Huygens synchronisation of three clocks equidistant from each other

In this paper we study the synchronisation of three identical oscillators, i.e., clocks, hanging from the same hard support. We consider the case where each clock interacts with the other two clocks. The synchronisation is attained through the exchange of small impacts between each pair of oscillators. The fundamental result of this article is that the final locked state is at phase difference of ((2{\pi})/3) from successive clocks (clockwise or counter-clockwise). Moreover, the locked states attract a set whose closure is the global set of initial conditions. The methodology of our analysis consists in the construction a model, which is a non-linear discrete dynamical system, i.e. a non-linear difference equation. The results are extendable to any set of three oscillators under mutual symmetric interaction, despite the particular models of the oscillators

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

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

Effects of different degrees of sympathetic antagonism on cytokine network in patients with ischemic dilated cardiomyopathy

BACKGROUND: The proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Recent studies have shown that beta-adrenergic blockade can modulate cytokine production. This study investigates the different impact of different degrees of sympathetic antagonism on circulating levels of cytokines in patients with heart failure resulting from ischemic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Thirty-five patients with IDC were randomly assigned to receive metoprolol or carvedilol in an open-label study. Echocardiographic measurements and circulating levels of tumor necrosis (TNF)-alpha and interleukin (IL)-1beta and IL-6 were obtained at baseline and after 3 months of treatment. The 2 beta-blockers significantly improved the left ventricular ejection fraction and reduced end-diastolic and end-systolic volume. The magnitude of these changes was greater with carvedilol than with metoprolol (respectively P < .001, P < .05, and P < .05). Both treatments induced a significant decrease in the levels of cytokines (for all P < .01), but the decrease in TNF-alpha and IL-1beta was more consistent in the carvedilol group ( P < .01). CONCLUSION: Our results support the hypothesis that a more complete block of sympathetic activity by carvedilol induces a greater decrease in the circulating levels of proinflammatory cytokines that could explain, at least in part, the better improvement in the left ventricular remodelling and systolic function in patients with IDC

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

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

INTRA-DUODENAL RELEASE OF A BITTER COMPOUND DECREASES CALORIC INTAKE IN HEALTHY VOLUNTEERS

Background and aim: α-gustducin and bitter taste receptors (T2R) are expressed both in the oral cavity and in the gastrointestinal (GI) tract. Experimental data showed that bitter tastants induce the release of gut hormones from enteroendocrine cells in the gut, suggesting a possible role of bitter taste receptors in the control of food intake and GI functions. We aimed to test the effects of a bitter taste receptor agonist on food intake and GI feelings. Material and methods: We enrolled 19 healthy subjects (9 males, age 27±7, BMI 24±6) in a double-blind placebo controlled study. Each subject randomly received an acid-resistant capsule containing placebo or 18 mg of quinine HCl. 60 minutes after capsule administration, the subjects underwent to an ad libitum test, until the maximum satiation. Meal test was composed by white bread, cheese and meat cream (89 kcal/portion: 50% carbohydrate, 31% fat, 19% protein). Caloric intake, meal duration and satiation levels, scored on a Visual Analogue Scale (VAS) were calculated at the end of the meal test. A questionnaire assessing GI sensations (bloating, fullness, nausea, epigastric discomfort and hunger) was administered before and at the end of the test. Data (mean ± SD) were compared by using paired t test. Results: No oral bitter sensation or side effects was observed both with quinine HCland placebo. No significant differences in terms of GI sensations and hunger feelings were observed between the two sessions of the study. The amount of calories ingested was significantly lower when subjects received quinine HCl than placebo (564±262 vs 667±278 kcal; p=0.02). Conversely, quinine HCl did not affect the meal duration (14.4±4.2 vs 16.6±4.6 min; p=NS) and the satiationintensity (82 vs 82 mm; p=NS). Conclusions: The intra-duodenal release of a bitter compound significantly decreases caloric intake in an ad libitum test meal without affecting GI sensations and hunger feeling. As the bitter compound does not influence meal duration, we hypothesize that quinine HCl decreases the caloric intake by affecting the rate of meal portions consumption. Evaluation of gut hormones kinetics and studies with other bitter taste receptor agonist are needed to establish the role of gastrointestinal bitter taste receptor in the control of food intak

CHRONIC CONSTIPATION IS A RISK FACTOR FOR METABOLIC SYNDROME

Background and aim: A recent epidemiologic survey in the U.S. provides indirect evidence that constipation is a risk factor for cardiovascular disease in postmenopausal females. To characterize the related factors involved in and to further analyse if this assumption also applies to an Italian population, we studied the impact of chronic constipation on ischemic cardiopathy and predisposing risk factors in a large population of female patients in a primary care setting. Material and methods: We retrospectively evaluated 754 female patients (mean age 46±20 years) on data file of a primary care setting. All subjects requiring medical referral for constipation were screened and presence of chronic constipation was confirmed by standardized questionnaires. The presence of clinical and/or instrumental diagnosis of ischemic cardiopathy, metabolic syndrome, diabetes and blood hypertension was scored in patients with and without chronic constipation. In all patients the consumption of drugs potentially delaying colonic transit (calcium channel blockers and beta blockers) was recorded. Patients on opioid or analgesic treatment were excluded. Results: The overall prevalence of chronic constipation was 9.4% (71/754) with the age being similar in patients with and without constipation (46±19 vs. 51±22, p=NS). The prevalence of metabolic syndrome was significantly higher in subjects with chronic constipation (5/66 vs 16/667, OR=3.1, 95% CI 1.1–8.9, p=0.03). Conversely, prevalence of diabetes, blood hypertension, ischemic cardiopathy was similar in patients with and without constipation (59/624 vs 10/61; 204/478 vs 28/43; 46/637 vs 6/65, respectively p= all NS). No significant difference was also observed as far as calcium channel blockers (64/619 vs 9/62) and beta blockers (81/602 vs 9/62) consumption in patients with or without constipation respectively. Conclusions: We showed that chronic constipation is a risk factor for metabolic syndrome in female patients. Although we did not find any significant association between chronic constipation and ischemic cardiopathy, our findings support the hypothesis that constipation may act as cardiovascular risk factor. Whether this association is dependent on dietary or hormonal factors deserves further investigation

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

Numerical modelling of masonry infill walls in existing steel frames

It is now widely recognised that masonry infill plays an essential role in the seismic behaviour of existing steel buildings; however, there is still a lack of clear guidance on the modelling of masonry infill in the current Eurocode 8-Part 3. Several methods for the numerical modelling of masonry infills have been proposed in literature over the past few decades, which either adopt a detailed approach (micro-model) or a simplified approach (macromodel). In the former case, bricks are individually modelled, taking into account the brickmortar cohesive interface, which is able to provide detailed insights of the behaviour of masonry infills and the frame-wall interaction but usually at a high computational cost. On the other hand, a simplified model can be easily built within finite element software, most of which replace the infill wall panel with one or more equivalent struts in the diagonal direction. It has been demonstrated that the strut models can simulate RC infilled structures’ global response with acceptable accuracy; however, there are still no adequate recommendations for their modelling within steel frames. Besides, these models are generally incapable of capturing the interactions between the infills and the frame members. To this end, the present paper numerically investigates an Abaqus macro-model of the infilled steel frame, which was experimentally tested as part of the recent SERA HITFRAMES project. The preliminary re-sults shows that the different detailing of steel frames could lead to different damage patterns in the infill walls when compared to RC frames. In particular, instead of a single diagonal strut, at most three struts were observed in this study. The results also suggested that the number and geometry of struts could change with increasing displacement demands, hence it might not be appropriate to use the same strut model for infill walls on different floors