Evaluation of a Novel Non-Penetrating Electrode for Use in DNA Vaccination

Current progress in the development of vaccines has decreased the incidence of fatal and non-fatal infections and increased longevity. However, new technologies need to be developed to combat an emerging generation of infectious diseases. DNA vaccination has been demonstrated to have great potential for use with a wide variety of diseases. Alone, this technology does not generate a significant immune response for vaccination, but combined with delivery by electroporation (EP), can enhance plasmid expression and immunity. Most EP systems, while effective, can be invasive and painful making them less desirable for use in vaccination. Our lab recently developed a non-invasive electrode known as the multi-electrode array (MEA), which lies flat on the surface of the skin without penetrating the tissue. In this study we evaluated the MEA for its use in DNA vaccination using Hepatitis B virus as the infectious model. We utilized the guinea pig model because their skin is similar in thickness and morphology to humans. The plasmid encoding Hepatitis B surface antigen (HBsAg) was delivered intradermally with the MEA to guinea pig skin. The results show increased protein expression resulting from plasmid delivery using the MEA as compared to injection alone. Within 48 hours of treatment, there was an influx of cellular infiltrate in experimental groups. Humoral responses were also increased significantly in both duration and intensity as compared to injection only groups. While this electrode requires further study, our results suggest that the MEA has potential for use in electrically mediated intradermal DNA vaccination

Measuring the economic sustainability of Italian farms using FADN data

In recent literature, the issue of sustainability and its measure has been addressed with different approaches that depend on the multidimensional nature of the concept and the specific sector and context to which it applies. The present work focuses on the economic sustainability component and suggests an operative measure at the farm level. The measure of economic sustainability has been applied to Italian family farms using Farm Accountancy Data Network (FADN). Based on this data, an efficiency indicator (EI) and two income indicators [a factor profitability indicator (FPI) and a comparable income indicator (CII)] expressing the ability to remunerate the entrepreneur's production factors at their opportunity cost and the farm's income capacity have been used in a principal component analysis (PCA) to build an economic sustainability index (SI). The index was used to describe Italian farms' economic sustainability levels but was also the cue to discuss problems related to identifying economic sustainability thresholds and the trade-off between efficiency and income components

Ameliorating a Complex Urban Ecosystem Through Instrumental Use of Softscape Buffers: Proposal for a Green Infrastructure Network in the Metropolitan Area of Naples

Green Infrastructure (GI) definition, deriving from the United States green infrastructure for hydro-geological rebalancing through imitating the nature stormwater management, was consolidated in Europe by GI Planning Guide. Nowadays GI can be considered a valid and meaningful approach for ameliorating urban complex ecosystems, and could also be considered as mitigation action of land consumption, according to the guidelines on the soil sealing of the European Commission (2012). The metropolitan area of Naples located in south Italy is characterized by an unauthorized and chaotic urban development. The land-use map reported an average of 30% of urbanization in the metropolitan area, rising up to 50–60% and as high as 98% in the north core area of the city. This high level of urbanization is directly related to the habitat fragmentation. The National Biodiversity Conservation Strategy defines several challenges and targets to counteract the biodiversity loss in Italy, identifying urban areas as places exposed to the greatest pressures on ecosystems. Therefore, the integration of different policies limiting habitat fragmentation, heat island effect and natural soil hydro-geological degradation into spatial planning, especially through green corridors and ecosystem enhancement in urban areas is an urgent need for the society. Spatial planning has to be renewed in metropolitan areas, where threats and weaknesses to biodiversity conservation are stronger than in any other place, according to the Law n. 56/2014, (Gazzetta Ufficiale della Repubblica Italiana, 2014) committing metropolitan cities to the enactment of General Territorial Plan. In the current paper, we aim at designing an ecological network for the metropolitan area of Naples one of the biggest city of southern Italy. The analyses include the adopted methodological procedure, i.e., ecological network analysis and design, and the introductory elements of a spatial analysis on a pilot ecological network of several patches. Finally, the paper illustrates the network analysis conceived as a monitoring system and also in future perspective, as a planning support system

Whole Genome Sequencing Analysis of a Stage IV Colon Cancer Patient with a 10-Year Disease-Free Survival following Systemic Chemotherapy/Bevacizumab

It is rare that stage IV colon cancer is cured with chemotherapy. Here we report the long-term survival of a patient who presented with highly advanced disease characterized by a papillary architecture as well as porta hepatis lymph nodes but responded extremely well to FOLFIRI/bevacizumab. His original tumor underwent comprehensive genomic testing that included whole genome DNA sequencing, targeted sequencing, and RNA sequencing. These genetic results suggest the patient’s tumor harbored mutations in APC, KRAS, and TP53 as well as in PIK3CB. Moreover, the RNA-seq data suggested that the tumor belonged to the consensus molecular subtype 4, the “inflamed, immune phenotype,” with increased angiogenesis. Deep sequencing of highly responsive cancers may yield molecular insights into mechanisms underpinning a remarkable response

A Comparative Cost-Benefit Analysis of Conventional and Organic Hazelnuts Production Systems in Center Italy

In this study, the economic profitability of hazelnut production in central Italy using conventional and organic farming systems was evaluated using the cost–benefit analysis methodology. Viterbo’s province is the leading province in Italy in terms of quantity produced. Three indicators were calculated for both farming systems: net present value, payback time, internal rate of return. The analysis was conducted utilizing primary data collected by means of interviews and surveys with local farmers and organizations of producers. The collected production data refer to the decade 2008–2018; a global area of 100.34 ha and 6.14 ha were considered for conventional and organic cultivation, respectively. Sensitivity analysis was carried out considering different discount rates, price variability, and inflation rates. The net present value is equal to 92,800 €/ha and to 3778 €/ha, the payback time is 10.47 years and 42.94 years, while the internal rate of return is 12.2% and 1.1% for the conventional and organic production systems, respectively. The conventional production system performs significantly more remuneratively, considering that the price premium paid by the market for the organic product and the subsidies granted to organic farmers are not sufficient to balance the lower yield

Evaluation of Toxicity Following Electrically Mediated Interleukin-12 Gene Delivery in a B16 Mouse Melanoma Model

PURPOSE: Interleukin-12 (IL-12) has potential as an immunotherapeutic agent for the treatment of cancer but is unfortunately associated with toxicity. Delivery of a plasmid encoding IL-12 with electroporation induces an antitumor effect in the B16 mouse melanoma model without serious side effects. To translate this observation to the clinic, an evaluation of toxicity was done in the mouse model. EXPERIMENTAL DESIGN: Weight change, tumor response, blood chemistry and hematology values, and serum IL-12 levels were evaluated. Multiple tissues were analyzed histopathologically. RESULTS: A pronounced reduction in tumor volume, including a large percentage of complete regressions, was observed after electrically mediated gene therapy. No significant increases in serum IL-12 levels were detected. Tumor-bearing mice showed an increased number of atypical hematology values when compared with normal naive controls. Statistically significant differences in chemistry and hematology values were observed sporadically in most of the standard chemistry and hematology categories in all groups. The only histopathologic abnormality specific to the animals receiving both plasmid and electroporation was inflammation associated with the kidney at the last time point. CONCLUSIONS: In general, mice that received both plasmid and electroporation showed the least abnormal histopathologic findings and were found to be in the best health, reflecting the reduced burden of disease. No significant toxic effects due to the IL-12 gene therapy were observed

The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial

Simple SummaryThere is no clear evidence on the most effective method of pathological analysis and clearance definition (0 vs. 1 mm) to define R1 resection after pancreatoduodenectomy (PD). However, several studies showed that the R1 resection is a poor prognostic factor in patients that have undergone PDs for periampullary cancers. In this randomized clinical trial, specimens were randomized with two pathological methods, the Leeds Pathology Protocol (LEEPP) or the conventional method adopted before the study. The 1 mm clearance is the most effective factor in determining R1 rate after PD but only when adopting the LEEP, the R1 resection represents a significant prognostic factor.Background: There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. Methods: PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. Results. One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. Conclusions. The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis

Post-orthodontic position of lower incisors and gingival recession : a retrospective study

To evaluate if changes in lower incisor position following orthodontic treatment are correlated with development of gingival recessions. Pre- and post-treatment digital models and lateral cephalograms of 22 subjects were collected retrospectively. The clinical crown length, gingival scallop, and papilla height of the central lower incisor were measured along with the cephalometric incisor?s inclination, the distance from the mandibular plane, and the distance between the Infradentale and Menton points. Statistical correlations between gingival and cephalometric variables were studied. In addition, two groups were defined based on the post-treatment incisor inclination value (?normal? or ?proclined?) and compared. The incisor inclination was correlated with the change in gingival scallop and papilla height. Moreover, there was a statistically significant difference in clinical crown height and gingival scallop between the ?normal? group and the ?proclined? group. Changes in lower incisor position, especially an excessive proclination, after orthodontic treatment may play a role in the development of gingival recession

Plasma methionine sulfoxide in persons with familial Alzheimer’s disease mutations

The final, published version of this article is available at http://www.karger.com/?doi=10.1159/000338546.BACKGROUND: Convergent evidence suggests that oxidative stress plays a central role in the pathology of Alzheimer’s disease (AD). We asked if consequently, oxidation of methionine residues to methionine sulfoxide (MetO) increased in plasma proteins of persons carrying familial AD (FAD) mutations. METHODS: Plasma was collected from 31 persons from families harboring PSEN1 or APP mutations. Using Western blot analysis with a novel anti-MetO polyclonal antibody, MetO levels were measured and compared between FAD mutation carriers (MCs) and non-mutation carrying (NCs) kin. RESULTS: A MetO-positive 120 kDa gel band distinguished FAD MCs and NCs (mean 11.4 ± 2.8 vs. 4.0 ± 3.1, p = 0.02). In a subset of subjects for whom both measurements were available, MetO levels correlated well with plasma F2-isoprostane (r = 0.81, p < 0.001) and superoxide dismutase 1 (r = 0.52, p = 0.004) levels. CONCLUSIONS: Our data provide evidence for elevated MetO levels in persons carrying FAD mutations that correlate with other indices of oxidative stress and suggest that plasma oxidative stress markers may be useful for diagnosis of AD

Longitudinal study on low-dose aspirin versus placebo administration in silent brain infarcts: the silence study

Background. We investigated low-dose aspirin (ASA) efficacy and safety in subjects with silent brain infarcts (SBIs) in preventing new cerebrovascular (CVD) events as well as cognitive impairment. Methods. We included subjects aged ≥45 years, with at least one SBI and no previous CVD. Subjects were followed up to 4 years assessing CVD and SBI incidence as primary endpoint and as secondary endpoints: (a) cardiovascular and adverse events and (b) cognitive impairment. Results. Thirty-six subjects received ASA while 47 were untreated. Primary endpoint occurred in 9 controls (19.1%) versus 2 (5.6%) in the ASA group (p=0.10). Secondary endpoints did not differ in the two groups. Only baseline leukoaraiosis predicts primary [OR 5.4 (95%CI 1.3-22.9, p=0.022)] and secondary endpoint-A [3.2 (95%CI 1.1-9.6, p=0.040)] occurrence. Conclusions. These data show an increase of new CVD events in the untreated group. Despite the study limitations, SBI seems to be a negative prognostic factor and ASA preventive treatment might improve SBI prognosis. EU Clinical trial is registered with EudraCT Number: 2005-000996-16; Sponsor Protocol Number: 694/30.06.04