Resilience and susceptibility to stress-related disorders: insights from animal models

Stressful experiences can produce both accurate or generalized memories, reflecting an interindividual difference in response to stress. Psychostimulants outcomes on memory enhancement are known from many years, but literature data also show their memory generalization effects. However, the mechanisms through which psychostimulants affect memory quality is still poor investigated. In Chapter 1 we explored the memory generalization effects induced by amphetamine and a new psychostimulant: the 3,4-methylenedioxypyrovalerone (MDPV), also called “bath salt”. Both psychostimulants share a similar, yet not identical mechanism of action, augmenting noradrenaline and dopamine levels in the synaptic cleft. Thus, in a second experiment we aimed at evaluating the different involvement of the noradrenergic and dopaminergic system in the effects on memory enhancement, and on memory generalization. Treatment with the anesthetic ketamine, a renowned drug of abuse, in trauma patients during emergency care aggravated early post-traumatic stress reaction which is highly predictive of post-traumatic stress disorder (PTSD) development and severity. Based on the evidence that ketamine induces a robust central and peripheral adrenergic/noradrenergic potentiation and that activation of this system is essential for the formation of memory for stressful events, in Chapter 2 we explored the possibility that the strong sympathomimetic action of ketamine might underlie its memory enhancing effects. Given that PTSD is a chronic psychiatric disease, it is of critical importance to evaluate whether animal model of PTSD resemble the chronicity nature of this pathology. The single prolonged stress (SPS) paradigm has been extensively shown to induce behavioral and endocrine effects resembling the hallmark symptoms observed in PTSD patients and, similarly to PTSD, the manifestation of these effects is time-dependent and requires a 1-2 weeks incubation period. Although women have a two-fold greater risk to develop PTSD, most preclinical studies have been carried out in males. In Chapter 3 we aimed at investigating whether SPS induced persistent PTSD-like behavioral alterations in rats long after trauma exposure and whether these effects are sex-dependent. Another important aspect of PTSD is the susceptibility to develop this pathology. Animal models are a useful tool to investigate this issue. However, in the sparse studies considering the individual variability in response to trauma, only the anxiety symptoms are used to discern between different PTSD-like phenotypes, without considering the cognitive aspects of PTSD. In Chapter 4 we aimed at the development of an animal model of PTSD, with translational value, able to predict the susceptibility and the resilience phenotype considering both the cognitive and emotional alterations long after trauma. For this purpose, we outstretched our previously validated animal model in order to identify susceptible and resilient rats in terms of over- consolidation, impaired extinction and social behavior alterations. Nowadays there are different hypotheses to explain the interindividual variability in response to stress. Different studies used the “two hit” stress model to investigate whether exposure to two different stressors at different ages may increase (or decrease) the risk to develop psychopathologies after experiencing the second stressor. However, how a social stress similar to bullying in humans experienced at adolescence may affect the reaction to additional stressor later in life are less investigated. Adolescence is a period of impressive brain maturation in which the structure of the brain is ever-changing. Thus, maintaining a correct balance between mediators that sustain synaptic plasticity is of utmost importance. In Chapter 5 we evaluated whether the exposure to social defeat stress, a highly validated animal model of bullying in rodents, at adolescence and/or single prolonged stress experienced at adulthood affect the later development of emotional and cognitive alterations and whether the behavioral alterations are linked to any modification of hippocampal brain derived neurotrophic factor (BDNF) expression and plasma corticosterone levels. While adolescent bullying occurs in a small subset of population, a more common social stressor is represented by the deprivation of social interactions with conspecifics which is able to induce profound behavioral changes in rodents. Social isolation stress paradigm is commonly used to reproduce schizophrenia in rodents and it is conducted chronically from weaning to adulthood. However, long-term effects induced by a briefer period of social isolation stress during adolescence, which is a critical window for brain development, are not investigated. Moreover, it is known that in mammals, females have greater risk to develop stress-related disorders than males. In Chapter 6 we firstly evaluated whether repeated brief periods of social isolation stress may alter emotionality and cognitive functions in adult male rats. Secondly, we examined whether brief and repeated social isolation stress during at adolescence and/or single prolonged stress at adulthood affect the later development of alteration on emotionality and cognition. Further, we aimed at evaluating whether such effects are sex-dependent

Improving Projects Performance With Lean Construction: State Of The Art, Applicability And Impacts

Construction projects are not often delivered on time and on budget and re-workings are usually required to satisfy customer’s needs. This papers aims to present an overview of Lean Construction (LC) and how this construction philosophy tackles the aforementioned problems. The research is empirical and based on data from the literature, 7 new Case Studies built with primary data, 12 Case Studies on CLIP (Construction Lean Improvement Programme) projects, 4 semi-structured Interviews with Firms adopting LC and several interviews (face to face and email) with LC experts. The results show as LC can achieve astonishing results focusing on reducing waste caused by unpredictable work-flow, paying attention on how every single activity affects the next one and avoiding reworking considered as no valued-added activity. The paper provides three original set of results: (1) a fuzzy cognitive map of LC showing how the different elements are linked to each other; (2) a pathway for the implementation of LC; (3) a synthesis of the strengths and the weaknesses of LC merging literature review with case studies analysis. In particular (3) shows the dimensions of projects adequate for lean construction, the increase of productivity and time reduction due to LC implementation and finally the reasons moving firms to adopt LC

Revising the Emergency Management Requirements for new generation reactors

The paper presents the application of a new risk-informed methodology for the identification of the Emergency Management Requirements (EMR) to a Generation II, Large size Reactor and a Generation III+ Small Modular Reactor. The results obtained in this test case demonstrate that the actual EMR is conservative, as expected, for the GenII reactor, while the new methodology could be applied for the definition of EMRs for the new generation Nuclear Power Plants, with a possible reduction of the emergency area without loss of safety level. By adopting both probabilistic and deterministic approaches, the study addresses possible accidents and corresponding release scenarios for the two types of reactor, calculates the areas where the accidents have an impact on the population and defines the new EMR considering the health effects on the population

A Tiny Convolutional Neural Network driven by System Identification for Vibration Anomaly Detection at the Extreme Edge

Vibration data analysis is the driving tool for the Structural Health Monitoring (SHM) of structures in the dynamic regime, i.e., structures showing important oscillatory behaviours, which largely dominate the transportation back-bone: from terrestrial/aerial vehicles (e.g., trains, aircraft, etc.) to the supporting infrastructures (e.g., bridges, viaducts, etc.). Outstanding opportunities have recently been disclosed in the field of Intelligent Transportation Systems (ITS) by the advent of sensor-near processing functionalities, eventually empowered by Artificial Intelligence (AI). The latter allow for the extraction of damage-sensitive features at the extreme edge, without the need of transmitting long time series over the monitoring network. In this work, we explore for the first time a novel anomaly detection workflow for on-sensor vibration diagnostics, which combines the unique advantages of embedded System Identification (eSysId) as a data compression strategy with the computational/energy advantages of Tiny Machine Learning (TinyML). Experimental results conducted on a representative SHM dataset demonstrate that the proposed pipeline can achieve high classification scores (above 90%) for the health assessment of the well-known Z24 bridge. In particular, the minimal inference time (less than 44 ms) and power consumption performed while running on three different general-purpose microprocessors make it a promising solution for the development of the next generation of SHM-oriented ITS

Risk factors for Haemophilus influenzae and pneumococcal respiratory tract colonization in CVID

To the Editor: Disease-specific studies focused on infection risk in common variable immune deficiencies (CVIDs) are needed to define strategies for controlling respiratory infections predominantly due to bacteria such as Streptococcus pneumoniae and Haemophilus influenzae.1 Little information is available on the rate of airway bacterial carriage and its consequence in hypogammaglobulinemias. Despite IgG replacement, recurrent respiratory infections are common in CVID, possibly leading to chronic lung damage2 and poor quality of life.3 Thus, patients are often prescribed antibiotics and/or long-term antimicrobial prophylactic regimens. Several regimens are used including rotation or periodically changing antibiotics.4 However, antibiotics influence antimicrobial resistance among airway microbiota. In a recent meta-analysis on patients with chronic lung diseases, 30% of S pneumoniae showed resistance to macrolides.

Harmonious and obsessive involvement, self-esteem, and well-being. A longitudinal study on MMORPG players

Starting from the dualistic model of passion by Vallerand and colleagues (2003), this study aimed to identify "obsessive" and "harmonious" involvements in MMORPGs and to verify their relationships with players' self-esteem and well-being. An international sample of 147 MMORPG players participated in a longitudinal design filling out for 3 times an online questionnaire measuring game involvement (in terms of Internet Gaming Disorder [IGD] symptoms, time spent playing the video game, sense of presence while playing, and avatar identification), global self-esteem, and well-being (i.e., meaningful life, engaged life, and pleasant life). Results supported the presence of these two different types of involvement: Obsessive involvement, characterized by a close association between IGD symptoms and playing time; Harmonious involvement, characterized by a close association between presence, avatar identification, and IGD symptoms. Cross-lagged effects showed that, over time, low self-esteem and low meaningful life predicted obsessive involvement, which in turn predicted engaged life. The present study contributes to a better understanding of the effects between video games use and the users' self-esteem and well-being. Furthermore, it contributes to the theoretical debate about problematic involvement in videogames, also providing some indications about problematic gaming assessment and prevention

Insertion polymorphisms of SINE200 retrotransposons within speciation islands of Anopheles gambiae molecular forms

<p>Abstract</p> <p>Background</p> <p>SINEs (Short INterspersed Elements) are homoplasy-free and co-dominant genetic markers which are considered to represent useful tools for population genetic studies, and could help clarifying the speciation processes ongoing within the major malaria vector in Africa, <it>Anopheles gambiae </it>s.s. Here, we report the results of the analysis of the insertion polymorphism of a nearly 200 bp-long SINE (<it>SINE200</it>) within genome areas of high differentiation (i.e. "speciation islands") of M and S <it>A. gambiae </it>molecular forms.</p> <p>Methods</p> <p>A <it>SINE</it>-PCR approach was carried out on thirteen <it>SINE200 </it>insertions in M and S females collected along the whole range of distribution of <it>A. gambiae </it>s.s. in sub-Saharan Africa. Ten specimens each for <it>Anopheles arabiensis</it>, <it>Anopheles melas, Anopheles quadriannulatus </it>A and 15 M/S hybrids from laboratory crosses were also analysed.</p> <p>Results</p> <p>Eight loci were successfully amplified and were found to be specific for <it>A. gambiae </it>s.s.: 5 on 2L chromosome and one on X chromosome resulted monomorphic, while two loci positioned respectively on 2R (i.e. <it>S200 </it>2R12D) and X (i.e. <it>S200 </it>X6.1) chromosomes were found to be polymorphic. <it>S200 </it>2R12D was homozygote for the insertion in most S-form samples, while intermediate levels of polymorphism were shown in M-form, resulting in an overall high degree of genetic differentiation between molecular forms (Fst = 0.46 p < 0.001) and within M-form (Fst = 0.46 p < 0.001). The insertion of <it>S200 </it>X6.1 was found to be fixed in all M- and absent in all S-specimens. This led to develop a novel easy-to-use PCR approach to straightforwardly identify <it>A. gambiae </it>molecular forms. This novel approach allows to overcome the constraints associated with markers on the rDNA region commonly used for M and S identification. In fact, it is based on a single copy and irreversible <it>SINE200 </it>insertion and, thus, is not subjected to peculiar evolutionary patterns affecting rDNA markers, e.g. incomplete homogenization of the arrays through concerted evolution and/or mixtures of M and S IGS-sequences among the arrays of single chromatids.</p> <p>Conclusion</p> <p>The approach utilized allowed to develop new easy-to-use co-dominant markers for the analysis of genetic differentiation between M and S-forms and opens new perspectives in the study of the speciation process ongoing within <it>A. gambiae</it>.</p

Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery in locally advanced rectal cancer: preliminary results of a phase II study

PURPOSE: To report preliminary results of induction chemotherapy (IC) followed by neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer (LARC) patients.MATERIALS AND METHODS: This is the preliminary evaluation of a phase II study. Patients with histologically proven rectal adenocarcinoma, stage II-III disease, who met the inclusion criteria, received induction FOLFOXIRI (5-FU, leucovorin, oxaliplatin and irinotecan) regimen in combination with targeted agents followed by CRT and surgery. Analysis of the first 8 patients was required to confirm the treatment feasibility before the accrual of 20 additional patients. RESULTS: The first 8 patients were evaluated. The median follow-up time was 23 months. There were no treatment-related deaths. Trimodality strategy was well tolerated with high compliance and a good level of toxicity. There were no evidence of febrile neutropenia and any grade 4 adverse events were recorded. Three patients had pathologic complete response (pCR) and 1 patient had a nearly pCR (ypT1 ypN0). CONCLUSION: Preliminary results are encouraging. FOLFOXIRI regimen plus targeted agents followed by CRT and surgery seems a safe approach. Longer follow-up and higher number of patients are mandatory to confirm such findings

Assessment of perfluorooctane sulfonate and perfluorooctanoic acid exposure through fish consumption in Italy

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are pollutants of anthropic origin with possible side effects on human health. Diet, and in particular fish and seafood, is considered the major intake pathway for humans. The present study investigated the levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) contamination in twenty-five samples of fresh fillet of five widely consumed fish species purchased from large retailers in Italy, to be used for an estimation of the Italian population exposure to these contaminants. PFOS and PFOA were found in all samples, at concentrations up to 1,896 (mean = 627 ng/kg) and 487 ng/kg (mean = 75 ng/kg), respectively, confirming the role of fish as high contributor to human exposure. However, a remarkable inter-species variability was observed, and multiple factors were suggested as potentially responsible for such differences, suggesting that the preferential consumption of certain species could likely increase the intake, and thus the exposure. The exposure estimates for both average and high fish consumers resulted far below the TDIs for PFOS and PFOA in all age groups, confirming the outcomes of EFSA\u2019s scientific report. In particular, the calculated total dietary exposure for the 95th percentile consumers belonging to the toddler age class, the most exposed group, resulted equal to 9.72 ng/kg b.w./day for PFOS and 8.39 ng/kg b.w./day for PFOA