Roles of medial prefrontal cortex subregions in modulation of active and inhibitory action selection during aversively-motivated behaviours

Decision making in stressful and potentially aversive situations is an evolutionary trait functionally vital to avoid dangerous situations. It can either require action performance to actively avoid negative outcomes, or behavioural suppression to stay safe from danger. Failure to coordinate behaviour discrimination in real-life conflicting threatening situations can lead to aversive consequences because of improper inhibition of motor output when action is needed or, vice versa, when defensive actions are performed instead of withheld. These disruptions of appropriate functioning in avoidance behaviours can lead to improper action selection and increase negative outcomes as seen in disorders such as substance abuse, anxiety and depression. It has already been shown that striatal regions (namely the core and shell of the nucleus accumbens) are involved in regulation of avoidance behaviours with distinct roles in suppression and promotion of behaviour. Following the cortico-striatal connections with the prefrontal cortex (PFC), we investigated how active and inhibitory avoidance are controlled by the prelimbic cortex (PL) and infralimbic cortex (IL), which have been differentially implicated in instrumental response acquisition and expression. We also probed the extent to which the contribution of these regions is restricted to responding that is aversive and flexible. Separate groups of animals were trained to criteria on three distinct tasks and learned to avoid foot-shock delivery or to obtain sucrose by performing or suppressing lever-press behaviour. Pharmacological inactivation of these prefrontal regions revealed a role for PL in facilitating promotion and inhibition of goal- directed actions to oppose prepotent responding only when response allocation is under flexible conflicting conditions. IL inactivation, instead, was found to be necessary to refine action selection by inhibiting inappropriate responses while promoting instrumental active behaviour through suppression of fearful reactions. These results add a link in the neural network of avoidance processing and help further our understanding of how conditioned instrumental behaviours in threatening situations are processed by cortical regions and how pathological avoidance can arise in neuropsychiatric disorders.Arts, Faculty ofPsychology, Department ofGraduat

Feature selection for gesture recognition in Internet-of-Things for healthcare

Internet of Things is rapidly spreading across several fields, including healthcare, posing relevant questions related to communication capabilities, energy efficiency and sensors unobtrusiveness. Particularly, in the context of recognition of gestures, e.g., grasping of different objects, brain and muscular activity could be simultaneously recorded via EEG and EMG, respectively, and analyzed to identify the gesture that is being accomplished, and the quality of its performance. This paper proposes a new algorithm that aims (i) to robustly extract the most relevant features to classify different grasping tasks, and (ii) to retain the natural meaning of the selected features. This, in turn, gives the opportunity to simplify the recording setup to minimize the data traffic over the communication network, including Internet, and provide physiologically significant features for medical interpretation. The algorithm robustness is ensured both by consensus clustering as a feature selection strategy, and by nested cross-validation scheme to evaluate its classification performance

Resonance Raman Spectroscopy of Mn-Mg<i>_k</i> Cation Complexes in GaN

Resonance Raman analysis is performed in order to gain insight into the nature of impurity-induced Raman features in GaN:(Mn,Mg) hosting Mn-Mgk cation complexes and representing a prospective strategic material for the realization of full-nitride photonic devices emitting in the infra-red. It is found that in contrast to the case of GaN:Mn, the resonance enhancement of Mn-induced modes at sub-band excitation in Mg co-doped samples is not observed at an excitation of 2.4 eV, but shifts to lower energies, an effect explained by a resonance process involving photoionization of a hole from the donor level of Mn to the valence band of GaN. Selective excitation within the resonance Raman conditions allows the structure of the main Mn-induced phonon band at ~670 cm&#8722;1 to be resolved into two distinct components, whose relative intensity varies with the Mg/Mn ratio and correlates with the concentration of different Mn-Mgk cation complexes. Moreover, from the relative intensity of the 2LO and 1LO Raman resonances at inter-band excitation energy, the Huang-Rhys parameter has been estimated and, consequently, the strength of the electron-phonon interaction, which is found to increase linearly with the Mg/Mn ratio. Selective temperature-dependent enhancement of the high-order multiphonon peaks is due to variation in resonance conditions of exciton-mediated outgoing resonance Raman scattering by detuning the band gap

Thanatogenic Anthrosols: a geoforensic approach to the exploration of the Sepolcreto of the Ca’ Granda (Milan)

Soil is a dynamic matrix which can rapidly respond to disturbance events, such as the death and the deposition of an organism. Moreover, soil can be considered an archive of data due to its ability to record the traces of disturbance events. Accordingly, the biogeochemical analysis of the geopedological evidence could turn into a valuable tool for the study of decomposition processes. Hence, the aim of the present research is to detect the evidence of material exchange, linked to decomposition, between the bone tissue from two skeletal remains of the Sepolcreto (i.e., burial ground) in the crypt of the Ca’ Granda (Milan, Italy), and the pedosedimentary matrix from the stratigraphic unit US3 in which they were immersed. Both biological and geopedological specimens were analysed using a Scanning Electron Microscope equipped with facility for energy-dispersive spectroscopy (SEM-EDS) which pointed out the presence of a mutual exchange of material between the two substrates, underlying the intensity of the interaction between organisms (even if dead) and the environment in which they are located. The results were also able to lead to the detection of an inedited kind of material, mainly composed of organic matter resulted from the decomposition of human remains and preserved bone and soft tissues, which could be considered for introducing a new type of Anthrosol

Comparison of JAK2V617F mutation assessment employing different molecular diagnostic techniques

Background. The JAK2V617F mutation is present in the majority of patients with polycythaemia vera and in approximately half of patients with essential thrombocythaemia and primary myelofibrosis. In this study we compare the results of JAK2V617F mutation detection using three different molecular techniques in the same group of patients affected by essential thrombocythaemia. Patients and methods. The JAK2 mutation was investigated with a qualitative method in 115 consecutive outpatients with a diagnosis of essential thrombocythaemia made according to WHO 2001 criteria. In 48/115 (41.7%) the allele burden was also evaluated with two different qualitative methods, of which one was a method developed in-house and the other was a commercially available method. Results. The JAK2V617F mutation was detected by the qualitative method in 81/115 (69.6%) of the patients. Among the 48/115 patients in whom all three methods were applied, the qualitative method detected the mutation in 38 (79%). According to the quantitative method developed in-house, the mutation was present in 35/48 (73%) of the patients: of these, 2/35 (5.7%) patients were homozygous for the JAK2V617F mutation. The commercial quantitative method showed the mutation in 37/48 (77%) patients: of these, 9/37 (18%) patients were homozygous. Three of the 13 patients in whom no mutation was detected by the in-house method were positive for the JAK2V617F according to the commercial method. In one patient the search for the JAK2V617F mutation was positive with the in-house method but negative with the commercial kit. Conclusion. Detection of the JAK2V617F mutation may depend on the molecular technique used. Considering that detection of this mutation will not only have a diagnostic value, but also a role in treatment given the development of JAK2 V617F pathway inhibiting drugs, indications on a reference molecular diagnostic technique for JAK2V617F assessment and quantification of its allele burden from a panel of experts are warranted

Chronic intestinal pseudo-obstruction: is there a connection with gut microbiota?

La pseudo-ostruzione intestinale cronica (CIPO) è una sindrome clinica rara caratterizzata da grave compromissione della motilità gastrointestinale (GI) e i suoi sintomi suggeriscono un'ostruzione intestinale parziale o completa in assenza di qualsiasi lesione che restringe il lume intestinale. La diagnosi e la terapia dei pazienti CIPO rappresentano ancora una sfida significativa per i medici, nonostante i loro sforzi per migliorare l'iter diagnostico e le strategie di trattamento per questa malattia. Lo scopo di questa revisione è quello di comprendere meglio ciò che è attualmente noto sulla relazione tra i pazienti CIPO e il microbiota intestinale, con un focus sul ruolo del sistema nervoso enterico (ENS) e del sistema endocrino intestinale (IES) nella motilità intestinale, sottolineando l'importanza di ulteriori studi per comprendere a fondo le cause della disfunzione della motilità intestinale in questi pazienti.Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome characterized by severe impairment of gastrointestinal (GI) motility, and its symptoms are suggestive of partial or complete intestinal obstruction in the absence of any lesion restricting the intestinal lumen. Diagnosis and therapy of CIPO patients still represent a significant challenge for clinicians, despite their efforts to improve diagnostic workup and treatment strategies for this disease. The purpose of this review is to better understand what is currently known about the relationship between CIPO patients and intestinal microbiota, with a focus on the role of the enteric nervous system (ENS) and the intestinal endocrine system (IES) in intestinal motility, underling the importance of further studies to deeply understand the causes of gut motility dysfunction in these patients

Vasostatin-1: A novel circulating biomarker for ileal and pancreatic neuroendocrine neoplasms

<div><p>Background</p><p>Chromogranin A (CgA) is a plasma biomarker widely used in the follow-up of patients with neuroendocrine neoplasms (NENs). However, its accuracy as a tumor biomarker is relatively low because plasma CgA can increase also in patients with other diseases or in subjects treated with proton-pump inhibitors (PPIs), a class of widely-used drugs.</p><p>Methods</p><p>In the attempt to identify a more reliable biomarker for NENs, we investigated, by ELISA, the circulating levels of full-length CgA (CgA_1-439) and of various CgA-derived fragments in 17 patients with ileal or pancreatic NENs, 10 healthy controls, and 21 healthy volunteers before and after treatment with PPIs.</p><p>Results</p><p>Patients with ileal or pancreatic NENs showed increased plasma levels of total-CgA and CgA_1-76 fragment (vasostatin-1, VS-1) compared to controls [median (25^th-75^th-percentiles); total-CgA: 1.85 nM (1.01–4.28) <i>vs</i> 0.75 nM (0.52–0.89), <i>p</i> = 0.004; VS-1: 2.76 nM (1.09–7.10) <i>vs</i> 0.29 nM (0.26–0.32), <i>p</i><0.001, respectively], but not of CgA_1-439 or CgA_1-373 fragment. VS-1 positively correlated with total-CgA (r = 0.65, <i>p</i><0.001). The Receiver Operating Characteristic area under the curve was 0.9935 for VS-1 and 0.8824 for total-CgA (<i>p</i> = 0.067). Treatment of patients with somatostatin analogues decreased both total-CgA and VS-1. In contrast, administration of PPIs increased the plasma levels of total-CgA, but not of VS-1.</p><p>Conclusion</p><p>These findings suggest that plasma VS-1 is a novel biomarker for ileal and pancreatic NENs. Considering that VS-1 is a well-defined fragment not induced by proton-pump inhibitors, this polypeptide might represent a biomarker for NENs diagnosis and follow-up more accurate and easier to standardize than CgA.</p></div

Levels of VS-1, CgA_1-373 and CgA_1-439 relative to the total-CgA in the plasma of patients with ileal and pancreatic NENs (cases) and healthy subjects (controls).

<p>Box-plots with median (middle line), 75^th percentile (top line) and 25^th percentile (bottom line). The top and bottom whiskers represent the upper and lower adjacent values, respectively. Values outside the whiskers are plotted individually (circles). Cases (n = 17); controls (n = 10). * (<i>p</i> < 0.05), **(<i>p</i> < 0.01), by analysis of covariance. As total-CgA does not include VS-1, VS-1/total-CgA ratio can be also greater than 1.</p

Effect of therapy with somatostatin analogues (SSAs) on the plasma levels of total-CgA and VS-1 in patients with ileal and pancreatic NENs.

<p>(A, B) Plasma levels of total-CgA and VS-1 in NENs cases (ileal plus pancreatic NENs) before and after the administration of octreotide LAR. ** (<i>p</i> < 0.01), by Wilcoxon signed-rank test. (C) Correlation between the decrease (%) of the plasma levels of VS-1 and total-CgA after therapy.</p