Effetti di nocicettina/orfanina FQ e di UFP-101, antagonista selettivo del recettore NOP, in un modello di colite sperimentale nel ratto

Nocicettina/orfanina FQ (N/OFQ) e recettori NOP costituiscono un sistema endogeno (sistema N/OFQergico), ampiamente distribuito a livello centrale e periferico capace di modulare alcune funzioni gastrointestinali sia in condizioni fisiologiche che in alcune condizioni sperimentali di alterata funzionalità (diarrea da olio di ricino, defecazione da stress e ulcere da etanolo). E’ stato recentemente dimostrato che il sistema N/OFQergico è anche coinvolto nella riduzione dell’ipersensibilità viscerale alla distensione colon-rettale da colite di tipo infiammatorio indotta da instillazione di 2,4,6 acido trinitrobenzensolforico (TNBS). Inoltre, sebbene i recettori NOP siano ampiamente espressi nel sistema immunitario (linfociti B e T), il loro preciso ruolo non è stato ancora chiarito dal momento che, studi in vitro ed in vivo hanno evidenziato che la loro attivazione determina effetti sia pro- che anti-infiammatori. Scopo del progetto è stato studiare gli effetti della ripetuta somministrazione periferica di N/OFQ e del suo antagonista recettoriale UFP-101, in un modello sperimentale di colite da instillazione di TNBS (che riproduce nel ratto la malattia infiammatoria intestinale nell’uomo). Gli esperimenti sono stati condotti in ratti maschi del ceppo Wistar. La colite post-infiammatoria è stata indotta mediante una instillazione intra-colonica di TNBS alla dose di 60mg/Kg in 0,3 ml di una soluzione di etanolo al 50%; gli animali di controllo sono stati invece infusi con salina. Ventiquattro ore dopo l’induzione della colite i ratti hanno ricevuto, per 3 giorni consecutivi e per 2 volte al giorno, un’iniezione intraperitoneale di: (i) salina (controlli), (ii) N/OFQ (0,02- 0,2- 2- 20 nmol/Kg), (iii) UFP-101 (1- 3- 10 nmoli/Kg) o (iv) N/OFQ (0.2 nmol/Kg) + UFP-101 (10 nmol/Kg); UFP101 è stato somministrato 15 minuti prima dell’iniezione di N/OFQ. Il quinto giorno gli animali sono stati sacrificati e campioni di colon sono stati prelevati per valutare il danno colonico (analisi istologica microscopica), l’attività dell’enzima mieloperossidasi (MPO) e i livelli di citochine (IL1 β e IL-10) nella mucosa colonica. Inoltre sono stati misurati i livelli plasmatici di N/OFQ in ratti sani di controllo e in ratti con colite. Il TNBS causa negli animali, rispetto a quelli di controllo infusi con salina, un aggravamento di tutti i parametri infiammatori considerati. La ripetuta somministrazione periferica di basse dosi di N/OFQ (0,02 e 0,2 nmoli/Kg), riduce in modo significativo il danno colonico microscopico, l’attività della MPO, e i livelli di IL-1 β colonica rispetto agli animali trattati con il solo TNBS. Alla dose di 2 nmoli/Kg non si sono evidenziati cambiamenti, mentre, alla dose di 20 nmol/Kg, la N/OFQ determina un aggravamento della colite indotta da TNBS. L’effetto protettivo di basse dosi di N/OFQ (0,2 nmoli/Kg) è completamente antagonizzato dal pretrattamento con l’antagonista selettivo per i recettori NOP, UFP-101 (1 nmol/kg; dose priva di attività intrinseca) confermando l’ipotesi che l’azione antinfiammatoria di basse dosi di N/OFQ è mediata dal recettore NOP. UFP-101 somministrato ad alte dosi (3- 10 nmoli/Kg) causa un aggravamento della colite indotta dal TNBS e una significativa riduzione dei livelli plasmatici di N/OFQ; ciò mette in evidenza un ruolo protettivo endogeno del sistema N/OFQergico periferico,sulla colite da TNBS. Riassumendo: (i) la ripetuta somministrazione periferica di basse dosi di N/OFQ (0,02 e 0,2 nmoli/Kg) ha un effetto protettivo sulla colite indotta da TNBS; (ii) N/OFQ, a dosi 1000- 100 volte superiori aggrava il danno da TNBS; (iii) il sistema N/OFQergico endogeno periferico ha un ruolo protettivo nelle nostre condizioni sperimentali. Su questa base, si apre la strada ad ulteriori ricerche che consentiranno di approfondire le conoscenze sugli effetti del sistema N/OFQergico in presenza di patologie infiammatorie intestinali e di aggiungere un nuovo target terapeutico nella sempre più crescente lista dei potenziali rimedi in queste patologie

Faecal corticosterone metabolite assessment in socially housed male and female wistar rats

Knowledge of animals’ hormonal status is important for conservation studies in wild or semi-free-ranging conditions as well as for behavioural and clinical experiments conducted in laboratory research, mostly performed on rats and mice. Faecal sampling is a useful non-invasive method to obtain steroid hormone assessments. Nevertheless, in laboratory studies, unlike other contexts, faecal sampling is less utilised. One of the issues raised is the necessity to collect samples belonging to different animals, separately. Usually, researchers using faecal sampling solve this problem through the isolation of animals or taking the cage rather than single animal as unit of study. These solutions though, could lead to unreliable measurements, and cannot be applied in many studies. Our aim was to show the biological reliability of individual faecal corticosterone metabolite (FCM) assessments in socially housed male and female Wistar rats. We analytically validated the enzyme immunoassay kit used for FCM assessments. Then, we exposed the animals to two different stress stimuli that are known to activate the hypothalamus–pituitary–adrenal axis and the following release of corticosterone to biologically validate the EIA kit: environmental enrichment and predator odour. Individual faecal sampling from social animals was collected through short-time handling. The results demonstrated that both the stimuli increased FCM levels in male and female rats showing the reliability of EIA kit assessment and the applicability of our sampling method. We also found a diurnal rhythm in FCM levels. These results could help to increase the use of faecal hormone metabolite determinations in studies conducted on rats

Spirituality for Late Adolescents Coping with Grief and Loss

Experiencing the death of a loved one is often life changing, and learning ways to cope is an important part of the healing process. Such a change can be particularly difficult for late adolescents (individuals between 18 and 25 years of age) who are already going through significant life changes. Spirituality and mental health has received increasing scholarly attention in recent years, and the Association for Spirituality, Ethics, and Religious Values in Counseling has developed competencies for counselors to use when working with clients who wish to incorporate spirituality in their treatment. Despite increased interest in the field, there is little scholarly literature on the use of spirituality in counseling late adolescents who are experiencing grief and loss. The purpose of this hermeneutic phenomenological study was to explore the meaning and role of spirituality and spiritual practices in the grieving processes of late adolescents. Existential theory provided the framework for the study. Participants were recruited from a local grief center, college, and university as well as CESnet and ASERVIC listservs. Seven late adolescents took part in semistructured interviews regarding their grieving process. Lindseth and Norberg\u27s phenomenological hermeneutical method was used to analyze the data consisting of naïve reading, structural analysis, and comprehensive understanding. Themes included experiences with death, surviving the loss, and changes. Findings indicated that spiritual practices were beneficial in helping grieving late adolescents cope with the death of a loved one. Results may provide counselors with additional ways to work with this population during their grieving process

towards a restful architecture for managing a global distributed interlinked data content information space

The current debate around the future of the Internet has brought to front the concept of "Content-Centric" architecture, lying between the Web of Documents and the generalized Web of Data, in which explicit data are embedded in structured documents enabling the consistent support for the direct manipulation of information fragments. In this paper we present the InterDataNet (IDN) infrastructure technology designed to allow the RESTful management of interlinked information resources structured around documents. IDN deals with globally identified, addressable and reusable information fragments; it adopts an URI-based addressing scheme; it provides a simple, uniform Web-based interface to distributed heterogeneous information management; it endows information fragments with collaboration-oriented properties, namely: privacy, licensing, security, provenance, consistency, versioning and availability; it glues together reusable information fragments into meaningful structured and integrated documents without the need of a pre-defined schema

Infestazione intestinale da Schistosoma mansoni: un caso emblematico di importazione

Viene descritto, sia dal punto di vista clinico che parassitologico, un caso di importazione di schistosomiasi intestinale da S. mansoni contratta durante un soggiorno in Tanzania. Dopo circa 50 giorni da un contatto casuale ma ripetuto con le acque del Lago Vittoria, al soggetto, giovane adulto in missione umanitaria, compare febbre elevata, accompagnata da astenia (presente da più giorni) cui segue un episodio di diarrea acuta. La comparsa anche di una ipereosinofilia, dapprima assente, spinge il curante ad eseguire immediatamente un esame coproparassitologico standard (in precedenza sempre negativo) che risulta positivo per uova di S. mansoni. La terapia condotta con praziquantel risolve il caso e porta a guarigione il soggetto, cui inizialmente era stata esclusa la malaria, allorché dopo circa 1 mese dal rientro aveva presentato rialzo termico con disturbi respiratori

Gut microbiota composition in COVID-19 hospitalized patients with mild or severe symptoms

Background and aimCOVID-19, the infectious disease caused by SARS-CoV-2 virus that has been causing a severe pandemic worldwide for more than 2 years, is characterized by a high heterogeneity of clinical presentations and evolution and, particularly, by a varying severity of respiratory involvement. This study aimed to analyze the diversity and taxonomic composition of the gut microbiota at hospital admission, in order to evaluate its association with COVID-19 outcome. In particular, the association between gut microbiota and a combination of several clinical covariates was analyzed in order to characterize the bacterial signature associate to mild or severe symptoms during the SARS-CoV-2 infection.Materials and methodsV3–V4 hypervariable region of 16S rRNA gene sequencing of 97 rectal swabs from a retrospective cohort of COVID-19 hospitalized patients was employed to study the gut microbiota composition. Patients were divided in two groups according to their outcome considering the respiratory supports they needed during hospital stay: (i) group “mild,” including 47 patients with a good prognosis and (ii) group “severe,” including 50 patients who experienced a more severe disease due to severe respiratory distress that required non-invasive or invasive ventilation. Identification of the clusters of bacterial population between patients with mild or severe outcome was assessed by PEnalized LOgistic Regression Analysis (PELORA).ResultsAlthough no changes for Chao1 and Shannon index were observed between the two groups a significant greater proportion of Campylobacterota and Actinobacteriota at phylum level was found in patients affected by SARS-CoV-2 infection who developed a more severe disease characterized by respiratory distress requiring invasive or non-invasive ventilation. Clusters have been identified with a useful early potential prognostic marker of the disease evolution.DiscussionMicroorganisms residing within the gut of the patients at hospital admission, were able to significantly discriminate the clinical evolution of COVID-19 patients, in particular who will develop mild or severe respiratory involvement. Our data show that patients affected by SARS-CoV-2 with mild or severe symptoms display different gut microbiota profiles which can be exploited as potential prognostic biomarkers paving also the way to new integrative therapeutic approaches

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements