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Gastrointestinal (GI) endoscopy is the gold standard in the detection and treatment of early and advanced GI cancers. However, conventional endoscopic techniques are technically demanding and require visual-spatial skills and significant hands-on experience. GI endoscopy simulators represent a valid solution to allow doctors to practice in a pre-clinical scenario. From the first endoscopy mannequin, developed in 1969, several simulation platforms have been developed, ranging from purely mechanical systems to more complex mechatronic devices and animal-based models. Considering the recent advancement of technologies (e.g., artificial intelligence, augmented reality, robotics), simulation platforms can now reach high levels of realism, representing a valid and smart alternative to standard trainee/mentor learning programs. This is particularly true nowadays, when the current demographic trend and the most recent pandemic demand, more than ever, the ability to cope with many patients. This review offers a broad view of the technology available for GI endoscopy training, including platforms currently in the market and the relevant advancements in this research and application field. Additionally, new training needs and new emerging technologies are discussed to understand where medical education is heading.

The oxygen in Earth’s atmosphere is there primarily because of water oxidation performed by photosynthetic organisms using solar light and one specialized protein complex, photosystem II (PSII). High-resolution imaging of the PSII ‘core’ complex shows the ideal co-localization of multi-chromophore light-harvesting antennas with the functional reaction centre. Man-made systems are still far from replicating the complexity of PSII, as the majority of PSII mimetics have been limited to photocatalytic dyads based on a 1:1 ratio of a light absorber, generally a Ru–polypyridine complex, with a water oxidation catalyst. Here we report the self-assembly of multi-perylene-bisimide chromophores (PBI) shaped to function by interaction with a polyoxometalate water-oxidation catalyst (Ru4POM). The resulting [PBI]5Ru4POM complex shows a robust amphiphilic structure and dynamic aggregation into large two-dimensional paracrystalline domains, a redshifted light-harvesting efficiency of >40% and favourable exciton accumulation, with a peak quantum efficiency using ‘green’ photons (λ > 500 nm). The modularity of the building blocks and the simplicity of the non-covalent chemistry offer opportunities for innovation in artificial photosynthesis.

While future climate scenarios predict declines in precipitations in many regions of the world, little is known of the mechanisms underlying community resilience to prolonged dry seasons, especially in 'naive' Neotropical rainforests. Predictions of community resilience to intensifying drought are complicated by the fact that the underlying mechanisms are mediated by species' tolerance and resistance traits, as well as rescue through dispersal from source patches. We examined the contribution of in situ tolerance-resistance and immigration to community resilience, following drought events that ranged from the ambient norm to IPCC scenarios and extreme events. We used rainshelters above rainwater-filled bromeliads of French Guiana to emulate a gradient of drought intensity (from 1 to 3.6 times the current number of consecutive days without rainfall), and we analysed the post-drought dynamics of the taxonomic and functional community structure of aquatic invertebrates to these treatments when immigration is excluded (by netting bromeliads) or permitted (no nets). Drought intensity negatively affected invertebrate community resistance, but had a positive influence on community recovery during the post-drought phase. After droughts of 1 to 1.4 times the current intensities, the overall invertebrate abundance recovered within invertebrate life cycle durations (up to 2 months). Shifts in taxonomic composition were more important after longer droughts, but overall, community composition showed recovery towards baseline states. The non-random patterns of changes in functional community structure indicated that deterministic processes like environmental filtering of traits drive community re-assembly patterns after a drought event. Community resilience mostly relied on in situ tolerance-resistance traits. A rescue effect of immigration after a drought event was weak and mostly apparent under extreme droughts. Under climate change scenarios of drought intensification in Neotropical regions, community and ecosystem resilience could primarily depend on the persistence of suitable habitats and on the resistance traits of species, while metacommunity dynamics could make a minor contribution to ecosystem recovery. Climate change adaptation should thus aim at identifying and preserving local conditions that foster in situ resistance and the buffering effects of habitat features.

Background Triple-drug regimens are the gold standard for HIV therapy. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs) reducing regimens are used to decrease drugs toxicity, exposure and costs. Aim of our study was to evaluate trends of biochemical and inflammatory indices in patients switching to dual therapy (DT). Methods We included patients that a) switched to a DT from 2007 to 2015 from a tenofovir/abacavir-based triple regimen b) previously maintained a triple and c) subsequently a dual regimen for 12 months with virological suppression. We retrieved data measured at 5 points (at the switch, 6 and 12 months before and after switch). We used platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and CD4/CD8 ratio as inflammatory indices. We assessed temporal trends of viro-immunological, biochemical and inflammatory parameters. Results Overall, 364 and 65 patients switched from a tenofovir- and an abacavir-triple regimen, respectively. In the tenofovir-reducing group, creatinine clearance and lipids raised after the switch. There was a significant increase in both CD4+ cells and CD4/CD8. CD8+ cells rose after the switch, while opposite trend was found for PLR. In the abacavir-reducing group total lipids showed a decrease during the first 6 months after the switch and then stabilized. An increase of CD4+ and a decrease of CD8+ cells was observed during the study period, although not statistically significant. While CD4/CD8 remained stable after simplification, PLR decreased significantly after 6 months, then returning to baseline. CD8+ cells increased in the tenofovir-reducing group despite a viro-immunological response. Intriguingly, PLR decreased, maintaining this trend for 12 and 6 months after tenofovir and abacavir interruption respectively. Conclusions Increased PLR has been linked to hypercholesterolemia and metabolic-syndrome, while high CD8+ cells count to increased risk of non-AIDS-related events regardless of CD4 T-cell recovery and to virological failure. Whether these findings may have clinical implications, and which role DT plays on the immune system and on inflammation should be further investigated.

Eugenia Allegra,1 Vincenzo Saita,2 Massimo De Natale,2 Nicolò Marino,2 Serena Trapasso,1 Stefania Tamburrini,3 Caterina Alessio,4 Massimo Ippolito5 1Otolaryngology, Department of Health Sciences, University of Catanzaro, Catanzaro, 2Department of Otolaryngology, Cannizzaro Hospital, Catania, 3Department of Radiology, Pellegrini Hospital, Naples, 4Department of Experimental and Clinical Medicine-Radiology, University of Catanzaro, Catanzaro, 5Department of Nuclear Medicine, Cannizzaro Hospital, Catania, Italy Background: Laryngeal cancer is the second most common cancer of the head and neck after cancer of the oral cavity. The primary causes of death in cases of laryngeal cancer are the recurrence of locoregional disease and distant metastasis. Anatomic and tissue alterations resulting from surgery and/or radiotherapy of primary laryngeal tumors can make it difficult to determine a locoregional recurrence or residual disease by physical examination or computed tomography (CT)/magnetic resonance imaging (MRI). The majority of studies have shown a high accuracy in the detection of local and regional recurrence of head and neck cancer after different treatment modalities, using fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT.Aim: To determine the diagnostic accuracy of PET/CT in patients with suspicion of locoregional recurrence from laryngeal carcinoma after surgery with or without adjuvant radiotherapy.Materials and methods: This was a retrospective study. Forty-five patients who previously underwent surgical treatment with or without adjuvant radiotherapy for primary laryngeal squamous cell carcinoma and who underwent examination using FDG-PET/CT imaging after clinical and instrumental (CT/MRI) suspicion of locoregional recurrence (T or N) were recruited.Results: Overall specificity, sensitivity, and accuracy of PET/CT were found to be 88%, 100%, and 93.3%, respectively. With respect to the suspected cases of recurrence in the primary site, sensitivity, specificity, and accuracy of PET/CT were found to be 100%, 87.5%, and 91.6%, respectively. In patients with suspected metastatic neck disease, PET/CT revealed a sensitivity, specificity, and accuracy of 100%, 90%, and 95.4%, respectively.Conclusion: According to the results of this study, PET/CT imaging in laryngeal tumors is a useful tool in case of suspected locoregional recurrence where conventional imaging (CT and MRI) is unable to resolve the diagnostic doubt. Keywords:laryngealcancer, PET/CT imaging, laryngeal cancer recurrence, laryngeal cancer PET/CT imaging

Background: Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE). Methods Patients highly-active antiretroviral therapy (HAART) with 50. Results: 1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9%infectious, 17.4%renal, 17.4Êrdiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95% CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE. Conclusions: Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.

1. Despite ongoing research in food web ecology and functional biogeography, the links between food web structure, functional traits and environmental conditions across spatial scales remain poorly understood. Trophic niches, defined as the amount of energy and elemental space occupied by species and food webs, may help bridge this divide. 2. Here, we ask how the functional traits of species, the environmental conditions of habitats and the spatial scale of analysis jointly determine the characteristics of trophic niches. We used isotopic niches as a proxy of trophic niches, and conducted analyses at spatial scales ranging from local food webs and metacommunities to geographically distant sites. 3. We sampled aquatic macroinvertebrates from 104 tank bromeliads distributed across five sites from Central to South America and compiled the macroinvertebrates' functional traits and stable isotope values (delta N-15 and delta C-13). We assessed how isotopic niches within each bromeliad were influenced by the functional trait composition of their associated invertebrates and environmental conditions (i.e., habitat size, canopy cover [CC] and detrital concentration [DC]). We then evaluated whether the diet of dominant predators and, consequently, energy pathways within food webs reflected functional and environmental changes among bromeliads across sites. At last, we determined the extent to which the isotopic niches of macroinvertebrates within each bromeliad contributed to the metacommunity isotopic niches within each site and compared these metacommunity-level niches over biogeographic scales. 4. At the bromeliad level, isotopic niches increased with the functional richness of species in the food web and the DC in the bromeliad. The diet of top predators tracked shifts in prey biomass along gradients of CC and DC. Bromeliads that grew under heterogeneous CC displayed less trophic redundancy and therefore combined to form larger metacommunity isotopic niches. At last, the size of metacommunity niches depended on within-site heterogeneity in CC. 5. Our results suggest that the trophic niches occupied by food webs can predictably scale from local food webs to metacommunities to biogeographic regions. This scaling process is determined by both the functional traits of species and heterogeneity in environmental conditions.

Nitric oxide (NO) is a key signaling molecule in biological systems. New tools are required to therapeutically modulate NO levels with confined precision. This study explores the photoactivatable properties of an NO releasing compound (CPA), based on cupferron O-alkylated with an anthracene derivative. Upon light stimulation, CPA uncages two species: cupferron, which liberates NO, and an anthrylmethyl carbocation, which evolves into a fluorescent reporter. Proof-of-principle is demonstrated using one- and two-photon excitation (1PE and 2PE) in a cellular system (A431 cells). It was found that 1PE induces cell toxicity, while 2PE does not. Since 1PE using UV light is more likely to generate cellular photodamage, the cell toxicity observed using 1PE is most likely a combinatory effect of NO release and other UV-induced damage, which should be subject to further investigation. On the other hand, absence of phototoxicity using 2PE suggests that NO alone is not cytotoxic. This leads to the conclusion that the concept of 2PE photorelease of NO from CPA enable opportunities for biological studies of NO signaling with confined precision of NO release with minimal cytotoxicity.

ANALISIS FINGERPRINT DAUN GEDI HIJAU (Abelmoschus manihot L) UNTUK MEMPREDIKSI AKTIVITAS ANTIOKSIDAN MENGGUNAKAN KOMBINASI SPEKTROSKOPI IR DENGAN PARTIALLEAST SQUAREREGRESSION Marino Novri Warongan1), Sri Sudewi1), Adithya Yudistira1)1)Program Studi Farmasi FMIPA UNSRAT Manado, 95115 ABSTRACT The study aims to determine the antioxidant activity, infrared spectra and correlation between spectral data and antioxidant activity of green gedi leaves. Method of determining prediction of antioxidant activity through fingerprint analysis using combination of IR spectroscopy and Chemometric Partial Least Square Regression (PLSR). DPPH method is used to prevent free radical and free-radical yield of free radical or concentration 150 ppm Bitung A sample 91.392 ± 1.125, Bitung B sample 88.493 ± 1.515 dan Bitung C sample 91.663 ± 1.184, Manado A sample 89.464 ± 1.642, Manado B sample 90.096 ± 3.510, and Manado C sample 89.477 ± 0.850, and in the Kotamobagu sample A 86.678 ± 3.703, Kotamobagu sample B 82.963 ± 2.991 and Kotamobagu sample C 83.163 ± 6.354. Gedi leaves from the city of Bitung, Manado, and Kotamobagu has a relatively similar spectrum. This combination involves the FTIR spectrum as the “x” variabel and the result data of the DPPH method as the “y” variabel. The prediction model can be used because it has error value ( standar error calibration (SEC = 0.0615), standard error of prediction (SEP = 0.0763)) and calibration value of 0.4181, and r validation of 0.2917. Keywords: Antioxidant, Green Gedi Leaves, FTIR Spectrophotometry, UV-VIS Spectrophotometry, Chemometric . ABSTRAK Penelitian ini bertujuan untuk mengetahui aktivitas antioksidan, spektrum infra merah dan korelasi antara data spektrum dan aktivitas antioksidan daun gedi hijau. Metode penentuan prediksi aktivitas antioksidan melaui analisis fingerprint menggunakan kombinasi Spektroskopi IR dan Kemometrik Partial Least Square Regression (PLSR). Metode DPPH digunakan untuk menangkal radikal bebas dan hasil persen penangkal radikal bebas pada konsentrasi 150 ppm Sampel Bitung A 91.392 ± 1.125, Sampel Bitung B 88.493 ± 1.515 dan Sampel Bitung C 91.663 ± 1.184, Sampel Manado A 89.464 ± 1.642, Sampel Manado B 90.096 ± 3.510, dan Sampel Manado C 89.477 ± 0.850, dan terakir pada Sampel Kotamobagu A 86.678 ± 3.703, Sampel Kotamobagu B 82.963 ± 2.991 dan Sampel Kotamobagu C 83.163 ± 6.354.Daun Gedi dari kota Bitung, Manado dan Kotamobagu ini memiliki spektrum yang relatif sama. Kombinasi ini melibatkan dari spektrum FTIR sebagai variabelx dan data hasil analisis metode DPPH sebagai variabely. Model prediksi dapat digunakan karena memiliki nilai kesalahan (standar error calibration (SEC = 0.0615), standard error of prediction (SEP = 0.0763)) dan nilai r kalibrasi 0.4181, serta r validasi 0.2917. Kata Kunci : Antioksidan, Daun Gedi Hijau, Spektrofotometri FTIR, Spektrofotometri UV-VIS, Kemometrik.

Background and Objectives: Renal toxicity due to tenofovir (TDF) has been largely described in patients with HIV infection. However, other antiretroviral drugs (such as atazanavir [ATV], especially when boosted by ritonavir, ATV/r) could perpetuate some degrees of renal impairment with or without TDF co-administration. Also, possible benefits of stopping TDF in patients without renal diseases is not well known. This study aimed at exploring evolution of renal function and lipid profile after switching from tenofovir/emtricitabine (TDF/FTC) to abacavir/lamivudine (ABC/3TC), maintaining the ATV/r component of the regimen. Methods: Patients in the Italian MASTER Cohort, who switched from TDF/FTC plus ATV/r to ABC/3TC plus ATV/r were included, provided that major renal diseases were not diagnosed before switching (i.e., baseline). Serum creatinine, estimated glomerular filtration rate (eGFR), total cholesterol, HDL and triglycerides were evaluated at baseline and at month 18 after switching. Results: 126 patients were selected (80% males). Patients were mostly Italians (92%). 79% had undetectable HIV-RNA and 44% were coinfected by HBV and/or HCV. Median age at switch was 47 years (IQR 43-55). A small but significant decrease in serum creatinine [from 1.06 mg/dl (SD: 0.3) to 0.94 mg/dl (SD: 0.2); p

It is increasingly clear that a tailored therapeutic approach to patients with hepatitis C virus infection is needed. Success rates in difficult to treat and low-responsive hepatitis C virus patients are not completely satisfactory, and there is the need to optimise treatment duration and intensity in patients with the highest likelihood of response. In addition, the management of special patient categories originally excluded from phase III registration trials needs to be critically re-evaluated. This article reports the recommendations for the treatment of hepatitis C virus infection on an individual basis, drafted by experts of three scientific societies.

A multicentre cross-sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1-1.3, P < 0.001), HBeAg positivity (aOR 1.8, 95% CI 1.1-2.8, P < 0.001), cirrhosis (aOR 3.6, 95% CI 2-6.3, P = 0.012), HDV (aOR 1.6, 95% CI 1.02-2.5, P = 0.042) and HIV positivity (aOR 6.5, 95% CI 4-10.8, P < 0.001). Conversely, a decreased chance was associated with female gender (aOR 0.6, 95% CI 0.5-0.7, P < 0.001), immigration (aOR 0.6, 95% CI 0.5-0.9, P = 0.009), alcohol consumption (aOR 0.7, 95% CI 0.5-0.98, P = 0.04) and HCV positivity (aOR 0.5, 95% CI 0.3-0.8, P = 0.005). Our study shows that Italian IDCs treat a high percentage of patients with CHB. Nevertheless, disparities exist which are not related to the severity of disease limiting access to antiviral therapy of CHB, even in a country with a universal healthcare system.

Trttasi di un testo corredato da diverse immagini che illustra le varie e complesse fasi di un restauro monumentale. Dall'analisi storico-critica del manufatto,attraverso un raffronto con l'origine e l'evoluzione del teatro all'italiana,il saggio tratta della metodologia di intervento in ordine alle tecniche di consolidameto, agli aspetti impiantistici,al ripristino degli apparati decorativi ed al restauro pittorico.Il confronto tra l'opera prima dell'intervento e la sua rstituzione è condotto attraverso la illustrazione delle diverse fasi in cui si è sviluppato il cantiere, seguendo i metodi più moderni del restauro scientifico.

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/mm3 plus HIV-RNA

Purpose: The h-prune gene is involved in cellular motility and metastasis formation in breast cancer through interacting with the nm23-H1 protein. The aim of this study was to better define the clinical and pathologic role of h-prune in breast cancer patients. Experimental Design: Using immunohistochemistry, we assessed h-prune and nm23-H1 protein expression in two series of breast cancer patients: (i) in 2,109 cases with pathologic reports on primary tumors and (ii) in 412 cases with detailed clinical information. To assess the role of DNA amplification in gene activation, the h-prune copy number was evaluated by fluorescence in situ hybridization analysis in 1,016 breast cancer cases. Results: In the patients tested (n = 2,463), 1,340 (54%) had an increased level of h-prune expression; a positive immunostaining for nm23-H1 was observed in 615 of 2,061 (30%) cases. Overexpression of h-prune was associated with multiple gene copy number at chromosome 1q21.3 in a very limited fraction of cases (68 of 1,016; 6.7%), strongly indicating that alternative pathways induce h-prune activation in breast cancer. Multivariate Cox regression analysis showed that neither h-prune overexpression nor decreased nm23-H1 immunostaining is independent prognostic factors. However, a significant association of h-prune overexpression with either advanced lymph node status (P = 0.017) or presence of distant metastases (P = 0.029) was observed. Conclusions: Although not significantly correlated with overall survival, positive h-prune immunostaining identifies subsets of breast cancer patients with higher tumor aggressiveness. Further investigations using larger collections of advanced breast cancer patients are required for assessing the predictive role of h-prune in breast cancer.

In this paper, a new stand-alone board explicitly designed to active noise and vibration control and for damage detection, is presented. The system is based on ADSP-21060 SHARK and for flexibility the hardware is divided in two parts: the main processor board, containing the A/D and D/A converters, able to work as stand-alone or in a multiprocessor system being configurable without any hardware change; the I/O interface boards. All the boards are accommodated in a compact rack. The authors have developed all the software tools needed for application in the active noise control or damage detection framework. The software parameters may be changed by the user via a user friendly interface from a host PC connected to the system via a RS232 port. The system has been extensively testes in different applications with encouraging results, work in progress are related to the use of the platform to implement M.I.M.O. ANC systems.