N-Methyl-D-aspartic Acid (NMDA) in the nervous system of the amphioxus Branchiostoma lanceolatum

<p>Abstract</p> <p>Background</p> <p>NMDA (<it>N</it>-methyl-D-aspartic acid) is a widely known agonist for a class of glutamate receptors, the NMDA type. Synthetic NMDA elicits very strong activity for the induction of hypothalamic factors and hypophyseal hormones in mammals. Moreover, endogenous NMDA has been found in rat, where it has a role in the induction of GnRH (Gonadotropin Releasing Hormone) in the hypothalamus, and of LH (Luteinizing Hormone) and PRL (Prolactin) in the pituitary gland.</p> <p>Results</p> <p>In this study we show evidence for the occurrence of endogenous NMDA in the amphioxus <it>Branchiostoma lanceolatum</it>. A relatively high concentration of NMDA occurs in the nervous system of this species (3.08 ± 0.37 nmol/g tissue in the nerve cord and 10.52 ± 1.41 nmol/g tissue in the cephalic vesicle). As in rat, in amphioxus NMDA is also biosynthesized from D-aspartic acid (D-Asp) by a NMDA synthase (also called D-aspartate methyl transferase).</p> <p>Conclusion</p> <p>Given the simplicity of the amphioxus nervous and endocrine systems compared to mammalian, the discovery of NMDA in this protochordate is important to gain insights into the role of endogenous NMDA in the nervous and endocrine systems of metazoans and particularly in the chordate lineage.</p

Simultaneous onset of infantile spasms in monozygotic twins.

The clinical, electroencephalographic, and genetic findings are reported for three pairs of monozygotic twins who developed infantile spasms in their first year. In all three pairs, the spasms started on the same day in each member of the pair. Neither sequencing of the ARX and CDKL5 (alias STK9) genes nor array comparative genomic hybridization assessment revealed any abnormalities. The long-term outcome was poor in all twins, although with different severity in individual pairs. These findings suggest that genes other than those currently known likely play a role in predisposition to infantile spasms, and that genetic susceptibility is linked to a variable phenotypic expression, ranging from quite benign to very severe, in monozygotic twins with no other apparent risk factors

Ovariectomy impairs socio-cognitive functions in dogs

Recent studies have underlined the effect of ovariectomy on the spatial cognition of female dogs, with ovariectomized dogs showing a clear preference for an egocentric rather than an allocentric navigation strategy whereas intact females did not show preferences. Intact females had better performances than gonadectomized females in solving a learning task in a maze. Ovariectomy also affects socio-cognitive abilities, reducing the dog's level of attention on the owner. We tested dogs (Canis lupus familiaris) in the object choice task paradigm to assess whether an ovariectomy could impair females' ability to follow human signals. Forty pet dogs (18 intact females (IF) and 22 gonadectomized females (GF)) were tested in the object choice task paradigm using the human proximal pointing gesture. For the analysis, the frequency of correct, wrong and no-choices was collected; moreover, the latency of the correct choices was also considered. The IF group followed the pointing gestures more often than the GF group and with a lower latency, whereas a significantly higher no-choice frequency was recorded for the GF group. These results show a detrimental effect of ovariectomy on dogs' socio-cognitive skills related to the responsiveness to human pointing gestures

Assessing safety functionalities in the design and validation of driving automation

This paper aims to contribute to the comprehensive and systematic safety assessment of Automated Driving Systems (ADSs) by identifying unknown hazardous areas of operation. The current methodologies employed in this domain typically involve estimating the distributions of situational variables based on human-centered field test, crash databases, or expert knowledge of critical values. However, due to the lack of a-priori knowledge regarding the influential factors, their critical ranges, and their distributions, these approaches may not be entirely suitable for the assessment of emerging automated driving technologies. To deal with this challenging problem, here we propose a testing methodology incorporating realistic yet unobserved driving conditions, distinguished by numerous situational variables, so to encompass unknown unsafe conditions comprehensively. Our methodology utilizes stochastic simulation and uncertainty modeling techniques to account for the variability of realistic driving conditions and their impact on ADSs' performances. By doing so, we aim to identify unsafe operational regions and triggering conditions that can lead to hazardous behaviors, thus improving the development and safety of automated driving functions. For our purposes, the Latin Hypercube Sampling technique and the recently proposed PAWN density-based sensitivity analysis method are employed. We apply this methodology for the first time in the specific field of ADSs design and validation, using an exemplificative use case. We discuss and compare the results obtained from our approach with those obtained from a traditional approach

CORRELATES TO ABDOMINAL PAIN IN CONSTIPATION PREVALENT IBS PATIENTS

Background and aim: Symptoms of irritable bowel syndrome (IBS) have been associated to altered motility and sensation. In constipated prevalent-IBS patients, a clear association between bowel habit and abdominal pain remains to be established, and it is not known whether factors related to patients daily life may play a role in symptoms generation. Our aim was to evaluate the association between abdominal pain, bowel habit, demographic factors, alimentary/voluptuary habits and colonic transit in constipated-IBS patients. Material and methods: 68 patients complaining of chronic constipation were selected on the basis of the Rome 3 criteria for IBS. Colonic transit time (CTT) was studied and alimentary attitudes and smoking habit were recorded. Presence of mild or severe abdominal pain was scored, as well as the prevalent pain characteristics, defined as diffuse or localized, chronic or acute, with cramps or gradually distending. Data were analysed by univariate and stepwise multiple logistic regression analysis was also used to verify the risk association between pain and all other variables. Results: 40 patients were classified as constipated and 28 had alternating evacuation. Constipated patients had a lower scholar degree, consumed more laxatives, had a longer transit time in the right colon and scored more chronic pain than alternating ones, but it was not confirmed by multivariate analysis. When severity of abdominal pain was used as discriminating factor, a significant number of subjects reporting severe pain were males (16/30 vs 4/38, p<0.01) and smokers (20/30 vs 4/38, p<0.001). Multivariate analysis confirmed that only smoking was an independent factor associated with severe abdominal pain (OR 14.3, CI 2–99, p= 0.007). Conclusions: Abdominal pain is similarly reported by constipated or alternating IBS patients and it is not associated with colonic transit time or demographics. Smoking is the only factor constantly and independently associated to severe abdominal pain. As smoking does not seem likely to affect colonic transit time we suggest that smoking may act on the visceral perception in IBS-constipated patients

The scent of emotions: A systematic review of human intra- and interspecific chemical communication of emotions.

The sense of olfaction has been considered of minor importance in human communication. In recent years, evidence has emerged that humans might be influenced by unconscious messages sent through chemosignals in body odors. Data concerning the ability of humans to recognize fear, maybe related to the evolutionary role of these emotions in the fight-or-flight reactions, are well known. To further understand the role of emotional chemosignals in mediating communication in humans and its influence on animal behaviors, we conducted a systematic literature review. Chemosignals derived from axillary odors collected under a variety of emotional stimuli and sad tears in humans affect receivers' social interactions, danger detection and risk-taking behavior, social aspects of eating, and performance under stressing conditions. In addition, beyond the fight-or-flight response, even the body odors of happiness can be perceived by others. Furthermore, human chemosignals can influence behaviors and stressful responses in animals, particularly dogs and horses, which may partially explain their special relationship with humans. Our review highlights the importance of chemosignaling in human intra- and interspecific interactions and suggests the need for further investigations, both in physiological conditions and in patients with psychiatric or neurodegenerative disorders

Induction of Cytotoxic Oxidative Stress by d-Alanine in Brain Tumor Cells Expressing Rhodotorula gracilis d-Amino Acid Oxidase: A Cancer Gene Therapy Strategy

Overview summary Gene-directed enzyme prodrug therapy (GDEPT) is an antineoplastic treatment strategy designed to overcome the systemic toxicity of chemotherapy by specifically expressing a foreign enzyme in malignant cells that converts a nontoxic prodrug into a cytotoxic metabolite. The relative inefficiency of current in situ gene transfer methodology suggests that enzyme/prodrug combinations that produce membrane permeable metabolites will elicit a more favorable therapeutic response. Ideally, the agent produced by the transduced cell “factories” would be cytotoxic toward both proliferating and quiescent cells. We describe a novel GDEPT approach using d-amino acid oxidase from the red yeast Rhodotorula gracilis and d-alanine as a substrate that generates hydrogen peroxide, a reactive metabolite of oxygen that has both these characteristics. We also demonstrate the ability to sensitize tumor cells to this GDEPT protocol by manipulating cellular antioxidant pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63220/1/hum.1998.9.2-185.pd

Low glycemic index diet in children and young adults with refractory epilepsy: first Italian experience.

This is the report on the first Italian experience with the low glycemic index diet (LGIT) in a group of children, adolescents and young adults with refractory epileptic encephalopathies. A retrospective chart review was performed on patients initiating the LGIT in an outpatient setting from 2005 to 2010. Demographic and clinical information including seizure type, baseline seizure frequency, medications, blood chemistry, side effects, and anthropometrics were collected. Patients were educated and followed by a dietician to restrict foods with high glycemic index and to limit total daily carbohydrates to 40-60g. Change in seizure frequency was assessed at each 3-month follow-up intervals in the first year and then at each 6-month intervals. Fifteen consecutive patients (13 males and 2 females, aged between 11.3 years and 22 years), almost all affected by generalized cryptogenic or symptomatic refractory epilepsy, were enrolled in the study. After a mean follow-up period of 14.5±6.5 months (median 12.0; range 1-60 months), 6 patients (40%) had a 75-90% seizure reduction, while seizures decreased by 50% in other 2 (13.3%) and were unchanged in 7 (46.7%). The diet was discontinued in 4 patients within the first 5 months. No adverse events occurred during the diet. In conclusion, this initial experience confirms that some refractory patients may improve on the LGIT, even as first dietary option

ACHALASIA TREATMENT IMPROVES SPECIFIC SYMPTOMS AND QUALITY OF LIFE: VALIDATION OF AN ACHALASIA SPECIFIC QUALITY OF LIFE QUESTIONNAIRE

Background and aim: Therapies for achalasia aim to patients’ symptom relief, but they affect patient’s quality of life (QoL), too. An ad hoc question- naire evaluating both achalasia-related symptoms and disease related QoL is lacking. Aim: To validate a disease specific QoL questionnaire in perspectively evaluated Italian achalasia patients. Material and methods: 22 consecutive achalasia patients (4 men, age range 19–86 years) were included in the study. At baseline a structured question- naire was used to evaluate both esophageal symptoms and disease specific QoL. Questionnaire graded achalasia-related symptoms severity (dysphagia for solids and liquids, food regurgitation, chest pain, nocturnal cough) from 0 to 3, based on their impact on daily activities. Also a disease specific QoL was evaluated by a self administred questionnaire, the AE-18, that investigated four domains (physical, psychological and social functioning, and sleep dis- turbance). Scores for each item range from 1 (“always”) to 5 (“never”); higher scores corresponding to better quality of life. All patients were questioned before, 1 and 6 months after a specific t reatment regimen, that according to patients clinical status consisted in pneumatic dilation, botulinum toxin injection or surgical myotomy. Results: Patients within each specific treatment groups were the following (3/22 surgical myotomy, 14/22 pneumatic dilation and 5/22 Botox injections, respectively. In the table are reported the baseline demographics and achalasia- related symptoms’ severity and QoL (data are expressed as mean ± SD) within each treatments group. Table 1 Surgery group Dilation group Botox group p Age at diagnosis 42.3 ± 6.5 42.3 ± 13 81.8 ± 4.8 < 0.001 Age at onset of symptoms 39.3 ± 7.5 40.3 ± 12.4 80.8 ± 5.6 < 0.001 Dysphagia for solids 2.7 ± 0.6 2.2 ± 0.7 2.2 ± 0.5 0.5 Dysphagia for liquids 2.0 ± 1.0 2.1 ± 0.7 2.2 ± 0.5 0.9 Regurgitation of undigested food 1.0 ± 1.7 0.7 ± 0.8 0.6 ± 1.3 0.8 Chest pain 0.7 ± 1.1 1.1 ± 1.1 1.0 ± 1.4 0.8 Nocturnal cough 1.3 ± 1.5 1.3 ± 1.2 1.0 ± 1.4 0.9 AE-18 total score 54 ± 14 53 ± 12 53 ± 11 0.9 At both 1 and 6 months of the follow-up, the severity mean scores of dysphagia achalasia-related symptoms severity were significantly reduced compared to baseline (p < 0.05). Similarly, the AE-18 total score was significantly improved (p < 0.001). Conclusions: We showed that therapy-induced improvement of achalasia- related symptoms correlate with a significant improvement of patients quality of life as assessed by a specific questionnaire

Valproic acid and phenobarbital blood levels during the first month of treatment with the ketogenic diet.

Objective – The aim of this study was to assess how the ketogenic diet influences the blood levels of antiepileptic drugs in the first month of treatment in a pediatric population with drug-resistant epilepsy. Methods – The plasma concentrations of antiepileptic drugs were investigated in an open study on 36 consecutive children and adolescents (20 males), aged between 6 months and 16 years (mean age 4.7 years), who were put on the ketogenic diet because of medically refractory epilepsy. The plasma levels of antiepileptic drugs were determined 30 days and immediately before the diet and on days 8, 15, 22 and 29 after the start of the diet. The daily dose of each drug was not changed during the first month of treatment, while the daily dose of benzodiazepines was reduced by up to 30% if excessive sedation or drowsiness occurred. Results – While plasma concentrations of phenobarbital did not change in the first month on the ketogenic diet (mean increase of 2.3 mg ⁄ l 1.0), valproic acid showed a slight but not significant decrease (mean decresase of 6.7 mg ⁄ l 3.2), 2 weeks after the start of the diet. Conclusions – Adjustments in the daily dose of either drug before the start of the diet do not however appear to be justified