Phenomenological and Formulation Aspects in Tailored Nanoliposome Production

Liposomes as cell‐mimetic system have attracted wide attention of researchers in various branches of the drug delivery topic as they can be highly functionalized and personalized, thus solving the major drawbacks of bioactive molecules linked to their low stability, limited membrane permeability, short half‐life and low bioavailability. The development of sustainable processes able to produce ad hoc liposomes in a rapid manner through the use of not‐laboured techniques, avoiding drastic conditions, is of great relevance for the industrial sector. In this chapter, two novel liposome production processes, the ultrasound‐assisted thin‐film hydration and the simil‐microfluidic techniques sharing the same size reduction/homogenization preparative step, are presented. The phenomenological aspects involved in vectors constitution through the duty cycle sonication process (bilayer rupture/vesicles formation mechanisms) and through the simil‐microfluidic approach (intubated flows interdiffusion mechanisms) are described. Finally, two applications as case histories involving the use of the developed techniques for relevant classes of active molecule delivery are described. In particular, a pharmaceutical application concerns the encapsulation of short‐interfering RNA (siRNA) molecule, used for gene therapy, inside cationic nanoliposomes, and a nutraceutical application consists in the production of ferrous sulphate anionic liposomal formulations with improved features compared to those already present on the market

Novel strategies for the treatment of myelofibrosis driven by recent advances in understanding the role of the microenvironment in its etiology

Myelofibrosis is the advanced stage of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), characterized by systemic inflammation, hematopoietic failure in the bone marrow, and development of extramedullary hematopoiesis, mainly in the spleen. The only potentially curative therapy for this disease is hematopoietic stem cell transplantation, an option that may be offered only to those patients with a compatible donor and with an age and functional status that may face its toxicity. By contrast, with the Philadelphia-positive MPNs that can be dramatically modified by inhibitors of the novel BCR-ABL fusion-protein generated by its genetic lesion, the identification of the molecular lesions that lead to the development of myelofibrosis has not yet translated into a treatment that can modify the natural history of the disease. Therefore, the cure of myelofibrosis remains an unmet clinical need. However, the excitement raised by the discovery of the genetic lesions has inspired additional studies aimed at elucidating the mechanisms driving these neoplasms towards their final stage. These studies have generated the feeling that the cure of myelofibrosis will require targeting both the malignant stem cell clone and its supportive microenvironment. We will summarize here some of the biochemical alterations recently identified in MPNs and the novel therapeutic approaches currently under investigation inspired by these discoveries

supporting continuous improvement in care management with bpm

The present work analyzes the results of an Italian care management project, called Leonardo, promoted by Apulia Region, in the south of Italy, in partnership with Pfizer. The work starts from the consideration that care management represents an innovation in the management of the chronic diseases because it introduces a new model in the organization of healthcare services. Such a model needs gradual refinements in a continuous improvement perspective, in order to be effective. The proposed approach is about the adoption of a Business Process Modelling technique to "model" all phases and activities of the care management process as developed in Leonardo Project. Then this model is used to define the key performance indicators, to analyze the Leonardo Project results and to enhance the underlying care management process. Specific attention has been dedicated to analyze the impact of the software proposed by Pfizer and used to support the care managers and the family doctors in the Leonardo Project. The process model, in fact, helped us to identify several limitations related to the adopted software and to formulate the correct requirements to overcome these issues. In other words, the paper aims to illustrate how tools borrowed from enterprise modelling domain can help to identify and overcome the weaknesses of a care management process and to design more effective software tools in a continuous refinement cycle

Heparan sulfates facilitate harmless amyloidogenic fibril formation interacting with elastin-like peptides

Heparan sulfates (HSs) modulate tissue elasticity in physiopathological conditions by interacting with various matrix constituents as tropoelastin and elastin-derived peptides. HSs bind also to protein moieties accelerating amyloid formation and influencing cytotoxic properties of insoluble fibrils. Interestingly, amyloidogenic polypeptides, despite their supposed pathogenic role, have been recently explored as promising bio-nanomaterials due to their unique and interesting properties. Therefore, we investigated the interactions of HSs, obtained from different sources and exhibiting various degree of sulfation, with synthetic amyloidogenic elastin-like peptides (ELPs), also looking at the effects of these interactions on cell viability and cell behavior using in vitro cultured fibroblasts, as a prototype of mesenchymal cells known to modulate the soft connective tissue environment. Results demonstrate, for the first time, that HSs, with differences depending on their sulfation pattern and chain length, interact with ELPs accelerating aggregation kinetics and amyloid-like fibril formation as well as self-association. Furthermore, these fibrils do not negatively affect fibroblasts' cell growth and parameters of redox balance, and influence cellular adhesion properties. Data provide information for a better understanding of the interactions altering the elastic component in aging and in pathologic conditions and may pave the way for the development of composite matrix-based biomaterials

Parenting Desire and Minority Stress in Lesbians and Gay Men: A Mediation Framework

Despite the rapid increase in lesbian and gay (LG) people who desire and decide to become parents, LG childless individuals may encounter serious obstacles in the parenthood process, such as minority stress. Notwithstanding, the psychological processes by which prejudice events might affect the desire to become parents are still understudied. As an extension of the minority stress theory, the psychological mediation framework sheds light on these psychological processes, as it encompasses a more clinical view of stress. Within this framework, the current study aimed at assessing the role of prejudice events in affecting parenting desire in 290 childless Italian LG individuals (120 lesbians and 170 gay men), as well as the role of internalized heterosexism and sexual orientation concealment in mediating the relationship between prejudice events and parenting desire. The results suggest that only in lesbians prejudice events were negatively associated with parenting desire, and that sexual orientation concealment and internalized heterosexism were also negatively associated with parenting desire. Furthermore, sexual orientation concealment, and not internalized heterosexism, mediated the relationship between prejudice events and parenting desire in lesbians, but not gay men. The findings have important implications for clinical practice

Pre-service teachers’ approaches to gender-nonconforming children in preschool and primary school: Clinical and educational implications

Corrective approaches taken by teachers towards gender nonconformity in childhood may increase the gender pressure that children feel, negatively affecting well-being and development. This study was aimed at assessing whether the approaches of 305 pre-service preschool and primary school teachers towards gender nonconformity in childhood are influenced by sexist and homophobic attitudes and feelings. The results indicated that the majority of the sample would adopt a supportive and affirmative approach towards gender nonconformity in childhood. Notwithstanding, the results also showed that sexism influenced the likelihood of adopting corrective approaches only to gender-nonconforming primary school children, whilst homophobia was positively associated with adoption of a corrective approach to gender nonconformity in both preschool and primary school children. Suggestions for educational and clinical practice are discussed

Minority Stress and Mental Health in Italian Bisexual People

Bisexual people are a strongly stigmatized population experiencing health disparities caused by social stigmatization. The predominant framework helping to understand these health disparities and the impact of stigma on mental health of social groups belonging to a sexual minority identity constitutes the minority stress theory. In Italy, studies assessing this model in bisexual populations are very limited. Within this framework, the current study aimed at assessing in 381 Italian bisexual individuals (62 men and 319 women) the effects of anti-bisexual discrimination, proximal stressors (i.e., anticipated binegativity, internalized binegativity, and outness), and resilience on psychological distress. The results suggested that only anti-bisexual discrimination and internalized binegativity were positively associated with psychological distress, and that resilience was negatively associated with mental health issues. Furthermore, the results suggested that internalized binegativity mediated the relationship between anti-bisexual discrimination and mental health problems. No moderating effect of resilience was found. This is the first study to have thoroughly applied minority stress in Italian bisexual people, providing Italian clinicians and researchers with an outline of the associations between minority stress, stigma, resilience, and psychological distress within this population

The Conundrum of Cancer-Associated Thrombosis:Lesson Learned from Two Intriguing Cases and Literature Review

The correlation between cancer and venous thromboembolism (VTE) is solid, whereas the knowledge about cancer-related arterial thromboembolism (ATE) still needs a deeper investigation to clarify its pathogenesis. We describe two cases that represent useful hints for a comprehensive review of the thrombotic issue. A 75-year-old man with advanced rectal cancer treated with fluoropyrimidines suffered two catheter-related VTE events managed according to current guidelines. There was no indication for “extended” anticoagulant therapy for him, but during antithrombotic wash-out and fluoropyrimidines plus panitumumab regimen, he suffered a massive right coronary artery (RCA) thrombosis. Another patient with no cardiovascular (CV) risk factors and affected by advanced bladder cancer was treated with a platinum-containing regimen and suffered an acute inferior myocardial infarction 2 days after chemotherapy administration. He was successfully treated with primary Percutaneous Transluminal Coronary Angioplasty of RCA, discontinuing platinum-based therapy. Our observations raise the issue of cancer-associated thrombosis (CAT) complexity and the potential correlation between arterial and venous thrombotic events. Moreover, physicians should be aware of the thrombotic risk associated with anticancer therapies, suggesting that an appropriate prophylaxis should be considered

The Conundrum of Cancer-Associated Thrombosis:Lesson Learned from Two Intriguing Cases and Literature Review

The correlation between cancer and venous thromboembolism (VTE) is solid, whereas the knowledge about cancer-related arterial thromboembolism (ATE) still needs a deeper investigation to clarify its pathogenesis. We describe two cases that represent useful hints for a comprehensive review of the thrombotic issue. A 75-year-old man with advanced rectal cancer treated with fluoropyrimidines suffered two catheter-related VTE events managed according to current guidelines. There was no indication for “extended” anticoagulant therapy for him, but during antithrombotic wash-out and fluoropyrimidines plus panitumumab regimen, he suffered a massive right coronary artery (RCA) thrombosis. Another patient with no cardiovascular (CV) risk factors and affected by advanced bladder cancer was treated with a platinum-containing regimen and suffered an acute inferior myocardial infarction 2 days after chemotherapy administration. He was successfully treated with primary Percutaneous Transluminal Coronary Angioplasty of RCA, discontinuing platinum-based therapy. Our observations raise the issue of cancer-associated thrombosis (CAT) complexity and the potential correlation between arterial and venous thrombotic events. Moreover, physicians should be aware of the thrombotic risk associated with anticancer therapies, suggesting that an appropriate prophylaxis should be considered