Biocomposites based on PHBs and natural fibers for commodity applications in different environments: processing, performance in soil, compost and sea water

Composites based on poly(3-hydroxybutyrate) (PHB) and natural fibres such as fibres of Posidonia oceanica (PO), wood saw dust (WSD) and bran were produced by extrusion in presence of appropriate amounts of plasticizer (Acetyl Tri-n- Butyl Citrate, ATBC) and filler (calcium carbonate). Thermal, rheological, mechanical and morphological characterizations of the developed composites were conducted in order to optimize formulations in terms of processability and mechanical performance. The biodegradability of the optimized composites was investigated under controlled composting conditions in accordance with standard methods (ASTM D5338-98, ISO 20200-2004) and in soil for the PHB/WSD composites, because their expected fate is to be treated in composting plants or used for applications in agriculture; in simulated and natural marine sediments in mesocosms and dune habitat for the PHB/PO composites, because their potential applications are in marine environment, such as natural engineering interventions (restoration of seagrass habitats). The optimized PHB/WSD compounds were used for the production of pots for terrestrial plants, PHB/PO compounds for pots and other items usable in the sea and sand dunes, such as transplanting tools and structures for restoration or protection of coastal habitats, and the PHB/bran fibres for the production of food contact containers. The results showed that the industrial processing by extrusion of the composites did not show any difficulty up to 20 wt. % fibres and the presence of the fibres (PO or WSD) facilitated the disintegration of the PHB matrix and, consequently, accelerated its biodegradation both in compost, soil, sea water and dune. The PHB/WSD composites resulted no-phytotoxic by using cress (Lepidium sativum L.) germination test, compostable in accordance with EN 13427:2000, biodegradable in soil at controlled degradation rate. The PHB/PO composites showed a good controlled biodegradation rate in marine sediments and were suitable to manufacture items usable, for example, in natural engineering interventions and represent an interesting valorisation of the PO fibrous wastes accumulated in large amounts on coastal beaches

Growth Inhibition of Retinoblastoma Cell Line by Exosome-Mediated Transfer of miR-142-3p

Retinoblastoma (Rb) is the most common ocular paediatric malignancy and is caused by a mutation of the two alleles of the tumor suppressor gene, RB1. The tumor microenvironment (TME) represents a complex system whose function is not yet well defined and where microvesicles, such as exosomes, play a key role in intercellular communication. Micro-RNAs (mRNAs) have emerged as important modifiers of biological mechanisms involved in cancer and been able to regulate tumor progression. Methods: Co-culture of monocytes with retinoblastoma cell lines, showed a significant growth decrease. Given the interaction between Rb cells and monocytes, we investigated the role of the supernatant in the cross-talk between cell lines, by taking the product of the co-culture and then using it as a culture medium for Rb cells. Results: miR-142-3p showed to be particularly over-expressed both in the Rb cell line and in the medium used for their culture, comparing to control cell line and the normal supernatant, respectively. Therefore, we provided evidence that miR-142-3p is released by monocytes in the co-culture medium's exosomes and that it is subsequently up-taken by Rb cells, causing the inhibition of proliferation of Rb cell line by affecting cell cycle progression. Conclusion: This study highlights the role of exosomic miR-142-3p in the TME of Rb and identifies new molecular targets, which are able to control tumor growth aiming the development of a forward-looking miR-based strategy

Cell-Cycle Inhibition by Helicobacter pylori L-Asparaginase

Helicobacter pylori (H. pylori) is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

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 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

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

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 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

Functional neurobiology in normal aging, mild cognitive impairment and Alzheimer´s disease : Focus on on visuospatial processing using functional magnetic resonance imaging

p> With the proportional increase of the aging population in the coming decades as well as a continuously augmenting life expectancy, the effects of neurodegeneration on brain function are a topic of increasing importance. Of special interest are tools that probe the functional consequences of neurodegenerative processes and possible compensatory mechanisms that might emerge. This thesis uses functional magnetic resonance imaging, fMRI to investigate visuospatial processing in early adulthood, old age and during different stages in the course of Alzheimer s disease, AD (including mild cognitive impairment, MCI), with the aim to relate the functional activation changes in aging and dementia to the task demand (assessed by reaction time, RT), and task performance (% correct responses). Using an angle discrimination task with varying task demand we could demonstrate that all groups engaged a visuospatial network including bilateral core regions in parietal, occipital, and frontal cortex as well as basal ganglia. In these regions a general pattern of a linear relationship (either by using correlation analysis (study I) or by incorporating a reaction time dependent hemodynamic response predictor in the statistical model (study II-V)) between cortical activation and behavioral performance could be observed, reflecting increased cortical processing due to increased task demand. However, t he processing efficiency or relative contribution of the components in this network differed depending on age and disease . In study III we found an age-related task demand dependent change of activation, suggesting that age modulates the utilization of cerebral networks, which has bearing on the behavioral response in the elderly subjects. The results of a weaker relation between task demand and brain activity in several areas of the visuospatial network in elderly compared to young subjects indicate that age-related decrease in processing speed is related to a decline in the neural correlates of processing efficiency. In study V we found an enhanced parietal activation (especially left sided) pattern in patient that later progressed to AD compared to patients that remained stable (SMCI) and controls. This could reflect a reduced neuronal efficacy due to accumulating AD pathology, in which the increased activation could serve as a compensatory role for PMCI patients to achieve the same level of behavioral task performance as the controls and SMCI. However, as the pathological changes progress in AD, abnormal brain function was observed in the parietal cortices. A weak and sometimes absent increase in BOLD signal with increasing task demand was demonstrated in study IV in several regions in the dorsal visual pathway in AD patients compared to controls, suggesting a failure to modulate the neural response to increased task demand. Further, it was shown that the groups also differed with respect to the general BOLD signal increase of activation irrespective of task demand. In study III-IV, an age- and disease related reduction in occipital activity was discovered. These findings could be due to a decline in sensory processing due to age which is worsening further by the neurodegenerative disease. However, in study III we also found an age-related increase in several prefrontal regions, which was interpreted to reflect a compensatory pathway in which older brains may apply a different strategy in order to solve the task with similar task performance as the younger subjects. A similar compensatory effect could be demonstrate in the PMCI patients (study V), reflected as an increase of activation in left precuneus (as compared to SMCI and controls). In study IV, AD patients demonstrated a weaker general increase in BOLD signal in these areas (e.g. left precuneus, and prefrontal cortex) suggesting that the above reported compensatory pathways are limited in AD patients. Instead, we found a n increased activation in the right ventral pathway, which might reflect a potential secondary compensatory mechanism for the reduced functional capacity of the parietal regions in AD patients. A proposed integrative model that applies to the functional activation studies of both healthy aging and Alzheimer s disease and its precursors is presented. This model reveals that alterations in the visuospatial network, independently of its cause, lead to changes in functional activation which seems to follow similar rules in aging and dementia. Thus, the findings presented in this thesis are providing one step in the unraveling of the physiological and pathophysiological mechanisms behind age- and disease related cognitive decline

Il tutor del tirocinante, tra pratiche scolastiche e pratiche formative

Le autrici analizzano ruolo e funzioni del Tutor dei tirocinanti a partire dall'esperienza del corso di laurea per la formazione iniziale dei maestri in Scienze della formazione primar