Hindcast and forecast of the Parsifal storm

On 2 November 1995 a Mistral storm in the Gulf of Lions sank the 16 metre yacht Parsifal claiming six lives out of the nine member crew. We analyse the storm with different meteorological and wave models, verifying the results against the available buoy and satellite measurements. Then we consider the accuracy of the storm forecasts and the information available the days before the accident. The limitations related to the resolution of the meteorological models are explored by hindcasting the storm also with the winds produced by some limited area models. Finally, we discuss the present situation of wind and wave hindcast and forecast in theMediterranean Sea, and the distribution of these results to the public

Hindcast and forecast of the Parsifal storm

On 2 November 1995 a Mistral storm in the Gulf of Lions sank the 16 metre yacht Parsifal claiming six lives out of the nine member crew. We analyse the storm with different meteorological and wave models, verifying the results against the available buoy and satellite measurements. Then we consider the accuracy of the storm forecasts and the information available the days before the accident. The limitations related to the resolution of the meteorological models are explored by hindcasting the storm also with the winds produced by some limited area models. Finally, we discuss the present situation of wind and wave hindcast and forecast in theMediterranean Sea, and the distribution of these results to the public

Modulation of opportunistic species Corynebacterium diphtheriae, Haemophilus parainfluenzae, Moraxella catarrhalis, Prevotella denticola, Prevotella melaninogenica, Rothia dentocariosa, Staphylococcus aureus and Streptococcus pseudopneumoniae by intranasal administration of Streptococcus salivarius 24SMBc and Streptococcus oralis 89a combination in healthy subjects

\u2013 OBJECTIVE: Probiotics S. salivarius 24SMBc and S. oralis 89a comprised in the nasal spray Rinogermina are known to exert inhibition of harmful pathogens and ameliorate the outcome of patients with chronic upper airways infections. In this study, for the first time, the effect of this formulation on the modulation of the microflora of healthy subjects was evaluated, with particular interest on pathobionts and pathogens present. PATIENTS AND METHODS: Metagenomic identification and quantification of bacterial abundances in healthy subjects were carried out by means of Ion Torrent Personal Machine. In particular, nasal swabs were sampled one, two and four weeks after seven days of treatment with Rinogermina. RESULTS: The modulation of the abundance of pathobionts and pathogenic species (i.e., Corynebacterium diphtheriae, Haemophilus parainfluenzae, Moraxella catarrhalis, Prevotella denticola, Prevotella melaninogenica, Rothia dentocariosa, Staphylococcus aureus and Streptococcus pseudopneumoniae) was characterized and a significant temporary decrease in their presence was identified. CONCLUSIONS: The beneficial effects of S. salivarius 24SMBc and S. oralis 89a nasal intake was assessed but seemed to be restricted in specific temporal windows. Thus it would be interesting to evaluate also this positive impact of longer administration of this probiotic formulation

Data repurposing from digital home cage monitoring enlightens new perspectives on mouse motor behaviour and reduction principle

: In this longitudinal study we compare between and within-strain variation in the home-cage spatial preference of three widely used and commercially available mice strains-C57BL/6NCrl, BALB/cAnNCrl and CRL:CD1(ICR)-starting from the first hour post cage-change until the next cage-change, for three consecutive intervals, to further profile the circadian home-cage behavioural phenotypes. Cage-change can be a stressful moment in the life of laboratory mice, since animals are disturbed during the sleeping hours and must then rapidly re-adapt to a pristine environment, leading to disruptions in normal motor patterns. The novelty of this study resides in characterizing new strain-specific biological phenomena, such as activity along the cage walls and frontality, using the vast data reserves generated by previous experimental data, thus introducing the potential and exploring the applicability of data repurposing to enhance Reduction principle when running in vivo studies. Our results, entirely obtained without the use of new animals, demonstrate that also when referring to space preference within the cage, C57BL/6NCrl has a high variability in the behavioural phenotypes from pre-puberty until early adulthood compared to BALB/cAnNCrl, which is confirmed to be socially disaggregated, and CRL:CD1(ICR) which is conversely highly active and socially aggregated. Our data also suggest that a strain-oriented approach is needed when defining frequency of cage-change as well as maximum allowed animal density, which should be revised, ideally under the EU regulatory framework as well, according to the physiological peculiarities of the strains, and always avoiding the "one size fits all" approach

Neuronal Phenotype of col4a1 and col25a1: An Intriguing Hypothesis in Vertebrates Brain Aging

Collagens are the most abundant proteins in vertebrates and constitute the major components of the extracellular matrix. Collagens play an important and multifaceted role in the development and functioning of the nervous system and undergo structural remodeling and quantitative modifications during aging. Here, we investigated the age-dependent regulation of col4a1 and col25a1 in the brain of the short-lived vertebrate Nothobranchius furzeri, a powerful model organism for aging research due to its natural fast-aging process and further characterized typical hallmarks of brain aging in this species. We showed that col4a1 and col25a1 are relatively well conserved during vertebrate evolution, and their expression significantly increases in the brain of N. furzeri upon aging. Noteworthy, we report that both col4a1 and col25a1 are expressed in cells with a neuronal phenotype, unlike what has already been documented in mammalian brain, in which only col25a1 is considered a neuronal marker, whereas col4a1 seems to be expressed only in endothelial cells. Overall, our findings encourage further investigation on the role of col4a1 and col25a1 in the biology of the vertebrate brain as well as the onset of aging and neurodegenerative diseases

Case Report: Rehabilitation After Platelet-Rich Growth Factors\u2019 Intra-Articular Injections for Knee Osteoarthritis: Two Case Reports of a Home-Based Protocol

Knee osteoarthritis (KOA) is a chronic progressive disease that can cause pain, functional impairment, and ultimately disability. A novel and promising therapeutic approach to KOA is the so-called regenerative medicine, a set of procedures designed to harness tissue regenerative capacity and optimize functional recovery. Increasing evidence points out that platelet-rich plasma (PRP) intra-articular injections can decrease pain and improve functional abilities in KOA patients. In the present case reports, we analyze two patients who were treated with PRP injections coupled with a posttreatment home-based rehabilitation program. The two patients were selected to represent two different populations: patient 1 was an 85-year-old with severe impairment of functional abilities, while patient 2 was a younger (59 years old) and more active patient. The protocol consisted in a series of exercise to be performed at home, during the five days following PRP injection for two consecutive weeks (10 days in total). The exercises were designed to reduce the inflammation after the injection, enhance the proprioceptive control of the treated lower limb, and strengthen hip and knee flexors and extensors, mainly by isometric work. Results were evaluated at two time points: before and 2 months after the first PRP injection. The outcomes considered were as follows: visual analog scale for pain, EuroQol 5 dimensions questionnaire, Tegner Activity Scale for functioning, and Knee Injury and Osteoarthritis Outcome Score (KOOS). Both patients did not report any side effects from the treatment. Improvement in patient 1 was drastic at the two months follow-up as far as pain and functional abilities are concerned. Patient 2\u2019s improvement was less evident, probably due to the higher starting point in both pain and functionality. Overall, the developed program seemed safe and was tolerated by the patients analyzed in the study, who performed it with good compliance

Immunolocalization of Nesfatin-1 in the Gastrointestinal Tract of the Common Bottlenose Dolphin Tursiops truncatus

SIMPLE SUMMARY: Nesfatin-1 (Nesf-1) is a neuropeptide that plays important roles in regulating food intake, mainly related to its anorexigenic effect, and it is mainly distributed in the digestive systems of all vertebrates. With this study, we expand knowledge on the localization of Nesf-1 in the digestive tract of an aquatic mammalian species, the common bottlenose dolphin (Tursiops truncatus), allowing comparative study on terrestrial mammals. Dolphin tissue samples (three gastric chambers and intestine) were provided by the Mediterranean Marine Mammal Tissue Bank of the Department of Comparative Biomedicine and Food Science of the University of Padova (Italy). ABSTRACT: First identified as an anorexigenic peptide, in the last decades, several studies have suggested that Nesfatin-1 (Nesf-1) is a pleiotropic hormone implicated in numerous regulatory processes in peripheral organs and tissues. In vertebrates, Nesf-1 is indeed expressed in the central nervous system and peripheral organs. In this study, we characterized the pattern of Nesf-1 distribution within the digestive tract of the common bottlenose dolphin (Tursiops truncatus), composed of three gastric chambers and an intestine without a clear subdivision in the small and large intestine, also lacking a caecum. Our results indicated that Nesf-1 is widely distributed in cells of the mucosal epithelium of the gastric chambers. Most of the immunoreactivity was observed in the second chamber, compared to the first and third chambers. Immunopositivity was also found in nerve fibers and neurons, scattered or/and clustered in ganglion structures along all the examined gastrointestinal tracts. These observations add new data on the highly conserved role of Nesf-1 in the mammalian digestive system

Orexin-A/Hypocretin-1 Controls the VTA-NAc Mesolimbic Pathway via Endocannabinoid-Mediated Disinhibition of Dopaminergic Neurons in Obese Mice

Disinhibition of orexin-A/hypocretin-1 (OX-A) release occurs to several output areas of the lateral hypothalamus (LH) in the brain of leptin knockout obese ob/ob mice. In this study, we have investigated whether a similar increase of OX-A release occurs to the ventral tegmental area (VTA), an orexinergic LH output area with functional effects on dopaminergic signaling at the mesolimbic circuit. By confocal and correlative light and electron microscopy (CLEM) morphological studies coupled to molecular, biochemical, and pharmacological approaches, we investigated OX-A-mediated dopaminergic signaling at the LH-VTA-nucleus accumbens (NAc) pathway in obese ob/ob mice compared to wild-type (wt) lean littermates. We found an elevation of OX-A trafficking and release to the VTA of ob/ob mice and consequent orexin receptor-1 (OX1R)-mediated over-activation of dopaminergic (DA) neurons via phospholipase C (PLC)/diacylglycerol lipase (DAGL-α)-induced biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). In fact, by retrograde signaling to cannabinoid receptor type 1 (CB1R) at inhibitory inputs to DA neurons, 2-AG inhibited GABA release thus inducing an increase in DA concentration in the VTA and NAc of ob/ob mice. This effect was prevented by the OX1R antagonist SB-334867 (30 mg/Kg, i.p.), or the CB1R antagonist AM251 (10 mg/Kg, i.p.) and mimicked by OX-A injection (40 μg/Kg, i.p.) in wt lean mice. Enhanced DA signaling to the NAc in ob/ob mice, or in OX-A-injected wt mice, was accompanied by β-arrestin2-mediated desensitization of dopamine D2 receptor (D2R) in a manner prevented by SB-334867 or the D2R antagonist L741 (1.5 mg/Kg, i.p.). These results further support the role of OX-A signaling in the control of neuroadaptive responses, such as compulsive reward-seeking behavior or binge-like consumption of high palatable food, and suggest that aberrant OX-A trafficking to the DA neurons in the VTA of ob/ob mice influences the D2R response at NAc, a main target area of the mesolimbic pathway, via 2-AG/CB1-mediated retrograde signaling

Central and Peripheral NPY Age‐Related Regulation: A Comparative Analysis in Fish Translational Models

NPY is among the most abundant neuropeptides in vertebrate brain and is primarily involved in the regulation of food intake. The NPY system is also associated with the aging process showing beneficial effects on neuronal survival via autophagy modulation. Here, we explore the age‐related regulation of NPY in the brain and foregut of the shortest‐ and longest‐lived fish species, Nothobranchius furzeri and Danio rerio, respectively. These two research models, despite some similarities, display profound biological differences making them attractive vertebrates to elucidate the mechanisms underlying the regulation of neuropeptide synthesis and function. It is noteworthy that in both fish species only Npya has been identified, while in the other teleosts two classes of NPY (Npya and Npyb) have been annotated. Our findings document that in both species: i) NPY is centrally regulated; ii) NPY levels increase in the brain during aging; iii) NPY is localized in the enteroendocrine cells as well as in the myenteric plexus and drastically decreases in old animals. According to our data, the age‐related regulation in the gut resembles that described in other vertebrate species while the increased levels in the brain offer the unique possibility to explore the role of NPY in model organisms to develop future experimental and translatable approaches