The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation.

Background: Accumulation of β-amyloid (Aβ) in the brain is a hallmark of Alzheimer's Disease (AD). Cerebral deposition of Aβ initiates deteriorating pathways which eventually can lead to AD. However, the exact mechanisms are not known.

Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial.

Objective: This clinical trial investigated the safety and efficacy of single-cycle pembrolizumab in patients with localized deficient mismatch repair (dMMR) colon cancer.

Background: Neoadjuvant immunotherapy has induced remarkable rates of pathological complete response in patients with dMMR colon cancer. However, the optimal length and type of treatment are yet to be determined.

Cognitive aging and reserve factors in the Metropolit 1953 Danish male cohort.

Identifying early predictors of cognitive decline and at-risk individuals is essential for timely intervention and prevention of dementia. This study aimed to detect neurobiological changes and factors related to cognitive performance in the Metropolit 1953 Danish male birth cohort. We analyzed data from 582 participants, aged 57-68 years, using machine learning techniques to group cognitive trajectories into four clusters differentiating high- and low-performing groups.

Early cerebral amyloid-β accumulation and hypermetabolism are associated with subtle cognitive deficits before accelerated cerebral atrophy.

Aims: Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) in the brain. The deposition of Aβ is believed to initiate a detrimental cascade, including cerebral hypometabolism, accelerated brain atrophy, and cognitive problems-ultimately resulting in AD. However, the timing and causality of the cascade resulting in AD are not yet fully established.

Prospective evaluation of bowel function and quality of life after colon cancer surgery - is it time for routine screening for late sequelae?

Aim: Bowel dysfunction after colon cancer (CC) surgery is widely neglected in current follow up programmes. This study explored changes in bowel function and quality of life (QoL) from three (3 m) to twelve months (12 m) after surgery in CC patients undergoing right- or left-sided colon resection (RightSCR/LeftSCR) and investigated differences between the two groups 12 m after surgery.

Method: CC patients undergoing surgical resection in 2018-2020 at five surgical departments were included in this population-based prospective cohort study.

Preserved blood-brain barrier and neurovascular coupling in female 5xFAD model of Alzheimer's disease.

Introduction: Dysfunction of the cerebral vasculature is considered one of the key components of Alzheimer's disease (AD), but the mechanisms affecting individual brain vessels are poorly understood.

Methods: Here, using two-photon microscopy in superficial cortical layers and imaging across brain regions, we characterized blood-brain barrier (BBB) function and neurovascular coupling (NVC) at the level of individual brain vessels in adult female 5xFAD mice, an aggressive amyloid- (A) model of AD.

Results: We report a lack of abnormal increase in adsorptive-mediated transcytosis of albumin and preserved paracellular barrier for fibrinogen and small molecules despite an extensive load of A.

Impaired dynamics of precapillary sphincters and pericytes at first-order capillaries predict reduced neurovascular function in the aging mouse brain.

The microvascular inflow tract, comprising the penetrating arterioles, precapillary sphincters and first-order capillaries, is the bottleneck for brain blood flow and energy supply. Exactly how aging alters the structure and function of the microvascular inflow tract remains unclear. By in vivo four-dimensional two-photon imaging, we reveal an age-dependent decrease in vaso-responsivity accompanied by a decrease in vessel density close to the arterioles and loss of vascular mural cell processes, although the number of mural cell somas and their alpha smooth muscle actin density were preserved.

PV interneurons evoke astrocytic Ca responses in awake mice, which contributes to neurovascular coupling.

Neurovascular coupling (NVC) modulates cerebral blood flow to match increased metabolic demand during neuronal excitation. Activation of inhibitory interneurons also increase blood flow, but the basis for NVC caused by interneurons is unclear. While astrocyte Ca levels rise with excitatory neural transmission, much less is known with regards to astrocytic sensitivity to inhibitory neurotransmission.

MEMS micro-coils for magnetic neurostimulation.

Micro-coil magnetic stimulation of brain tissue presents new challenges for MEMS micro-coil probe fabrication. The main challenges are threefold; (i) low coil resistance for high power efficiency, (ii) low leak current from the probe into the in vitro experimental set-up, (iii) adaptive MEMS process technology because of the dynamic research area, which requires agile design changes. Taking on these challenges, we present a MEMS fabrication process that has three main features; (i) multilayer resist lift-off process to pattern up to 1800-nm-thick metal films, and special care is taken to obtain high conductivity thin-films by physical vapor deposition, and (ii) all micro-coil Al wires are encapsulated in at least 200 nm of ALD alumina and 6-μm-thick parylene C such the leak resistance is high (>210 GΩ), (iii) combining a multi-step DRIE process and maskless photolithography for adaptive design and device fabrication.

Power and distribution of evoked gamma oscillations in brain aging and cognitive performance.

Aims: Gamma oscillations (≈25-100 Hz) are believed to play an essential role in cognition, and aberrant gamma oscillations occur in brain aging and neurodegeneration. This study examined age-related changes in visually evoked gamma oscillations at two different time points 5 years apart and tested the hypothesis that the power of gamma oscillations correlated to cognitive skills.

Methods: The cohort consists of elderly males belonging to the Metropolit 1953 Danish Male Birth Cohort (first visit, N=124; second visit, N=88) over a 5-year period from 63 to 68 years of age.

Bowel dysfunction following pelvic organ cancer: a prospective study on the treatment effect in nurse-led late sequelae clinics.

Background: Bowel dysfunction following treatment of pelvic organ cancer is prevalent and impacts the quality of life (QoL). The present study aimed to evaluate the feasibility and effects of treating bowel dysfunction in two nurse-led late sequelae clinics.

Material And Methods: Treatment effects were monitored prospectively by patient-reported outcome measures collected at baseline and discharge.

Changes in hippocampal volume during a preceding 10-year period do not correlate with cognitive performance and hippocampal blood‒brain barrier permeability in cognitively normal late-middle-aged men.

Hippocampal blood-brain barrier (BBB) permeability may increase in normal healthy ageing and contribute to neurodegenerative disease. To examine this hypothesis, we investigated the correlation between blood-brain barrier (BBB) permeability, regional brain volume, memory functions and health and lifestyle factors in The Metropolit 1953 Danish Male Birth Cohort. We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a gadolinium-based contrast agent to assess BBB permeability in 77 participants in the cohort.

Blood-Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles.

The blood-brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for the delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation.

Practical considerations for navigating the regulatory landscape of non-clinical studies for clinical translation of radiopharmaceuticals.

Background: The development of radiopharmaceuticals requires extensive evaluation before they can be applied in a diagnostic or therapeutic setting in Nuclear Medicine. Chemical, radiochemical, and pharmaceutical parameters must be established and verified to ensure the quality of these novel products.

Main Body: To provide supportive evidence for the expected human in vivo behaviour, particularly related to safety and efficacy, additional tests, often referred to as "non-clinical" or "preclinical" are mandatory.

Subclinical cognitive deficits are associated with reduced cerebrovascular response to visual stimulation in mid-sixties men.

Reduced cerebrovascular response to neuronal activation is observed in patients with neurodegenerative disease. In the present study, we examined the correlation between reduced cerebrovascular response to visual activation (ΔCBF) and subclinical cognitive deficits in a human population of mid-sixties individuals without neurodegenerative disease. Such a correlation would suggest that impaired cerebrovascular function occurs before overt neurodegenerative disease.

Shedding Light on the Blood-Brain Barrier Transport with Two-Photon Microscopy In Vivo.

Treatment of brain disorders relies on efficient delivery of therapeutics to the brain, which is hindered by the blood-brain barrier (BBB). The work of Prof. Margareta Hammarlund-Udenaes was instrumental in understanding the principles of drug delivery to the brain and developing new tools to study it.

The Effect of Wearable Tracking Devices on Cardiorespiratory Fitness Among Inactive Adults: Crossover Study.

Background: Modern lifestyle is associated with a high prevalence of physical inactivity.

Objective: This study aims to investigate the effect of a wearable tracking device on cardiorespiratory fitness among inactive adults and to explore if personal characteristics and health outcomes can predict adoption of the device.

Methods: In total, 62 inactive adults were recruited for this study.

Brain barriers and their potential role in migraine pathophysiology.

Migraine is a ubiquitous neurologic disease that afflicts people of all ages. Its molecular pathogenesis involves peptides that promote intracranial vasodilation and modulate nociceptive transmission upon release from sensory afferents of cells in the trigeminal ganglion and parasympathetic efferents of cells in the sphenopalatine ganglion. Experimental data have confirmed that intravenous infusion of these vasoactive peptides induce migraine attacks in people with migraine, but it remains a point of scientific contention whether their site of action lies outside or within the central nervous system.

A Simple and Cost-Effective Method for Measuring Hemolysis in Biobank Serum Specimens.

During sampling and processing, blood samples can be affected by hemolysis. Information is lacking regarding hemolysis for biobank samples. There is a need for a method that can easily measure hemoglobin as an indicator of hemolysis in stored samples before they are included in research projects.

Automatic continuous EEG signal analysis for diagnosis of delirium in patients with sepsis.

Objective: In critical care, continuous EEG (cEEG) monitoring is useful for delirium diagnosis. Although visual cEEG analysis is most commonly used, automatic cEEG analysis has shown promising results in small samples. Here we aimed to compare visual versus automatic cEEG analysis for delirium diagnosis in septic patients.

Post-capillary venules are the key locus for transcytosis-mediated brain delivery of therapeutic nanoparticles.

Effective treatments of neurodegenerative diseases require drugs to be actively transported across the blood-brain barrier (BBB). However, nanoparticle drug carriers explored for this purpose show negligible brain uptake, and the lack of basic understanding of nanoparticle-BBB interactions underlies many translational failures. Here, using two-photon microscopy in mice, we characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery to the brain in vivo.

Precapillary sphincters and pericytes at first-order capillaries as key regulators for brain capillary perfusion.

Rises in local neural activity trigger local increases of cerebral blood flow, which is essential to match local energy demands. However, the specific location of microvascular flow control is incompletely understood. Here, we used two-photon microscopy to observe brain microvasculature in vivo.

Ultralow amounts of DNA from long-term archived serum samples produce high-quality methylomes.

Background: Long-term stored serum is considered challenging for epigenomic analyses: as there are no cells, circulating DNA is scarce, and amplification removes epigenetic signals. Additionally, pre-analytical treatments and storage might introduce biases and fragmentation to the DNA. In particular, starting with low-input DNA can result in low-diversity libraries.