Risultati per: Scoperto il gene che può rallentare l’invecchiamento

Nei test efficace contro infezioni resistenti

È la Monarda didyma. Ricerca dell’Università di Padova

Objectives
Women diagnosed with BRCA1/2 mutations face significantly elevated lifetime risks of breast and ovarian cancer. Due to the distinctive biopsychosocial implications of a BRCA diagnosis, the care trajectory for these women is highly personalised, yet their care needs frequently remain unmet. The aim was to provide a first overview of the evidence of women’s experiences with person-centred care (PCC) within BRCA care and their needs for further PCC implementation.

Design
A scoping review, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, was conducted.

Data sources
Medline, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, CINAHL Plus and Google Scholar were searched for literature published between January 2004 and February 2024.

Eligibility criteria
Peer-reviewed, primary studies on BRCA and PCC using quantitative, qualitative and mixed-methods designs were eligible. The criteria were iteratively refined to include publications based on samples that were >80% female and >80% BRCA positive.

Data extraction and synthesis
Titles and abstracts were screened with ASReview, a validated AI-driven tool. Data on PCC evidence and needs were extracted based on the eight Picker Principles of PCC and synthesised by describing themes within each principle.

Results
Of the 3801 articles identified as potentially relevant, 18 were included in the review. PCC needs were more prevalent than evidence of their implementation. Most of women’s positive experiences with PCC focused on ‘clear information, communication and support for self-care’, while limited to no evidence existed for other principles. The highest needs were found for increased ‘emotional support, empathy and respect’, ‘attention to physical and environmental needs’, and ‘clear information, communication and support for self-care’. All articles reported demands for more holistic, yet personalised care, though PCC was not mentioned explicitly.

Conclusions
This review suggests a person-centred approach is relevant to improving the standard of BRCA care for women. The first evidence of women’s experiences with PCC demonstrates how care delivered with sensitivity and respect for individual backgrounds can support women throughout their BRCA trajectory. Yet, substantial unmet needs remain among female BRCA carriers, highlighting the importance of further research and PCC implementation to enhance the quality of postdiagnostic care.

Studio italiano, la chiave è in una particolare trasformazione delle cellule

Introduction
The standard first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC) is chemotherapy combined with immunotherapy. However, owing to the immune microenvironment imbalance and immune status impairment caused by repeated chemotherapy, as well as the primary or secondary resistance to immune checkpoint inhibitors, the efficacy of immunotherapy combined with chemotherapy remains unsatisfactory. Recent studies have shown that faecal microbiota transplantation (FMT) can modulate the intestinal microflora, influence the tumour immune microenvironment and even enhance the efficacy of immunotherapy. Hence, we conduct such a prospective, exploratory study to evaluate the efficacy and safety of integrating FMT with standard first-line treatment in patients with driver-gene negative advanced NSCLC.

Methods and analysis
FMT-JSNO-02 (NCT06403111) is a prospective, multicentre, single-arm exploratory study. It is planned to include 62 cases of previously untreated driver-gene negative, Eastern Cooperative Oncology Group Performance Status 0–1, programmed death ligand 1

La pneumologa Dagmar Rinnenburger: “L’aspirazione per evitare infezione da ingestione”

Massimo impatto da fumo e attività fisica, ma pesa anche il reddito

Studio prende in esame un campione di oltre 300 donne

New England Journal of Medicine, Ahead of Print.

Stroke, Volume 56, Issue Suppl_1, Page ATP377-ATP377, February 1, 2025. Introduction:Intracranial aneurysms (IAs) are weak outpouchings on cerebral vessels that can rupture, causing subarachnoid hemorrhage. Timely and accurate risk stratification of IAs is paramount.Objective:Aneurysm wall enhancement (AWE) is a potential imaging biomarker for risk stratification. We propose to combine this with whole blood RNA sequencing to improve IA risk stratification.Methods:We retrospectively collected images and blood of patients who had undergone vessel wall imaging. We performed RNA sequencing and radiomics analysis on the IA sacs on pre- and post-contrast T1 MRI scans. Using univariate analysis, we selected significantly different radiomic features (RFs). We removed all collinear features, and pooled radiomic and expression features. We classified each IA as symptomatic or asymptomatic based on symptoms at presentation. We then built separate machine learning models: one based solely on the radiomics features and another with combined features. We performed principal component analysis (PCA) and a leave-one-out (LOO) cross validation to quantify models’ performances.Results:Our final cohort consisted of 7 patients. We found 34 significantly different RFs between symptomatic and asymptomatic IAs. The final feature set consisted of 9 RFs and 6 genes. PCA of whole dataset using the RFs alone reflected variances of 38% and 29% on the best principal components. We trained a random forest model using LOO cross validation and observed an accuracy of 57.1% (33.3% sensitivity, 75% specificity). With the addition of the gene expression features, we found the PCA explained variance to be 41% and 26%. The LOO accuracy improved to 85.7% (66.6% sensitivity, 100% specificity).Conclusion:In this study, we demonstrated that radiomics from the aneurysm wall alone have a low predictive value in identifying symptomatic IAs. However, adding gene expression levels improves the predictive value. Future work will be aimed at adding more cases.

Stroke, Volume 56, Issue Suppl_1, Page A78-A78, February 1, 2025. Introduction:Intracranial aneurysm (IA), a cerebrovascular disease affecting 3-5% of US population, leads to subarachnoid hemorrage. A non-invasive diagnostic to identify those with an IA could facilitate more widespread screening and better disease management.Objective:We have designed a PCR-based diagnostic assay for IA, AneuScreenTM, that is comprised of a previously-published 50-gene panel. This project aimed to further develop the assay’s predictive model in a large cohort and its predictive power in independent cases.Methods:Before testing, the assay underwent rigorous standardization to test signal strength, dynamic range and linearity, and variation across replicates. Blood from consenting individuals with/without IA (angiogram confirmed) were collected under IRB approval from University at Buffalo, University of Pennsylvania, and University of South Florida. One mL of blood was collected into DxTerity RNA-stabilizing blood tube. After running each sample on the assay and standardizing data, gene expression levels of all 50 genes (as well as gene ratios and patient data) were used for support vector machine (SVM) model development in 85% of the data. Top 50 features selected by statistical filtering and ranking were used in nested loops to maximize training performance. Optimal model was validated in remaining 15% of samples.Results:We enrolled 497 individuals (276 had IAs). In training, 12 features were most important. The final SVM model performed well in testing set without showing evidence of overfitting, achieving an AUC of 0.74. In independent validation set, the model reached an AUC of 0.80 (Fig. 1A and B).Conclusion:SVM model developed using expression data from AneuScreenTMin a large cohort of individuals with and without IA was able to predict IA cases with an AUC of 0.80. This demonstrates the potential of using circulating blood to screen for IA presence. Additional testing is required to finetune model and improve accuracy.

Stroke, Volume 56, Issue Suppl_1, Page AWP67-AWP67, February 1, 2025. Introduction:Senescent cells accumulate with advancing age, and exposure to cellular stressors, such as oxidative and inflammatory molecules, which can be circulating in blood. Senescent endothelial cells have altered cellular functions that may influence stroke outcomes. Studying senescence might reveal improved strategies to improve vascular health and prevent stroke or better outcomes.Hypothesis:Acute ischemic stroke patients with enriched senescence gene set expression have worse 90-day stroke outcomes.Methods:In 225 patients with acute ischemic stroke, RNA was isolated from whole blood and transcriptome measured by microarray. Enrichment of senescence genes was assessed using the SenMayo gene set in Gene Set Enrichment Analysis (GSEA). The relationship between the SenMayo senescence score and patients’ 90-day modified Rankin scale (mRS) outcome was determined.Results:SenMayo senescence genes are enriched (p=0.05) in circulation of patients of acute ischemic stroke with bad outcome (90 day mRS >2) and not in patients with good outcomes (90 day mRS≤2) (fig.1). This suggests a role for senescent cells in the pathophysiology of stroke or as a contributing factor to the failure of the patient’s full recovery.Conclusion:In acute ischemic stroke patients, increased senescence gene expression is associated with worse stroke outcome. Further evaluation is needed to determine whether targeting senescence could be a strategy to improve outcome in stroke.

Stroke, Volume 56, Issue Suppl_1, Page ADP56-ADP56, February 1, 2025. Introduction:We discovered a marked upregulation of MMP-12 levels in the brain following an ischemic stroke and demonstrated that reducing MMP-12 levels in otherwise healthy rodents decreases brain damage and facilitates functional recovery. This study aimed to assess the effectiveness of MMP-12 gene silencing in improving sensorimotor function recovery in aged mice and hypertensive rats.Methods:Both male and female C57BL/6 mice (≥16 months old) and male spontaneously hypertensive rats (SHRs) (2-3 months old) were subjected to 35-min and 1-h transient right middle cerebral artery occlusion (MCAO), respectively. Appropriate cohorts of animals (25 mice/group; 18 rats/group) received either control shRNA or MMP-12 shRNA plasmids (1 mg/kg) formulated as nanoparticles that were administered intravenously via tail vein 2 h after reperfusion. In mice, stroke symptoms were evaluated using the neurological deficit score at 2-4 hours and 1 day after reperfusion, while the modified neurological severity score was used in rats. Sensorimotor functions were assessed using the sticky tape test, pole test, and rotarod test at baseline (before MCAO) and at regular intervals post-MCAO (days 3, 5, and 7 in mice, and days 1, 3, 5, 7, and 14 in rats).Results:MMP-12 expression in the ischemic brain was significantly increased by 35-min MCAO in aged mice and 1-h MCAO in SHRs, as was previously observed in healthy young mice and rats that were subjected to 1-h and 2-h MCAO, respectively. In comparison to the control shRNA treatment, MMP-12 shRNA treatment facilitated a greater mean recovery of somatosensory function in aged mice (sticky tape latency was significant on day 3 and day 5; sticky tape interaction was significant on day 5) and in SHRs (sticky tape ratio was significant on day 14). Furthermore, MMP-12 shRNA treatment resulted in a greater mean recovery of motor function across all tested time points in aged mice (pole descent score was significant on day 7; rotarod latency was significant on day 7) and in SHRs (rotarod latency was significant on day 5 and day 14).Conclusions:Reducing MMP-12 expression in the ischemic brain facilitates the recovery of both somatosensory and motor function in aged mice and hypertensive rats after transient focal cerebral ischemia. Our findings further reinforce the potential benefits of MMP-12 gene silencing as a therapeutic approach for improving recovery outcomes in stroke patients.

New England Journal of Medicine, Volume 392, Issue 4, Page 412-414, January 23, 2025.