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Vortioxetine is a novel multimodal antidepressant that modulates a wide range of neurotransmitters throughout the brain. Preclinical and clinical studies have shown that vortioxetine exerts positive effects on different cognitive domains and neuroprotective effects. Considering the key role of microglial cells in brain plasticity and cognition, we aimed at investigating the effects of pretreatment with vortioxetine in modulating behavioral and molecular effects induced by an immune challenge: peripheral injection of lipopolysaccharide (LPS). To this purpose, C57BL/6J male mice were first exposed to a 28-day standard diet or vortioxetine-enriched diet, which was followed by an acute immune challenge with LPS. Sickness symptoms and depressive-like behaviors (anhedonia and memory impairment) were tested 6 and 24 h after exposure to LPS, respectively. Moreover, the expressions of markers of immune activation and M1/M2 markers of microglia polarization were measured in the dorsal and ventral parts of the hippocampus. The pretreatment with vortioxetine did not affect both LPS-induced sickness behavior and anhedonia but prevented the deficit in the recognition memory induced by the immune challenge. At the transcriptional level, chronic exposure to vortioxetine did not prevent LPS-induced upregulation of proinflammatory cytokines 6 h after the immune challenge but rather seemed to potentiate the immune response to the challenge also by affecting the levels of expression of markers of microglia M1 phenotype, like cluster of differentiation (CD)14 and CD86, in an area-dependent manner. However, at the same time point, LPS injection significantly increased the expression of the M2 polarization inducer, interleukin 4, only in the hippocampus of animals chronically exposed to vortioxetine. These results demonstrate that a chronic administration of vortioxetine specifically prevents LPS-induced memory impairment, without affecting acute sickness behavior and anhedonia, and suggest that hippocampal microglia may represent a cellular target of this novel antidepressant medication. Moreover, we provide a useful model to further explore the molecular mechanisms specifically underlying cognitive impairments following an immune challenge.

The escape behaviour is one of the many behavioural responses that can be operantly conditioned in a stimulus-dependent manner in both vertebrates and invertebrates. By exposing the pond snail Lymnaea stagnalis repeatedly to a negative reinforcement its natural tendency to explore its surroundings can be operantly conditioned in both adult and aged snails. When adult snails were trained with 100 mM of KCl their number of escapes was significantly decreased and the latency to first escape was significantly increased. Our behavioural protocol allowed us to investigate memory acquisition, consolidation, and retrieval in pre- and post-training sessions over different days. From the 3rd day of training the learned response was strengthened: the number of the escapes in the post-test session remained significantly reduced even when animals were presented with distilled water. Moreover, adult snails exposed to the negative reinforcement for at least 4 days started to escape significantly less than the control group also in the pre-test session. This effect became more pronounced in the following days and was accompanied by a significant increase in the latency to first escape at the beginning of the pre-test on day 6 and 7. Aged snails, instead, showed selective deficiencies when operantly conditioned: memory retention appeared only after 7 days, while memory retrieval could not be induced. This redefined paradigm can help unravelling a variety of sophisticated cognitive phenomena in L. stagnalis and could be employed also to study the basis of memory impairment occurring during neuro-aging., Invertebrate Survival Journal, Vol 17 No 1 (2020)

Purpose: To study and compare the efficacy of different therapeutic options for the treatment of central serous chorioretinopathy (CSCR). Methods: This is a nonrandomized, international multicentre study on 1719 patients (1861 eyes) diagnosed with CSCR, from 63 centres (24 countries). Reported data included different methods of treatment and both results of diagnostic examinations [fluorescein angiography and/or optical coherent tomography (OCT)] and best-corrected visual acuity (BCVA) before and after therapy. The duration of observation had a mean of 11 months but was extended in a minority of cases up to 7 years. The aim of this study is to evaluate the efficacy of the different therapeutic options of CSCR in terms of both visual (BCVA) and anatomic (OCT) improvement. Results: One thousand seven hundred nineteen patients (1861 eyes) diagnosed with CSCR were included. Treatments performed were nonsteroidal anti-inflammatory eye drops, laser photocoagulation, micropulse diode laser photocoagulation, photodynamic therapy (PDT; Standard PDT, Reduced-dose PDT, Reduced-fluence PDT), intravitreal (IVT) antivascular endothelial growth factor injection (VEGF), observation and other treatments. The list of the OTHERS included both combinations of the main proposed treatments or a variety of other treatments such as eplerenone, spironolactone, acetazolamide, beta-blockers, anti-anxiety drugs, aspirin, folic acid, methotrexate, statins, vitis vinifera extract medication and pars plana vitrectomy. The majority of the patients were men with a prevalence of 77%. The odds ratio (OR) showed a partial or complete resolution of fluid on OCT with any treatment as compared with observation. In univariate analysis, the anatomical result (improvement in subretinal fluid using OCT at 1 month) was favoured by age 500 μm (p = 0.03). The OR for obtaining partial or complete resolution showed that anti-VEGF and eyedrops were not statistically significant; whereas PDT (8.5), thermal laser (11.3) and micropulse laser (8.9) lead to better anatomical results with less variability. In univariate analysis, the functional result at 1 month was favoured by first episode (p = 0.04), height of subretinal fluid >500 μm (p

The serotonin system (5HT) is highly conserved in both vertebrates and invertebrates, and numerous evidence supports a biological link between 5HT and numerous animal function. In the present paper we evaluated the transcriptional effects of a serotonergic stimulation on selected targets involved in 5HT signalling and neurotransmission in the central nervous system of the great pond snail Lymnaea stagnalis. Adult snails were treated acutely (6 h) or chronically (48 h) with either 5-hydroxytrypthophan (5-HTP 1mM), the immediate precursor of serotonin, fluoxetine (FLX 1μM), a selective serotonin reuptake inhibitor, or a combination of two. The central ring ganglia were dissected and used for q-PCR gene expression analysis. Transcription was strongly induced following a chronic, but not an acute, exposure to 5-HTP in the ganglia of Lymnaea. In particular, LymCREB1 and LymP2X mRNA levels were decreased following a 6 h exposure and increased in snails receiving 5-hydroxytryptophan for 48 h. Interestingly, this effect was reduced when snails were exposed chronically to both 5-HTP and FLX, suggesting a role for SERT in mediating the effect of 5-hydroxytryptophan. These data suggest that L. stagnalis is suited to unravel the complexity of the serotonin signaling pathway., Invertebrate Survival Journal, Vol 14 No 1 (2017)

The contribution which Prof. Edmondo Malan gave to the world of surgery is matched only by the number of disciples that are working every day in his memory. Yet, the heritage of the Master is not limited to mere surgical teaching. Because of his willpower, many surgical departments have been inaugurated, many teaching schools have been founded, the boundaries of general surgery and many specialties have been crossed; in his memory, vascular research went far beyond expectations, reaching a level of excellence he could have only dreamed of. His heirs, once more, have perpetuated his lessons in surgery, keeping alive the true spirit of medicine, which is our foundation: the art of teaching and learning, as a never-ending process. Professor Edmondo Malan is not vanished. His name is not buried in history books. He is constantly alive, every day, a vivid presence in every surgical skill that reminds the audacity and the dedication of a man, not only a doctor, focused on caring and healing, from the bottom of his heart

Contains fulltext : 81133.pdf (Publisher’s version ) (Closed access) BACKGROUND: Case and single center reports have documented the feasibility and suggested the effectiveness of endovascular aneurysm repair (EVAR) of ruptured abdominal aortic aneurysms (RAAAs), but the role and value of such treatment remain controversial. OBJECTIVE: To clarify these we examined a collected experience with use of EVAR for RAAA treatment from 49 centers. METHODS: Data were obtained by questionnaires from these centers, updated from 13 centers committed to EVAR treatment whenever possible and included treatment details from a single center and information on 1037 patients treated by EVAR and 763 patients treated by open repair (OR). RESULTS: Overall 30-day mortality after EVAR in 1037 patients was 21.2%. Centers performing EVAR for RAAAs whenever possible did so in 28% to 79% (mean 49.1%) of their patients, had a 30-day mortality of 19.7% (range: 0%-32%) for 680 EVAR patients and 36.3% (range: 8%-53%) for 763 OR patients (P < 0.0001). Supraceliac aortic balloon control was obtained in 19.1% +/- 12.0% (+/-SD) of 680 EVAR patients. Abdominal compartment syndrome was treated by some form of decompression in 12.2% +/- 8.3% (+/-SD) of these EVAR patients. CONCLUSION: These results indicate that EVAR has a lower procedural mortality at 30 days than OR in at least some patients and that EVAR is better than OR for treating RAAA patients provided they have favorable anatomy; adequate skills, facilities, and protocols are available; and optimal strategies, techniques, and adjuncts are employed.

Obiettivo; In letteratura è riportato che solo il 50% dei pazienti con aneurisma toracico rotto raggiunge l’Ospedale ancora in vita, ed il 75% di questi muore nelle 24 ore successive. L’elevata percentuale di mortalità e paraplegia, in seguito a trattamento chirurgico di un aneurisma dell’aorta toracico rotto, limita di molto tale procedura. Il trattamento endovascolare offre un’alternativa meno invasiva alla chirurgia tradizionale, in quanto evita la toracotomia, la terapia anticoagulante e il clampaggio aortico. In questo lavoro riportiamo la nostra iniziale esperienza riguardante il trattamento endovascolare in urgenza dell’aneurisma dell’aorta toracico rotto. Metodi: La nostra esperienza è iniziata nel maggio 2004, da allora abbiamo trattato 11 pazienti con rottura franca di aneurisma dell’aorta toracica (10 aneurismi toracici rotti ed un caso di aneurisma dissecante rotto). I pazienti trattati presentavano un’età media di 76.2 anni (min. 69, max 88), 10 maschi ed una femmina. Tutti i casi, tranne uno, si sono presentati in Pronto Soccorso in condizioni emodinamicamente stabili (PA>70mmHg) e sono stati sottoposti ad un esame Angio TC dell’aorta toracica, addominale e degli assi iliaco femorali. Le condizioni cliniche e la valutazione strumentale hanno evidenziato la possibilità di un trattamento endovascolare. In un solo caso, presentandosi in shock emorragico, la diagnosi e la fattibilità endovascolare è stata fatta direttamente in sala operatoria, dopo un accurato studio angiografico e con IVUS (Intavascular Ultrasound). Risultati: Tutti i pazienti sono stati trattati entro 12 ore dall’arrivo in Ospedale e tutte le procedure sono state eseguite in sala operatoria e in anestesia generale. Le endoprotesi utilizzate sono state in 9 casi Endofit/Endomed, in un caso Talent/Medtronic ed in un altro Zenith/Cook, con un accesso femorale chirurgico ed uno percutaneo. Solo in un caso è stato necessario coprire l’arteria succlavia sinistra, mentre in un altro caso è stato necessario coprire l’origine dell’arteria succlavia e della carotide comune sinistra previo bypass carotido-carotideo. Il successo tecnico è stato del 100%, in due casi la presenza di on endoleak di tipo 1° ha reso necessario l’utilizzo di cuffs prossimali. La mortalità post-operatoria è stata del 54,5% (6/11), in tutti i casi si trattava di pazienti molto compromessi dal punto di vista cardiologico e respiratorio. Conclusioni: I risultati della nostra limitata esperienza e della letteratura evidenziano una percentuale di complicanze post-operatorie, in termini di mortalità, accettabile. Nella nostra esperienza la percentuale di successo, in termini d’esclusione dell’aneurisma, è stata del 100% e la maggior parte delle complicanze post-operatorie si è verificata in pazienti con preesistenti patologie cardiorespiratorie. Il trattamento endovascolare degli aneurismi rotti dell’aorta toracica sembra essere, dai dati della letteratura, abbastanza promettente. La presenza di un team endovascolare preparato e sempre reperibile e la disponibilità di apparecchiature e di materiale protesico a disposizione sono assolutamente necessarie per l’ottimizzazione dei risultati. Objective; In literature it is reported that only 50% of patients with ruptured thoracic aneurysm reaches the hospital alive, and 75% of these die within 24 hours. The high percentage of mortality and paraplegia after surgical treatment of a ruptured thoracic aortic aneurysm, limits indications to this procedure. Endovascular treatment offers a less invasive alternative to traditional surgery, as it avoids thoracotomy, anticoagulant therapy and aortic clamping. In this paper we report our initial experience regarding the endovascular treatment in emergency of broken thoracic aortic aneurysm. Methods: Our experience began in May 2004, since then we have treated 11 patients with frank rupture of the thoracic aortic aneurysm (10 aneurysms and a case of dissecting aneurysm). These patients had a mean age of 76.2 years (min. 69, max 88), 10 males and one female. All cases except one, were presented to the emergency department under hemodynamically stable (BP> 70 mm Hg) and were subjected to CT angiography of the thoracic aorta, abdominal aorta and iliac femoral axis. The clinical and instrumental evaluation have shown the possibility of endovascular treatment. In one case, presenting in hemorrhagic shock, the endovascular feasibility was made in the operating theater, after a careful study with angiography and IVUS (Intavascular Ultrasound). Results: All patients were treated within 12 hours of arrival in hospital and all procedures were performed in the operating room under general anesthesia. The endoprostheses used were in 9 cases Endofit / Endomed, in a case Talent / Medtronic and in another Zenith / Cook, with a surgical femoral access and percutaneous one. Only in one case it was necessary to cover the left subclavian artery, while in another case it was necessary to cover the origin of the subclavian artery and left common carotid artery after carotid-carotid bypass. The technical success was 100%, in two cases the presence of endoleaks on type 1 has necessitated the use of proximal cuffs. The post-operative mortality was 54.5% (6/11), in all cases the patients were very compromise in cardiac and respiratory systems. Conclusions: The results of our limited experience and related literature show an acceptable percentage of postoperative complications, in terms of mortality. In our experience, the success rate in terms of exclusion of the aneurysm, was 100% and the majority of post-operative complications occurred in patients with preexisting cardiopulmonary disease. Endovascular treatment of ruptured aneurysms of the thoracic aorta appears to be, from the literature, quite promising. The presence of an endovascular team prepared and always available and the availability of equipment and prosthetic materials are absolutely necessary for best results.

Emergency Surgical Conversion for Rupture of Abdominal Aortic Aneurysms after EVAR - The rare observations of rupture of abdominal aortic aneurysm (AAA), which had been excluded by endograft, are becoming more frequent, because of the spreading use of endovascular aneurysms exclusion (EVAR). Clinical presentation of AAA rupture after EVAR could be misleading, because of the possible plugging by the endograft and delayed haemorrhage, as in the presented clinical case. Some particular surgical techniques can assist the procedure of open repair, such as supra-renal clamping, which can be accomplished by aortic balloon, and arterial reconstruction, sewing a new vascular graft on the proximal and distal segments of the endograft, cut and left in situ, thus avoiding damage to the native arteries and facilitating surgical fixation.

Introduzione e Scopo del Lavoro - Le osservazioni di rottura di aneurisma aortico, trattato in precedenza con endoprotesi, sono aumentate negli anni più recenti, per l’uso più frequente della metodica di esclusione endovascolare degli aneurismi (EVAR). Le differenze nella presentazione clinica e nell’approccio terapeutico devono essere conosciute e valutate nel trattamento di rotture dopo EVAR. Materiali e Metodi - Partendo dalla descrizione di un caso trattato, vengono considerati, alla luce dei dati riportati nella recente letteratura, i fattori di rischio, le caratteristiche cliniche e le tecniche chirurgiche particolari, da adottarsi nel trattamento di questa patologia di ormai meno raro riscontro. Discussione - Il trattamento degli aneurismi dell’aorta addominale mediante esclusione con endograft è andato progressivamente estendendosi negli ultimi anni. L’esclusione della sacca aneurismatica mediante stent graft ha il fine di impedire la progressiva dilatazione e rottura dell’aneurisma. Nonostante i miglioramenti nelle endoprotesi arteriose, con adattamento alla morfologia variabile dell’aneurisma e maggior fissazione dell’endograft, è riportata, su aneurismi trattati con EVAR, un’incidenza di rottura tardiva dell’1,5% per anno. Tra i vari fattori che causano tale rottura, risultano statisticamente significativi in primo luogo la presenza di endoleak di primo e terzo tipo, quindi la migrazione dell’endoprotesi e l’aumento nel diametro dell’aneurisma. A differenza della rottura di aneurisma aortico non trattato in precedenza, la rottura dopo EVAR può più facilmente tamponarsi, per la presenza dell’endograft e le pressioni più ridotte all’interno della sacca aneurismatica. La sintomatologia classica di ipotensione ed anemizzazione acuta può quindi mancare e può protrarsi la condizione di “fissurazione” dell’aneurisma, rendendo particolarmente subdolo il quadro clinico e quindi maggiormente pericolosa la rottura in due tempi. Conclusioni - La rottura di aneurisma aortico dopo EVAR è sempre meno rara. Il quadro clinico può essere ingannatore, per l’eventuale tamponamento e rottura in due tempi. Svariati accorgimenti di tecnica chirurgica facilitano il trattamento di questa patologia. Introduction and Aim of Work - The observations of rupture of aortic aneurysms, previously treated with endoprosthesis, have increased in recent years, for the most frequent use of endovascular exclusion of aneurysms (EVAR). The differences in clinical presentation and therapeutic approach must be recognized and evaluated in the treatment of ruptures after EVAR. Materials and Methods - Starting from the description of a clinical case, in the light of recent data reported in the literature, risk factors, clinical characteristics and surgical techniques are considered, which have to be considered in this increasing pathology. Discussion - The treatment of abdominal aortic aneurysms by exclusion with endograft has been gradually extending in recent years. The exclusion of the aneurysmal sac through the stent graft is intended to prevent progressive dilatation and aneurysm rupture. Despite the improvements in arterial endoprosthesis, with better adaptation to the morphology of the aneurysm and most valid fixation, recent articles report, about aneurysms treated with EVAR, an incidence of late rupture of 1, 5% per year. Among the various factors that cause such breakage, are statistically significant in the first place the presence of first and third type endoleak, then endoprosthesis migration and increase in the diameter of the aneurysm. In contrast to the rupture of aortic aneurysm not previously treated, the break after EVAR can evenctually stop by tamponade, for the presence endograft and smaller pressures inside the aneurysm sac. The classic symptoms of acute anemia and hypotension may lack misleading prompt diagnosis of the condition of "cracking" of the aneurysm, making it particularly insidious the clinical picture and therefore more dangerous a break down into two stages. Conclusions – Although rare, the rupture of aortic aneurysm after EVAR is increasing. The clinical picture can be deceptive, for the eventual plugging and breakage in two stages. Several expedients of surgical technique are useful tools to improve the handling of this pathology.