IRIS UniSR (’Università Vita-Salute San Raffaele)
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The Experts, the Virtuous and the Wounded. Who Should Take Part in an «Ideal Conversation»?
No full textElisabetta Lalumera and Sarah Songhorian discuss Philip Kitcher’s Moral Progress. Lalumera focuses on the notion of «ideal conversation» as central to Kitcher’s democratic contractualism, raising concerns about the criteria for inclusion, the role of expertise, and the tension between inclusivity and the requirement for virtuous participants. Songhorian explores the interplay between individual and social dimensions of moral progress, highlighting Kitcher’s rejection of teleological or discovery-based conceptions in favor of a pragmatic, problem-solving approach
Systematic Review of Clinical Utility of Multimodal Imaging in Noninfectious Posterior Uveitis: MUV Project Report 3
No full textTopic: The clinical utility of multimodal imaging for diagnosis and management of non-infectious posterior uveitis. Relevance: Advances in multimodal imaging support amendment of the imaging strategies in the authoritative classification criteria published by the Standards of Uveitis Nomenclature II in 2021. Methods: Peer-reviewed electronic search in OVID MEDLINE, Embase, Cochrane, Scopus, last accessed August 6, 2024. Medical literature published from January 1, 2018, to July 12, 2024, for the primary analysis and from 2012-2017 inclusive for the secondary analysis. Independent reviewers extracted data using the Covidence Systematic Review Tool and assessed quality and bias with the Mixed Methods Assessment Tool, followed by a consensus process. Statements of imaging findings and clinical utility were tabulated. Main outcome measures were: (1) factual imaging findings for acute posterior multifocal placoid pigment epitheliopathy (APMPPE), birdshot chorioretinitis, multifocal choroiditis, punctate inner choroidopathy, multifocal evanescent white dot syndrome (MEWDS) and serpiginous choroiditis. Imaging modalities included color fundus (CFP), autofluorescence (FAF), OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA) and OCT angiography; (2) subjective or objective statements of clinical utility for diagnosis, detection of activity, monitoring, or detection of complications. The level of evidence was evaluated using the GRADE process. Results: 70 studies from 2018-2024 met inclusion criteria and quality standards for study type. Combined with 63 foundational studies from 2012-2017, there were 292 specific imaging statements based on imaging examinations of 6537 patients in the primary analysis. There were 124 statements of clinical utility, with OCT or OCTA accounting for 66/124 (53%), plus an additional 29 statements of clinical utility for multimodal imaging (MMI). Evidence was ranked high for OCT on at least one outcome measure for each disease, followed by CFP, FAF, and FA in 4 of 5 diseases (80%), OCTA in 3 of 5 (60%), and ICGA in 1 of 5 (20%). Conclusion: Substantial information exists regarding the imaging findings in noninfectious posterior uveitis. Expert opinions generally favor the clinical utility of MMI. Additional research with efficient imaging strategies and objective outcome measures is warranted. Revision of current classification guidelines should be considered. Other: Protocol registration CRD42024576867 with PROSPERO (https://crd.york.ac.uk/prospero/)
A Core Outcome Set for Clinical Studies on Chronic Venous Disease Involving the Deep Veins
No full textObjective: Chronic venous disease (CVD) is a debilitating disease that results in significant morbidity and costs. A lack of standardised outcome reporting has made it difficult to evaluate the impact of interventions for CVD involving the deep veins. This study aimed to develop a core outcome set (COS) for studies evaluating interventions for this subset of CVD. Methods: The COS was developed using the Core Outcome Measures in Effectiveness Trials (COMET) methodology. A systematic review and interviews with 19 patients experiencing post-thrombotic syndrome after deep vein thrombosis generated a longlist of outcomes, which was then refined by a steering group. Each outcome was rated on importance by patients and healthcare practitioners using a 9 point Likert scale within a Delphi survey. Outcomes not meeting consensus criteria in the first round were re-prioritised in a second round. Outcomes meeting the criteria for being critically important were discussed in a final meeting between patients and international experts to develop the COS. Results: The review and interviews generated 80 outcomes, which entered the Delphi process. In total, 233 stakeholders responded in the first round and 143 in the second round. Consensus was reached on 29 outcomes deemed critically important. These outcomes were discussed in the final meeting to yield seven general outcomes and six procedure specific outcomes, since some outcomes were not relevant to all patients with CVD. The general outcomes were death, lower limb ulceration, venous thromboembolism, bleeding, quality of life, limb pain, and oedema or limb swelling. The procedure specific outcomes were device migration, device mechanical failure, patency, technical and/or procedural success, re-intervention, and vascular complications. Conclusion: A COS was developed for studies evaluating interventions for CVD involving the deep veins, comprising seven general outcomes and six procedure specific outcomes. Reporting these outcomes will promote comparison of interventions for CVD involving the deep veins
Hmgb2 improves astrocyte to neuron conversion by increasing the chromatin accessibility of genes associated with neuronal maturation in a proneuronal factor-dependent manner
No full textBackground: Direct conversion of reactive glial cells to neurons is a promising avenue for neuronal replacement therapies after brain injury or neurodegeneration. The overexpression of neurogenic fate determinants in glial cells results in conversion to neurons. For repair purposes, the conversion should ideally be induced in the pathology-induced neuroinflammatory environment. However, very little is known regarding the influence of the injury-induced neuroinflammatory environment and released growth factors on the direct conversion process. Results: We establish a new in vitro culture system of postnatal astrocytes without epidermal growth factor that reflects the direct conversion rate in the injured, neuroinflammatory environment in vivo. We demonstrate that the growth factor combination corresponding to the injured environment defines the ability of glia to be directly converted to neurons. Using this culture system, we show that chromatin structural protein high mobility group box 2 (HMGB2) regulates the direct conversion rate downstream of the growth factor combination. We further demonstrate that Hmgb2 cooperates with neurogenic fate determinants, such as Neurog2, in opening chromatin at the loci of genes regulating neuronal maturation and synapse formation. Consequently, early chromatin rearrangements occur during direct fate conversion and are necessary for full fate conversion. Conclusions: Our data demonstrate novel growth factor-controlled regulation of gene expression during direct fate conversion. This regulation is crucial for proper maturation of induced neurons and could be targeted to improve the repair process
The problems of empathy
No full textWhile empathy has certainly been considered prominent in fostering helping, care, and altruistic behaviour, its dark sides have often been disregarded. This chapter aims to delve into the problems and issues that empathy, as a psychological mechanism enabling us to share others’ emotions, has. Before doing so, one must define what empathy means and contrast it with other related concepts often conflated with it (in §2). Once the definitional issues have been clarified (although certainly not solved), I will focus on how an excess of empathy can lead one to lose herself and to burnout (in §3) and on empathy’s intrinsic limitations (in §4). The former is particularly relevant in healthcare settings, although it is also a general issue, and the latter has to do with the biases and partialities that empathy always incorporates. Finally, I will consider whether regulating empathy can solve its problems (in §5)
Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases
No full text: Duodenal neuroendocrine tumors (Duo-NETs) may arise in the ampullary and non-ampullary duodenum. Non-functioning Duo-NETs (NF-Duo-NETs), which account for most cases, may express various hormones. Previous studies have suggested that hormone production might be associated with biological aggressiveness. Current treatment protocols are based on functionality, tumor size, and location, but small NF-Duo-NETs may also have metastatic potential. We aimed to investigate whether tumor cell subtyping, based on hormone expression, could provide further insights into NF-Duo-NET biological behavior. We analyzed the clinico-pathological correlates of hormone expression in a multicenter series of 151 NF-Duo-NETs, subdividing tumors into five subtypes: gastrin-producing G-cell NETs (Gas-NETs), somatostatin-producing D-cell NETs (Som-NETs), serotonin-producing enterochromaffin-cell NETs (Ser-NETs), plurihormonal NETs, and gastrin-, somatostatin-, and serotonin-negative NETs (GSSN-NETs). Som-NETs were the most frequent (31%), followed by plurihormonal NETs (26%), Gas-NETs (24%), GSSN-NETs (13%), and Ser-NETs (4%). Som-NETs and GSSN-NETs were more commonly located in the ampullary region and showed significantly larger size, more frequent lymphatic and/or vascular invasion, and higher pT, pN, and American Joint Committee on Cancer (AJCC-9th edition) stages compared to Gas-NETs, which were often (77%) diagnosed at AJCC stage I. Ampullary Som-NETs showed a more invasive and metastatic potential compared to non-ampullary Som-NETs, while, among plurihormonal NETs, the predominantly expressed hormone influenced tumor biological features, with gastrin-predominant NETs showing less invasive potential. At logistic regression, both tumor cell subtype and tumor size were independently associated with aggressiveness (pT3, pN1, or pM1 stage at diagnosis). Hormonal expression profiling may be clinically relevant in NF-Duo-NETs, independently of tumor size
Correction: Apache is a neuronal player in autophagy required for retrograde axonal transport of autophagosomes (Cellular and Molecular Life Sciences, (2024), 81, 1, (416), 10.1007/s00018-024-05441-7)
No full textVitamin D and hip protectors in osteosarcopenia: a combined hip fracture preventing approach
No full textOsteosarcopenia is an emerging clinical condition highly prevalent in the older people. Affected subjects due to their intrinsic skeletal fragility and propensity to falls are at elevated risk of hip fractures which can increase morbidity and mortality. Strategies for attenuating the impact of predisposing factors on hip fractures are not yet well defined and should derive from multidisciplinary care and collaborations. Our aim was to narratively review available data on the preventive role of vitamin D and hip protectors on hip fractures in older patients with sarcopenia. Older subjects are at high risk of vitamin D deficiency and of falls due to several concomitant factors besides osteosarcopenia. Vitamin D protective actions against hip fractures may be mediated by both skeletal (increased mineralization) and extra-skeletal (reduced risk of falls) actions. Hip protectors may act downstream attenuating the effects of falls although their use is still not yet enough widespread due to the suboptimal compliance obtained by traditional hard devices. Concomitant use of vitamin D and hip protectors may represent an effective strategy in the prevention of hip fractures which need to be tested in ad hoc designed clinical trials
Attribution of colorectal cancer symptoms to medications for pre-existing chronic conditions: a secondary analysis of a vignette study in England
No full textObjective: To investigate the likelihood of attributing colorectal cancer (CRC) symptoms to medications for chronic conditions. Methods: The online vignette survey included 1287 participants aged ≥50 years, with quota sampling to recruit sufficient participants with type 2 diabetes. Participants self-reported chronic conditions and answered questions on symptom attribution and help-seeking, after reading vignettes describing new-onset rectal bleeding or change in bowel habit. Using multivariable logistic regression, we analyzed the association between specific conditions and attributing new-onset CRC symptoms to medications, controlling for demographics. Results: Among participants, 25% reported type 2 diabetes, 31% being overweight, 25% hypertension and 22% arthritis. Participants with diabetes, versus those without, had a higher likelihood of attributing change in bowel habit to medications [7% vs 3%; adjusted Odds Ratio (aOR) 2.55, Confidence Interval (95% CI) 1.30-5.00]. This was also the case for participants reporting being overweight (7% vs 2%; aOR 2.36, 95% CI 1.25-4.44), arthritis (8% vs 3%; aOR 2.27, 95% CI 1.19-4.35), but not for hypertension. No significant association was found regarding attribution of rectal bleeding to medications. Conclusions: Patients with common chronic conditions have a higher likelihood of attributing change in bowel habit to medications. Tailored information is needed for these patients, encouraging them to discuss any new symptom with their doctor
Altering the biophysical properties of ERC1/ELKS-driven condensates interferes with cell motility.
No full textCell migration is orchestrated by molecular networks supporting motility. The scaffolds ERC1/ELKS and Liprin-α1 sustain cell migration and invasion by assembling dynamic plasma membrane-associated platforms. ERC1/ELKS forms cytoplasmic condensates with liquid–like behavior. In this study we tested whether the ability of ERC1 to form condensates is relevant to its function in cell motility. We identified the shortest N-terminal region of ERC1 sufficient to drive phase separation in vitro and in cells. Fluorescence recovery after photobleaching confirmed the dynamic behavior of ERC1(1-244) condensates. Surprisingly, deletion of ERC1(1-244) including an intrinsically disordered region did not abolish the ability of ERC1DΔN to form condensates. Although the interactions of ERC1ΔN with partners were unaffected, the biophysical properties of ERC1ΔN condensates were altered, with consequences on cell motility. These findings highlight the importance of ERC1/ELKS to assemble functional networks, and show that altering the properties of ERC1–driven condensates interferes with tumor cell motility