Novel Approach for Evaluation of Bacteroides fragilis Protective Role against Bartonella henselae Liver Damage in Immunocompromised Murine Model

Bartonella henselae is a gram-negative facultative intracellular bacterium and is the causative agent of cat-scratch disease. Our previous data have established that Bacteroides fragilis colonization is able to prevent B. henselae damages through the polysaccharide A (PSA) in an experimental murine model. In order to determine whether the PSA is essential for the protection against pathogenic effects of B. henselae in immunocompromised hosts, SCID mice were co-infected with B. fragilis wild type or its mutant B. fragilis 1PSA and the effects of infection on murine tissues have been observed by High-Frequency Ultrasound (HFUS), histopathological examination, and Transmission Electron Microscopy (TEM). For the first time, echostructure, hepatic lobes length, vascular alterations, and indirect signs of hepatic dysfunctions, routinely used as signs of disease in humans, have been analyzed in an immunocompromised murine model. Our findings showed echostructural alterations in all infected mice compared with the Phosphate Buffer Solution (PBS) control group; further, those infected with B. henselae and co-infected with B. henselae/B. fragilis 1PSA presented the major echostructural alterations. Half of the mice infected with B. henselae and all those co-infected with B. henselae/B. fragilis 1PSA have showed an altered hepatic echogenicity compared with the renal cortex. The echogenicity score of co-infected mice with B. henselae/B. fragilis 1PSA differed significantly compared with the PBS control group (p < 0.05). Moreover the inflammation score of the histopathological evaluation was fairly concordant with ultrasound findings. Ultrastructural analysis performed by TEM revealed no significant alterations in liver samples of SCID mice infected with B. fragilis wild type while those infected with B. fragilis 1PSA showed the presence of collagen around the main vessels compared with the PBS control group. The liver samples of mice infected with B. henselae showed macro-areas rich in collagen, stellate cells, and histiocytic cells. Interestingly, our data demonstrated that immunocompromised SCID mice infected with B. henselaeand co-infected with B. henselae/B. fragilis ΔPSA showed the most severe morpho-structural liver damage. In addition, these results suggests that the HFUS together with histopathological evaluation could be considered good imaging approach to evaluate hepatic alterations

Campania and cancer mortality: An inseparable pair? The role of environmental quality and socio-economic deprivation

The region of Campania in Southern Italy features high levels of socio-economic deprivation and low levels of environmental quality. A vast strand of the scientific literature has tried to verify whether poor environmental quality and widespread socio-economic deprivation might explain the high cancer mortality rates (CMRs) observed, especially in the municipalities – infamously labelled as the ‘Land of Fires’ – that were hit most severely by the crisis. While some studies managed to identify links between these two confounding factors and cancer mortality, the evidence is overall mixed. Interesting information may be drawn from the observation of municipal data: in spite of previous claims, some municipalities featuring high environmental quality and low socio-economic deprivation also display high CMRs, while other Campanian municipalities facing disastrous environmental and socio-economic conditions are characterised by low CMRs. These figures, in contrast to common sentiment and previous studies, need to be investigated thoroughly in order to assess the exact role of the confounding factors. In this work, we aim to identify the municipalities where confounding factors act as driving forces in the determination of high CMRs through an original multi-step analysis based on frequentist and Bayesian analysis. Pinpointing these municipalities could allow policymakers to design targeted and effective policy measures aimed at reducing cancer mortality

The effect of sustainable business practices on profitability. Accounting for strategic disclosure

This work tackles from an empirical perspective the widely debated relationship between sustainability in business practices and profitability, focusing on a sample of listed European firms. To measure the extent of sustainable practices at the firm level, the Comprehensive Environmental, Social, and Governance (ESG) score is proposed. The indicator, computed using the Mazziotta-Pareto method, combines qualitative ratings on adherence to ESG standards with quantitative observations on the extent of data disclosure. Firms failing to pursue full disclosure are penalized. Focusing on the constituents of the Euro Stoxx 300 index, a dynamic panel model is implemented, where profitability is explained by the indicator. The results show that sustainability in business practices reduces profitability. These findings are in line with a strand of literature that highlights the role of strategic disclosure of ESG information on part of firms. Strategic disclosure occurs as a combination of greenwashing and social washing, with firms overstating the extent of their positive behaviors. The integration of sustainable practices within successful business models thus remains a relevant societal problem. The current EU policy framework is discussed in line with our findings

NSAIDS: Design and Development of Innovative Oral Delivery Systems

Recently, different technologies have been used to transform active pharmaceutical ingredients (APIs) into new dosage forms. Engineered drug delivery systems may modify biopharmaceutical properties of the API achieving either immediate or delayed release according to specific therapeutic needs. Particularly, preprogrammed release of oral formulations delivering the drug at expected times may be useful in chronotherapy of early morning pathologies. The conventional approach when dealing with such diseases is to administer NSAIDs two to three times daily. This approach does not allow to fit drug release with symptoms onset resulting in inefficient therapy and poor patient compliance. NSAIDs may be very effective if administered at least 4–6 h before the pain reaches its peak in the early morning. The solution could be to design delayed drug delivery systems allowing one administration before going to sleep acting in the early morning. This chapter highlights new approaches in developing controlled delivery systems of NSAIDs potentially useful to treat both acute and chronic inflammation. The chapter illustrates the versatility of laminar jet break‐up technology (prilling) to produce gel beads able to control rate and time of drug delivery. A special focus will be on particle‐engineering strategies, i.e., prilling and prilling technique in tandem with microwave or supercritical fluid‐assisted drying

Chronotherapeutic Drug Delivery in Early Morning Pathologies: Design and Production of new NSAIDs/SAIDs polysaccharide-based systems

2014 - 2015The major technological challenge encountered when formulating new dosage forms is to find a way to adapt drug release kinetics to specific clinical requirements, with the aim to enhance the therapeutic action of both new and old drugs. Research in chronopharmacology has demonstrated the importance of biological rhythms in drug therapy and this has led to a new approach to the development of drug delivery systems which are required to enable the drug release timing and control. This approach has a strong impact on the treatment of chronic inflammatory-based diseases which symptoms are circadian-dependent such as the so-called early morning pathologies (EMPs_e.g. arthritis, arthrosis). The conventional treatment of these pathologies consists of daily administrations of anti-inflammatory medicines (NSAIDs or SAIDs), which are often unable to coordinate drug release with clinical symptoms onset resulting in inefficient therapy and poor patient compliance. In the case of individuals who suffer from rheumatoid arthritis and related painful joint disorders, the NSAIDS may be more effective when the drug is administered at least 4 to 6 hours before the pain reaches its peak in the early morning. In this context, my PhD project focused on the design and development of chronotherapeutic drug delivery systems characterized by time-specific and prolonged release of model anti-inflammatory drugs able to fit with the specific therapeutic needs of EMPs. In particular the PhD program involved the design and development of: chronotherapeutic systems loaded with short half life (Ketoprofen and Ketoprofen lysine salt) or with long half life NSAIDs (Piroxicam); and chronotherapeutic systems loaded with SAIDs (Prednisolone). These formulations were designed as monolayer, core/shell and floating microparticles tested as self-consistent formulation or into specific capsules as final dosage form. Formulations were produced by prilling/ionotropic gelation technique using natural (alginate, pectin), semi-synthetic (hydroxypropilmethylcellulose) or synthetic (methacrylic acid - methyl methacrylate copolymer) polymeric carriers as release modifiers. These formulations were characterized in terms of drug content and encapsulation efficiency (UV), morphology (SEM, SEM-EDX), solid state (DSC, FT-IR) swelling behavior and drug release profile (USP apparati II and IV). The in vivo anti-inflammatory effectiveness of the formulations showing the better in vitro technological features was studied using a modified protocol of carrageenan induced edema in rats. The optimized drug delivery systems showing a delayed and time-specific drug release in vitro as well as a delayed and prolonged in vivo anti-inflammatory effect compared to pure drugs, could be considered as potential chronotherapeutic agents to be taken at bedtime and able to act in the early morning. [edited by author]XV n.s.(XXIX ciclo

A Regional Perspective on Social Exclusion in European Regions: Context, Trends and Policy Implications

Social exclusion has become a popular topic in the policy agendas of European governments, especially after the global financial crisis of 2007–2009 hit the continent as hard as it could. The existing literature highlights the presence of spatial patterns in social exclusion, although previous contributions consist of local or national level studies, lacking a broader continental perspective. This work resorts to regional data covering 20 EU countries and aims to characterise the nature of spatial patterns, distinguishing between spatial heterogeneity and pure spatial autocorrelation. Using the Spatial Markov Chain Matrix, we find that the strong clusterisation process unfolded by previous studies tends to become less intense if the role of socio-economic covariates is taken into account. Socio-economic factors represent in other words a containment cage that reduces the extent of neighbour influence. Net of the covariates, we identify clusters of regions in Southern Europe where high levels of social exclusion constitute a structural problem, calling for long-term public intervention. The policy implications of our findings are then outlined

A Regional Perspective on Social Exclusion in European Regions: Context, Trends and Policy Implications

Social exclusion has become a popular topic in the policy agendas of European governments, especially after the global financial crisis of 2007–2009 hit the continent as hard as it could. The existing literature highlights the presence of spatial patterns in social exclusion, although previous contributions consist of local or national level studies, lacking a broader continental perspective. This work resorts to regional data covering 20 EU countries and aims to characterise the nature of spatial patterns, distinguishing between spatial heterogeneity and pure spatial autocorrelation. Using the Spatial Markov Chain Matrix, we find that the strong clusterisation process unfolded by previous studies tends to become less intense if the role of socio-economic covariates is taken into account. Socio-economic factors represent in other words a containment cage that reduces the extent of neighbour influence. Net of the covariates, we identify clusters of regions in Southern Europe where high levels of social exclusion constitute a structural problem, calling for long-term public intervention. The policy implications of our findings are then outlined

Myyntiprosessien kehittäminen asiakaskokemuksen avulla

Tämän opinnäytetyön tarkoituksena oli selkeyttää Herkkukonttorin myyntiprosesseja ja kehittää asiakaskokemusta. Tavoitteena oli tunnistaa nykyisen myyntiprosessin vahvuudet ja kehityskohteet sekä tuottaa toimeksiantajalle selkeä ja käytännönläheinen kokonaiskuva myyntiprosessin kehittämistarpeista. Taustalla oli tarve ohjata asiakkaita keskittämään hankintansa yksittäisten tuotteiden sijaan laajempaan tuotevalikoimaan. Hyödyn saajana oli erityisesti toimeksiantajaorganisaation myyntihenkilöstö sekä asiakasrajapinnassa toimivat henkilöt. Kehittämistehtävänä oli analysoida myynnin nykytila ja tuottaa konkreettisia kehittämisehdotuksia, jotka pohjautuivat asiakas- ja myyntihenkilöstönhaastatteluihin. Tutkimuksen teoreettisessa viitekehyksessä käsiteltiin liiketoiminnan kehittämistä, myyntiprosessin rakennetta sekä asiakaskokemusta. Menetelmänä käytettiin teemahaastattelua eli puolistrukturoituja haastatteluita, joilla saatiin syvällistä ymmärrystä asiakkaiden tarpeista kuin henkilöstön näkemyksistä. Haastatteluihin osallistui Herkkukonttorin myyntihenkilöstöä ja asiakkaita, joiden vastauksista kartoitettiin sekä sisäisiä että ulkoisia näkökulmia myyntiprosessiin ja asiakaskokemukseen. Haastattelurunko testattiin etukäteen ja aineisto analysoitiin teemoittelemalla. Tuloksissa korostui asiakasviestinnän kehittäminen sekä tuotevalikoiman esille tuomista esimerkiksi tarinankerronnan avulla. Johtopäätöksissä esitettiin seuraavanlaisia toimintaehdotuksia, kuten tuotevalikoiman esilletuominen, markkinointiviestinnän kehittäminen sekä asiakaslähtöinen hinnoittelu. Tuloksia voidaan hyödyntää erityisesti elintarviketukkukaupan asiakaslähtöisyyden ja myynnin tehokkuuden kehittämisessä.The purpose of this thesis was to clarify Herkkukonttori’s sales processes and to improve the customer experience. The objective was to identify the strengths and development areas of the current sales process and to provide the client with a clear and practical overview of its development needs. The underlying goals was to guide customers to focus their purchases on a broader product selection rather than on individual itsems. The main beneficiaries were the client organization’s sales personnel and orher customer-facing employees. The development task was to analyze the current state of sales and to produce concrete development proposals based on interviews with customers and sales staff. The theoretical framework of the study covered business development, the structure of the sales process, and customer experience. The chosen method was theme interviews, so in other words, semi structured interviews, which provided in-depth insight into both customer needs and staff perspectives. Participants inclueded Herkkukonttori’s sales personnel and customers, whose responses revealed both internal and external perspectives on the sales process and customer experience. The interview guide was pre-tested, and the data was analyzed thematically. The results highlighted the need to develop customer communication and to present the product range more effectively, fot example, through storytelling. The conclusions inclueded suggestion such as showcasing the product range, improving marketing communications, and implementing customer-centricity and sales efficiency in the food wholsale sector

Oxidation of solid carbon materials : Structural and Thermochemical Analysis

This Thesis project aimed at giving a contribution to further unravel selected aspects of the chemistry and physics of carbon combustion and gasification relevant to implementation of novel clean coal technologies for Carbon Capture and Storage (CCS)-ready conversion. Aspects that have been specifically scrutinized are: a) surface oxides as intermediates of carbon combustion and gasification; b) Chemico-physical characterization of chars generated under oxyfiring conditions. The chemical nature of carbon oxides that populate the char surface and their evolution throughout thermochemical processing has been clarified combining C1s and O1s core-level XPS Spectra acquired at high-resolution using Synchrotron radiation and thermoanalytical analysis. Results are consistent with the hypothesis represented by a semi-lumped kinetic model based on four steps: formation of ‘metastable’ surface oxides by oxygen chemisorption, rearrangement of metastable oxides into stable complexes either by thermally activated rearrangement/isomerization or by complex-switch-over driven by molecular oxygen, desorption of surface oxides with release of CO and CO2. The “metastable” oxides may prevailingly consist of epoxy functionalities, whereas the more stable oxides would be composed by ether and carbonyl moieties. Results are helpful not only in view of applications to stationary combustion or gasification of carbons, but also to shed light on the dynamical patterns of carbon chemisorption/desorption under alternating oxidizing conditions, relevant to “looping combustion” of carbon, as in the “Carboloop” concept proposed by the Naples group. Along a different path, it is recognized that coal combustion is significantly changed in CO2-rich atmospleres as oxyfiring. In an international collaboration between three institutions from Aachen, Bochum and Naples, pyrolysis experiments have been carried out to investigate the influence of inert (N2) vs reactive (CO2) gas atmospheres as well as reactor type (and associated test conditions) on properties of gas, tar and char. At low heating rates/ temperature or high heating rates /temperature, the differences between N2 and CO2 pyrolysis products were marginal. A CO2 rich atmosphere, instead, impacted severely the properties of pyrolysis products under the fast heating-short residence time conditions in drop tube reactor. In particular, in the course of pyrolysis experiments in drop tube reactor in CO2, the appearance on the wall of the ceramic filter of a fluffy carbonaceous solid material was noticed. What emerged is that such fine carbon particulate is mostly ash-free, suggesting that its formation occurs in the gas phase. In order to investigate chemical and structural effects on char reactivity, DTR chars prepared in N2 and CO2 were subjected to combustion and oxy-combustion experiments in TGA. The CO2 chars resulted to be less reactive than the N2 chars by one order of magnitude in combustion, oxy combustion and gasification TGA experiments. The difference in reactivity between the two chars seems to correlate well with differences in the C-O functionalities which reside on their surface, as detected by XPS. Finally, in order to investigate the effect of substituting N2 with CO2 under ‘realistic’ combustion conditions, combustion and oxy-combustion experiments of coal have been carried out in a drop tube reactor. Chemico-physical analysis suggests an enhanced degree of char burn out and graphitization in CO2 rich atmospheres. XPS analysis supports the hypothesis that CO2 could be involved in some cross-linking reactions enhanced by the formation of carboxyl and lacton surface oxide complexes