Digital determinants of health as a way to address multilevel complex causal model in the promotion of Digital health equity and the prevention of digital health inequities: A scoping review

Background: With the progressive digitization of health services and the current spread of Telemedicine and e-Health, it became clear that promoting Digital health equity (DHE) is necessary to support health potential, to avoid that some individuals can incur in unintended inequities. In this paper, we address the complex causal process(es) that may generate risk of inequities, considering the so-called “Digital Determinants of health” (DDoH) and their relationship with determinants of health (DoH). Design and methods: We conducted a scoping review, according to methodological framework proposed in PRISMA-ScR guidelines, on the definition of DDoH (Scopus, Pubmed and Web of Science electronic databases). Inclusion criteria: papers on the definition of DDoH, no time limits, all study designs eligible. Results: There is an agreement on the link between DDoHs and “digital divide” and on their effects on a wide range of health, functioning outcomes, both as barriers and as facilitators. Authors proposed to modify or integrate with DDoHs the “Rainbow model” or other conceptual models on DoH. To promote DHE, authors suggest considering a multidimensional complex causal model, with interdependence among the different levels and the mutually reinforcing effects. Conclusion: To study DDoH and their relationship with main determinants of health could be a way to address the complex causal model in the promotion of DHE. However, as they act in a multidimensional causal context, any intervention may consider the interdependence among different involved levels, within them, and the mutually reinforcing effects. Further research is needed to gain a more complete picture of the field

Telemedicine, e-Health, and Digital Health Equity: A Scoping Review

Background: With the progressive digitization of people's lives and in the specific healthcare context, the issue of equity in the healthcare domain has extended to digital environments or e-environments, assuming the connotation of “Digital Health Equity” (DHE). Telemedicine and e-Health, which represent the two main e-environments in the healthcare context, have shown great potential in the promotion of health outcomes, but there can be unintended consequences related to the risk of inequalities. In this paper, we aimed to review papers that have investigated the topic of Digital Health Equity in Telemedicine and e-Health [definition(s), advantages, barriers and risk factors, interventions]. Methods: We conducted a scoping review according to the methodological framework proposed in PRISMA-ScR guidelines on the relationship between Digital Health Equity and Telemedicine and e-Health via Scopus and Pubmed electronic databases. The following inclusion criteria were established: papers on the relationship between Digital Health Equity and Telemedicine and/or e-Health, written in English, and having no time limits. All study designs were eligible, including those that have utilized qualitative and quantitative methods, methodology, or guidelines reports, except for meta-reviews. Results: Regarding Digital Health Equity in Telemedicine and e-Health, even if there is no unique definition, there is a general agreement on the idea that it is a complex and multidimensional phenomenon. When promoting Digital Health Equity, some people may incur some risk/s of inequities and/or they may meet some obstacles. Regarding intervention, some authors have proposed a specific field/level of intervention, while other authors have discussed multidimensional interventions based on interdependence among the different levels and the mutually reinforcing effects between all of them. Conclusion: In summary, the present paper has discussed Digital Health Equity in Telemedicine and e-Health. Promoting equity of access to healthcare is a significant challenge in contemporary times and in the near future. While on the one hand, the construct “equity” applied to the health context highlights the importance of creating and sustaining the conditions to allow anyone to be able to reach (and develop) their “health potential”, it also raises numerous questions on “how this can happen”. An overall and integrated picture of all the variables that promote DHE is needed, taking into account the interdependence among the different levels and the mutually reinforcing effects between all of them

Definitions of Ageing According to the Perspective of the Psychology of Ageing: A Scoping Review

In the last decades, the scientific interest in ageing has increased due to the progressive ageing of the global population and due to the importance of guaranteeing the elder people and the next generations a good quality of life and biopsychological well-being. However, nowadays, there is not a common and accepted definition of ageing. This situation may refer to the complexity and relevance of the ageing topic and it means that the concept of ageing needs to be understood in a deeper way as a multidimensional and complex process that includes different elements distinctive. The main goal of this review is to explore the definitions and conceptual models of ageing according to a psychological point of view, through a biopsychosocial approach, that integrates biological, psychological, and social aspects with the main goal of a better understanding of the complexity of the process itself. Methods: We conducted a review of the literature through PubMed, Scopus, Web of Science and Google Scholar databases, and we followed the PRISMA-ScR guidelines, analysing papers written in English between 2002 and 2023. Results: The review showed different conceptual models of ageing, including Rowe and Kahn’s successful ageing model, the World Health Organization’s models, and others like the “Selection, Optimization and Compensation” Model. Also, the determinants and predictors of ageing have been analysed highlighting the individual variability and the multidimensional nature of ageing. The geographic diversity of the included studies allowed for the analysis of cultural, socioeconomic, and environmental differences in the conceptualisation of ageing. Conclusions: The results emphasise the importance of targeted interventions and programs aimed at promoting well-being during ageing, considering the complexity and multidimensionality of the ageing process

Hazelnut extract-loaded nanostructured lipid carriers and evaluation of their antioxidant properties

Reactive oxygen species (ROS) are a common hallmark of many degenerative diseases, developing in all those cases where a failure of physiological antioxidant mechanisms occurs (in particular, antioxidant enzymes and the glutathione system), or in case of exposure to an extremely high level of oxidants. In this regard, antioxidant natural extracts are promising compounds as preventive or therapeutic agents against ROS-dependent degenerations. In this study, a deep investigation of hazelnut (Corylus avellana) extract has been performed in terms of mass spectroscopy, evaluation of phenolic content, and antioxidant capacity. Then, nanostructured lipid carriers (NLCs) have been exploited for encapsulation of the hazelnut extracts in order to achieve prolonged bioactivity, increased stability, and targeting through a sustainable delivery approach. The hazelnut extract-loaded NLCs (NE_NLCs) have been deeply characterized for their stability, production yield, and encapsulation efficiency. Moreover, NE_NLCs showed optimal cytocompatibility on human dermal fibroblast (HDF) cells, as well as excellent antioxidant activity, upon pro-oxidant stimulus on HDF cells

Liposomes loaded with polyphenol-rich grape pomace extracts protect from neurodegeneration in a rotenone-based in vitro model of Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disease with no satisfactory therapy options. Similar to other neurodegenerative conditions, such as Alzheimer's and Huntington's diseases, oxidative stress plays a key factor in the neurodegeneration process. To counteract the uncontrolled increase of reactive oxygen species (ROS) and oxidative stress-dependent cell death, several preclinical and clinical tests exploit natural-derived organic antioxidants, such as polyphenols. Despite some promising results, free antioxidants show scarce brain accumulation and may exhaust their scavenging activity before reaching the brain. In this work, we developed an antioxidant therapeutic nanoplatform consisting of nano-sized functionalized liposomes loaded with selected polyphenol-rich vegetal extracts with high blood-brain barrier crossing capabilities. The antioxidant extracts were obtained from the grape seeds and skins as a byproduct of wine production (i.e., pomace), following a sustainable circular approach with reduced environmental impact. The antioxidant nanoplatform was successfully tested in a relevant in vitro model of PD, where it completely rescued the ROS levels, prevented the aggregation of alpha-synuclein fibrils, and restored cell viability, paving the way for preclinical translation of the approach

Sumac (Rhus coriaria) Extract-Loaded Polymeric Nanosheets Efficiently Protect Human Dermal Fibroblasts from Oxidative Stress

Under healthy physiological conditions, living organisms possess a variety of antioxidant mechanisms to scavenge overproduced reactive oxygen species (ROS). However, under pathological circumstances, endogenous antioxidant systems may not be adequate to eliminate the excessive amount of oxidants, and thus, a continuous exogenous antioxidant income is required. In this regard, sumac (Rhus coriaria) extract is a good candidate for therapeutic applications, because of its high content of antioxidant polyphenolic compounds. In this work, sumac extract-loaded nanosheets (sumac-nanosheet) have been exploited for loading and controlled release of sumac extract, envisioning topical drug delivery applications. Sumac extract has been obtained through the solvent extraction method, and polymeric nanosheets have been thereafter prepared through the spin coating-assisted layer-by-layer deposition of polycaprolactone (PCL), sumac extract, and poly(d,l-lactic acid) (PDLLA). The collected data show a rich content of the sumac extract in terms of polyphenolic compounds, as well as its strong antioxidant properties. Moreover, for the first time in the literature, we demonstrated the possibility of efficiently loading such extract in polymeric nanosheets and the suitability of this nanoplatform as a reactive oxygen species scavenger in human dermal fibroblasts treated with a pro-oxidant insult

Novel Immunoregulatory Functions of IL-18, an Accomplice of TGF-\u3b21

TGF-\u3b21 is a pleiotropic factor exerting a strong regulatory role in several cell types, including immune cells. In NK cells it profoundly alters the surface expression of crucial activating and chemokine receptors. To understand which soluble signals might better contrast these effects, we cultured human NK cells in the presence of TGF-\u3b21 and different innate and adaptive cytokines, generally referred as "immunostimulatory". These included IL-2, IL-15, IL-21, IL-27, and IL-18. Unexpectedly, IL-18 strengthened rather than contrasting important TGF-\u3b21-mediated functions. In particular, IL-18 further reduced the expression of CX\u2083CR1 and NKp30, leading to the virtual abrogation of the triggering capability of this activating receptor. Moreover, IL-18 further increased the expression of CXCR4. The IL-18-mediated additive effect on NKp30 and CXCR4 expression involved transcriptional regulation and activation of MEK/ERK and/or p38MAPK. A proteomic approach quantified both surface and intracellular proteins significantly modified in cytokine-treated NK cells, thus giving global information on the biological processes involving TGF-\u3b21 and IL-18. Our data support the concept that IL-18 may have a different behavior depending on the type of soluble factors characterizing the microenvironment. In a TGF-\u3b21 rich milieu such as tumors, it may contribute to the impairment of both NK cells recruitment and killing capability

A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions

This paper describes a new nuclear imaging agent, 2-(4-isothiocyanatobenzyl) 121,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid of human albumin (HAC), potentially suitable for application in the Radio-guided Occult Lesion Localization (ROLL) of non-palpable mammalian cancerous lesions, as a tool to overtake the short radio-signal half-life of the technetium-99m based radiopharmaceutical currently used. This conjugate is a microsized powder aggregate, water-insoluble between pH 3 and 8.5, obtained by conjugating the protein with the macrocyclic chelating agent DOTA through a one-pot reaction in aqueous medium. The product has been fully characterized and is stable to the thermal conditions adopted for labeling; after radiolabeling with longer half-life radionuclides such as 177 Lu or 111 In, it has shown radiochemical purity (RCP) >90% and resulted stable when stored in saline or plasma for 6 days at 37 \ub0C. A \u3bcPET/CT study, performed in vivo on adult female rats, showed that the radioactivity of HAC labeled with 64 Cu remained located in the mammary glands for at least 40 h, without diffusion or drainage in healthy tissues or in the lymphatic circulation. This new imaging agent might make the ROLL procedure more accessible, safe and flexible, promoting a significant time and cost reduction of this intervention. Moreover, HAC might also be used in other radio-guided surgical procedures in oncology

Sphingomyelin and medullary sponge kidney disease: a biological link identified by omics approach

Background: Molecular biology has recently added new insights into the comprehension of the physiopathology of the medullary sponge kidney disease (MSK), a rare kidney malformation featuring nephrocalcinosis and recurrent renal stones. Pathogenesis and metabolic alterations associated to this disorder have been only partially elucidated.Methods: Plasma and urine samples were collected from 15 MSK patients and 15 controls affected by idiopathic calcium nephrolithiasis (ICN). Plasma metabolomic profile of 7 MSK and 8 ICN patients was performed by liquid chromatography combined with electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Subsequently, we reinterrogated proteomic raw data previously obtained from urinary microvesicles of MSK and ICN focusing on proteins associated with sphingomyelin metabolism. Omics results were validated by ELISA in the entire patients' cohort.Results: Thirteen metabolites were able to discriminate MSK from ICN (7 increased and 6 decreased in MSK vs. ICN). Sphingomyelin reached the top level of discrimination between the two study groups (FC: -1.8, p < 0.001). Ectonucleotide pyrophophatase phosphodiesterase 6 (ENPP6) and osteopontin (SPP1) resulted the most significant deregulated urinary proteins in MSK vs. ICN (p < 0.001). ENPP6 resulted up-regulated also in plasma of MSK by ELISA.Conclusion: Our data revealed a specific high-throughput metabolomics signature of MSK and indicated a pivotal biological role of sphingomyelin in this disease