Sex-dependent efficacy of sphingosine-1-phosphate receptor agonist FTY720 in mitigating Huntington's disease.

Huntington's disease (HD) is a debilitating neurodegenerative disorder characterized by severe motor deficits, cognitive decline and psychiatric disturbances. An early and significant morphological hallmark of HD is the activation of astrocytes triggered by mutant huntingtin, leading to the release of inflammatory mediators. Fingolimod (FTY), an FDA-approved sphingosine-1-phosphate (S1P) receptor agonist is used to treat multiple sclerosis (MS), a neuroinflammatory disease, and has shown therapeutic promise in other neurological conditions.

Yellow meconium.

The intestinal content of newborns is known as meconium, usually described as a black-greenish slimy substance. However, in rare cases, meconium might be yellow. This is of great relevance with regard to the forensic assessment of life birth, i.

Metastasis-directed stereotactic radiotherapy in patients with breast cancer: results of an international multicenter cohort study.

Metastasis-directed therapy (MDT) for oligometastatic breast cancer (≤ 5 metastases) has shown little effect in specific scenarios of randomized trials. Therefore, we aimed to assess outcomes after metastasis-directed stereotactic radiotherapy (SRT) in various clinical scenarios. We conducted an international retrospective cohort study in thirteen centers including breast cancer patients receiving SRT to any metastatic site.

Artificial intelligence in surgical pathology - Where do we stand, where do we go?

Surgical and neuropathologists continuously search for new and disease-specific features, such as independent predictors of tumor prognosis or determinants of tumor entities and sub-entities. This is a task where artificial intelligence (AI)/machine learning (ML) systems could significantly contribute to help with tumor outcome prediction and the search for new diagnostic or treatment stratification biomarkers. AI systems are increasingly integrated into routine pathology workflows to improve accuracy, reproducibility, productivity and to reveal difficult-to-see features in complicated histological slides, including the quantification of important markers for tumor grading and staging.

Robotic Laser Tissue Soldering for Atraumatic Soft Tissue Fusion Guided by Fluorescent Nanothermometry.

Minimally invasive surgical techniques, including endoscopic and robotic procedures, continue to revolutionize patient care, for their ability to minimize surgical trauma, thus promoting faster recovery and reduced hospital stays. Yet, the suturing of soft tissues ensuring damage-free tissue bonding during these procedures remains challenging due to missing haptics and the fulcrum effect. Laser tissue soldering has potential in overcoming these issues, offering atraumatic seamless tissue fusion.

Creating a Culture of an Awake and Walking Intensive Care Unit: In-Hospital Strategies to Mitigate Post-Intensive Care Syndrome.

The ABCDEF bundle and Awake and Walking intensive care unit (ICU) approach aim to prevent the long-term consequences of critical illness (ie, post-intensive care syndrome) by promoting patient wakefulness, cognition, and mobility. Humanizing the ICU experience is the key, preserving patients' function and autonomy. Successful implementation requires cultivating an ICU culture focused on avoiding sedatives and initiating prompt mobilization, addressing organizational barriers through tailored strategies.

Does the gender of emergency physicians have an impact on the prehospital care of psychiatric emergencies? a retrospective cohort analysis.

Background: Psychiatric emergencies pose a special challenge for emergency physicians. It is known from other areas of medicine that the influence of a doctor's gender can have an impact on the type of treatment and quality of patient care. However, this has not yet been investigated in the context of prehospital care in psychiatric emergencies.

Computed tomography for the detection of myocardial hypoperfusion in acute myocardial infarction and the associated CT-to-catheter time.

Emergency computed tomography (CT) often does not allow for comprehensive coronary artery assessment. However, CT may reveal pathological myocardial hypoperfusion suggestive of acute myocardial infarction (AMI), especially in patients presenting with a different diagnostic hypothesis. CT hypoperfusion is known to be associated with myocardial infarction, however the diagnostic value of CT hypoperfusion for the detection of AMI is still not well evaluated.

Phosphoproteomics-directed manipulation reveals SEC22B as a hepatocellular signaling node governing metabolic actions of glucagon.

The peptide hormone glucagon is a fundamental metabolic regulator that is also being considered as a pharmacotherapeutic option for obesity and type 2 diabetes. Despite this, we know very little regarding how glucagon exerts its pleiotropic metabolic actions. Given that the liver is a chief site of action, we performed in situ time-resolved liver phosphoproteomics to reveal glucagon signaling nodes.

Autoantigen-specific CD4 T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases.

Pro-inflammatory autoantigen-specific CD4 T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocyte antigen (HLA)-tetramer-based and activation-based multidimensional ex vivo analyses. In aquaporin4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) patients, auto-Th cells expressed CD154, but proliferative capacity and pro-inflammatory cytokines were strongly reduced.

Integrin αVß6 - autoantigen and driver of epithelial remodeling in colon and bile ducts in primary sclerosing cholangitis and inflammatory bowel disease.

Objective: Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified which strongly associate with ulcerative colitis (UC). We aimed to elucidate whether anti-integrin αVβ6 (anti- αVβ6) is present in primary sclerosing cholangitis (PSC), its associated inflammatory bowel disease or other cholestatic liver diseases and their persistence after proctocolectomy.

Design: We detected anti- αVβ6 by an enzyme-linked immunosorbent assay in sera collected at two German tertiary centers, including healthy controls (N=62), UC (N=36), Crohn's disease (CD, N=65), PSC-IBD (78 samples from N=41 patients), PSC without IBD (PSC, 41 samples from N=18 patients), primary biliary cholangitis (PBC, N=24), autoimmune hepatitis (AIH, N=32), secondary sclerosing cholangitis (SSC, N=12) and metabolic dysfunction-associated steatotic liver disease (MASLD, N=24).

ABCC1 Is a ΔNp63 Target Gene Overexpressed in Squamous Cell Carcinoma.

The transcription factor ΔNp63 plays a pivotal role in maintaining the integrity of stratified epithelial tissues by regulating the expression of distinct target genes involved in lineage specification, cell stemness, cell proliferation and differentiation. Here, we identified the ABC transporter subfamily member as a novel ΔNp63 target gene. We found that in immortalized human keratinocytes and in squamous cell carcinoma (SCC) cells, ∆Np63 induces the expression of ABCC1 by physically occupying a p63-binding site (p63 BS) located in the first intron of the gene locus.

Neuropelveology for Endometriosis Management: A Systematic Review and Multilevel Meta-Analysis.

: Despite the availability of treatments such as surgery and hormonal therapy, women with endometriosis often endure chronic problems. This review aims to evaluate the effectiveness and safety of neuropelveology. : In a systematic review with a meta-analysis, we searched three electronic databases: MEDLINE (PubMed), Scopus, Embase, and Web of Science (WOS).

25-Hydroxycholesterol attenuates tumor necrosis factor alpha-induced blood-brain barrier breakdown in vitro.

Intracellular cholesterol metabolism is regulated by the SREBP-2 and LXR signaling pathways. The effects of inflammation on these molecular mechanisms remain poorly studied, especially at the blood-brain barrier (BBB) level. Tumor necrosis factor α (TNFα) is a proinflammatory cytokine associated with BBB dysfunction.

Evaluation of cerebrospinal fluid (CSF) and interstitial fluid (ISF) mouse proteomes for the validation and description of Alzheimer's disease biomarkers.

Background: Mass spectrometry (MS)-based cerebrospinal fluid (CSF) proteomics is an important method for discovering biomarkers of neurodegenerative diseases. CSF serves as a reservoir for interstitial fluid (ISF), and extensive communication between the two fluid compartments helps to remove waste products from the brain.

New Method: We performed proteomic analyses of both CSF and ISF fluid compartments using intracerebral microdialysis to validate and detect novel biomarkers of Alzheimer's disease (AD) in APPtg and C57Bl/6J control mice.

Sexual health-a topic for cancer patients receiving oncological treatment with palliative intent.

Objectives: Sexuality is an important dimension of health-related quality of life (HRQOL) in cancer patients. Studies evidence that most patients report impairments of their sexual health related to their disease or its treatment. The Quality of Life Group of the European Organization for the Research and Treatment of Cancer (EORTC) developed a patient reported outcome measure assessing multidimensional aspects of sexual health.

Preventive effects of early immunosuppressive treatment on the development of interstitial lung disease in systemic sclerosis.

Background: Hypothesizing that early treatment yields improved prognosis, we aimed to investigate how the timing of immunosuppressive treatment relates to interstitial lung disease (ILD) development and the course of pulmonary function in systemic sclerosis (SSc).

Methods: A cohort was created using data from the EUSTAR database and Nijmegen Systemic Sclerosis cohort, including adult patients who started their first immunosuppressive treatment (ie mycophenolate mofetil, methotrexate, cyclophosphamide, tocilizumab or rituximab) after SSc diagnosis, and no signs of ILD on high-resolution CT. ILD-free survival and the course of forced vital capacity % predicted (ppFVC) were assessed for up to 5 years follow-up comparing patients who started early (disease duration ≤ 3 years) vs late with immunosuppression.

Dose prescription for stereotactic body radiotherapy: general and organ-specific consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery.

Purpose And Objective: To develop expert consensus statements on multiparametric dose prescriptions for stereotactic body radiotherapy (SBRT) aligning with ICRU report 91. These statements serve as a foundational step towards harmonizing current SBRT practices and refining dose prescription and documentation requirements for clinical trial designs.

Materials And Methods: Based on the results of a literature review by the working group, a two-tier Delphi consensus process was conducted among 24 physicians and physics experts from three European countries.

A world-wide study on delirium assessments and presence of protocols.

Background: Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities.

Objective: To assess the worldwide use of validated delirium assessment tools and the presence of delirium management protocols.

Design: Secondary analysis of a worldwide one-day point prevalence study on World Delirium Awareness Day, 15 March 2023.

Cognitive training and promoting a healthy lifestyle for individuals with isolated REM sleep behavior disorder: study protocol of the delayed-start randomized controlled trial CogTrAiL-RBD.

Background: Isolated REM sleep behavior disorder (iRBD) is an early α-synucleinopathy often accompanied by incipient cognitive impairment. As executive dysfunctions predict earlier phenotypic conversion from iRBD to Parkinson's disease and Lewy body dementia, cognitive training focusing on executive functions could have disease-modifying effects for individuals with iRBD.

Methods: The study CogTrAiL-RBD investigates the short- and long-term effectiveness and the feasibility and underlying neural mechanisms of a cognitive training intervention for individuals with iRBD.

Gait Variability as a Potential Motor Marker of Cerebellar Disease-Relationship between Variability of Stride, Arm Swing and Trunk Movements, and Walking Speed.

Excessive stride variability is a characteristic feature of cerebellar ataxias, even in pre-ataxic or prodromal disease stages. This study explores the relation of variability of arm swing and trunk deflection in relationship to stride length and gait speed in previously described cohorts of cerebellar disease and healthy elderly: we examined 10 patients with spinocerebellar ataxia type 14 (SCA), 12 patients with essential tremor (ET), and 67 healthy elderly (HE). Using inertial sensors, recordings of gait performance were conducted at different subjective walking speeds to delineate gait parameters and respective coefficients of variability (CoV).