GALNT2 mRNA levels are associated with serum triglycerides in humans

Atherogenic dyslipidemia, characterized by high triglycerides (TG) and low high density lipoprotein (HDL)-cholesterol levels, is a feature of patients with insulin resistance, obesity, and type 2 diabetes (T2D) [1] and plays a major role in shaping the risk of cardiovascular disease. Both TG and HDL-cholesterol serum concentrations are under the control of both environmental factors and up to 95 genetic loci, unraveled by a very large genome-wide association study (GWAs) in approximately 100,000 individuals [2]. Among these loci is GALNT2, which encode for ppGal-NAc-T2, involved in O-linked glycosylation. Similarly, studies in rodents have shown that liver GALNT2 expression modulates HDL-cholesterol concentrations [2]. Based on such studies, it is conceivable that GALNT2 expression changes play a role on TG and/or HDL-cholesterol levels. To gain further insights about this hypothesis, GALNT2 expression was measured in peripheral white blood cells (PWBC), from 224 individuals with a wide range of TG and HDL-cholesterol levels, as well as other metabolic parameters and clinical conditions

Geometrical and functional criteria as a methodological approach to implement a new cycle path in an existing Urban Road Network: A Case study in Rome

Most road accidents occur in urban areas and notably at urban intersections, where cyclists and motorcyclists are the most vulnerable. In the last few years, cycling mobility has been growing; therefore, bike infrastructures should be designed to encourage this type of mobility and reduce motorized and/or private transport. The paper presents a study to implement a new cycle path in the existing cycle and road network in Rome, Italy. The geometric design of the new path complies with Italian standards regarding the technical characteristics of bicycle paths, while the Highway Capacity Manual has been considered for the traffic analysis. In particular, a before-after approach has been adopted to examine and compare the traffic flow at more complex and congested intersections where the cycle path will pass. Trams, buses, cars, bikes and pedestrians were the traffic components considered in each analysis. The software package PTV VISSIM 8 allowed the simulations of traffic flows at traffic-light intersections; an original linear process has been proposed to model dynamic intelligent traffic controls, which are not admitted by the software used. The traffic analysis allowed the identification of the best option for each of the five examined intersections. Particularly, the maximum queue length value and the total number of passed vehicles have been considered in order to optimize the transport planning process. The results of this study highlight the importance of providing engineered solutions when a cycle path is implemented in a complex road network, in order to avoid negative impacts on the citizens and maximize the expected advantages

Relationship between cervical spine and skeletal class II in subjects with and without temporomandibular disorders

AIM. To assess changes of cranio-cervical structure and of hyoid bone position in skeletal Class II subjects with and without Temporomandibular disorders (TMD). MATERIAL AND METHODS. The cephalometric analysis of 59 subjects with skeletal Class II were evaluated and compared. The measurements considerated were: ANB as parameter of Class II and C0-C1 distance, C1-C2 distance, cranio-cervical angle and hyoid bone position for the cervical spine analysis. Patients were divided into two subgroups: patients with TMD (group A) and patients without TMD (group B). TMD were evaluated with the Diagnostic Criteria for TMD (DC/TMD). Descriptive statistics and Pearson and Spearman correlation analysis, with p-value <0,005, were performed. RESULTS. C0-C1 and C1-C2 distance values and hyoid bone position resulted within normal range in the majority of patients examined. Cranio-cervical angle was alterated in 33 patients. The reduction of this angle with the increase of the ANB value resulted statistically significant in the group A, according to Pearson correlation index. No other data was statistically significant. CONCLUSIONS. Significant relationship between skeletal Class II and cervical spine cannot be highlighted. The alteration of cranio-cervical angle seems to be mildly present, with backward counterclockwise rotation of the head upon the neck in the sample (group A and B). The presence of TMDs as key factor in changes of neck posture could explain the different result between the two groups about relationship between ANB and cranio-cervical angle. This result should be further analyzed in order to better understand if cervical spine changes could be related to mandibular postural ones in the cranio-cervical space or to temporomandibular joints retropositioning, more recognizable in Class II with TMD, which could determine functional changes in other structures of this unit; neck posture also could be the result of a compensatory/ antalgic mechanism in response to TM

Deciphering the loop of epithelial-mesenchymal transition, inflammatory cytokines and cancer immunoediting

Tumorigenesis and tumor progression relies on the dialectics between tumor cells, the extracellular matrix and its remodelling enzymes, neighbouring cells and soluble cues. The host immune response is crucial in eliminating or promoting tumor growth and the reciprocal coevolution of tumor and immune cells, during disease progression and in response to therapy, shapes tumor fate by activating innate and adaptive mechanisms. The phenotypic plasticity is a common feature of epithelial and immune cells and epithelial-mesenchymal transition (EMT) is a dynamic process, governed by microenvironmental stimuli, critical in tumor cell shaping, increased tumor cell heterogeneity and stemness. In this review we will outline how the dysregulation of microenvironmental signaling is crucial in determining tumor plasticity and EMT, arguing how therapy resistance hinges on these dynamics

Body composition and metabolic status of Italian and Spanish university students: relationship with fruit and vegetable consumption

Most university students do not follow recommendations for fruit and vegetable intake, with a consequent increase in the prevalence of cardiovascular disease (CVD) risk factors. The aim of this study was to compare obesity prevalence and biomarkers of metabolic status between Italian and Spanish university students, in relation with the consumption of fruits and vegetables. Food consumption, adherence to a Mediterranean diet (MD), level of physical activity (PA), blood glucose, total cholesterol, triglycerides and ketones, blood pressure, and body composition were evaluated. Among CVD risk factors, only glucose was significantly higher in Spaniards (SP), and only 3.1% of SP presented ketosis. SP had a higher percentage of energy from fat. Although adherence to MD and fruit and vegetable consumption did not differ between Italians and SP, students who consumed at least four servings of fruit and vegetables (FV group) showed better values for pressure and metabolic parameters than the no FV group. We observed an association between consumption of fruit and PA. Students who consumed more vegetables than fruit reported a better body composition profile and lower glucose concentrations. As previously suggested, in addition to PA, two servings of fruit and three servings of vegetables per day should be recommended

quantitative risk assessment of temporary hazards and maintenance worksites in the airport safety areas a case study

Abstract Airports are complex environments where the operational conditions are subjected to different risks, both due to the intrinsic nature of the manoeuvres themselves and to the external factors, as for human actions or environmental causes. An important risk factor is the presence of temporary hazards on the runway or taxiway safety area, including work in progress related to maintenance or construction operations. Both ICAO (International Civil Aviation Organization) and FAA (Federal Aviation Administration) defined their own approach on this topic. The FAA, in the Advisory Circular "Operational Safety on Airports During Construction", states the impossibility of any construction activities within the safety area when the runway is active, while the ICAO, in the Doc 9137 "Airport Service Manual" Part 6, states specific operational restrictions for the airport which allow the presence of temporary hazard in the safety area. This paper analyses the impact of temporary hazards (for example worksites) in the safety areas, according to ICAO requirements, by using a performance approach. The method has been applied to an international airport, using the software RSARA e LRSARA, provided by ACRP (The Airport Cooperative Research Program), in order to calculate the expected risk level within the safety area. This method provides a rapid and practical evaluation of risk level, according to the ICAO Safety Management System approach, in order to optimize the maintenance operation and construction in the safety area, minimizing the closing time of the runway. The main aim of this study is to verify if, under temporary restrictive operational condition (such as the limitation on available runway length and on traffic mix and weather conditions) related to the temporary hazard presence, it is possible to guarantee sufficient safety level, without occurring in runway closures. From the analysis arose that the first factor that affects the risk level for a runway is the temporary hazard dimension: while the environmental conditions (crosswind and pavement conditions) have a minor effect

Amino-functionalized poly(l-lactide) lamellar single crystals as a valuable substrate for delivery of HPV16-E7 tumor antigen in vaccine development

Background: Poly(L-lactide) (PLLA) is a biodegradable polymer currently used in many biomedical applications, including the production of resorbable surgical devices, porous scaffolds for tissue engineering, nanoparticles and microparticles for the controlled release of drugs or antigens. The surfaces of lamellar PLLA single crystals (PLLAsc) were provided with amino groups by reaction with a multifunctional amine and used to adsorb an Escherichia coli-produced human papillomavirus (HPV)16-E7 protein to evaluate its possible use in antigen delivery for vaccine development. Methods: PLLA single crystals were made to react with tetraethylenepentamine to obtain amino-functionalized PLLA single crystals (APLLAsc). Pristine and amino-functionalized PLLAsc showed a two-dimensional microsized and one-dimensional nanosized lamellar morphology, with a lateral dimension of about 15–20 µm, a thickness of about 12 nm, and a surface specific area of about 130 m2/g. Both particles were characterized and loaded with HPV16-E7 before being administered to C57BL/6 mice for immunogenicity studies. The E7-specific humoral-mediated and cell-mediated immune response as well as tumor protective immunity were analyzed in mice challenged with TC-1 cancer cells. Results: Pristine and amino-functionalized PLLAsc adsorbed similar amounts of E7 protein, but in protein-release experiments E7-PLLAsc released a higher amount of protein than E7-APLLAsc. When the complexes were dried for observation by scanning electron microscopy, both samples showed a compact layer, but E7-APLLAsc showed greater roughness than E7-PLLAsc. Immunization experiments in mice showed that E7-APLLAsc induced a stronger E7-specific immune response when compared with E7-PLLAsc. Immunoglobulin G isotyping and interferon gamma analysis suggested a mixed Th1/Th2 immune response in both E7-PLLAsc-immunized and E7-APLLAsc-immunized mice. However, only the mice receiving E7-APLLAsc were fully protected from TC-1 tumor growth after three doses of vaccine. Conclusion: Our results show that APLLA single crystals improve the immunogenicity of HPV16-E7 and indicate that E7-APLLAsc could be used for development of an HPV16 therapeutic vaccine against HPV16-related tumors

Identification of the zinc finger 216 (ZNF216) in human carcinoma cells. A potential regulator of EGFR activity

Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family of receptor tyrosine kinase (RTK) proteins, is aberrantly expressed or deregulated in tumors and plays pivotal roles in cancer onset and metastatic progression. ZNF216 gene has been identified as one of Immediate Early Genes (IEGs) induced by RTKs. Overexpression of ZNF216 protein sensitizes 293 cell line to TNF-α induced apoptosis. However, ZNF216 overexpression has been reported in medulloblastomas and metastatic nasopharyngeal carcinomas. Thus, the role of this protein is still not clearly understood. In this study, the inverse correlation between EGFR and ZNF216 expression was confirmed in various human cancer cell lines differently expressing EGFR. EGF treatment of NIH3T3 cells overexpressing both EGFR and ZNF216 (NIH3T3-EGFR/ZNF216), induced a long lasting activation of EGFR in the cytosolic fraction and an accumulation of phosphorylated EGFR (pEGFR) more in the nuclear than in the cytosolic fraction compared to NIH3T3-EGFR cells. Moreover, EGF was able to stimulate an increased expression of ZNF216 in the cytosolic compartment and its nuclear translocation in a time-dependent manner in NIH3T3-EGFR/ZNF216. A similar trend was observed in A431 cells endogenously expressing the EGFR and transfected with Znf216. The increased levels of pEGFR and ZNF216 in the nuclear fraction of NIH3T3-EGFR/ZNF216 cells were paralleled by increased levels of phospho-MAPK and phospho-Akt. Surprisingly, EGF treatment of NIH3T3-EGFR/ZNF216 cells induced a significant increase of apoptosis thus indicating that ZNF216 could sensitize cells to EGF-induced apoptosis and suggesting that it may be involved in the regulation and effects of EGFR signaling

Suggestive evidence of a multi-cytokine resistin pathway in humans and its role on cardiovascular events in high-risk individuals

In cells and tissues resistin affects IL-1β, IL-6, IL-8, IL-12 and TNF-α expression, thus suggesting the existence of a multi-cytokine "resistin pathway". We investigated whether such pathway does exist in humans and, if so, if it is associated with cardiovascular risk factors and with major adverse cardiovascular events (MACE). Serum cytokines were measured in 280 healthy subjects from the Gargano Study 2 (GS2) whose BMI, waist circumference, HOMA IR, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure data were available and in 353 patients with type 2 diabetes and coronary artery disease from the Gargano Heart Study (GHS)-prospective design (follow-up 5.4 ± 2.5 years; 71 MACE). In GS2, cytokines mRNA levels in white blood cells were also measured. In GS2, resistin mRNA was correlated with all cytokines expression (all p &lt; 0.001), but IL-12B. Consistently, serum resistin was correlated with all serum cytokines (all p &lt; 0.001), but IL-12. Expression (eRPS) and serum (sRPS) resistin pathway scores (excluding IL-12) were each other correlated (p &lt; 0.001) and both associated with cardiovascular risk factors (all p &lt; 0.01). In GHS, sRPS was independently associated with MACE (HR = 1.44, 95% CI = 1.10-1.90). Our data indicate the existence of a resistin pathway, which is associated with cardiovascular risk factors and which strongly and independently predicts MACE

Effectiveness of psycho-educational intervention to promote mental health focused on emotional intelligence in middle-school

Purpose. The specific “outcome-oriented” pattern of the emotional intelligence (EI) should be considered of capital importance for teenagers in order to promote mental health. Nevertheless it is rarely evaluated because a specific tool, useful for routinely use, is not available. In this paper the authors describe the effectiveness of a new approach of public health to improve the EI “outcome-oriented”, by a specific index.Design. A comparison of two samples: experimental (i.e. applying the program) vs control group, without randomization.Setting. 12 classes belonging to 3 different schools.Subjects. A sample of 276 students, 146 (53%) belonging to the experimental classes. Intervention. A program of 20 meetings, once a week, based on the handbook Intervento psicoeducativo per la promozione del benessere psicologico e dell’intelligenza emotiva nelle scuole (Psycho-educational intervention for promoting psychological well-being and emotional intelligence at school) in order to stimulate a “peer to peer student approach”.Measures. Index of emotional intelligence (15 items), inventory idea questionnaire (19 items), learning ability questionnaire (6 items).Analysis. Nonparametric tests were used.Results. The authors found significant statistical differences at the conclusion of the study for all considered measures.Conclusion. The results show a remarkable and positive impact of the approach above all on the “outcome-oriented” EI. Significant results were also observed about the indicator concerning irrational beliefs. The same significant results were found about learning abilities (goal definition, problem-solving and communication skills). The main limit is the study design (lack of randomization). Further evaluation is needed