Brain Distribution of Dual ABCB1/ABCG2 Substrates Is Unaltered in a Beta-Amyloidosis Mouse Model.

Background: ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) are co-localized at the blood-brain barrier (BBB), where they restrict the brain distribution of many different drugs. Moreover, ABCB1 and possibly ABCG2 play a role in Alzheimer's disease (AD) by mediating the brain clearance of beta-amyloid (Aβ) across the BBB. This study aimed to compare the abundance and activity of ABCG2 in a commonly used β-amyloidosis mouse model (APP/PS1-21) with age-matched wild-type mice.

Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations.

Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs.

Distinct Pattern of Endoplasmic Reticulum Protein Processing and Extracellular Matrix Proteins in Functioning and Silent Corticotroph Pituitary Adenomas.

Functioning (FCA) and silent corticotroph (SCA) pituitary adenomas act differently from a clinical perspective, despite both subtypes showing positive TBX19 (TPIT) and/or adrenocorticotropic hormone (ACTH) staining by immunohistochemistry. They are challenging to treat, the former due to functional ACTH production and consequently hypercortisolemia, and the latter due to invasive and recurrent behavior. Moreover, the molecular mechanisms behind their distinct behavior are not clear.

Accuracy of breast MRI in patients receiving neoadjuvant endocrine therapy: comprehensive imaging analysis and correlation with clinical and pathological assessments.

Purpose: To assess the accuracy of magnetic resonance imaging (MRI) measurements in locally advanced oestrogen receptor-positive and human epidermal growth factor receptor 2-negative breast tumours before, during and after neoadjuvant endocrine treatment (NET) for evaluation of tumour response in comparison with clinical and pathological assessments.

Methods: This prospective study enrolled postmenopausal patients treated neoadjuvant with letrozole and exemestane given sequentially in an intra-patient cross-over regimen. Fifty-four patients were initially recruited, but only 35 fulfilled the inclusion criteria and confirmed to participate with a median age of 77.

Fingolimod as a Treatment in Neurologic Disorders Beyond Multiple Sclerosis.

Fingolimod is an approved treatment for relapsing-remitting multiple sclerosis (MS), and its properties in different pathways have raised interest in therapy research for other neurodegenerative diseases. Fingolimod is an agonist of sphingosine-1-phosphate (S1P) receptors. Its main pharmacologic effect is immunomodulation by lymphocyte homing, thereby reducing the numbers of T and B cells in circulation.

Early Cognitive Training Rescues Remote Spatial Memory but Reduces Cognitive Flexibility in Alzheimer's Disease Mice.

Background: Spatial memory dysfunction has been demonstrated in mouse models of Alzheimer's disease (AD) which is consistent with the clinical finding that the early signature of AD includes difficulties in the formation and/or storage of a memory. A stored memory-a long term memory-can be modulated via process called as memory retrieval that can either lead toward memory reconsolidation or even memory extinction.

Objective: We aim to shed light on the fate of the spatial memory during memory reactivation and memory extinction using a water maze task.

Impairments in spatial navigation during walking in patients 70 years or younger with mild stroke.

: Spatial navigation, the ability to determine and maintain a route from one place to another, is needed for independence in everyday life. Knowledge about impairments in spatial navigation in people with mild stroke is scarce.: To explore impairments in spatial navigation in patients ≤70 years after first-ever mild ischemic stroke (NIHSS≤3) and to explore which variables are associated with these impairments 12 months later.

The operating room as a learning arena: Nurse anaesthetist and student nurse anaesthetist perceptions.

Aim: To examine which competencies mentors and student nurse anaesthetists perceive as important in a clinical anaesthesia education practice.

Background: Mentoring during clinical placement in the operating room can be challenging from the viewpoint of both a nurse anaesthetist and their students. The operating room is a work environment with many restrictions, and the nurse anaesthetist's work requires prompt decisions and actions.

Short-term perioperative parecoxib is not detrimental to shaft fracture healing in a rat model.

Objectives: Experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) may have negative effects on fracture healing. This study aimed to assess the effect of immediate and delayed short-term administration of clinically relevant parecoxib doses and timing on fracture healing using an established animal fracture model.

Methods: A standardized closed tibia shaft fracture was induced and stabilized by reamed intramedullary nailing in 66 Wistar rats.

Energy-efficiency of Cardiomyocyte Stimulation with Rectangular Pulses.

In cardiac pacemaker design, energy expenditure is an important issue. This work aims to explore whether varying stimulation pulse configuration is a viable optimization strategy for reducing energy consumption by the pacemaker. A single cardiomyocyte was used as an experimental model.

French maritime pine bark treatment decelerates plaque development and improves spatial memory in Alzheimer's disease mice.

Background: Plant extracts are increasingly investigated as potential drugs against Alzheimer's disease (AD) and dementia in general. Pycnogenol is an extract from the bark of the French maritime pine (Pinus pinaster Aiton subsp. atlantica) with known anti-oxidative and neuroprotective effects.

Intralymphatic Immunotherapy: Update and Unmet Needs.

Allergen-specific immunotherapy (AIT) is the only allergy treatment that confers long-term symptom amelioration for patients suffering from allergy. The most frequently used allergen application route is subcutaneous injection (SCIT), commonly taken as the gold standard, followed by sublingual (SLIT) or oral (OIT) application of allergen preparations. This is an up-to-date review of the clinical evidence for a novel route of allergen application, i.

Age dependency of cerebral P-glycoprotein function in wild-type and APPPS1 mice measured with PET.

P-glycoprotein (P-gp, ABCB1) is an efflux transporter at the blood-brain barrier (BBB), which mediates clearance of beta-amyloid (Aβ) from brain into blood. We used ()-[C]verapamil PET in combination with partial P-gp inhibition with tariquidar to measure cerebral P-gp function in a beta-amyloidosis mouse model (APPtg) and in control mice at three different ages (50, 200 and 380 days). Following tariquidar pre-treatment (4 mg/kg), whole brain-to-plasma radioactivity concentration ratios () were significantly higher in APPtg than in wild-type mice aged 50 days, pointing to decreased cerebral P-gp function.

A comparative study about motivations, expectations and future plans for professional development in four European radiography programs.

Introduction: This study aims to compare motivations, expectations and work plans of students and teaching-staff from four different European radiography programs, it aims also to explore areas that could be included to advance post graduate studies.

Methods: Two different questionnaires (open- and closed-end questions) were applied to key-informants, students who had just completed their bachelor thesis and teaching-staff, to collect data regarding motivations, expectations, challenges and potentials for radiography education and, plans for further work. Descriptive statistics and thematic analysis were performed according to the nature of the questions.

Intrinsic Xenobiotic Resistance of the Intestinal Stem Cell Niche.

The gut absorbs dietary nutrients and provides a barrier to xenobiotics and microbiome metabolites. To cope with toxin exposures, the intestinal epithelium is one of the most rapidly proliferating tissues in the body. The stem cell niche supplies essential signaling factors including Wnt proteins secreted by subepithelial myofibroblasts.

Re-view and view on maturation disorders in the placenta.

Until delivery, the placenta plays an important mediator role between mother and fetus. This unit is affected by peristatic conditions, such as acute or chronic maternal diseases, malnutrition, drugs, and others. But also genetic factors and fetal malformations due to embryonic developmental disorders may contribute to macroscopically visible changes and functional disorders of the placenta.

The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM.

The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic hallmark of Alzheimer's disease (AD). The blood-brain barrier (BBB) provides a large surface area and has been shown to be an important mediator for removal of brain Aβ. Both, the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) have been implicated to play crucial roles in Aβ efflux from brain.

Short-Term Effects of Microglia-Specific Mitochondrial Dysfunction on Amyloidosis in Transgenic Models of Alzheimer's Disease.

Reduction of mitochondrial activity is a subtle and early event in the pathogenesis of Alzheimer's disease. Mitochondrial damage and consequentially enhanced production of reactive oxygen species is particularly occurring in the vicinity of amyloid plaques. Since all cells are affected by mitochondrial damage, analyses of cell type-specific effects are challenging.

Curricula, attributes and clinical experiences of radiography programs in four European educational institutions.

Introduction: The aim of this study was to compare radiography curricula, teaching/learning strategies, skill development, clinical practice outcomes and research development delivered by four European educational institutions.

Methods: This study was carried out in two phases: the first focused on curricula analysis; the second involved online questionnaires to ascertain data from two key-informants: students who had recently completed their bachelor thesis and teaching-staff. Questionnaires were designed to capture teaching and learning strategies, skill acquisition and outcomes of clinical practice and research.

Influence of Multidrug Resistance-Associated Proteins on the Excretion of the ABCC1 Imaging Probe 6-Bromo-7-[C]Methylpurine in Mice.

Purpose: Multidrug resistance-associated proteins (MRPs) mediate the hepatobiliary and renal excretion of many drugs and drug conjugates. The positron emission tomography (PET) tracer 6-bromo-7-[C]methylpurine is rapidly converted in tissues by glutathione-S-transferases into its glutathione conjugate, and has been used to measure the activity of Abcc1 in the brain and the lungs of mice. Aim of this work was to investigate if the activity of MRPs in excretory organs can be measured with 6-bromo-7-[C]methylpurine.

Negative effect of zoledronic acid on tendon-to-bone healing.

Background and purpose - Outcome after ligament reconstruction or tendon repair depends on secure tendon-to-bone healing. Increased osteoclastic activity resulting in local bone loss may contribute to delayed healing of the tendon-bone interface. The objective of this study was to evaluate the effect of the bisphosphonate zoledronic acid (ZA) on tendon-to-bone healing.