IRIS UniSR (’Università Vita-Salute San Raffaele)
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Clinical management and therapeutic optimization of patients with heart failure with reduced ejection fraction and low blood pressure. A clinical consensus statement of the Heart Failure Association (HFA) of the ESC
No full textDespite major advancements in heart failure (HF) management and guideline recommendations over the past two decades, real-world evidence highlights suboptimal implementation of guideline-directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF). Low blood pressure (BP) is common in HFrEF patients and represents a major perceived barrier to implementing life-saving treatments in clinical practice, as physicians are often concerned about symptomatic hypotension and its consequences. Although low BP can be seen in those hospitalized with signs of shock, the most common scenario involves non-severe, asymptomatic hypotension in patients receiving foundational therapy for HFrEF, where premature down-titration or discontinuation of GDMT should be avoided. This clinical consensus statement provides a comprehensive overview of low BP in HFrEF, including its definition, risk factors, and effects of HF therapies on BP. We propose management pathways to optimize HFrEF treatment in the context of low BP, ultimately aiming to improve patient outcomes
MRI protocols and sequences for amyloid-related imaging abnormalities monitoring in Alzheimer’s disease patients treated with monoclonal antibodies
No full textImprints of somatic hypermutation on B-cell receptor immunoglobulins post-infection versus post-vaccination against SARS-CoV-2
Full text linkPublished evidence supports significant heterogeneity of immune responses among individuals infected with or vaccinated against SARS-CoV-2. This highlights the need for in-depth investigation of the implicated processes toward refined understanding and improved management of COVID-19. The main objective of the present study was to investigate the dynamics of B cell responses to SARS-CoV-2, focusing on how initial infection and subsequent vaccination influence the immunoglobulin gene repertoire, with special emphasis on the impact of somatic hypermutation (SHM) on antibody maturation. Samples were collected from 81 individuals infected by SARS-CoV-2 in the municipality of Vo' during the first pandemic wave in 2020. For 25 of them, sampling was repeated 7 d after completing the primary vaccination series. Deep immunogenetic analysis of the B-cell receptor immunoglobulin (BcR IG) gene repertoire was performed using targeted next-generation sequencing. Bioinformatics analysis focused on repertoire metrics, prediction of IG antigen specificity, and detailed profiling of the SHM patterns. Significant expansions of unmutated sequences early post-infection suggest extrafollicular B cell maturation. In contrast, vaccination promoted SHM acquisition, indicating a germinal center–dependent response, and pronounced repertoire renewal. Restricted SHMs in SARS-homologous clonotypes along with preferential targeting of specific codons within the VH domain post-vaccination support ongoing affinity maturation within germinal centers. Differences in the BcR IG profiles post-infection versus post-vaccination allude to distinct trajectories in B cell maturation. Distinct profiles of SHM targeting reflect ongoing affinity maturation post-vaccination, with implications for optimizing preventive and therapeutic interventions against COVID-19
Nietzsche. Settantacinque anni dopo Benn
No full textThe article is about the essay written by Benn fifty years after Nietzsche’s death. In particular, it seeks to answer again the three main questions posed by Benn: where Nietzsche’s thought has become obsolescent; the relationship between Nietzsche and his contemporaries; Nietzsche and his illness
Animals among Public Reason, Justice, and Rights. A Review of Recent Philosophical Debate
No full textThis paper examines the recent research in political philosophy about animals and state policies. Moreover, it assesses the recent literature about the potentialities of public reason liberalism for justifying coercive policies before animals. After highlighting the main features of public justification, it collects two emerging trends for animal politics: the political turn in animal ethics and the inquiries into the interweave of science and public reason liberalism. Three attitudes about the usefulness of public justification before animals’ predicaments are assessed: scholars who enthusiastically embrace public justification, scholars who reject this procedure for the issue of animals, and scholars who adjust public justification to the specificities of our duties to animals. Last, future pathways will be explored
T cell-derived IFN-γ Suppresses T Follicular Helper Cell Differentiation and Antibody Responses
No full text: CD4 + T cells play a critical role in antiviral humoral and cellular immune responses. We have previously reported that subcutaneous lymphocytic choriomeningitis virus (s.c. LCMV) infection is characterized by a stark compartmentalization of CD4 + T cells, leading to strong T H 1 polarization but virtually absent T follicular helper (T FH ) cells, a key driver of humoral immunity. Here, we investigated the mechanisms responsible for this impaired T FH differentiation. We found that T-bet + cells induced by s.c. LCMV infection encompass a T H 1 subset expressing Granzyme-B (GzmB) and a Tcf-1 + subset that retains the potential for T FH differentiation without expressing mature T FH markers. Interestingly, IFN-γ blockade enables full differentiation of Tcf-1 + cells into T FH , formation of germinal centers and increased antibody production. Of note, the suppression of T FH cells by IFN-γ is not directly mediated through CD4 + T cells but rather involves another cell type, likely dendritic cells (DCs). Our study provides novel insights into the mechanisms directing early CD4 + T cell polarization and affecting humoral responses to viruses, laying a foundation for the development of effective vaccine strategies
Imaging, genetic and biomarkers characterization of arrhythmic mitral valve prolapse
No full textAssociation between genotype and phenotype in mitral valve prolapse patients and their impact on arrhythmic outcomesAssociation between genotype and phenotype in mitral valve prolapse patients and their impact on arrhythmic outcome
Enhancing the Efficacy of Melanoma Treatment: The In Vitro Chemosensitising Impact of Vipera ammodytes Venom on Human Melanoma Cell Lines
No full textResearch on viper venom has expanded into diverse medical applications, including cancer treatment. This study investigates the potential of Vipera ammodytes venom in oncology, evaluating its cytotoxicity and chemosensitising effects on malignant melanoma cells. Proteomic analysis identified 125 proteins in the venom, with Phospholipases A2, C-type lectins, and metalloproteinases among the most abundant components. These proteins are associated with cytotoxic, anti-proliferative, and tumor-inhibiting properties. Three melanoma cell lines (M001, Me501, and A375) were used to assess venom cytotoxicity. The IC50 values demonstrated consistent venom sensitivity across cell lines (approximately 1.1 μg/mL). Combined treatment with venom and cisplatin significantly increased the cytotoxicity compared to single-agent treatments. Notably, venom enhanced the sensitivity of cisplatin in resistant cell lines (M001 and Me501), increasing cell mortality by up to 40%. The A375 cell line, inherently more sensitive to cisplatin, exhibited additional cytotoxic effects only at higher venom doses. The morphological changes observed under microscopy confirmed venom-induced cellular changes, further supporting its potential as an anti-cancer agent. The selective targeting of melanoma cells by venom components, particularly in muscle-associated metastases, suggests a unique therapeutic niche. While cisplatin was chosen for this pilot study due to its established cytotoxicity, future research will explore venom combinations with contemporary treatments such as immunotherapy and targeted therapies. Although preliminary, these findings provide a foundation for integrating venom-based strategies into advanced melanoma protocols, aiming to improve outcomes in resistant or metastatic cases
Nursing staffing and skill mix in nursing homes in Italy: An observational cross-sectional study
No full textIntroduction/Objective: The relationship between staffing levels and skill mix in nursing homes is poorly documented in Italy. This study aimed to investigate nursing staffing levels and skill mix in Northern Italian nursing homes. Methods: A cross-sectional observational study was conducted using a questionnaire sent to several nursing homes. Results: Twenty-three nursing homes participated. Data were collected on organizational models, daily hours of support staff, and daily hours of care per resident, categorized by professional profile. The predominant models were "by sector or modular" and "Team nursing". Daily hours of nursing care were minimal; in most nursing homes, daily hours of support staff exceed those of nurses and healthcare assistants. Total daily hours of care per resident were 2.75, below international and recommended standards. Discussion: Organizational settings can be improved by adjusting staffing, particularly by rebalancing the ratio of nursing to support staff, to improve outcomes and prevent missed care. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies
The HTT gene influences plasma neurofilament light chain and brain metabolism in prodromal Alzheimer’s disease
No full textObjective: HTT, encoding a protein involved in axonal trafficking, contains a key region of CAG repeats. When expanded beyond 39 repeats, this region leads to Huntington's disease (HD). However, several studies have suggested that increasing the number of CAG repeats below the pathological threshold may confer functional advantages by enhancing HTT activity. In the present study, we aim to investigate the association between CAG repeat length below the pathological threshold and neurodegeneration biomarkers in prodromal Alzheimer's disease (AD). Methods: Ninety-five patients (36 with SCD and 59 with MCI) underwent blood collection for NfL measurement and HTT genetic analysis. Cerebrospinal fluid was collected for the measurement of Aβ42, Aβ40, total tau, and phosphorylated tau, and/or amyloid PET imaging was performed. Thirty-nine patients who were positive for both Aβ and phosphorylated tau biomarkers were classified as "A+/T+", while 56 patients who were either negative for both markers or positive for only one were classified as "isolated Aβ/non-AD." Results: In the A+/T+ group, quadratic models described the association between CAG repeat length with NfL concentrations and 18F-FDG uptake. In particular, a concave curve was observed in the medial and middle frontal gyri, while a convex curve was found in the parahippocampal and fusiform gyri. Interpretation: Among individuals with SCD and MCI who show evidence of AD pathology, CAG repeat length in the HTT gene below the HD pathological threshold is associated with biomarkers of neurodegeneration in a region-specific and U-shaped manner. These findings suggest a modulatory role of HTT in prodromal AD