Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction.

Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.

Definitions matter: Multicenter investigation of incidence and outcome of poor graft function after hematopoietic cell transplantation.

Despite advances in allogeneic hematopoietic cell transplantation (HCT), poor graft function (PGF) remains an important complication with substantial morbidity and mortality. The investigation of preventive and therapeutic PGF treatments is hindered by inconsistencies in reported incidence and outcomes across studies, which may be explained by heterogeneity in PGF definition. To assess the impact of definition heterogeneity, we conducted a multicenter study, analyzing over 35.

Different dynamics of soluble inflammatory mediators after clearance of respiratory SARS-CoV-2 versus blood-borne hepatitis C virus infections.

Viral infections can be acute or chronic, with the immune system pivotal in immunopathogenesis. The potential reversibility of inflammation post-viral elimination is of current interest. This study compares the dynamics of soluble inflammatory mediators (SIM) during and after respiratory infections with SARS-CoV-2 and blood-borne acute and chronic hepatitis C virus (HCV) infections.

Agreement of in-ear temperature to core body temperature measures during invasive whole-body cooling for hypothermic circulatory arrest in aortic arch surgery.

Targeted temperature management (TTM) with therapeutic hypothermia (TH) during aortic arch surgery requires valid estimations of core body temperature. The ear canal and epitympanic region might be an easy-to-assess, noninvasive site for the read-out of supra-aortic, cerebral temperature. This observational cohort study comparatively investigated in-ear temperature and different core body temperature (cBT) measurements during TTM/TH for moderate hypothermic circulatory arrest (mHCA) in aortic arch surgery.

Exploring the cognitive effects of hearing loss in adult rats: Implications for visuospatial attention, social behavior, and prefrontal neural activity.

Age-related hearing loss in humans has been associated with cognitive decline, though the underlying mechanisms remain unknown. We investigated the long-term effects of hearing loss on attention, impulse control, social interaction, and neural activity within medial prefrontal cortex (mPFC) subregions. Hearing loss was induced in adult rats via intracochlear neomycin injection (n = 13), with non-operated rats as controls (n = 10).

Intrathecal IgG and IgM synthesis correlates with neurodegeneration markers and corresponds to meningeal B cell presence in MS.

Intrathecal synthesis of immunoglobulins (Igs) is a key hallmark of multiple sclerosis (MS). B cells are known to accumulate in the leptomeninges of MS patients and associate with pathology in the underlying cortex and a more severe disease course. However, the role of locally produced antibodies in MS brain pathology is poorly understood.

Evaluation and management of hepatic dysfunction, portal hypertension and portal/splanchnic vein thrombosis in patients with myelofibrosis undergoing allogeneic haematopoietic cell transplantation: A practice based survey on behalf of the Chronic Malignancies Working Party of the EBMT.

Heterogeneous approaches exist in regard to the management of disease-related co-morbidities in potential allogeneic haematopoietic cell transplantation (allo-HCT) candidates with myelofibrosis (MF). The EBMT Chronic Malignancies Working Party launched an electronic survey to evaluate how MF-specific comorbidities are approached and whether they ultimately affect the decision to transplant. A total of 41/63 (65%) Centers, all of whom were experienced in the management of MF allo-HCT, responded.

Looking Backward and Looking Forward: Revisiting "Clinical Usefulness of Thoracic Duct Cannulation".

Over the past decade, there has been a resurgence of interest in the thoracic duct and central lymphatic system and its disorders, stimulated by advances in interventional magnetic resonance imaging techniques and urgent challenges in the clinical management of lymphatic malformations and lymphatic complications from congenital heart disease. The following chapter reprinted here written shortly after the formal founding of the discipline of lymphology and the International Society of Lymphology, describes early efforts, and also suggests future directions now being revisited and others yet to be explored (1).

Brain Lymphatics: Rediscovery and New Insights into Lymphatic Involvement in Diseases of Human Brains.

The brain's lymphatic system is comprised of a glymphatic-meningeal-cervical lymphatic vessel pathway. The study of its mechanism and pathophysiology in neurodegenerative disease has been one of the most exciting topics in basic and translational neuroscience of the last decade. However, while there has been some debate about when the meningeal lymphatics were discovered, it cannot be denied that studies in preclinical models and humans in this century represent a monumental step forward in our understanding of how the brain removes metabolic waste, the role this system plays in neurodegenerative disease, and, most importantly, its potential as a novel therapeutic target.

Returning the Central Lymphatic System to the Center of Lymphology.

After the introduction of conventional oil contrast lymphography and the founding of the discipline of lymphology, great impetus was given to investigating central lymphatic system and its disorders along with lymphatic involvement and specifically lymphostasis in common diseases of major organs such as the liver (cirrhosis) and heart (heart failure). Gradually interest shifted to more peripheral disorders such as limb lymphedema and its treatment by physical and surgical measures. At the same time, basic lymphology turned to the study of isolate-ed ex vivo and in vitro, including lymphatic endothelial models and more recently, molecular lymphology focusing on lymphatic growth and modulating factors, genes and proteins under-lying primary lymphedema, and more potential biomarkers of lymphatic disease have gained prominence.

Busulfan Exposure Target Attainment in Adults Undergoing Allogeneic Hematopoietic Cell Transplantation: A Single Day Versus a Multiple Day Therapeutic Drug Monitoring Regimen.

Busulfan exposure has previously been linked to clinical outcomes, hence the need for therapeutic drug monitoring (TDM). Study objective was to evaluate the effect of day 1 TDM-guided dosing (regimen d1) versus days 1 + 2 TDM-guided dosing (regimen d1 + 2) on attaining adequate busulfan exposure. In this observational study, we included all adults who received an allogeneic HCT with intravenous once daily busulfan over 4 days as part of the conditioning regimen at the University Medical Centre Utrecht or between July 31, 2014 and November 12, 2021.

Protein-free media for cardiac differentiation of hPSCs in 2000 mL suspension culture.

Background: Commonly used media for the differentiation of human pluripotent stem cells into cardiomyocytes (hPSC-CMs) contain high concentrations of proteins, in particular albumin, which is prone to quality variations and presents a substantial cost factor, hampering the clinical translation of in vitro-generated cardiomyocytes for heart repair. To overcome these limitations, we have developed chemically defined, entirely protein-free media based on RPMI, supplemented with L-ascorbic acid 2-phosphate (AA-2P) and either the non-ionic surfactant Pluronic F-68 or a specific polyvinyl alcohol (PVA).

Methods And Results: Both media compositions enable the efficient, directed differentiation of embryonic and induced hPSCs, matching the cell yields and cardiomyocyte purity ranging from 85 to 99% achieved with the widely used protein-based CDM3 medium.

Total synthesis of dissectol A, using an enediolate-based Tsuji-Trost reaction.

Dissectol A is a rearranged terpene glycoside isolated from several flowering plants. Starting from glucose, the densely functionalized bicyclic structure has been prepared site-selective oxidation and an intramolecular allylic alkylation reaction with an enediolate as the nucleophile. Despite earlier reports, dissectol A is not effective at inhibiting DevRS signaling in whole-cell and does not inhibit growth of the bacterium.

The effects of music-based interventions on behavioural and psychological symptoms of people living with dementia: a systematic review and network meta-analysis protocol.

Objectives: People living with dementia often experience behavioural and psychological symptoms of dementia (BPSD), which severely affect their well-being during the course of the disease. Particularly for BPSD outcomes, there is a high demand for increasing the evidence-based knowledge of non-pharmacological approaches, such as music-based interventions. Although previous reviews emphasize the potential effects of music-based interventions in people with dementia, they cover a wide range of different interventions and outcomes.

Cancer metastasis through the lymphatic versus blood vessels.

Whether cancer cells metastasize from the primary site to the distant sites via the lymphatic vessels or the blood vessels directly into the circulation is still under intense study. In this review article, we follow the journey of cancer cells metastasizing to the sentinel lymph nodes and beyond to the distant sites. We emphasize cancer heterogeneity and microenvironment as major determinants of cancer metastasis.

Interobserver variation in tumor delineation of liver metastases using Magnetic Resonance Imaging.

Background And Purpose: Magnetic Resonance Imaging (MRI) guided stereotactic body radiotherapy (SBRT) of liver metastases is an upcoming high-precision non-invasive treatment. Interobserver variation (IOV) in tumor delineation, however, remains a relevant uncertainty for planning target volume (PTV) margins. The aims of this study were to quantify IOV in MRI-based delineation of the gross tumor volume (GTV) of liver metastases and to detect patient-specific factors influencing IOV.

Fabrication of heart tubes from iPSC derived cardiomyocytes and human fibrinogen by rotating mold technology.

Due to its structural and functional complexity the heart imposes immense physical, physiological and electromechanical challenges on the engineering of a biological replacement. Therefore, to come closer to clinical translation, the development of a simpler biological assist device is requested. Here, we demonstrate the fabrication of tubular cardiac constructs with substantial dimensions of 6 cm in length and 11 mm in diameter by combining human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and human foreskin fibroblast (hFFs) in human fibrin employing a rotating mold technology.

Torpor induces reversible tau hyperphosphorylation and accumulation in mice expressing human tau.

Tau protein hyperphosphorylation and aggregation are key pathological events in neurodegenerative tauopathies such as Alzheimer's disease. Interestingly, seasonal hibernators show extensive tau hyperphosphorylation during torpor, i.e.

Characterizing the treatment patterns, medication burden, and patient demographics of older adults with major depressive disorder treated with antidepressants with or without selected comorbidities.

Objective: Evaluate clinical characteristics, comorbidity burden, major depressive disorder (MDD)-related healthcare resource utilization (HCRU), medication burden, and antidepressant treatment (ADT) patterns among older adults with MDD with and without selected comorbidities.

Methods: Using Komodo's Healthcare Map claims data (1/1/2016-9/30/2022), patients with MDD (≥65 years) treated with ADTs were assessed 24 months preceding (baseline) and 12 months following (follow-up) first observed ADT prescription fill (index). Patients were separated into cohorts of those with ≥1 of 5 selected comorbidities and those without.