Impact of a nutrition/educational program in a group of type 2 diabetes patients, already involved in a wider “Group Care” plan and not achieving complete target: an observational study

Type 2 diabetes is one of the most frequent chronic degenerative diseases in the world (5.4% in Italy); it has many chronic consequences with a significant impact either on expectation or quality of life. About 80-90% of type 2 diabetes patients is either overweight or obese, condition that can cause many more negative consequences than in individuals in the same conditions but with normal weight. The aim of the research is to assess if diabetic people who cannot reach the goals of glycemic control, good eating habits and weight loss can eventually obtain, with an individualized care plan, long lasting improvements. This study involved a little group of diabetic patients who did not achieve an optimal therapeutic target. These patients have been individually followed by a dietician for six months through a program of dietetic counseling and regular controls and at the end we compare the results of another group of diabetic people, involved in the Group Care Plan (but without the support of the dietitian). The nutrition educational program determined a significant weight loss (- 4.62 kg vs + 3.46 kg; p<0.05), a reduction of waist circumference (-5.34 cm vs + 4.15 cm; p<0.05), an improvement of glycemic control (Hb1Ac: - 0.67 % vs + 0.57%; p<0.05), lipidic profile (total cholesterol: - 1 mg/dl vs + 12.85 mg/dl; p<0.05) and perceived quality of life (Test Att 19: 0 subjects vs 6 subjects). An individualized nutrition educational program in patients with type 2 diabetes not achieving a therapeutic target can optimize global care of the disease.

Oncolytic adenovirus drives specific immune response generated by a poly-epitope pDNA vaccine encoding melanoma neoantigens into the tumor site

Background: DNA vaccines against cancer held great promises due to the generation of a specific and long lasting immune response. However, when used as a single therapy, they are not able to drive the generated immune response into the tumor, because of the immunosuppressive microenvironment, thus limiting their use in humans. To enhance DNA vaccine efficacy, we combined a new poly-epitope DNA vaccine encoding melanoma tumor associated antigens and B16F1-specific neoantigens with an oncolytic virus administered intratumorally. Methods: Genomic analysis were performed to find specific mutations in B16F1 melanoma cells. The antigen gene sequences were designed according to these mutations prior to the insertion in the plasmid vector. Mice were injected with B16F1 tumor cells (n = 7-9) and therapeutically vaccinated 2, 9 and 16 days after the tumor injection. The virus was administered intratumorally at day 10, 12 and 14. Immune cell infiltration analysis and cytokine production were performed by flow cytometry, PCR and ELISPOT in the tumor site and in the spleen of animals, 17 days after the tumor injection. Results: The combination of DNA vaccine and oncolytic virus significantly increased the immune activity into the tumor. In particular, the local intratumoral viral therapy increased the NK infiltration, thus increasing the production of different cytokines, chemokines and enzymes involved in the adaptive immune system recruitment and cytotoxic activity. On the other side, the DNA vaccine generated antigen-specific T cells in the spleen, which migrated into the tumor when recalled by the local viral therapy. The complementarity between these strategies explains the dramatic tumor regression observed only in the combination group compared to all the other control groups. Conclusions: This study explores the immunological mechanism of the combination between an oncolytic adenovirus and a DNA vaccine against melanoma. It demonstrates that the use of a rational combination therapy involving DNA vaccination could overcome its poor immunogenicity. In this way, it will be possible to exploit the great potential of DNA vaccination, thus allowing a larger use in the clinic.Peer reviewe

Oncolytic adenovirus drives specific immune response generated by a poly-epitope pDNA vaccine encoding melanoma neoantigens into the tumor site

Abstract Background DNA vaccines against cancer held great promises due to the generation of a specific and long-lasting immune response. However, when used as a single therapy, they are not able to drive the generated immune response into the tumor, because of the immunosuppressive microenvironment, thus limiting their use in humans. To enhance DNA vaccine efficacy, we combined a new poly-epitope DNA vaccine encoding melanoma tumor associated antigens and B16F1-specific neoantigens with an oncolytic virus administered intratumorally. Methods Genomic analysis were performed to find specific mutations in B16F1 melanoma cells. The antigen gene sequences were designed according to these mutations prior to the insertion in the plasmid vector. Mice were injected with B16F1 tumor cells (n = 7–9) and therapeutically vaccinated 2, 9 and 16 days after the tumor injection. The virus was administered intratumorally at day 10, 12 and 14. Immune cell infiltration analysis and cytokine production were performed by flow cytometry, PCR and ELISPOT in the tumor site and in the spleen of animals, 17 days after the tumor injection. Results The combination of DNA vaccine and oncolytic virus significantly increased the immune activity into the tumor. In particular, the local intratumoral viral therapy increased the NK infiltration, thus increasing the production of different cytokines, chemokines and enzymes involved in the adaptive immune system recruitment and cytotoxic activity. On the other side, the DNA vaccine generated antigen-specific T cells in the spleen, which migrated into the tumor when recalled by the local viral therapy. The complementarity between these strategies explains the dramatic tumor regression observed only in the combination group compared to all the other control groups. Conclusions This study explores the immunological mechanism of the combination between an oncolytic adenovirus and a DNA vaccine against melanoma. It demonstrates that the use of a rational combination therapy involving DNA vaccination could overcome its poor immunogenicity. In this way, it will be possible to exploit the great potential of DNA vaccination, thus allowing a larger use in the clinic

Peptides-Coated Oncolytic Vaccines for Cancer Personalized Medicine

Publisher Copyright: Copyright © 2022 Feola, Russo, Martins, Lopes, Vandermeulen, Fluhler, De Giorgi, Fusciello, Pesonen, Ylösmäki, Antignani, Chiaro, Hamdan, Feodoroff, Grönholm and Cerullo.Oncolytic Viruses (OVs) work through two main mechanisms of action: the direct lysis of the virus-infected cancer cells and the release of tumor antigens as a result of the viral burst. In this sc.enario, the OVs act as in situ cancer vaccines, since the immunogenicity of the virus is combined with tumor antigens, that direct the specificity of the anti-tumor adaptive immune response. However, this mechanism in some cases fails in eliciting a strong specific T cell response. One way to overcome this problem and enhance the priming efficiency is the production of genetically modified oncolytic viruses encoding one or more tumor antigens. To avoid the long and expensive process related to the engineering of the OVs, we have exploited an approach based on coating OVs (adenovirus and vaccinia virus) with tumor antigens. In this work, oncolytic viruses encoding tumor antigens and tumor antigen decorated adenoviral platform (PeptiCRAd) have been used as cancer vaccines and evaluated both for their prophylactic and therapeutic efficacy. We have first tested the oncolytic vaccines by exploiting the OVA model, moving then to TRP2, a more clinically relevant tumor antigen. Finally, both approaches have been investigated in tumor neo-antigens settings. Interestingly, both genetically modified oncolytic adenovirus and PeptiCRAd elicited T cells-specific anti-tumor responses. However, in vitro cross-representation experiments, showed an advantage of PeptiCRAd as regards the fast presentation of the model epitope SIINFEKL from OVA in an immunogenic rather than tolerogenic fashion. Here two approaches used as cancer oncolytic vaccines have been explored and characterized for their efficacy. Although the generation of specific anti-tumor T cells was elicited in both approaches, PeptiCRAd retains the advantage of being rapidly adaptable by coating the adenovirus with a different set of tumor antigens, which is crucial in personalized cancer vaccines clinical setting.Peer reviewe

An Integrated Approach for Evaluating the Restoration of the Salinity Gradient in Transitional Waters: Monitoring and Numerical Modeling in the Life Lagoon Refresh Case Study

Large lagoons usually show a salinity gradient due to fresh water tributaries with inner areas characterized by lower mean values and higher fluctuation of salinity than seawaterdominated areas. In the Venice Lagoon, this ecotonal environment, characterized in the past by oligo‐mesohaline waters and large intertidal areas vegetated by reedbeds, was greatly reduced by historical human environmental modifications, including the diversion of main rivers outside the Venice Lagoon. The reduction of the fresh water inputs caused a marinization of the lagoon, with an increase in salinity and the loss of the related habitats, biodiversity, and ecosystem services. To counteract this issue, conservation actions, such as the construction of hydraulic infrastructures for the introduction and the regulation of a fresh water flow, can be implemented. The effectiveness of these actions can be preliminarily investigated and then verified through the combined implementation of environmental monitoring and numerical modeling. Through the results of the monitoring activity carried out in Venice Lagoon in the framework of the Life Lagoon Refresh (LIFE16NAT/IT/000663) project, the study of salinity is shown to be a successful and robust combination of different types of monitoring techniques. In particular, the characterization of salinity is obtained by the acquisition of continuous data, field campaigns, and numerical modeling

Expected Shifts in Nekton Community Following Salinity Reduction: Insights into Restoration and Management of Transitional Water Habitats

Abstract: A restoration project is planned to take place in the northern Venice lagoon (northern Adriatic Sea, Italy), aiming at introducing freshwater into a confined shallow water lagoon area and recreating transitional water habitats. This work describes the shifts in the nekton (fish and decapods) community structure to be expected following the future salinity decrease in the restoration area. Nekton was sampled at a series of natural shallow water sites located along salinity gradients in the Venice lagoon. A multivariate GLM approach was followed in order to predict species biomass under the salinity and environmental conditions expected after restoration. Biomass of commercially important species, as well as species of conservation interest, is predicted to increase following salinity reduction and habitat changes. From a functional perspective, an increase in biomass of hyperbenthivores-zooplanctivores, hyperbenthivores-piscivores and detritivores is also expected. This study emphasises the ecacy of a predictive approach for both ecological restoration and ecosystem management in transitional waters. By providing scenarios of community structure, the outcomes of this work could be employed in future evaluations of restoration success in the Venice lagoon, as well as to develop management tools to forecast the eects of alterations of salinity regimes in coastal lagoons due to climate change

Pathology reporting in neuroendocrine neoplasms of the digestive system: everything you always wanted to know but were too afraid to ask

During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals

Commentary: Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management

In the issue of March 2021, Lenschow et al. reported the case of a 46-year-old woman with recurrent, programmed death-ligand-1 (PD-L1) negative, tumor mutational burden (TMB)-high parathyroid carcinoma (PC), who showed stable disease as her best response on imaging, and a three-fold drop in PTH after treatment with intravenous pembrolizumab. Given the remarkable results obtained by Lenschow et al. with the anti-PD-1 agent pembrolizumab in the above-mentioned case, we performed an extensive search for possible further relevant data sources, including a) full published articles in international online databases (PubMed, Web of Science, Scopus, and Embase); b) preliminary reports in selected international meeting abstract repositories (American Society of Clinical Oncology, ASCO; European Neuroendocrine Tumor Society, ENET; European Society for Medical Oncology, ESMO); c) registered clinical trials in the U.S. National Institutes of Health registry of clinical trials (http://clinicaltrials.gov) and in any primary register of the WHO International Clinical Trials Registry Platform (ICTRP)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Physical and numerical modelling of wave transformations in the Venice Lagoon

Aim of the study is to assess the capability of a numerical model to reproduce the wave modification when propagating in a very shallow water environment crossed by small canals. This is a typical situation within the Venice Lagoon, and it does appear that the wave transformation due to the cutting canals can be responsible of bank erosion and of other important phenomena (e.g. reflection and set-up/down). A suitable wave model was therefore applied to the \u201cacademic case\u201d of a rectangular trough of finite width, and compared with the results obtained through the laboratory tests, specifically performed in a wave flume. The applied model, SWAN, is an advanced third generation model, specifically developed for shallow waters. The model is based on the wave action balance equation with sources and sinks terms. Being the wave action conserved for a wave propagating in non-homogeneous media, the SWAN model seems to fit the requirements to correctly reproduce the wave evolution over a trough. Once validated with the laboratory data, the wave model could be applied to the convoluted bathymetry of the lagoon and used to get an estimate of the energy dissipation on the canals\u2019 edges and eventually an estimate of the slopes erosion