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.

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.

PCSK1N as a tumor size marker and an ER stress response protein in corticotroph pituitary adenomas.

Purpose: Silent corticotroph adenoma (SCA) exhibits more tumor aggressiveness features than functioning adenomas (FCA). We aimed to investigate PCSK1N expression in CA and examine if ER stress-induced responses affect cell survival in a corticotroph tumor cell model.

Methods: Clinical and imaging characteristics were recorded in 33 patients with FCA (20 women, 11 macroadenomas) and 18 SCA (8 women, all macroadenomas).

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.

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.

Emerging Role of ABC Transporters in Glia Cells in Health and Diseases of the Central Nervous System.

ATP-binding cassette (ABC) transporters play a crucial role for the efflux of a wide range of substrates across different cellular membranes. In the central nervous system (CNS), ABC transporters have recently gathered significant attention due to their pivotal involvement in brain physiology and neurodegenerative disorders, such as (AD). Glial cells are fundamental for normal CNS function and engage with several ABC transporters in different ways.

Long-term depot specific changes in adipose tissue after treatment of acromegaly.

Context: Patients with active acromegaly present a decreased adipose tissue (AT) mass, and short-term studies show that treatment leads to AT depot-specific gain. However, it remains unclear if the increase is persistent in the long-term perspective and/or is sex-dependent.

Design: To characterize the depot-specific changes of AT after treatment of acromegaly and identify contributing factors.

Apolar Extracts of St. John's Wort Alleviate the Effects of β-Amyloid Toxicity in Early Alzheimer's Disease.

(St. John's wort) has been described to be beneficial for the treatment of Alzheimer's disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp.

Performance and Sensitivity of [Tc]Tc-sestamibi Compared with Positron Emission Tomography Radiotracers to Measure P-glycoprotein Function in the Kidneys and Liver.

P-glycoprotein (P-gp, encoded in humans by the gene and in rodents by the genes) is a membrane transporter that can restrict the intestinal absorption and tissue distribution of many drugs and may also contribute to renal and hepatobiliary drug excretion. The aim of this study was to compare the performance and sensitivity of currently available radiolabeled P-gp substrates for positron emission tomography (PET) with the single-photon emission computed tomography (SPECT) radiotracer [Tc]Tc-sestamibi for measuring the P-gp function in the kidneys and liver. Wild-type, heterozygous (), and homozygous () knockout mice were used as models of different P-gp abundance in excretory organs.

Insulin initiation in patients with type 2 diabetes is often delayed, but access to a diabetes nurse may help-insights from Norwegian general practice.

: We opted to study how support staff operational capacity and diabetes competences may impact the timeliness of basal insulin-initiation in general practice patients with type 2 diabetes (T2D). This was an observational and retrospective study on Norwegian primary care patients with T2D included from the ROSA4-dataset. Exposures were (1) support staff size, (2) staff size relative to number of GPs, (3) clinic access to a diabetes nurse and (4) share of staff with diabetes course (1 and 2 both relate to staff operational capacity, whereas 3 and 4 are both indicatory of staff diabetes competences).

[C]metoclopramide is a sensitive radiotracer to measure moderate decreases in P-glycoprotein function at the blood-brain barrier.

The efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier limits the cerebral uptake of various xenobiotics. To assess the sensitivity of [C]metoclopramide to measure decreased cerebral P-gp function, we performed [C]metoclopramide PET scans without (baseline) and with partial P-gp inhibition by tariquidar in wild-type, heterozygous and homozygous mice as models with controlled levels of cerebral P-gp expression. Brains were collected to quantify P-gp expression with immunohistochemistry.

ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer's Disease.

Alzheimer's disease (AD), the leading cause of dementia, is a growing health issue with very limited treatment options. To meet the need for novel therapeutics, existing drugs with additional preferred pharmacological profiles could be recruited. This strategy is known as 'drug repurposing'.

Physiological expression of mutated TAU impaired astrocyte activity and exacerbates β-amyloid pathology in 5xFAD mice.

Background: Alzheimer's disease (AD) is the leading cause of dementia in the world. The pathology of AD is affiliated with the elevation of both tau (τ) and β-amyloid (Aβ) pathologies. Yet, the direct link between natural τ expression on glia cell activity and Aβ remains unclear.

Gene expression profiling of subcutaneous adipose tissue reveals new biomarkers in acromegaly.

Context: Active acromegaly is characterized by lipolysis-induced insulin resistance, which suggests adipose tissue (AT) as a primary driver of metabolic aberrations.

Objective: To study the gene expression landscape in AT in patients with acromegaly before and after disease control in order to understand the changes and to identify disease-specific biomarkers.

Methods: RNA sequencing was performed on paired subcutaneous adipose tissue (SAT) biopsies from six patients with acromegaly at time of diagnosis and after curative surgery.

Use of PET Imaging to Assess the Efficacy of Thiethylperazine to Stimulate Cerebral MRP1 Transport Activity in Wild-Type and APP/PS1-21 Mice.

Multidrug resistance-associated protein 1 (MRP1, encoded by the gene) may contribute to the clearance of amyloid-beta (Aβ) peptides from the brain into the blood and stimulation of MRP1 transport activity may be a therapeutic approach to enhance brain Aβ clearance. In this study, we assessed the effect of thiethylperazine, an antiemetic drug which was shown to stimulate MRP1 activity in vitro and to decrease Aβ load in a rapid β-amyloidosis mouse model (APP/PS1-21), on MRP1 transport activity by means of positron emission tomography (PET) imaging with the MRP1 tracer 6-bromo-7-[C]methylpurine. Groups of wild-type, APP/PS1-21 and mice underwent PET scans before and after a 5-day oral treatment period with thiethylperazine (15 mg/kg, once daily).

A New Tool for the Analysis of the Effect of Intracerebrally Injected Anti-Amyloid-β Compounds.

Background: A wide range of techniques has been developed over the past decades to characterize amyloid-β (Aβ) pathology in mice. Until now, no method has been established to quantify spatial changes in Aβ plaque deposition due to targeted delivery of substances using ALZET® pumps.

Objective: Development of a methodology to quantify the local distribution of Aβ plaques after intracerebral infusion of compounds.

Development of deep learning models for microglia analyses in brain tissue using DeePathology™ STUDIO.

Background: Interest in artificial intelligence-driven analysis of medical images has seen a steep increase in recent years. Thus, our paper aims to promote and facilitate the use of this state-of-the-art technology to fellow researchers and clinicians.

New Method: We present custom deep learning models generated in DeePathology™ STUDIO without the need for background knowledge in deep learning and computer science underlined by practical suggestions.

Analysis of autoantibody spectrum and human herpesvirus 6 in adult patients with 'early' versus 'late' diagnosis of 'possible limbic encephalitis'.

New onset temporal seizures are increasingly encountered in adult patients. Many of those fulfill diagnostic criteria for possible or definite limbic encephalitis (LE). LE is associated with autoantibodies (autoABs) against neuronal surface structures ('neuronal' autoABs), 'onconeuronal' or GAD65.

Dimethyl fumarate does not mitigate cognitive decline and β-amyloidosis in female APPPS1 mice.

Introduction: Alzheimer's disease (AD) is the leading cause of dementia and a major global health issue. Currently, only limited treatment options are available to patients. One possibility to expand the treatment repertoire is repurposing of existing drugs such as dimethyl fumarate (DMF).

Exploring participation in family and recreational activities among children with cerebral palsy during early childhood: how does it relate to motor function and parental empowerment?

Purpose: To explore participation in real-life activities during early childhood, compare children's participation based on motor function and investigate relationships between participation and parental empowerment.

Methods: Data derived from the Cerebral Palsy Follow-up Program (CPOP) in Norway and the research registry Habilitation Trajectories, Interventions, and Services for Young Children with CP (CPHAB). Fifty-six children (12-56 months, GMFCS levels I-IV, MACS levels I-V) and their families were included.

Factors Associated with Level of Physical Activity After Minor Stroke.

Objectives: To explore factors from the acute phase, and after three and 12 months, associated with level of self-reported physical activity 12 months after a minor ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) score ≤ 3 in persons 70 years or younger.

Materials And Method: In this longitudinal cohort study patients were recruited consecutively from two stroke units. Activity level were measured with three sets of questions addressing the average number of frequency (times exercising each week), the average intensity, and duration (the average time), and a sum score was constructed.

Machine Learning-Supported Analyses Improve Quantitative Histological Assessments of Amyloid-β Deposits and Activated Microglia.

Background: Detailed pathology analysis and morphological quantification is tedious and prone to errors. Automatic image analysis can help to increase objectivity and reduce time. Here, we present the evaluation of the DeePathology STUDIO™ for automatic analysis of histological whole-slide images using machine learning/artificial intelligence.

Traumatic stress, mental health, and quality of life in adolescents with esophageal atresia.

Introduction: We aimed to investigate QoL in EA patients in relation to comparison groups and to clinical factors including experienced traumatic stress.

Material And Methods: Adolescents with EA in Norway born between 1996 and 2002 were included. Clinical assessment and patient's characteristics were collected.