The Danish Dementia Research Centre: Integrating patient care, clinical research, and national educational services.

The Copenhagen Memory Clinic was established in 1995 and since 2007 a new national center for research and education was established, together forming the Danish Dementia Research Centre (DDRC). Our research and innovation programs have continuously been informed by clinical experience and inspired by the needs of our patients. The link between patient care, research, and education forming together a comprehensive dementia center is therefore of crucial importance.

The Ability of Electroencephalography Using Statistical Pattern Recognition to Predict Conversion from Subtypes of Mild Cognitive Impairment to Dementia: A 5-Year Follow-Up Study.

Introduction: Studies have shown that quantitative EEG is useful in predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease dementia (ADD) and dementia with Lewy bodies (DLBs). As subcortical pathology is present and executive impairment is common in DLB, we hypothesized that EEG could predict conversion in patients with impaired executive function and any subcortical pathology.

Methods: We included 113 patients with MCI from 5 Nordic memory clinics, 80 (71%) with amnestic MCI, 17 (15%) with dysexecutive MCI (deMCI), 3 (3%) with aphasic, 2 (2%) with visuospatial, and 11 (10%) with unspecific MCI.

Normal cerebral oxygen consumption and lactate levels in patients with Alzheimer's disease and Lewy body dementia.

Brain metabolism is reduced in patients with dementia disorders, as demonstrated by hypometabolism on 2-deoxy-2-[F]fluoroglucose ([F]FDG) positron emissions tomography. A contributing factor to the hypometabolism could be decreased cerebral blood flow (CBF) leading to a state of subtle hypoperfusion-induced tissue hypoxia causing a reduced brain oxygen metabolism and consequently elevated brain lactate. In the current exploratory study, we investigated brain lactate, global and regional CBF, and global cerebral metabolic rate of oxygen (CMRO) in patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLBs).

Mycotoxin-free Aspergillus oryzae strain lineage for alternative and novel protein production at industrial scale.

Advanced industrial strains of Aspergillus oryzae have been used for decades for the production of recombinant proteins including food and feed enzymes at large scale. The A. oryzae strain lineage evaluated in this review derives from the proprietary Novozymes (now Novonesis) strain collection.

Deletion of GFRAL blunts weight lowering effects of FGF21 in female mice.

The role of the GDF15 receptor, GDNF family receptor alpha-like (GFRAL), in the metabolic effects of FGF21 was investigated by treating female GFRAL knockout mice with recombinant human FGF21. In contrast to FGF21-treated wild-type mice, which lost 12% body weight relative to the vehicle, the absence of GFRAL coincided with a greater compensatory increase in food intake, and accordingly, the weight-lowering effect of FGF21 treatment was blunted. Interestingly, the glycemic benefits of FGF21 persisted in the absence of GFRAL.

Coronary revascularisation deferral based on quantitative flow ratio or fractional flow reserve: a post hoc analysis of the FAVOR III Europe trial.

Background: Safe deferral of revascularisation is a key aspect of physiology-guided percutaneous coronary intervention (PCI). While recent evidence gathered in the FAVOR III Europe trial showed that quantitative flow ratio (QFR) guidance did not meet non-inferiority to fractional flow reserve (FFR) guidance, it remains unknown if QFR might have a specific value in revascularisation deferral.

Aims: We aimed to evaluate the safety of coronary revascularisation deferral based on QFR as compared with FFR.

Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial.

Background: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires.

Housing mice near vs. below thermoneutrality affects drug-induced weight loss but does not improve prediction of efficacy in humans.

Evaluation of weight loss drugs is usually performed in diet-induced obese mice housed at ∼22°C. This is a cold stress that increases energy expenditure by ∼35% compared to thermoneutrality (∼30°C), which may overestimate drug-induced weight loss. We investigated five anti-obesity mechanisms that have been in clinical development, comparing weight loss in mice housed at 22°C vs.

Development of Zalfermin, a Long-Acting Proteolytically Stabilized FGF21 Analog.

Here, we describe the development of the FGF21 analog zalfermin (NNC0194-0499, ), intended for once-weekly sc dosing. Protein engineering was needed to address inherent druggability issues of the natural FGF21 hormone. Thus, deamidation of Asp121 was solved by mutation to glutamine, and oxidation of Met168 was solved by mutation to leucine.

A novel contaminant in museums? A cross-sectional study on xerophilic Aspergillus growth in climate-controlled repositories.

In the last decade, extensive fungal growth has developed in Danish museums parallel to climate change, challenging occupational health and heritage preservation. The growth was unexpected as the museums strived to control relative humidity below 60 %, and it should exceed 75 % to risk growth. A Danish case study found xerophilic Aspergillus species able to grow at low relative humidity in a museum repository.

An efficient mRNA display protocol yields potent bicyclic peptide inhibitors for FGFR3c: outperforming linear and monocyclic formats in affinity and stability.

Macrocyclization has positioned itself as a powerful method for engineering potent peptide drug candidates. Introducing one or multiple cyclizations is a common strategy to improve properties such as affinity, bioavailability and proteolytic stability. Consequently, methodologies to create large libraries of polycyclic peptides by phage or mRNA display have emerged, allowing the rapid identification of binders to virtually any target.

Subclinical epileptiform discharges in Alzheimer's disease are associated with increased hippocampal blood flow.

Background: In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer's disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF).

Damp Buildings: Associated Fungi and How to Find Them.

The number of buildings experiencing humidity problems and fungal growth appears to be increasing as energy-saving measures and changes in construction practices and climate become more common. Determining the cause of the problem and documenting the type and extent of fungal growth are complex processes involving both building physics and indoor mycology. New detection and identification methods have been introduced, and new fungal species have been added to the list of building-related fungi.

Identification and engineering of potent cyclic peptides with selective or promiscuous binding through biochemical profiling and bioinformatic data analysis.

As our understanding of biological systems grows, so does the need to selectively target individual or multiple members of specific protein families in order to probe their function. Many targets of current biological and pharmaceutical interest are part of a large family of closely related proteins and achieving ligand selectivity often remains either an elusive or time-consuming endeavour. Cyclic peptides (CPs) occupy a key niche in ligand space, able to achieve high affinity and selectivity while retaining synthetic accessibility.

Subclinical Epileptiform Activity in Dementia with Lewy Bodies.

Background: Patients with dementia with Lewy bodies (DLB) have a higher probability of seizures than in normal aging and in other types of neurodegenerative disorders. Depositions of α-synuclein, a pathological hallmark of DLB, can induce network excitability, which can escalate into seizure activity. Indicator of seizures are epileptiform discharges as observed using electroencephalography (EEG).

Renoprotective effects of genetically proxied fibroblast growth factor 21: Mendelian randomization, proteome-wide and metabolome-wide association study.

Background: Fibroblast growth factor 21 (FGF21) has demonstrated efficacy for reducing liver fat and reversing non-alcoholic steatohepatitis in phase 2 clinical trials. It is also postulated to have anti-fibrotic effects and therefore may be amenable to repurposing for the prevention and treatment of chronic kidney disease (CKD).

Methods: We leverage a missense genetic variant, rs739320 in the FGF21 gene, that associates with magnetic resonance imaging-derived liver fat as a clinically validated and biologically plausible instrumental variable for studying the effects of FGF21 analogs.

Detection of subclinical epileptiform discharges in Alzheimer's disease using long-term outpatient EEG monitoring.

Background: In patients with Alzheimer's disease (AD) without clinical seizures, up to half have epileptiform discharges on long-term in-patient electroencephalography (EEG) recordings. Long-term in-patient monitoring is obtrusive, and expensive as compared to outpatient monitoring. No studies have so far investigated if long-term outpatient EEG monitoring is able to identify epileptiform discharges in AD.

Hepatocyte mARC1 promotes fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) has a prevalence of ∼25% worldwide, with significant public health consequences yet few effective treatments. Human genetics can help elucidate novel biology and identify targets for new therapeutics. Genetic variants in mitochondrial amidoxime-reducing component 1 () have been associated with NAFLD and liver-related mortality; however, its pathophysiological role and the cell type(s) mediating these effects remain unclear.

Aerobic exercise does not affect serum neurofilament light in patients with mild Alzheimer's disease.

Introduction: Aerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration.

Objective: To investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer's disease (AD).

Methods: This is a secondary analysis of data from the multi-center Preserving Cognition, Quality of Life, Physical Health, and Functional Ability in Alzheimer's disease: The Effect of Physical Exercise (ADEX) study.

Quantitative flow ratio versus fractional flow reserve for guiding percutaneous coronary intervention: design and rationale of the randomised FAVOR III Europe Japan trial.

Quantitative flow ratio (QFR) is a computation of fractional flow reserve (FFR) based on invasive coronary angiographic images. Calculating QFR is less invasive than measuring FFR and may be associated with lower costs. Current evidence supports the call for an adequately powered randomised comparison of QFR and FFR for the evaluation of intermediate coronary stenosis.

Long-Term EEG Monitoring in Patients with Alzheimer's Disease Using Ear-EEG: A Feasibility Study.

Background: Previous studies have reported that epileptiform activity may be detectible in nearly half of patients with Alzheimer's disease (AD) on long-term electroencephalographic (EEG) recordings. However, such recordings can be uncomfortable, expensive, and difficult. Ear-EEG has shown promising results for long-term EEG monitoring, but it has not been used in patients with AD.

The Ostomy Skin Tool 2.0: a new instrument for assessing peristomal skin changes.

Background: Peristomal skin complications (PSCs) are frequently reported postoperative complications. PSCs can present visibly or as symptoms such as pain, itching or burning sensations.

Aim: To develop a new tool that can capture a range of sensation symptoms together with visible complications and an objective assessment of discolouration in the peristomal area.