189 research outputs found

    MANNERS MAKETH MAN Linguaggio e colonizzazione in "The Polished Hoe" di Austin Clarke

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    Oggetto della tesi è la traduzione di una parte del romanzo "The Polished Hoe" dello scrittore barbadiano Austin Clarke. Si tratta di un'opera complessa, che costituisce una summa del pensiero dell'autore: descrive qual è stato l'impatto del colonialismo nella società barbadiana e le conseguenze verificatesi a livello storico, economico e, soprattutto, culturale. Il romanzo è vincitore del Giller Prize for Fiction e del Commonwealth Writers' Best Book Award nel 2002. Il tema centrale del presente lavoro è l'analisi del linguaggio e della sua strumentalizzazione nei processi di colonizzazione e decolonizzazione

    Astrocytes’ Role in Alzheimer’s Disease Neurodegeneration

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    Central nervous system (CNS) astrocytes are glial cells performing crucial tasks encompassing energy metabolism, neurotransmission, ion and water stable levels, and immune defense and control local blood flow/oxygen levels. Arising from neural stem cells, astrocytes differentiate into subtypes that vary according to animal species. Human cerebral cortex astrocytes are sturdier and cytologically and functionally more complex, control wider domains, and spread calcium signals more quickly than their rodents’ counterparts. They actively partake in CNS homeostasis maintenance and functioning by teaming up with their client neurons, other glial cell types, and cerebrovascular cells. Alterations of astrocytes’ activities deeply impact on age-related chronic ailments like Alzheimer’s disease (AD), the commonest senile dementia; AD involves the growing accumulation of amyloid-β peptides (Aβs) and hyperphosphorylated Tau proteins the astrocytes, and neurons supply following the interaction of their calcium-sensing receptors (CaSRs) with exogenous Aβs. The activated Aβ∙CaSR signaling triggers a self-propagating mechanism that spreads the neuropathology among adjacent and far away astrocytes and their neuronal clients causing neurons’ death. CaSR antagonists or calcilytics suppress these noxious effects in vitro. Hence, calcilytics are potential therapeutics that could halt the spread of AD neuropathology and safeguard the patients’ neuronal viability, cognition, memory, and ultimately life

    CaSR Antagonist (Calcilytic) NPS 2143 Hinders the Release of Neuroinflammatory IL-6, Soluble ICAM-1, RANTES, and MCP-2 from A\u3b2-Exposed Human Cortical Astrocytes

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    Available evidence shows that human cortical neurons\u2019 and astrocytes\u2019 calcium-sensing receptors (CaSRs) bind Amyloid-beta (A\u3b2) oligomers triggering the overproduction/oversecretion of several Alzheimer\u2019s disease (AD) neurotoxinseffects calcilytics suppress. We asked whether A\u3b2CaSR signaling might also play a direct pro-neuroinflammatory role in AD. Cortical nontumorigenic adult human astrocytes (NAHAs) in vitro were untreated (controls) or treated with A\u3b225-35\uf020\ub1\uf020NPS 2143 (a calcilytic) and any proinflammatory agent in their protein lysates and growth media assayed via antibody arrays, enzyme-linked immunosorbent assays (ELISAs), and immunoblots. Results show A\u3b2\u2022CaSR signaling upregulated the synthesis and release/shedding of proinflammatory interleukin (IL)-6, intercellular adhesion molecule-1 (ICAM-1) (holoprotein and soluble [s] fragment), Regulated upon Activation, normal T cell Expressed and presumably Secreted (RANTES), and monocyte chemotactic protein (MCP)-2. Adding NPS 2143 (i) totally suppressed IL-6\u2032s oversecretion while remarkably reducing the other agents\u2019 over-release; and (ii) more effectively than A\u3b2 alone increased over controls the four agents\u2019 distinctive intracellular accumulation. Conversely, NPS 2143 did not alter A\u3b2-induced surges in IL-1\u3b2, IL-3, IL-8, and IL-16 secretion, consequently revealing their A\u3b2\u2022CaSR signaling-independence. Finally, A\u3b225-35\uf020\ub1\uf020NPS 2143 treatments left unchanged MCP-1\u2032s and TIMP-2\u2032s basal expression. Thus, NAHAs A\u3b2\u2022CaSR signaling drove four proinflammatory agents\u2019 over-release that NPS 2143 curtailed. Therefore, calcilytics would also abate NAHAs\u2019 A\u3b2\u2022CaSR signaling direct impact on AD\u2019s neuroinflammation

    Quality assessment of medical record as a tool for clinical risk management: a three year experience of a teaching hospital Policlinico Umberto I, Rome

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    Introduction: The medical record was defined by the Italian Ministry of Health in 1992 as "the information tool designed to record all relevant demographic and clinical information on a patient during a single hospitalization episode". Retrospective analysis of medical records is a tool for selecting direct and indirect indicators of critical issues (organizational, management and technical). The project’s aim being the promotion of an evaluation and self-evaluation process of medical records as a Clinical Risk Management tool to improve the quality of care within hospitals. Methods: The Authors have retrospectively analysed, using a validated grid, 1,184 medical records of patients admitted to the Teaching Hospital “Umberto I” in Rome during a three-year period (2013-2015). Statistical analysis was performed using SPSS for Windows © 19:00. All duly filled out criteria (92) were examined. “Strengths” and "Weaknesses" were identified through data analysis and Best and Bad Practice were identified based on established criteria. Conclusion: The data analysis showed marked improvements (statistically significant) in the quality of evaluated clinical documentation and indirectly upon behaviour. However, when examining some sub-criteria, critical issues emerge; these could be subject to future further corrective action

    Human Keratinocytes and Fibroblasts Co-Cultured on Silk Fibroin Scaffolds Exosomally Overrelease Angiogenic and Growth Factors

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    Objectives: The optimal healing of skin wounds, deep burns, and chronic ulcers is an important clinical problem. Attempts to solve it have been driving the search for skin equivalents based on synthetic or natural polymers. Methods: Consistent with this endeavor, we used regen- erated silk fibroin (SF) from Bombyx mori to produce a novel compound scaffold by welding a 3D carded/hydroentangled SF-microfiber-based nonwoven layer (C/H-3D-SFnw; to support dermis engineering) to an electrospun 2D SF nanofiber layer (ESFN; a basal lamina surrogate). Next, we assessed—via scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, differential scanning calorimetry, mono- and co-cultures of HaCaT keratinocytes and adult human dermal fibroblasts (HDFs), dsDNA assays, exosome isolation, double-antibody arrays, and angiogenesis assays—whether the C/H-3D-SFnws/ESFNs would allow the reconstitution of a functional human skin analog in vitro. Results: Physical analyses proved that the C/H-3D- SFnws/ESFNs met the requirements for human soft-tissue-like implants. dsDNA assays revealed that co-cultures of HaCaTs (on the 2D ESFN surface) and HDFs (inside the 3D C/H-3D-SFnws) grew more intensely than did the respective monocultures. Double-antibody arrays showed that the CD9+/CD81+ exosomes isolated from the 14-day pooled growth media of HDF and/or HaCaT mono- or co-cultures conveyed 35 distinct angiogenic/growth factors (AGFs). However, versus monocultures’ exosomes, HaCaT/HDF co-cultures’ exosomes (i) transported larger amounts of 15 AGFs, i.e., PIGF, ANGPT-1, bFGF, Tie-2, Angiogenin, VEGF-A, VEGF-D, TIMP-1/-2, GRO-alpha/beta/gamma, IL-1beta, IL-6, IL-8, MMP-9, and MCP-1, and (ii) significantly more strongly stimulated human dermal microvascular endothelial cells to migrate and assemble tubes/nodes in vitro. Conclusions: Our results showed that both cell–cell and cell–SF interactions boosted the exosomal release of AGFs from HaCaTs/HDFs co-cultured on C/H-3D-SFnws/ESFNs. Hence, such exosomes are an asset for prospective clinical applications as they advance cell growth and neoangiogenesis and consequently graft take and skin healing. Moreover, this new integument analog could be instrumental in preclinical and translational studies on human skin pathophysiology and regeneration

    Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery

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    The rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy

    Exosomes of adult human fibroblasts cultured on 3D silk fibroin nonwovens intensely stimulate neoangiogenesis

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    Bombyx mori silk fibroin (SF) is a biomacromolecule allowing to assemble scaffolds 7 for tissue engineering/regeneration purposes because of its cellular adhesiveness, high 8 biocompatibility, and low immunogenicity. Earlier work showed that two types of 3D-SF-based 9 nonwovens (3D-SFnws) implanted into mouse subcutaneous tissue were promptly vascularised via plates in exosome-depleted medium. DNA amounts and D-glucose consumption revealed HDFs 17 undefined molecular mechanisms. This study used nontumorigenic adult human dermal fibroblasts (HDFs) adhering to a third type of 3D-SFnws to test whether HDFs release exosomes whose contents promote neoangiogenesis
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