7T MRI as a powerful tool to detect small and medium size vessel CNS vasculitis.

Imaging can help to diagnose CNS vasculitis. Yet so far, no imaging studies of CNS vasculitis at 7T are available. We share our experience of vessel wall imaging (VWI) at 7T in patients with suspected vasculitis.

Assessment of the available evidence for the use of 7-Tesla (T) magnetic resonance imaging (MRI) in neurological and musculoskeletal disorders, with comparison to 3-T and 1.5-T MRI: A systematic scoping review.

Background: Ultra-high-field magnetic resonance imaging (MRI) at a field strength of 7 Tesla (T) has marked a significant milestone in diagnostic imaging since it was approved for clinical use in 2017. Despite the potential to improve image analysis by advances in signal-to-noise ratio, and improved spatial resolution and metabolic imaging, the clinical implementation of 7-T MRI remains limited. Factors that contribute to this limited availability are the high price, the operating costs, the need for specifically educated personnel, and lack of evidence of clinical benefit.

A flexible framework for the design and optimization of water-excitation RF pulses using B-spline interpolation.

Purpose: To implement a flexible framework, named HydrOptiFrame, for the design and optimization of time-efficient water-excitation (WE) RF pulses using B-spline interpolation, and to characterize their lipid suppression performance.

Methods: An evolutionary optimization algorithm was used to design WE RF pulses. The algorithm minimizes a composite loss function that quantifies the fat-water contrast using Bloch equation simulations.

Preclinical safety and efficacy of the recombinant CR1 drug product CSL040 in rats and cynomolgus monkeys.

CSL040 is a soluble, recombinant fragment of the complement receptor 1 (CR1) extracellular domain that acts as an inhibitor of all three pathways of the complement system. Systemic toxicity, toxicokinetics (TK), and pharmacodynamics (PD) of CSL040 were assessed in two-week intravenous (IV) bolus studies in Han Wistar rats and cynomolgus monkeys. Recovery from any effects was evaluated during a four-week recovery period.

Venous Leak Embolization Results in Clinical Improvement of Patients with Mixed Arterio-Venous Erectile Dysfunction Not Responding to Arterial Revascularization Alone.

Purpose: To analyze the safety and efficacy of additional venous leak embolization after an initial arterial revascularization to treat patients with combined arteriogenic and venogenic erectile dysfunction (ED).

Materials And Methods: Single-center observational study from October 1, 2019, to September 30, 2022, including 26 patients with ED resistant to phosphodiesterase-5-inhibitors (PDE5i) and without significant clinical benefit after arterial revascularization of erection-related arteries. Additional treatment with venous leak embolization was performed 458 ± 424 days after arterial revascularization.

Reversible white matter changes following a 4-week high phenylalanine exposure in adults with phenylketonuria.

Alterations in brain structure are frequently observed in adults with early-treated phenylketonuria (PKU) compared to healthy controls, with cerebral white matter (WM) being particularly affected. The extent to which temporary elevation of phenylalanine (Phe) levels impacts WM remains unclear. We conducted a double-blind, randomised, placebo-controlled crossover trial to investigate the effects of a 4-week high Phe exposure on cerebral WM and its relationship to cognitive performance and metabolic parameters in adults with PKU.

MRI Dixon Fat-Corrected Look-Locker T1 Mapping for Quantification of Liver Fibrosis and Inflammation-A Comparison With the Non-Fat-Corrected Shortened Modified Look-Locker Inversion Recovery Technique.

Objectives: This study evaluates the impact of liver steatosis on the discriminative ability for liver fibrosis and inflammation using a novel Dixon water-only fat-corrected Look-Locker T1 mapping sequence, compared with a standard shortened Modified Look-Locker Inversion Recovery (shMOLLI) sequence, with the aim of overcoming the limitation of steatosis-related confounding in liver T1 mapping.

Materials And Methods: 3 T magnetic resonance imaging of the liver including the 2 T1 mapping sequences and proton density fat fraction (PDFF) was prospectively performed in 24 healthy volunteers and 38 patients with histologically proven liver fibrosis evaluated within 90 days of liver biopsy. Paired Mann-Whitney test compared sequences between participants with and without significant liver steatosis (PDFF cutoff 10%), and unpaired Kruskal-Wallis test compared healthy volunteers to patients with early (F0-2) and advanced (F3-4) liver fibrosis, as well as low (A0-1) and marked (A2-3) inflammatory activity.

Effect of a colorectal bundle in an entire health care region in Switzerland: Results from a prospective cohort study (EvaCol study).

Introduction: Standardisation has the potential to serve as a measure to mitigate complication rates. The objective was to assess the impact of standardisation by implementing a colorectal bundle (CB), which comprises nine elements, on the complication rates in left-sided colorectal resections.

Patients And Methods: This prospective, multicentre, observational, cohort trial was conducted in Switzerland at nine participating hospitals.

Locus coeruleus co-activation patterns at rest show higher state persistence in patients with dissociative seizures: A Pilot Study.

Objective: Dissociative seizures are paroxysmal disruptions of awareness and behavioral control in the context of affective arousal. Alterations in stress-related endocrine function have been demonstrated, but the timescale of dissociation suggests that the central locus coeruleus (LC) noradrenergic system is likely pivotal. Here, we investigate whether LC activation at rest is associated with altered brain network dynamics.

Identifying health inequities faced by older adults with rare diseases: A systematic literature review and proposal for an ethical spectrum and resource allocation framework.

Ageism in healthcare has received increased attention in recent years, but literature focusing on how it affects individuals living with rare diseases remains scant. The rare disease population already faces obstacles when navigating health systems, and ageism has the potential to exacerbate existing health inequities. We conducted a systematic review of peer-reviewed and gray literature on health inequities in rare disease populations, seeking to identify publications that reported primary or secondary data on the equitable or inequitable treatment of these populations, or that discussed related regulatory, moral, or philosophical issues.

The challenges of regulatory pluralism.

Countries with small and/or less-resourced regulatory authorities that operate outside of a larger medical product regulatory system face a regulatory strategy dilemma. These countries may rely on foreign well-resourced regulators by recognising the regulatory decisions of large systems and following suit (regulatory reliance); alternatively, such countries may extend formal decision recognition to regulators in multiple other jurisdictions with similar oversight and public health goals, following a system which we call regulatory pluralism. In this policy comment, we discuss three potential limitations to regulatory pluralism: (i) regulatory escape, in which manufacturers exploit regulatory variation and choose the lowest regulatory threshold for their product; (ii) increased fragmentation and complexity for countries adopting this approach, which may, in turn, lead to inconsistent processes; and (iii) loss of international bargaining power in developing regulatory policies.

The modernisation of newborn screening as a pan-European challenge - An international delphi study.

Newborn screening is a public health measure to diagnose rare diseases at birth, thereby minimising negative effects of late treatment. Genomic technologies promise an unprecedented expansion of screened diseases at low cost and with transformative potential for newborn screening programmes. However, barriers to the public funding of genomic newborn screening are poorly understood, particularly in light of the heterogenous European newborn screening landscape.

Alterations of perfusion and functional connectivity of the cingulate motor area are associated with psychomotor retardation in major depressive disorder.

Psychomotor retardation, characterized by slowing of speech, thoughts, and a decrease of movements, is frequent in patients with major depressive disorder (MDD). However, its neurobiological correlates are still poorly understood. This study aimed to explore if cerebral blood flow (CBF) and resting state functional connectivity (rs-FC) of the motor network are altered in patients with MDD and if these changes are associated with psychomotor retardation.

Fat-free noncontrast whole-heart cardiovascular magnetic resonance imaging with fast and power-optimized off-resonant water-excitation pulses.

Background: Cardiovascular magnetic resonance imaging (CMR) faces challenges due to the interference of bright fat signals in visualizing structures, such as coronary arteries. Effective fat suppression is crucial, especially when using whole-heart CMR techniques. Conventional methods often fall short due to rapid fat signal recovery, leading to residual fat content hindering visualization.

Intra- and extracellular real-time analysis of perfused fibroblasts using an NMR bioreactor: A pilot study.

Introduction: Metabolomic discrimination of different mitochondrial defects is challenging. We describe an NMR-based bioreactor allowing real-time intra- and extracellular metabolic investigation of perfused fibroblasts.

Objectives: The objective of this study is (I) determining whether metabolic investigations of perfused fibroblasts overall and separated for intra- and extracellular contributions by real-time NMR allows for discrimination of different representative mitochondrial defects in a feasibility study and (II) gaining insight into physiological consequences of mitochondrial dysfunction in basal condition and during glycolysis inhibition.

Standardized Production of Anti-Desmoglein 3 Antibody AK23 for Translational Pemphigus Vulgaris Research.

Antibody-mediated receptor activation is successfully used to develop medical treatments. If the activation induces a pathological response, such antibodies are also excellent tools for defining molecular mechanisms of target receptor malfunction and designing rescue therapies. Prominent examples are naturally occurring autoantibodies inducing the severe blistering disease pemphigus vulgaris (PV).

Effect of a four-week oral Phe administration on neural activation and cerebral blood flow in adults with early-treated phenylketonuria.

Background: Phenylketonuria (PKU) is a rare inborn error of metabolism characterized by impaired catabolism of the amino acid phenylalanine (Phe) into tyrosine. Cross-sectional studies suggest slight alterations in cognitive performance and neural activation in adults with early-treated PKU. The influence of high Phe levels on brain function in adulthood, however, remains insufficiently studied.

Neuronal current imaging of epileptic activity: An MRI study in patients with a first unprovoked epileptic seizure.

Objective: This study evaluates the performance of the novel MRI sequence stimulus-induced rotary saturation (SIRS) to map responses to interictal epileptic activity in the human cortex. Spin-lock pulses have been applied to indirectly detect neuronal activity through magnetic field perturbations. Following initial reports about the feasibility of the method in humans and animals with epilepsy, we aimed to investigate the diagnostic yield of spin-lock MR pulses in comparison with scalp-EEG in first seizure patients.

Analyzing fractal dimension in electroconvulsive therapy: Unraveling complexity in structural and functional neuroimaging.

Background: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response.

Trajectory correction enables free-running chemical shift encoded imaging for accurate cardiac proton-density fat fraction quantification at 3T.

Background: Metabolic diseases can negatively alter epicardial fat accumulation and composition, which can be probed using quantitative cardiac chemical shift encoded (CSE) cardiovascular magnetic resonance (CMR) by mapping proton-density fat fraction (PDFF). To obtain motion-resolved high-resolution PDFF maps, we proposed a free-running cardiac CSE-CMR framework at 3T. To employ faster bipolar readout gradients, a correction for gradient imperfections was added using the gradient impulse response function (GIRF) and evaluated on intermediate images and PDFF quantification.

Mechanistic insights into complement pathway inhibition by CR1 domain duplication.

Complement receptor 1 (CR1) is a membrane glycoprotein with a highly duplicated domain structure able to bind multiple ligands such as C3b and C4b, the activated fragments of complement components C3 and C4, respectively. We have previously used our knowledge of this domain structure to identify CSL040, a soluble extracellular fragment of CR1 containing the long homologous repeat (LHR) domains A, B, and C. CSL040 retains the ability to bind both C3b and C4b but is also a more potent complement inhibitor than other recombinant CR1-based therapeutics.

BOLD signal variability as potential new biomarker of functional neurological disorders.

Background: Functional neurological disorder (FND) is a common neuropsychiatric condition with established diagnostic criteria and effective treatments but for which the underlying neuropathophysiological mechanisms remain incompletely understood. Recent neuroimaging studies have revealed FND as a multi-network brain disorder, unveiling alterations across limbic, self-agency, attentional/salience, and sensorimotor networks. However, the relationship between identified brain alterations and disease progression or improvement is less explored.