230582 research outputs found
Sort by
Temporal changes in first-phase ejection fraction during evolution of heart failure with preserved ejection fraction and afterload-induced heart failure in mice
Get PDFThe interplay between systolic and diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) progression is unclear. First-phase ejection fraction (EF1), a sensitive marker of early systolic function, aids in assessing systolic-diastolic relationships in human hypertension and aortic stenosis. This study examines temporal changes in these relationships in mouse models of HFpEF and elevated afterload. Mouse models of abdominal aortic banding (AAB) and HFpEF (induced by hypertension and high fat feeding) underwent comprehensive serial echocardiography. In AAB, EF1 significantly decreased at week 1 post-surgery (18.8 ± 1.2 vs 24.3 ± 0.8%, p<0.001) compared to controls, with further reduction at week 3 (16.8 ± 0.6%) and week 6 (13.9 ± 0.9%, both p<0.001). EF, global longitudinal strain (GLS) and longitudinal strain rate (LSR) remained unchanged until week 3. Isovolumic relaxation time (IVRT) was the only abnormal index of diastolic function at week 1. In the HFpEF model, EF1 significantly decreased at week 2 (19.1 ± 1.1 vs 25.8 ± 1.0%, p<0.001) compared to controls, while EF, GLS, and LSR were unaltered. At week 3, EF1 decreased further (18.1 ± 0.7%) alongside a significant reduction in GLS (p<0.01), while EF and LSR remained unchanged. IVRT increased early in the HFpEF model, followed by later left atrial (LA) enlargement. EF1, an early marker of systolic impairment, decreases early in HFpEF and afterload-induced dysfunction, accompanied by IVRT prolongation. LA dilatation appears later. These findings highlight the interplay between systolic and diastolic dysfunction in HFpEF progression.</p
Impact of adverse life experiences on pain, depression, anxiety, and comorbidities:a youth longitudinal sample
Get PDFAbstract – Introduction: – Exposure to adverse life experiences (ALEs) renders individuals vulnerable to the emergence of pain, depression, and anxiety. It remains unclear to what extent these symptom categories share common ALEs, especially in cases of comorbidity, and how these relationships manifest in developmental trajectories and neural pathways.Objectives: – In this study, we investigated the impact of ALEs, considering their timing, quality, and quantity, as well as structural brain changes, on pain, depression, and anxiety symptoms, and their comorbidity from adolescence to young adulthood.Methods: – We used prospective and retrospective questionnaires and magnetic resonance imaging data from a large European longitudinal cohort (N = 1700) spanning from 14 to 25 years. We conducted Latent-Class-Growth-Analysis for symptom levels of pain, depression, and anxiety, subsequent logistic regressions to explore prediction of ALEs on symptom classes, and mediation analysis to examine the role of insula in this association.Results: – Physical illness unrelated to pain, bullying, and abuse-maltreatment were associated with pain; sexual abuse, bullying, parental violence, and deprivation with depression; bullying and deprivation with anxiety; substance abuse in the household and abuse-maltreatment with pain–depression comorbidity; deprivation with pain–anxiety comorbidity. Smaller insula volume in late adolescence was a significant mediator for the association between deprivation-related ALEs and the pain–anxiety, but not the pain–depression comorbidity.Conclusion: – Together, although various and mainly different types of ALEs strongly impact pain, depression, and anxiety symptoms and their comorbidity, insula volume impacts are specific for pain–anxiety comorbidity. These findings may inform early screening and prevention for individuals affected by ALEs.</p
The use of virtual reality (VR) for managing complex upper limb rehabilitation: A scoping review
Get PDFUpper limb injuries frequently lead to significant post-operative complications such as disability, anxiety, and depression, imposing a substantial burden on healthcare systems. Traditional rehabilitation methods, while somewhat effective, often fail to meet the complex needs of these patients. Recent developments in Virtual Reality (VR) offer an innovative alternative, enabling immersive and personalized treatment that may improve rehabilitation outcomes.This scoping review aimed to explore the efficacy, safety, feasibility, and patient engagement of VR-based interventions in upper limb rehabilitation. Following Joanna Briggs Institute (JBI) guidelines, a comprehensive search was conducted across databases including Medline, Embase, CINAHL, and the Cochrane Library, with additional grey literature from Scopus and Web of Science. Studies included involved adults aged 18 or older who had undergone upper limb surgery and participated in VR rehabilitation programs.Fourteen studies (n=171 total participants across primary studies, plus 3 evidence syntheses) met inclusion criteria. The evidence reveals promising signals: five primary studies demonstrated range of motion improvements of 10-25%, while four studies reported clinically meaningful pain reduction (VAS decreases of 2-3 points). However, implementation challenges emerged: three studies documented cybersickness in 15-20% of participants, and two studies reported physical discomfort from headset equipment in approximately 25% of users. Critical research gaps included the absence of qualitative studies examining patient experiences, limited long-term follow-up data, and lack of standardized protocols across interventions. Additionally, the high cost of VR technologies raises concerns about equitable access and potential disparities in care.In conclusion, VR holds promise for improving upper limb rehabilitation outcomes. Future research should prioritize accessibility, equity, and holistic evaluation to ensure VR is effectively integrated into rehabilitation settings.<br/
CAR-mediated release of IL-10 increases the function of regulatory T cells:relevance for future clinical application
No full textRegulatory T cell (Treg) therapy emerges for various indications associated with a breakdown of immune tolerance. Antigen-specific CAR-Tregs are frontrunners for transplantation and auto-immune diseases and are currently clinically evaluated. We aimed to link CAR antigen-engagement with immunosuppressive cargo release into the local microenvironment to boost efficacy and reduce side effects. We used our HLA-A*02 CAR and immunosuppressive IL-10 as model components to generate human CAR-Tregs that release IL-10 upon CAR-engagement. They were compared to CAR-Tregs with constitutive or no IL-10 expression by evaluating phenotypes, antigen-specific IL-10 release, and suppression of effector cell proliferation in vitro and performance in vivo in a humanised xeno-GvHD model. We demonstrated successful multi-construct engineering of CAR-Tregs, which released upon CAR-engagement 2.5-fold more IL-10 than CAR-Tregs lacking the corresponding antigen-specific IL-10 secretion module. Neither phenotype nor function was affected by expressing this module. In the xeno-GvHD model, we showed the beneficial effect of IL-10 release, particularly evident when compared to constitutive IL-10 expression that impaired CAR-Treg efficacy. We provide first proof-of-principle for engineering human CAR-Tregs to release an immunosuppressive cytokine upon CAR-engagement. This approach will both enhance the potency of CAR-Tregs at the intended target sites and limit their off-target effects.</p
Divergent paths of political trust in Southern Europe:the roles of economic performance, corruption, congruence, and polarisation
Get PDFThis study examines long-term patterns of political trust in Southern Europe through a comparison of Greece, Portugal, and Spain— countries that led the third wave of democratisation. Drawing on data from 45 Eurobarometer surveys (1997–2022), it tests four explanations of political trust: macroeconomic performance, corruption, ideological congruence, and party-system polarisation. The analysis highlights the varying importance of these factors across countries. Economic performance and political polarisation consistently influence trust, while corruption is a significant factor in Greece and Spain. Ideological congruence shows no substantial effect, except in Portugal. The study demonstrates that countries exposed to a common systemic shock may nonetheless develop divergent trajectories of political trust, shaped by the interaction of economic and political conditions.<br/
Association between HbA1c chairside values and periodontitis
No full textDiabetes and prediabetes cases are steadily increasing worldwide every year. Screening and early detection are crucial to reduce complications and the related costs for its treatment to the healthcare services. Therefore, the aim of this cross-sectional study was to investigate the potential associations between HbA1c measured chairside and periodontitis and to assess the usefulness of a chairside test for diabetes screening in a dental setting. Data were collected from 911 patients participating in an Oral, Dental and Craniofacial Biobank at King's College London (United Kingdom). Self-reported medical and dental history were taken. HbA1c test was carried out chairside and associated with periodontal clinical data. From a total of 911 patients, 6.0 % were periodontally healthy, 11.3 % had gingivitis and 82.7 % had periodontitis stage I to IV. A total of 104 self-reported a diagnosis of diabetes type II. The mean HbA1c value was 5.71 ± 0.94 %. Excluding self-reported diabetics, 227 (28.7 %) were in the pre-diabetes range (HbA1c between 5.7–6.3 %) and 58 (7.3 %) were in the ‘diabetes range’. The HbA1c levels increased from diagnosis of periodontal health (5.43 ± 0.51 %), gingivitis (5.51 ± 0.91 %) and periodontitis (5.76 ± 0.97 %) (p = 0.004). Adjusted linear regression showed a significant association between age and HbA1c (p < 0.001), with a border-line association for periodontal diagnosis (p = 0.054). Age showed similar findings after excluding self-reported diabetics (p < 0.001). Logistic regression (HbA1c <5.7 % vs. ≥5.7 %) confirmed significant associations with age (p < 0.001) and BMI (p = 0.038), while periodontal diagnosis was not statistically significant (p = 0.070). Periodontitis showed a border-line association with higher levels of HbA1c after adjusted analysis. Around a third of patients seen in this secondary care dental setting were found to have HbA1c in the diabetes or pre-diabetes range while they were not aware about their diabetic status, confirming that the dental visit could be an important opportunity for early detection of undiagnosed hyperglycaemia.</p
Clinician’s Experience of Working with an Intensive Outpatient Programme for Child and Adolescent Eating Disorders—A Reflexive Thematic Analysis
Get PDFAlthough intensive outpatient programmes (IOPs) are becoming more prevalent, the evidence base, particularly within the UK, remains limited. Given clinicians’ central role in developing, delivering, and adapting these emerging models of care, their perspectives are essential to understanding how IOPs function in practice. This study therefore aims to address a significant gap in the literature by exploring clinicians’ experiences of working with an IOP and the strengths and opportunities arising from this. Fifteen experienced clinicians participated in individual semi-structured interviews after working with the IOP. Open-ended questions guided the discussions, which were recorded and transcribed verbatim. Data were analysed using the six stages of reflexive thematic analysis. The analysis generated three key themes: (1) Tri-directional Collaboration, (2) Creating Space for Change, and (3) Transitions as Turning Points. Clinicians felt that the IOP provided a structure that strengthened and reinforced the therapeutic alliance between parents and clinicians, helped arrest rapid deterioration, and created space for thoughtful planning. Embedding IOPs within stepped-care frameworks may offer an effective and scalable means of expanding system capacity while delivering enhanced, flexible support during periods of heightened risk. However, longitudinal, mixed-methods evaluations are needed to clarify the sustainability of progress post-IOP and to identify predictors of positive transitions
The 2024 Brain Tumor Segmentation Challenge Meningioma Radiotherapy (BraTS-MEN-RT) dataset
Get PDFMeningiomas are the most common primary intracranial tumors, frequently requiring radiotherapy as a part of management. Effective radiotherapy planning for meningiomas necessitates accurate and consistent segmentation of target volumes on MRI, a process that is complex, labor-intensive, and dependent on expert expertise. The 2024 Brain Tumor Segmentation Challenge Meningioma Radiotherapy (BraTS-MEN-RT) Dataset addresses this problem by providing the largest multi-institutional collection of systematically annotated radiotherapy planning MRIs for meningiomas. Publicly accessible, this dataset comprises 570 radiotherapy planning 3D T1-weighted post-contrast MRIs at native resolutions, with 500 cases featuring expert-annotated gross tumor volumes (GTV). Annotations follow standardized radiotherapy planning protocols and include both intact and postoperative meningioma cases, ensuring wide clinical relevance. Contributions from seven diverse medical centers across the United States and the United Kingdom enhance the dataset's generalizability. The dataset aims to accelerate the development of automated segmentation methods for radiotherapy planning, improving workflow efficiency, reducing interobserver variability, and ultimately enhancing patient outcomes.</p