Altered GABAergic, glutamatergic and endocannabinoid signaling is accompanied by neuroinflammatory response in a zebrafish model of social withdrawal behavior

IntroductionDeficits in social communication are in the core of clinical symptoms characterizing many neuropsychiatric disorders such as schizophrenia and autism spectrum disorder. The occurrence of anxiety-related behavior, a common co-morbid condition in individuals with impairments in social domain, suggests the presence of overlapping neurobiological mechanisms between these two pathologies. Dysregulated excitation/inhibition balance and excessive neuroinflammation, in specific neural circuits, are proposed as common etiological mechanisms implicated in both pathologies.Methods and ResultsIn the present study we evaluated changes in glutamatergic/GABAergic neurotransmission as well as the presence of neuroinflammation within the regions of the Social Decision-Making Network (SDMN) using a zebrafish model of NMDA receptor hypofunction, following sub-chronic MK-801 administration. MK-801-treated zebrafish are characterized by impaired social communication together with increased anxiety levels. At the molecular level, the behavioral phenotype was accompanied by increased mGluR5 and GAD67 but decreased PSD-95 protein expression levels in telencephalon and midbrain. In parallel, MK-801-treated zebrafish exhibited altered endocannabinoid signaling as indicated by the upregulation of cannabinoid receptor 1 (CB1R) in the telencephalon. Interestingly, glutamatergic dysfunction was positively correlated with social withdrawal behavior whereas defective GABAergic and endocannabinoid activity were positively associated with anxiety-like behavior. Moreover, neuronal and astrocytic IL-1β expression was increased in regions of the SDMN, supporting the role of neuroinflammatory responses in the manifestation of MK-801 behavioral phenotype. Colocalization of interleukin-1β (IL-1β) with β2-adrenergic receptors (β2-ARs) underlies the possible influence of noradrenergic neurotransmission to increased IL-1β expression in comorbidity between social deficits and elevated anxiety comorbidity.DiscussionOverall, our results indicate the contribution of altered excitatory and inhibitory synaptic transmission as well as excessive neuroinflammatory responses in the manifestation of social deficits and anxiety-like behavior of MK-801-treated fish, identifying possible novel targets for amelioration of these symptoms

Mid-term outcomes in the treatment of retroperitoneal sarcomas: a 12-year single-institution experience

Aim To present the experience from collective data regarding patients with retroperitoneal sarcomas that have been operated in and followed up by the University General Hospital of Patras in Rion, Greece, between 2009 and 2020. Methods A retrospective analysis of adult patients treated at our hospital with a diagnosis of primary retroperitoneal sarcoma who underwent tumour resection. Results Data from 29 patients were analysed. The mean age at diagnosis was 56.1 years; 55.2% of patients were male (n=16). Liposarcomas (on histology) were identified in 19 (65.5%) patients, leiomyosarcoma six (20.7%), and other histologic subtypes in four (13.8%) patients. Tumours >5cm were presented in 27 (93.1%) patients. Negative margins were attained in 13 (44.8%) of all patients who underwent surgical resection. Five (17.2%) patients received neoadjuvant radiation, four (13.8%) postoperative radiation, and three (10.3%) patients received both chemotherapy and radiation prior to surgery with the rest of the patients being treated with surgical excision alone. A 3-year follow-up was successful in 21 (72.4%) patients; five (23.8%) patients died. In total, 16 (55.2%) patients were found to have a local recurrence, with no significant difference in patients' age, gender, tumour size, histology, negative surgical margin (Ro) resection, neoadjuvant chemotherapy, or radiation therapy. There was a significant difference in the 3-year survival rate between patients having positive or negative surgical margins (p=0.027). Conclusion The higher 3-year survival rate in patients with retroperitoneal sarcomas when achieving Ro resection warrant further investigation with a larger sample size across different institutions

Neurobiological mechanisms and epigenetic regulation of impairments in social behavior

Deficits in social communication are in the core of clinical symptoms characterizing many neuropsychiatric disorders such as schizophrenia, autism spectrum disorders and depression. Also, increased anxiety levels are a common comorbidity in many disorders, lessening the quality of life of these individuals. The strong co-expression of social deficits and anxiety suggests that these two pathologies share common neurobiological mechanisms and brain neural networks, which remain largely unclear. The Excitation/Inhibition imbalance, in various cortical and sub-cortical regions of the Social Decision-Making Network (SDMN) as well as the increased levels of neuroinflammation have been proposed as common etiological mechanisms involved in the manifestation of both pathologies. However, the contribution of other neurotransmission systems, such as catecholaminergic and endocannabinoid system, in the co-expression of these two pathologies, have not been adequately studied, whilst also the role of adult neurogenesis remains largely unclear. Previous evidence from our laboratory have demonstrated high expression levels of adrenergic receptor as well as the existence of a significant rate of neurogenesis, within the SDMN of zebrafish, suggesting their possible contribution to the co-expression of these two pathologies.The results of the present thesis support that the imbalance between glutamatergic and GABAergic neurotransmission as well as the dysfunction of endocannabinoid signaling observed in zebrafish brain, characterized by NMDA receptor hypofunction, play an important role in the manifestation of social deficits and increased anxiety levels. Furthermore, elevated expression levels of the pro-inflammatory cytokine IL-1β, in neuronal or astroglial cells within specific SDMN nodes, highlight the critical role of neuro-inflammatory responses during the co-expression of these disorders. More specifically, based on our results we propose that alterations in glutamatergic neurotransmission are involved in the manifestation of social deficits while GABAergic and endocannabinoid system dysfunction are positively associated with anxiety-like behavior. In contrast, elevated IL-1β expression levels are associated with both behavioral states.Regarding catecholaminergic neurotransmission, our results demonstrate the existence of increased expression levels of dopamine transporter and β2-adrenergic receptor (β2-ARs) in the telencephalon of zebrafish characterized by social avoidance behavior and increased anxiety levels. Interestingly, the expression of β2-ARs is differentially regulated within different regions of the SDMN, exhibiting increased levels in ventral telencephalic area (Vv) and decreased expression in dorso-medial telencephalic area (Dm) as well as in anterior tuberal nucleus (ATN). Furthermore, the localization of β2-ARs in GABAergic and/or mGluR5+ cells supports the possible regulatory role of β2-ARs in the co-expression of social deficits and increased anxiety levels, by regulating the balance between excitation/inhibition. Finally, we propose that alterations in structural plasticity, and more particular in adult neurogenesis, in dorsal and ventral telencephalic regions, as indicated by the alterations in the proliferation pattern and survival rate of neural stem cells, characterize social avoidance behavior and elevated anxiety levels in our zebrafish model. Together, these findings suggest that NMDA receptor hypofunction and the subsequent induction of excitation/inhibition imbalance, within regions of the SDMN, are associated with the severe deficits in social behaviour and increased anxiety levels. In addition, alterations in catecholaminergic and endocannabinoid signaling, increased levels of neuroinflammation, and alterations in the pattern of adult neurogenesis, are likely to contribute to the comorbidity of the above pathologies. Our results therefore highlight the existence of additional neurobiological mechanisms and brain areas involved in the manifestation of social deficits and anxiety, following NMDA receptor hypofunction, thus providing new potential targets for the development of more effective and targeted therapeutic approaches, aiming to ameliorate the above symptoms.Τα ελλείμματα στην κοινωνική επικοινωνία αποτελούν τον πυρήνα των κλινικών συμπτωμάτων πολλών νευροψυχιατρικών διαταραχών όπως η σχιζοφρένεια, οι διαταραχές του φάσματος του αυτισμού και η κατάθλιψη. Επίσης, τα αυξημένα επίπεδα άγχους αποτελούν μία κοινή συννοσηρότητα σε πολλές διαταραχές, ελαττώνοντας την ποιότητα της ζωής των ατόμων αυτών. Η έντονη συνέκφραση κοινωνικών ελλειμάτων και άγχους υποδηλώνει ότι οι δύο αυτές παθολογίες μοιράζονται κοινούς νευροβιολογικούς μηχανισμούς και εγκεφαλικά νευρικά δίκτυα, τα οποία όμως παραμένουν σε μεγάλο βαθμό ασαφή. Η ανισορροπία μεταξύ Διέγερσης/Αναστολής, σε διάφορες φλοιϊκές και υπο-φλοιϊκές περιοχές του Δικτύου Λήψης Κοινωνικών Αποφάσεων καθώς και τα αυξημένα επίπεδα νευροφλεγμονής έχουν προταθεί ως κοινοί αιτιολογικοί μηχανισμοί που εμπλέκονται στην εκδήλωση και των δύο παθολογιών. Επίσης, η συμβολή άλλων συστημάτων νευροδιαβίβασης, όπως του νοραδρενεργικού και του ενδοκανναβινοειδούς συστήματος, καθώς και ο ρόλος της ενήλικης νευρογένεσης παραμένουν σε μεγάλο βαθμό ασαφή. Παλαιότερες μελέτες του εργαστηρίου μας έχουν καταδείξει τα υψηλά επίπεδα έκφρασης αδρενεργικών υποδοχέων καθώς και την ύπαρξη σημαντικού ρυθμού νευρογένεσης, εντός του SDMN ζεβροϊχθύων, προτείνοντας την πιθανή συμβολή τους στη συν-εκδήλωση των δύο αυτών παθολογιών.Τα αποτελέσματα της παρούσας διδακτορικής διατριβής υποστηρίζουν ότι η ανισορροπία μεταξύ γλουταμινεργικής και GABAεργικής νευροδιαβίβασης καθώς και η δυσλειτουργία της ενδοκανναβινοειδούς σηματοδότησης που παρατηρείται στον εγκέφαλο ζεβροϊχθύων, οι οποίοι χαρακτηρίζονται από υπολειτουργία των NMDA υποδοχέων, διαδραματίζουν σημαντικό ρόλο κατά την εκδήλωση των κοινωνικών ελλειμάτων και των αυξημένων επιπέδων άγχους. Επίσης, τα αυξημένα επίπεδα έκφρασης της προ-φλεγμονώδους κυτοκίνης IL-1β, σε νευρικά η αστρογλοιακά κύτταρα εντός συγκεκριμένων κόμβων του SDMN, αναδεικνύουν τον κρίσιμο ρόλο των νευρο-φλεγμονωδών αποκρίσεων κατά την συν-εκδήλωση των παραπάνω διαταραχών. Πιο συγκεκριμένα, βάσει των αποτελεσμάτων μας προτείνουμε ότι μεταβολές στην γλουταμινεργική νευροδιαβίβαση εμπλέκονται στην εκδήλωση των κοινωνικών ελλειμάτων ενώ η GABAεργική και ενδοκανναβινοειδής δυσλειτουργία συσχετίζεται θετικά με την αγχώδη συμπεριφορά. Αντιθέτως, τα αυξημένα επίπεδα έκφρασης της IL-1β συνδέονται και με τις δύο συμπεριφορικές καταστάσεις.Όσο αφορά την κατεχολαμινεργική νευροδιαβίβαση, τα αποτελέσματά μας καταδεικνύουν την ύπαρξη αυξημένων επιπέδων έκφρασης του μεταφορέα της ντοπαμίνης και των β2-αδρενενεργικών υποδοχέων (β2-ARs) στον τελεγκέφαλο ζεβροϊχθύων που χαρακτηρίζονται από συμπεριφορά κοινωνικής αποφυγής και αυξημένα επίπεδα άγχους. Μάλιστα, είναι ενδιαφέρον ότι η έκφραση των β2-ARs ρυθμίζεται διαφορετικά εντός διαφορετικών περιοχών του SDMN, παρουσιάζοντας αυξημένα επίπεδα στον κοιλιακό πυρήνα του κοιλιακού τελεγκεφάλου (Vv) και μειωμένη έκφραση στον έσω πυρήνα του ραχιαίου τελεγκεφάλου (Dm) καθώς και στον πρόσθιο φυματικό πυρήνα (ATN). Επιπλέον, ο εντοπισμός των β2-ARs σε GABAεργικά και/ή mGluR5+ κύτταρα, υποστηρίζει τον πιθανό ρυθμιστικό ρόλο των β2-ARs κατά την συνέκφραση των ελλειμάτων στην κοινωνική συμπεριφορά και των αυξημένων επιπέδων άγχους, ρυθμίζοντας την ισορροπία μεταξύ διέγερσης/αναστολής. Tέλος, προτείνουμε ότι μεταβολές της δομικής πλαστικότητας και ειδικότερα της ενήλικης νευρογένεσης, σε περιοχές του ραχιαίου και κοιλιακού τελεγκεφάλου, όπως προκύπτει από τις μεταβολές του προτύπου του κυτταρικού πολλαπλασιασμού και επιβίωσης των νευρικών βλαστικών κυττάρων, χαρακτηρίζει την συμπεριφορά κοινωνικής αποφυγής και τα αυξημένα επίπεδα άγχους των ζεβροϊχθύων. Συνοψίζοντας, τα ευρήματα της παρούσας διατριβής προτείνουν ότι η υπολειτουργία των NMDA υποδοχέων και η επακόλουθη πρόκληση ανισορροπίας μεταξύ Διέγερσης/Αναστολής, εντός περιοχών του SDMN, σχετίζεται με τα σοβαρά ελλείμματα στην κοινωνική συμπεριφορά και τα αυξημένα επίπεδα άγχους που εμφανίζουν οι ζεβροϊχθύες. Επιπρόσθετα, οι μεταβολές στην κατεχολαμινεργική και ενδοκανναβινοειδή σηματοδότηση, τα αυξημένα επίπεδα νευροφλεγμονής και οι μεταβολές του προτύπου της ενήλικης νευρογένεσης, πιθανόν συνεισφέρουν στη συννοσηρότητα των παραπάνω παθολογιών. Τα αποτελέσματά μας επομένως αναδεικνύουν την ύπαρξη επιπρόσθετων νευροβιολογικών μηχανισμών και περιοχών που εμπλέκονται στην εκδήλωση των κοινωνικών ελλειμμάτων και των αυξημένων επιπέδων άγχους, έπειτα από υπολειτουργία των NMDA υποδοχέων, παρέχοντας νέους πιθανούς στόχους για την ανάπτυξη πιο αποτελεσματικών και στοχευμένων θεραπευτικών προσεγγίσεων με στόχο την υποχώρηση των παραπάνω συμπτωμάτων

Recharge Assessment in Greek Karst Systems: Methodological Considerations and Implications

The recharge of karst aquifers is significant for the effective management of groundwater resources, and its estimation should be tailored to accommodate their specific hydrogeological characteristics. This study provides a two-step methodological approach for the determination of karst aquifer recharge. Initially, mean annual recharge rates were estimated in the karst system of Ziria (Southern Greece) utilizing the APLIS and modified APLIS methods in order to decipher which was the most suitable version for recharge assessments. The results indicated similar mean recharge rate values at 42.7% and 41.4%, respectively, but significant differences in the spatial distribution. The modified methodology emerged as a more accurate and realistic approach, mainly due to the incorporation of permeability assessments. The final phase of the methodological approach involved the application of modified APLIS in two additional karst hydrosystems, Planitero and Xiromero, while a quantitative cross-comparison of the recharge rates was obtained for a deeper understanding of the factors controlling the groundwater recharge process. In Ziria, recharge rates exhibit a relatively uniform distribution throughout the area, with a median value of 46.7%. Conversely, in Planitero, High recharge rates (60–80%) occupy 56.8% of the surface, while in Xiromero, Moderate recharge rates (40–60%) dominate, representing 53.4% of the land coverage. These variations underscore the spatial heterogeneity of recharge within the karst systems, highlighting the importance of considering local geological and hydrological conditions in its assessments. The methodological approach of this study is flexible and can be adapted to different karst sites for the determination of recharge regimes, contributing to the alleviation of the groundwater depletion issue

Population Growth Changes in Major Stored Product Insects on Rice Fortified with Spearmint and Basil

Rice is the most important durable food product for more than half of the world’s population, as it is very nutritious food in terms of carbohydrate containment and can meet a large part of human caloric needs on a daily basis. The sensitivity of a rice product fortified with spearmint or basil was evaluated for three stored product insect species: Sitophilus oryzae (L.) (Coleoptera: Curculionidae), Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae) and Oryzaephilus surinamensis (L.) (Coleoptera: Silvanidae). Five different containments of fortified rice were used (0, 25, 50, 75 and 100% of the total rice quantity), and the population growth of the above species was examined after 65 days. We found that fortification generally reduced the infestation level of the species tested and reduced their population growth, as compared with the control rice. In some of the treatments, there were some differences between the application of spearmint and basil. There was higher frass production in the rice that had been fortified with basil than that with spearmint, indicating different infestation patterns. For S. oryzae, with the gradual increase in fortification, the number of insect-damaged kernels and weight of damaged kernels reduced, and significant differences were recorded between the fortification with spearmint and that with basil. The results of the present study are certainly encouraging for further utilization of the characteristics of fortified rice for stored product insect control

Population Growth Changes in Major Stored Product Insects on Rice Fortified with Spearmint and Basil

Rice is the most important durable food product for more than half of the world’s population, as it is very nutritious food in terms of carbohydrate containment and can meet a large part of human caloric needs on a daily basis. The sensitivity of a rice product fortified with spearmint or basil was evaluated for three stored product insect species: Sitophilus oryzae (L.) (Coleoptera: Curculionidae), Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae) and Oryzaephilus surinamensis (L.) (Coleoptera: Silvanidae). Five different containments of fortified rice were used (0, 25, 50, 75 and 100% of the total rice quantity), and the population growth of the above species was examined after 65 days. We found that fortification generally reduced the infestation level of the species tested and reduced their population growth, as compared with the control rice. In some of the treatments, there were some differences between the application of spearmint and basil. There was higher frass production in the rice that had been fortified with basil than that with spearmint, indicating different infestation patterns. For S. oryzae, with the gradual increase in fortification, the number of insect-damaged kernels and weight of damaged kernels reduced, and significant differences were recorded between the fortification with spearmint and that with basil. The results of the present study are certainly encouraging for further utilization of the characteristics of fortified rice for stored product insect control

The 6th Albanian Congress of Trauma and Emergency Surgery

After a three-year quarantine from the deadliest global pandemic of the last century, ASTES is organizing to gather all health professionals in Tirana, The 6th Albanian Congress of Trauma and Emergency Surgery(ACTES 2022) on 11-12 November 2022, with the topic Trauma & Emergency Surgery and not only...with the aim of providing high quality, the best standards, and the best results, for our patients ...ACTES 2022 is the largest event that ASTES (Albanian Society for Trauma and Emergency Surgery) has organized so far with 230 presentations, and 67 foreign lecturers with enviable geography, making it the largest national and wider scientific event.The scientific program is as strong as ever, thanks to the inclusiveness, where all the participants with a mix of foreign and local lecturers, select the best of the moment in medical science, innovation, and observation.The scientific committee has selected all the presentations so that the participants of each medical discipline will have something to learn, discuss, debate, and agree with updated methods, techniques, and protocols.I hope you will join us on Friday morning, and continue the journey of our two-day event together