Design, characterization and efficacy evaluation of natural nasal sprays based on phospholipid vesicles loading plant-extracts.

Plants and their derivates have been used as medicines beneficial products for centuries and today is being re-discovered their usefulness for the human health is being re-discovered. The therapeutic properties of phytochemicals are re-evaluated under the light of medical and pharmacological research, pushed by a constantly growing market demand, where consumers trust more natural products than synthetic drugs. New studies are specifically focused on the effectiveness of phytochemicals against a wide range of ailments. In this thesis, the efficacy of topical formulations based on natural bioactive molecules in the treatment of nasal mucosal diseases, has been presented. Three nasal sprays based on phospholipid vesicles loading the extracts of C. halicacabum L., Z. officinalis and co-loading Z. officinalis plus citral, were designed to counteract disorders involving the upper airways, such as rhinitis and rhinosinusitis. For each formulation, physico-chemical characteristics, spray geometry, biocompatibility and biological activity were evaluated

Executive functions and symptom severity in an Italian sample of intellectually able preschoolers with autism spectrum disorder

A novel battery (BAFE; Valeri etal. 2015) was used in order to assess three executive function (EF) abilities (working memory, inhibition and shifting) in a sample of 27 intellectually able preschoolers with autism spectrum disorder (ASD) compared with 27 typically developing children matched on age and nonverbal IQ. Differences in EF skills were analyzed in participants with distinct ASD symptom severity. Children with ASD performed worse than typical controls on both set-shifting and inhibition, but not on visuo-spatial working memory. Additionally, children with more severe ASD symptoms showed a worse performance on inhibition than children with milder symptoms. These results confirm the presence of EF deficits and highlight a link between ASD symptoms and EF impairments in preschool age

Morphological Changes in Dental Surfaces Suggest Health Status and Alimentary Habits in the Subjects Belonging to the Copper Age in Sardinia Island (III Millennium BC)

The aim of this multidisciplinary study, which involved a team of archaeologists, odontologists, biologists, is to examine a set of dental health indicators, including caries, tooth wear, and enamel hypoplasia of a III millennium BC sample from the burial site of Scaba ’e Arriu (Siddi, South Sardinia), in order to evaluate the dental health status and the diet. Our purpose is to depict a timeline of dental health in Sardinia from prehistory to the present day, starting with a focus on a Copper Age population. Caries, dental wear, and enamel hypoplasia of 259 permanent teeth were evaluated. It was not possible to assign sex and age of each tooth because of the lack of bony support, lost due to taphonomy factors. 14,7% of Scaba‘e Arriu’s samples were affected by carious lesions, with greater involvement of the posterior teeth (12,7% against 1,9% of anterior ones). Interproximal caries was the most frequent. Dental wear affected 77,8% of the teeth, and its presence is preponderant over caries’ rate. The high percentage of dental wear suggests a diet based on abrasive foods. Further studies are necessary to delineate more accurately the modus vivendi, the nutrition, and, consequently, the health status of this sample

Nasal Spray Formulations Based on Combined Hyalurosomes and Glycerosomes Loading Zingiber officinalis Extract as Green and Natural Strategy for the Treatment of Rhinitis and Rhinosinusitis

A total green nanotechnological nasal spray has been manufactured and proposed as an alternative treatment of rhinitis and rhinosinusitis. It was obtained by combining the strengthening effect of liposomes on barrier function, the hydrating and lubricating properties of sodium hyaluronan and the anti-inflammatory and antioxidant activities of the extract of Zingiber officinalis. To this purpose, the extract was loaded in special phospholipid vesicles immobilized with hyaluronic acid (hyalurosomes), which were further enriched with glycerol in the water phase. Liposomes and glycerosomes were prepared as well and used as reference. Vesicles were oligolamellar and multicompartment, as confirmed by cryogenic transmission electron microscopy (cryo-TEM) observation, small in size (~140 nm) and negatively charged (~−23 mV). Spray characteristics were evaluated by using the Spraytec® and instant images, from which the plume angle was measured. The range of the droplet size distribution and the narrow spray angle obtained suggest a good nebulization and a possible local deposition in the nasal cavity. In vitro studies performed by using human keratinocytes confirmed the high biocompatibility of vesicles and their ability to effectively counteract oxidative damage on cells induced by hydrogen peroxide. The overall collected data suggest that our vesicles are suitable as nasal spray

Periodontal microbiota of Sardinian children: comparing 200-year-old samples to present-day ones

Introduction: The microrganisms of the human oral cavity include more than 700 species or phenotypes of bacteria. Some “diseases of civilization” are strictly correlated to changes in the microbiome following the food revolution that occurred after WWII. For that reason, a precise recognition of the microbiome profile before and after this period should be useful to determine the health-compatible model of icrobiome. The aim of this study was to compare the microbiome profiles (number of total cells, and pathogen types) of dental samples obtained from two distinct groups of children, a 200-year-old retrieved one and a present one. Methods: Two different groups of samples have been studied. The first group was a set of 50 recent subgingival plaque samples obtained from children of age 2-8 years, 14 males and 36 females. They were enrolled by the Department of Dental Disease Prevention (University of Cagliari, in Sardinia, Italy) during standard dental care procedures. None reported periodontal disease and none had been under antibiotic therapy during the previous 6 months. The second group was an old retrieved group that included 24 teeth from 6 different 6- to 8-year-old crania fragments; they were obtained from a 200-year-old charnel-house located in Villaputzu, a city close to Cagliari. Representative periodontal bacteria have been identified by a previously published real-time PCR procedure (Sokransky et al., 1998) in which P. gingivalis and T. forsythia (red complex), A. Original article 2/5 www.jpnim.com Open Access Journal of Pediatric and Neonatal Individualized Medicine • vol. 6 • n. 1 • 2017 Orrù • Contu • Casula • Demontis • Blus • Szmukler-Moncler • Serreli • Maserati • Steri • Fanos • Coghe • Denotti actinomycetemcomitans (green complex) and F. nucleatum (orange complex) were detected. In addition, the title of each pathogen was expressed as a percentage of the total bacteria (biofilm) in the sample. Results and discussion: The profile of periodontal microbiomes, between recent/ancient samples showed a significant difference relative to Sokransky’s red complex bacteria (p < 0.05). In all analyzed periodontal strains, the pathogenic bacteria P. gingivalis and T. forsythia showed the highest title in the recent group. Conclusions: Our hypothesis is that the transfer of “commensal-pathogen” as an absolute number on the oral biofilm might be linked to the distinct alimentary habits of the two populations. Some diet rich in reducing agents, such as processed meat-based foods, might be able to increase the average number of pathogen anaerobic bacteria in the oral microbiota. The outcome would be an increase of the oral systemic diseases reported with these pathogens. Our data suggest that the ancient Sardinian population was able to control the pathogen oral anaerobic biofilm by some diet rich in antioxidant compounds. Further investigations are required to focus on the genetic profile and the health status of this ancient population but it appears that molecular microbiology might be considered as the “time machine” in oral biology

From waste to health: sustainable exploitation of grape pomace seed extract to manufacture antioxidant, regenerative and prebiotic nanovesicles within circular economy

Pomace seed extract loaded vesicles were prepared as promising technological and green solution to exploit agri-food wastes and by-products, and develop high value-added products for human health. An antioxidant extract rich in bioactive compounds (epicatechins, catechin, gallic acid, quercetin and procynidins) was obtained from the seeds isolated from the pomace of Cannonau red grape cultivar. The extract was incorporated into phospholipid vesicles ad hoc formulated for intestinal delivery, by combining them, for the first time, whit a maltodextrin (Glucidex). Glucidex-transfersomes, glucidex-hyalurosomes and glucidex-hyalutransferomes were prepared, characterized and tested. Glucidex-liposomes were used as reference. All vesicles were small in size (~ 150 nm), homogeneously dispersed and negatively charged. Glucidex-transfersomes and especially glucidex-hyalutransfersomes disclosed an unexpected resistance to acidic pH and high ionic strength, as they maintained their physico-chemical properties (size and size distribution) after dilution at pH 1.2 simulating the harsh gastric conditions. Vesicles were highly biocompatible and able to counteract the oxidative damages induced in Caco-2 cells by using hydrogen peroxide. Moreover, they promoted the formation of Lactobacillus reuteri biofilm acting as prebiotic formulation. Overall results suggest the potential of glucidex-hyalutransfersomes as food supplements for the treatment of intestinal disorders

Complementary effect of Zingiber officinalis extract and citral in counteracting non allergic nasal congestion by simultaneous loading in ad hoc formulated phospholipid vesicles

5 figures, 4 tables.Natural nasal spray formulations were prepared by using Zingiber officinalis (Z. officinalis) extract and citral synergically loaded into specifically designed phospholipid vesicles. Phospholipid vesicles were selected according to their stabilizing effect on the nasal mucosal barrier, and their effectiveness was further potentiated by the co-loading of Z. officinalis extract as antioxidant and anti-inflammatory agent, and citral as antibacterial molecule. Cryo-TEM images confirmed the formation of morphologically homogeneous and small vesicles, sized around 100 nm, negatively charged (−44 mV) and highly biocompatible (viability ≥100%) as detected by using epithelial cells. The analysis of size distribution of sprayed droplets, average velocity module and spray cone angle suggested a good aptitude of the vesicles to be nebulized and their effective deposition in the nasal cavity. Moreover, vesicles were effectively capable of inhibiting some nasal pathogenic bacteria (i.e. Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli) and to protect the epithelial cells against oxidative damage. The formulations are natural and safe, and all of them have shown promising technological and biological properties suggesting their possible application in the nasal cavity for the treatment of congestions and non-allergic rhinitis.The authors thank PON-RI 2014–2020 Research and Innovation Program, grant number DOT1304004, for the support. The authors thank for technical and human support provided by TEM measurements carried out in the SGIker Polymer Characterization (UPV/EHU/ ERDF, EU); the NanoBioCel Group of the University of the Basque Country (UPV/EHU), in Vitoria-Gasteiz (Spain); the Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) of Zaragoza (Spain); the Molecular Biology Service Lab of the University of Cagliari.Peer reviewe

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups &lt;0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population