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

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

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

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

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

A Novel Generalized Semi-Analytical Approach for Flood Control Reservoir Design

Flood control reservoir design requires estimating the total storable water volume or the maximum allowable discharge. This study proposes a novel Generalized Semi-Analytical Approach (GS-AA) to identify the maximum outlet discharge a flood control reservoir can handle for a specific return period. The approach exploits the analytical expression of Flow Duration Reduction (FDR) curves and combines them with an optimization algorithm to find the critical hydrograph and, thus, the hydrograph providing the maximum outlet discharge from the reservoir. The approach models the runoff process of the basin upstream of the reservoir, allowing users to choose any runoff model (RM). The proposed approach shows faster computational times than a fully numerical procedure, enabling potential users to explore and compare multiple reservoir configurations easily. Moreover, this approach addresses flow data limitation issues that prevent FDR curve derivation by correlating them to Intensity Duration Frequency curve parameters, expanding the potential applicability of the procedure in ungauged basins. Finally, results demonstrated the functionality of the procedure regardless of the chosen RM, offering widespread flexibility for users. The proposed GS-AA is a robust and adaptable tool for design and verification purposes to improve flood management strategies

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

Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes

Epithelial-mesenchymal interactions are crucial for the development of numerous animal structures. Thus, unraveling how molecular tools are recruited in different lineages to control interplays between these tissues is key to understanding morphogenetic evolution. Here, we study Esrp genes, which regulate extensive splicing programs and are essential for mammalian organogenesis. We find that Esrp homologs have been independently recruited for the development of multiple structures across deuterostomes. Although Esrp is involved in a wide variety of ontogenetic processes, our results suggest ancient roles in non-neural ectoderm and regulating specific mesenchymal-to-epithelial transitions in deuterostome ancestors. However, consistent with the extensive rewiring of Esrp-dependent splicing programs between phyla, most developmental defects observed in vertebrate mutants are related to other types of morphogenetic processes. This is likely connected to the origin of an event in Fgfr, which was recruited as an Esrp target in stem chordates and subsequently co- opted into the development of many novel traits in vertebrates

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

Opsin evolution in the Ambulacraria

Opsins - G-protein coupled receptors involved in photoreception - have been extensively studied in the animal kingdom. The present work provides new insights into opsin-based photoreception and photoreceptor cell evolution with a first analysis of opsin sequence data for a major deuterostome clade, the Ambulacraria. Systematic data analysis, including for the first time hemichordate opsin sequences and an expanded echinoderm dataset, led to a robust opsin phylogeny for this cornerstone superphylum. Multiple genomic and transcriptomic resources were surveyed to cover each class of Hemichordata and Echinodermata. In total, 119 ambulacrarian opsin sequences were found, 22 new sequences in hemichordates and 97 in echinoderms (including 67 new sequences). We framed the ambulacrarian opsin repertoire within eumetazoan diversity by including selected reference opsins from non-ambulacrarians. Our findings corroborate the presence of all major ancestral bilaterian opsin groups in Ambulacraria. Furthermore, we identified two opsin groups specific to echinoderms. In conclusion, a molecular phylogenetic framework for investigating light-perception and photobiological behaviors in marine deuterostomes has been obtained