6 research outputs found
The concept of the mask and the doctor-patient relationship: insights from a (re)reading of Luigi Pirandello’s Six Characters in Search of an Author
No full textThe concept of the mask and the doctor-patient relationship: insights from a (re)reading of Luigi Pirandello's Six Characters in Search of an Author. The aim of this article is to explore the concept of the "mask" and its relevance within the doctor-patient relationship, as well as within the broader medical-scientific context. The primary reference for this analysis is Luigi Pirandello's work Six Characters in Search of an Author (1921), which embodies universal themes, supplemented by examples from figurative art. What emerges is the patient's necessity, utilizing artistic expression, to narrate their own experiences through a mask that serves as the vessel for their innermost emotions
The impact of mevastatin on HCV replication and autophagy of non-transformed HCV replicon hepatocytes is influenced by the extracellular lipid uptake
No full textStatins efficiently inhibit cholesterol synthesis by blocking 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase in the mevalonate pathway. However, the effect of statins on intracellular cholesterol is partially counterbalanced by a consequent increased uptake of extracellular lipid sources. Hepatitis C virus (HCV) infection induces intracellular accumulation of cholesterol by promoting both new synthesis and uptake of circulating lipoproteins, which is required for HCV replication and release. Hepatocytes respond to the increase in intracellular cholesterol levels by inducing lipophagy, a selective type of autophagy mediating the degradation of lipid deposits within lysosomes. In a cellular system of HCV replication based on HuH7 hepatoma cells, statin treatment was shown to be sufficient to decrease intracellular cholesterol, which is accompanied by reduced HCV replication and decreased lipophagy, and has no apparent impact on endocytosis-mediated cholesterol uptake. To understand whether these results were influenced by an altered response of cholesterol influx in hepatoma cells, we analyzed the effect of statins in non-transformed murine hepatocytes (MMHD3) harboring subgenomic HCV replicons. Notably, we found that total amount of cholesterol is increased in MMHD3 cells upon mevastatin treatment, which is associated with increased HCV replication and lipophagy. Conversely, mevastatin is able to reduce cholesterol amounts only when cells are grown in the presence of delipidated serum to prevent extracellular lipid uptake. Under this condition, HCV replication is reduced and autophagy flux is severely impaired. Altogether, these results indicate that both de novo synthesis and extracellular uptake have to be targeted in non-transformed hepatocytes in order to decrease intracellular cholesterol levels and consequently limit HCV replication. Copyright © 2019 Vescovo, Refolo, Manuelli, Tisone, Piacentini and Fimia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
‐19
No full textCoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its clinical spectrum ranges from mild to moderate or severe illness. A 78-year-old male was presented at emergency department with dyspnoea, dry cough and severe asthenia. The nasopharyngeal swab by real-time polymerase chain reaction confirmed a SARS-CoV-2 infection. The x-ray and the thoracic ultrasound revealed right pleural effusion. A diagnostic-therapeutic thoracentesis drained fluid identified as chylothorax. Subsequently, the patient underwent a chest computed tomography which showed the radiological hallmarks of COVID-19 and in the following weeks he underwent a chest magnetic resonance imaging to obtain a better view of mediastinal and lymphatic structures, which showed a partial thrombosis affecting the origin of superior vena cava and the distal tract of the right subclavian vein. For this reason, anticoagulant therapy was optimized and in the following weeks the patient was discharged for clinical and radiological improvement. This case demonstrates chylothorax as a possible and uncommon complication of COVID-19
Structured methodology review identified seven (RETREAT) criteria for selecting qualitative evidence synthesis approaches
No full textOBJECTIVE
To compare and contrast different methods of qualitative evidence synthesis (QES) against criteria identified from the literature and to map their attributes to inform selection of the most appropriate QES method to answer research questions addressed by qualitative research.
STUDY DESIGN AND SETTING
Electronic databases, citation searching and a study register were used to identify studies reporting QES methods. Attributes compiled from 26 methodological papers (2001-2014) were used as a framework for data extraction. Data were extracted into summary tables by one reviewer and then considered within the author team.
RESULTS
We identified seven considerations determining choice of methods from the methodological literature, encapsulated within the mnemonic RETREAT (Review question - Epistemology - Time/Timescale - Resources - Expertise - Audience and purpose - Type of Data). We mapped 15 different published QES methods against these seven criteria. The final framework focuses on stand-alone QES methods but may also hold potential when integrating quantitative and qualitative data.
CONCLUSION
These findings offer a contemporary perspective as a conceptual basis for future empirical investigation of the advantages and disadvantages of different methods of QES. It is hoped that this will inform appropriate selection of QES approaches
Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).
No full textThe emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality
Mitochondria, neurosteroids and biological rhythms : implications in health and disease states
No full textMitochondria are considered as the “powerhouses” of cells because they synthesize the universal source of energy under the form of adenosine triphosphate (ATP) molecules via oxidative phosphorylation from nutritional sources. Thus, impaired mitochondrial function, especially in neurons that have high energy requirements, lead inevitably to disease, ranging from subtle alterations in neuronal function to cell death and neurodegenerative diseases, such as Alzheimer’s disease (AD). The purpose of this PhD thesis was therefore to deepen our understanding of the regulation of mitochondrial function and to identify key factors that are critical in the control of mitochondrial bioenergetics and dynamics. To achieve this goal, the thesis was divided into two main parts:
1) Since a growing body of evidence suggests that neurosteroids have a strong neuroprotective potential, the first part is based on the hypothesis that neurosteroids may exert a determinant action against neurodegeneration by improving mitochondrial bioenergetics, (A) under “healthy” conditions as well as (B) under pathological conditions (AD);
2) In the second part (C), we determined whether the biological clock, which coordinates a whole range of daily behaviors and physiological processes, is involved in the endogenous regulation of mitochondrial dynamics and bioenergetics.
(A) In the first part of this thesis, we aimed to characterize the bioenergetic modulating profile of a panel of seven structurally diverse neurosteroids (progesterone, estradiol, estrone, testosterone, 3alpha-androstanediol, DHEA and allopregnanolone), known to be involved in brain function regulation. Our key findings were that: i) the majority of these steroids increased energy metabolism, mainly via an up-regulation of the mitochondrial activity and at least in part via receptor activation, and ii) neurosteroids regulated redox homeostasis by increasing the antioxidant activity as a compensatory mechanism to the reactive oxygen species (ROS) level enhancement which might result from the acceleration in oxygen consumption accompanied by a greater electron leakage from the electron transport chain. Additionally, each neurosteroid seems to have a specific bioenergetic profile.
Together, these first data indicated that neurosteroids were indeed able to boost mitochondrial function in a delicate balance, possibly by regulating the expression of genes involved in glycolysis and oxidative phosphorylation, but also the content and activity of mitochondrial respiratory complexes. Further investigations are required to determine the underlying molecular mechanisms.
(B) Based on these findings, we investigated in the next step whether neurosteroids were able to alleviate AD-related bioenergetic deficits. We distinguished the effects of several neurosteroids on ATP synthesis, mitochondrial membrane potential (MMP), mitochondrial respiration and glycolysis in two AD cellular models overexpressing either the amyloid precursor protein and amyloid-beta peptide (APP/Abeta) or the mutant form of tau producing abnormally hyperphosphorylated tau proteins, respectively. Key findings were that: i) APP/Abeta and mutant tau-overexpressing cells present distinct bioenergetic impairments, with APP/Abeta having the strongest deleterious effect on mitochondrial function; ii) the male steroid hormone, testosterone, was more efficient to alleviate mitochondrial deficits induced by APP/Abeta, whereas female steroid hormones, progesterone and estrogen, were more efficient to increase bioenergetic outcomes in our model of AD-related tauopathies. Together, our findings lend further evidence to the neuroprotective effects of neurosteroids in AD pathology and indicate that these molecules represent promising tools able to increase mitochondrial bioenergetics via enhanced mitochondrial respiration, in healthy and pathological conditions, respectively. Our results may open new avenues for drug development with regard to targeting mitochondria in neurodegeneration.
(C) The aim of the second part of this thesis was to investigate more closely how mitochondrial function is endogenously regulated within the cells. Since a growing body of evidences shows that the circadian clock and metabolic homeostasis are connected in numerous ways via reciprocal regulation, we asked whether mitochondrial bioenergetics and dynamics may exhibit circadian oscillations and whether mitochondria themselves may be able to influence the circadian clock. We found that mitochondrial bioenergetics, including mitochondrial respiration and, consequently, generation of the byproducts ATP and ROS, is directly coupled to mitochondrial network which is, at least in part, regulated by clock-controlled phosphorylation of Drp1, the main factor involved in mitochondrial fission. The time-dependent reorganization of mitochondrial architecture in turn regulates the clock through circadian oscillation of mitochondrial ATP which can act as input signal through activation of AMP-activated protein kinase (AMPK). Our findings highlight new insights in the understanding of the reciprocal temporal crosstalk that governs the molecular interplay between the coupling of mitochondrial dynamics and metabolism and circadian rhythms.
Overall, the studies performed in the present thesis importantly helped to deepen our knowledge about the modulation of mitochondrial function in health and disease states. Our findings could have multiple implications with regard to the regulation of metabolic homeostasis in health and disease states associated with mitochondrial impairments and / or circadian disruption
