Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes

Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice’s respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI). Twelve patients with relapse/refractory (R/R) HL (median age 28.5 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 9 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 3 responding patients received ALI alone, as a control cohort. No severe adverse events were recorded. HL-treated patients achieved negative PET scan CR and 8 are alive and disease-free after a median follow-up of 28 months. Four patients underwent subsequent allogeneic SCT. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients. Our data show anti-tumor activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favor the expansion of the "adaptive" NK cell compartment in patients with HCMV seropositivity, in the absence of HCMV reactivation

Arthroscopic Technique of Wafer Resection

Ulnar impaction syndrome, also called ulnocarpal abutment syndrome, is one of the most common causes of ulnar-sided wrist pain in the presence of a normal or positive variance of the distal ulnar head. Usually, it is associated with degeneration of the triangular fibrocartilage complex. This condition is commonly treated by debridement of the central part of the triangular fibrocartilage complex ligament followed by a wafer resection of the ulnar head. Alternative surgeries are wafer resection preserving an intact triangular fibrocartilage complex ligament and an inverted wafer resection corresponding to a lunate and triquetrum proximal resection with luno-triquetral ligament debridemen

The Pre-1D Lesion of the TFCC-A New Variant of the Palmer 1D Class

: The triangular fibrocartilage complex (TFCC) is the most important stabilizer of the distal radioulnar joint (DRUJ). Its injury is the main cause for ulnar sided pain after wrist trauma. In recent years, advancements of wrist arthroscopy improved the diagnostics and treatment of the TFCC tears. The purpose of this article is to describe a variant of radial tears (1D according to Palmer), in which the radio-ulnar ligaments were ruptured in the midsubstance just before (Pre) their insertion on the sigmoid notch and illustrate the arthroscopic surgical technique used for its treatment. We name this variant of the Palmer 1D lesion, the pre-1D TFCC lesion

Comparison between MRI and Arthroscopy of the Wrist for the Assessment of Posttraumatic Lesions of Intrinsic Ligaments and the Triangular Fibrocartilage Complex

Background Magnetic resonance imaging (MRI) has been considered the most appropriate examination for wrist ligament injuries diagnosis, but it frequently fails to assess the intrinsic ligament lesion. Therefore, wrist arthroscopy is required to enhance and define the diagnosis.Purpose We compare the MRI imaging with wrist arthroscopy for intrinsic wrist ligaments (scapholunate [SL] and lunotriquetral [LT]) and triangular fibrocartilage complex (TFCC) injuries detection.Patients and Methods From 2007 to 2014, 532 patients affected by suspected SL, LT, and TFCC posttraumatic ligament injury have been investigated by 1.5-Tesla MRI and wrist arthroscopy. Inclusion and exclusion criteria were adopted. Only for SL ligament injury, the arthroscopic findings of complete (stage IV) and partial (stages I-III) SL ligament injury were compared with MRI findings. Statistical analysis, including sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and the diagnostic odds ratio, was used to compare MRI with arthroscopic findings.Results A total of 146 patients were accepted in the study. In 68 cases of arthroscopic SL ligament lesion, MRI confirmed the diagnosis only in 50% of the cases. In partial SL lesions, MRI was positive in 24.3% and in complete SL lesions, MRI was positive in 80.6% of the cases. In 10 cases of arthroscopic LT ligament lesion, MRI was positive in 30.0% of the cases. In 33 patients with arthroscopic TFCC lesion, MRI was positive in 66.7% of the cases.Conclusion 1.5-T MRI demonstrated to fail in confirming the lesion of SL, LP, and TFCC ligaments respectively in 50, 70, and 33.3% of the cases positive at arthroscopy. In complete SL ligament lesion, MRI reaches a higher sensitivity than in partial lesion. Arthroscopy remains the best method to demonstrate the ligament lesion and obtain more information regarding the extent and quality of the ligament damage

PESInet: Automatic Recognition of Italian Statements, Questions, and Exclamations With Neural Networks

PESInet is an Automatic Prosody Recognition system aiming at classifying Infor- mation Units as Statement, Question or Exclamation. PESInet adopts a modular architecture, with a master NN evaluating the results of two independent BLSTM NNs that work on audio and its transcription. PESInet has been trained with our own three-class, balanced corpus composed of about 1.5 million text phrases and 60 000 utterances of recited and spontaneous speech. PESInet reached an accuracy of 80% on three classes, and 91% on two classes (Question vs Non-question). Finally PESInet, compared against human listeners on a two-class test based on a dif- ferent corpus, reached a better Accuracy (89% for PESInet, against 80% for human listeners)

Schizofrenia all'esordio e "gruppalit\ue0". Per una diversa cultura della cura.

Abstract Il presente studio \ue8 nato dall\u2019intenzione di descrivere gli effetti terapeutici di pratiche per la Salute Mentale progettate, e agite, all\u2019interno del Dipartimento di Salute Mentale di Trieste a favore di giovani adulti che, nel corso della propria storia di vita, hanno presentato l\u2019esordio di un disturbo schizofrenico. Il costrutto terapeutico analizzato \ue8 quello gruppale, inteso come strutturazione di momenti d\u2019incontro tra soggettivit\ue0, e quindi non appartenente a setting psico-terapeutici ben precisi. Il percorso proposto parte dalle \u201cpratiche\u201d, passa per le osservazioni, i dati, i numeri, le riflessioni, ma si torna continuamente alle soggettivit\ue0: pazienti e operatori.La cornice epistemologica \ue8 quella della psicopatologia fenomenologica, il paradigma utilizzato quello dell\u2019intersoggettivit\ue0: il disturbo schizofrenico \ue8 considerato come scacco del meccanismo intersoggettivo.Sono stati analizzati gli esiti terapeutici in due gruppi di giovani, con esordio schizofrenico recente, presi in carico nei servizi territoriali di Salute Mentale. In questo studio s\uec \ue8 posto in evidenza come il favorire l\u2019accesso a \u201cspazi\u201d intersoggettivi gruppali si traduca in migliori esiti psicopatologici, a prescindere dalle \u201ctecniche\u201d psicoterapeutiche utilizzate. Per \u201cdiversa cultura della cura\u201d s\u2019intende la capacit\ue0 (e la possibilit\ue0) di partire dalle \u201cpratiche\u201d di salute mentale, interrogandosi continuamente sui loro effetti e avendo la possibilit\ue0 di modificarle e perfezionarle rapidamente. Contemporaneamente questo significa la possibilit\ue0 che gli operatori hanno di \u201cspogliarsi\u201d di ruoli forti e di mettere cos\uec a disposizione dei pazienti uno spazio intersoggettivo pi\uf9 autentico e quindi, forse, pi\uf9 terapeutico

Serum changes in sTWEAK and its scavenger receptor sCD163 in ultramarathon athletes running the 24-h race

In the present investigation, the serum changes of sTWEAK levels, a multifunctional cytokine involved in tissue response to acute injury and inflammation, and of its scavenger receptor sCD163, were monitored for the first time in ultramarathon athletes running the 24-h competition, an extremely demanding race in terms of muscular and physiological exertion. To this aim, venous blood samples were collected from each participant (n = 22, M = 12, F = 10) both before and immediately after the 24-h running. Other than sTWEAK and sCD163, the common serum biomarkers of inflammation (namely CRP and IL-6) and tissue injury (such as CPK, LDH, CPK-MB, troponin-I, and NT- proBNP) were evaluated. All parameters were within the reference ranges at baseline, indicating no alterations of the normal phy- siological processes before the competition; on the contrary, most biomarkers of tissue damage and inflamma- tion strongly increased after the ultramarathon race. Interestingly, a significant decrement of sTWEAK levels associated with an increment of its scavenger receptor sCD163 was observed at post-race. Positive relationships were evidenced between IL-6 and sCD163 levels and the markers of cardiac damage troponin-I and NT-proBNP. On the contrary, sTWEAK showed an inverse correlation with IL-6 and NT-proBNP. This study opens the way to further investigations aimed at clarifying the role of TWEAK pathway during the prolonged ultraendurance activity, paying particular attention to the link of IL-6, CD163 and TWEAK with the cardiac function