tunisia was updated in the light of available data and new observations. A total of 27 alien marine macrophytes have been recorded so far from Tunisia: 18 Rhodophyta, 3 Ochrophyta, 5 Chlorophyta and 1 Magnoliophyta. For each species, the locality (-ies), the year (or) period and the source of the first observation in Tunisia are given. The distribution and the status (casual, cryptogenic, established or questionable) of species in Tunisia were evaluated and, where appropriate, discussed. Among them, Hypnea cornuta is reported for the first time from Tunisia. Fourteen alien marine macrophytes are established, whereas seven cryptogenic and two casual species require further investigation. Eleven species are considered as invasive or potentially invasive in the Mediterranean Sea: Acrothamnion preissii, Asparagopsis armata, A. taxiformis Indo-Pacific lineage, Hypnea cornuta, Lophocladia lallemandii, Womersleyella setacea, Caulerpa chemnitzia, C. cylindracea, C. taxifolia, Codium fragile subsp. fragile and Halophila stipulacea. Finally, the case of four questionable species is also discussed. The project “MAnagement of Port areas in the MEDiterranean Sea Basin (MAPMED)” has been funded by ENPI CBC MED Cross-Border Cooperation. This publication has been produced with the financial assistance of the European Union under the ENPI CBC Mediterranean Sea Basin Programme.

Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from the ventral tegmental area to the LS and express the DA transporter (DAT). Cocaine acts by altering DA bioavailability by targeting the DAT. Therefore, GLP-1R signaling might exert effects on DAT to account for its regulation of cocaine-induced behaviors. We show that the GLP-1R is highly expressed within the LS. GLP-1, in LS slices, significantly enhances DAT surface expression and DAT function. Exenatide (Ex-4), a long-lasting synthetic analog of GLP-1 abolished cocaine-induced elevation of DA. Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA). Notably, AA reduces septal DAT function pointing to AA as a novel regulator of central DA homeostasis. We further show that AA oxidation product γ-ketoaldehyde (γ-KA) forms adducts with the DAT and reduces DAT plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA.

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.

RESUMO – A adsorcao e uma tecnica que vem sendo aplicada com sucesso na industria textil, mas com custos elevados devido ao preco do adsorvente e a dificuldade de regenera-lo. Com o objetivo de utilizar adsorventes alternativos provenientes da gaseificacao do lodo residual de uma estacao de tratamento de efluentes texteis, foram feitos ensaios de adsorcao com o corante reativo vermelho remazol RGB. Nestes ensaios foram utilizados diferentes pHs para comparar a sua adsorcao com carvao ativado comercial, assim como as cineticas de adsorcao. O lodo gaseificado apresentou melhores resultados de adsorcao com solucao a pH inicial igual a 7.

NMR spectroscopy was used to investigate the association of four chiral molecules with the molecular micelle poly(sodium N-undecanoyl-l-leucylvalinate) (poly(SULV)). Adding poly(SULV) to the background electrolyte in electrokinetic chromatography (EKC) allows enantiomeric resolution to be achieved because enantiomers interact differentially with the chiral centers on the micelle headgroups as they both move in the electric field. Pulsed field gradient diffusion experiments were used to measure molecular micelle association constants for enantiomers of each analyte. These association constants were consistent with EKC elution order for the compounds 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNP), 1,1'-bi-2-naphthol (BOH), and Troger's base. In addition, nuclear Overhauser enhancement spectroscopy, nuclear Overhauser effect difference, and intermolecular cross relaxation diffusion experiments were used to generate binding interaction maps for each chiral analyte. These maps showed that BNP and BOH inserted into the surfactant headgroup's major chiral groove and interacted predominately with the leucine chiral center. (+)-Troger's base was also found to insert into the major chiral groove. However, this compound instead interacted with the valine chiral atom. In diffusion experiments with long diffusion times, the linearized diffusion plots for each analyte-molecular micelle mixture showed curvature characteristic of intermolecular cross relaxation. The magnitude of this effect scaled linearly with the analytes' free energies of binding.

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.

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.

It is well established that Ca 2+ plays a key role in promoting the physiological depolarization-induced release (DIR) of neurotransmitters from nerve terminals (Ca 2+ hypothesis). Yet, evidence has accumulated for the Ca 2+ -voltage hypothesis, which states that not only is Ca 2+ required, but membrane potential as such also plays a pivotal role in promoting DIR. An essential aspect of the Ca 2+ -voltage hypothesis is that it is depolarization that is responsible for the initiation of release. This assertion seems to be contradicted by recent experiments wherein release was triggered by high concentrations of intracellular Ca 2+ in the absence of depolarization [calcium-induced release (CIR)]. Here we show that there is no contradiction between CIR and the Ca 2+ -voltage hypothesis. Rather, CIR can be looked at as a manifestation of spontaneous release under conditions of high intracellular Ca 2+ concentration. Spontaneous release in turn is governed by a subset of the molecular scheme for DIR, under conditions of no depolarization. Prevailing estimates for the intracellular calcium concentration, [Ca 2+ ] i , in physiological DIR rely on experiments under conditions of CIR. Our theory suggests that these estimates are too high, because depolarization is absent in these experiments and [Ca 2+ ] i is held at high levels for an extended period.

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...

The flavivirus protease is composed of two viral proteins, NS2B and NS3. The amino-terminal portion of NS3 contains sequence and structural motifs characteristic of bacterial and cellular trypsin-like proteases. We have undertaken a mutational analysis of the region of NS3 which contains the catalytic serine, five putative substrate binding residues, and several residues that are highly conserved among flavivirus proteases and among all serine proteases. In all, 46 single-amino-acid substitutions were created in a cloned NS2B-NS3 cDNA fragment of dengue virus type 2, and the effect of each mutation on the extent of self-cleavage of the NS2B-NS3 precursor at the NS2B-NS3 junction was assayed in vivo. Twelve mutations almost completely or completely inhibited protease activity, 9 significantly reduced it, 14 decreased cleavage, and 11 yielded wild-type levels of activity. Substitution of alanine at ultraconserved residues abolished NS3 protease activity. Cleavage was also inhibited by substituting some residues that are conserved among flavivirus NS3 proteins. Two (Y150 and G153) of the five putative substrate binding residues could not be replaced by alanine, and only Y150 and N152 could be replaced by a conservative change. The two other putative substrate binding residues, D129 and F130, were more freely substitutable. By analogy with the trypsin model, it was proposed that D129 is located at the bottom of the substrate binding pocket so as to directly interact with the basic amino acid at the substrate cleavage site. Interestingly, we found that significant cleavage activity was displayed by mutants in which D129 was replaced by E, S, or A and that low but detectable protease activity was exhibited by mutants in which D129 was replaced by K, R, or L. Contrary to the proposed model, these results indicate that D129 is not a major determinant of substrate binding and that its interaction with the substrate, if it occurs at all, is not essential. This mutagenesis study provided us with an array of mutations that alter the cleavage efficiency of the dengue virus protease. Mutations that decrease protease activity without abolishing it are candidates for introduction into the dengue virus infectious full-length cDNA clone with the aim of creating potentially attenuated virus stocks.

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.

Polysensitization is very common in allergic patients and was previously reported to be associated with more severe symptoms and impaired quality of life. Polysensitization is often considered as a contraindication for specific immunotherapy (SIT). This study is aimed at evaluating the allergist attitude for decision making in choosing SIT in a cohort of Italian polysensitized patients. Moreover, the 1-year effectiveness of the prescribed sublingual immunotherapy (SLIT) in this cohort was evaluated. The study was performed on 244 patients (109 males, 135 females, mean age 28.7 years, S.D. 12.0) with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA criteria) treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, type of diagnosis, severity of symptoms, use of drugs, and adverse events were evaluated at baseline and after 1 year. A total of 230 patients were treated with SLIT: 165 with a single extract, and 65 with two different extracts (mix). SLIT treatment significantly improved disease staging, and reduced symptom severity and drug use. No systemic reaction was reported. In conclusion, these findings provide preliminary evidence that SIT is effective and safe in polysensitized patients after 1 year of treatment also using single extracts, and thus does not represent an obstacle for prescribing SIT.

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.

The development of non-invasive techniques of cortical stimulation, such as transcranial magnetic stimulation (TMS), has opened new potential avenues for the treatment of neuropsychiatric diseases. We hypothesized that an increase in the activity in the motor cortex by cortical stimulation would increase its inhibitory influence on spinal excitability through the corticospinal tract and, thus, reduce the hyperactivity of the gamma and alpha neurons, improving spasticity. Seventeen participants (eight males, nine females; mean age 9y 1mo [SD 3y 2mo]) with cerebral palsy and spastic quadriplegia were randomized to receive sham, active 1Hz, or active 5Hz repetitive TMS of the primary motor cortex. Stimulation was applied for 5 consecutive days (90% of motor threshold). The results showed that there was a significant reduction of spasticity after 5Hz, but not sham or 1Hz, stimulation as indexed by the degree of passive movement; however this was not evident when using the Ashworth scale, although a trend for improvement was seen for elbow movement. The safety evaluation showed that stimulation with either 1Hz or 5Hz did not result in any adverse events as compared with sham stimulation. Results of this trial provide initial evidence to support further trials exploring the use of cortical stimulation in the treatment of spasticity.

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.

Lung cancer remains the most common cause of cancer death in the US and worldwide. Currently, there is no implemented population-based screening for lung cancer. Of all the markers identified, none have achieved sufficient diagnostic significance to reach clinical application. Here we discuss the status of lung cancer early diagnostics, and the genomic and proteomic approaches currently undertaken for biomarker discovery. We then introduce the ANTIBIOMIX approach that enables high-throughput target discovery by interrogating biological samples using a collection of thousands of polyclonal antibodies. The development of specific and sensitive diagnostic assays using patient's biological fluids, such as sputum and serum, will improve screening, monitoring of disease progression and treatment response, and surveillance for recurrence.