Actigraphy-based assessment of circadian rhythmicity and sleep in patients with Usher syndrome type 2a: A case-control study.

This study aimed to improve our understanding of sleep problems as a comorbidity of hereditary deaf-blindness due to Usher syndrome type 2a. Fifteen patients with Usher syndrome type 2a with a conclusive genetic diagnosis and 15 unaffected controls participated in comprehensive sleep and activity assessments for 2 weeks, using the MotionWatch 8 actigraph and consensus sleep diary. Various sleep parameters including sleep opportunity window, sleep latency, sleep efficiency, and self-reported sleep quality were analysed.

Exploring non-coding variants and evaluation of antisense oligonucleotides for splicing redirection in Usher syndrome.

Exploring non-coding regions is increasingly gaining importance in the diagnosis of inherited retinal dystrophies. Deep-intronic variants causing aberrant splicing have been identified, prompting the development of antisense oligonucleotides (ASOs) to modulate splicing. We performed a screening of five previously described deep-intronic variants among monoallelic patients with Usher syndrome (USH) or isolated retinitis pigmentosa.

A proteogenomic atlas of the human neural retina.

The human neural retina is a complex tissue with abundant alternative splicing and more than 10% of genetic variants linked to inherited retinal diseases (IRDs) alter splicing. Traditional short-read RNA-sequencing methods have been used for understanding retina-specific splicing but have limitations in detailing transcript isoforms. To address this, we generated a proteogenomic atlas that combines PacBio long-read RNA-sequencing data with mass spectrometry and whole genome sequencing data of three healthy human neural retina samples.

variants cause cardiac dysfunction in a zebrafish model.

The Ras-related GTP-binding protein D () gene plays a crucial role in cellular processes. Recently, variants found in patients have been implicated in a novel disorder with kidney tubulopathy and dilated cardiomyopathy. Currently, the consequences of variants at the organismal level are unknown.

The relation between stress-induced dopamine release in the ventromedial prefrontal cortex, fronto-striatal functional connectivity, and negative urgency: A multimodal investigation using [F]Fallypride PET, MRI and experience sampling.

Negative urgency (NU), or the tendency to act rashly when stress of negative affect is high, could be the result of an insufficient control of the ventromedial prefrontal cortex (vmPFC) over the striatum, through an impaired dopamine (DA) transmission. Therefore, we investigated in vivo human stress-induced DA release in the vmPFC, its relation with fronto-striatal functional connectivity (FC), and NU in daily life. In total, 12 female healthy participants performed a simultaneous [18 F]fallypride PET and fMRI scan during which stress was induced.

Person-specific and pooled prediction models for binge eating, alcohol use and binge drinking in bulimia nervosa and alcohol use disorder.

Background: Machine learning could predict binge behavior and help develop treatments for bulimia nervosa (BN) and alcohol use disorder (AUD). Therefore, this study evaluates person-specific and pooled prediction models for binge eating (BE), alcohol use, and binge drinking (BD) in daily life, and identifies the most important predictors.

Methods: A total of 120 patients (BN: 50; AUD: 51; BN/AUD: 19) participated in an experience sampling study, where over a period of 12 months they reported on their eating and drinking behaviors as well as on several other emotional, behavioral, and contextual factors in daily life.

Rational design of a genomically humanized mouse model for dominantly inherited hearing loss, DFNA9.

DFNA9 is a dominantly inherited form of adult-onset progressive hearing impairment caused by mutations in the COCH gene. COCH encodes cochlin, a crucial extracellular matrix protein. We established a genomically humanized mouse model for the Dutch/Belgian c.

['Slimmer's paralysis': peroneal neuropathy in anorexia nervosa].

We describe the development of slimmer’s paralysis or ‘foot drop’ in a patient with anorexia nervosa caused by a transient peroneal nerve injury. This was caused by extreme weight loss in combination with frequently crossing the legs in the context of anorexia nervosa with body image distortion. The most important interventions were weight recovery, physical therapy and avoiding precipitating factors.

The role of short-chain fatty acids (SCFAs) in regulating stress responses, eating behavior, and nutritional state in anorexia nervosa: protocol for a randomized controlled trial.

Objective: This protocol proposes investigating the effects of short-chain fatty acids (SCFAs)-namely acetate, propionate, and butyrate-as mediators of microbiota-gut-brain interactions on the acute stress response, eating behavior, and nutritional state in malnourished patients with anorexia nervosa (AN). SCFAs are produced by bacterial fermentation of dietary fiber in the gut and have recently been proposed as crucial mediators of the gut microbiota's effects on the host. Emerging evidence suggests that SCFAs impact human psychobiology through endocrine, neural, and immune pathways and may regulate stress responses and eating behavior.

Neuronal activity and reward processing in relation to binge eating.

Purpose Of Review: Studies increasingly show the importance of reward processing in binge eating and provide evidence of associated changes in the neurobiological reward system. This review gives an up-to-date overview of the neurobiological substrates of reward processing subconstructs in binge eating. Neural findings are linked to different behavioral theories and the clinical relevance is discussed.

[Lichaam en geest bij anorexia nervosa; een systematisch literatuuroverzicht].

Background: Body image disturbance is a key component in anorexia nervosa (AN). In the treatment of AN this disturbed perception of the body poses a hindrance for clinical improvement and weight gain. Mindfulness and yoga are associated with a positive effect on the symptomatology of eating disorders.

Succinic semialdehyde dehydrogenase deficiency in mice and in humans: An untargeted metabolomics perspective.

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare neurometabolic disorder caused by disruption of the gamma-aminobutyric acid (GABA) pathway. A more detailed understanding of its pathophysiology, beyond the accumulation of GABA and gamma-hydroxybutyric acid (GHB), will increase our understanding of the disease and may support novel therapy development. To this end, we compared biochemical body fluid profiles from SSADHD patients with controls using next-generation metabolic screening (NGMS).

Generation and Characterization of a Zebrafish Model for Associated Retinal Dysfunction Using CRISPR/Cas9 Genome Editing Technology.

Worldwide, around 40,000 people progressively lose their eyesight as a consequence of retinitis pigmentosa (RP) caused by pathogenic variants in the gene, for which currently no treatment options exist. A model organism that mimics the human phenotype is essential to unravel the exact pathophysiological mechanism underlying associated RP, and to evaluate future therapeutic strategies. The introduction of CRISPR/Cas-based genome editing technologies significantly improved the possibilities of generating mutant models in a time- and cost-effective manner.

Evaluation of Sleep Quality and Fatigue in Patients with Usher Syndrome Type 2a.

Purpose: To study the prevalence, level, and nature of sleep problems and fatigue experienced by Usher syndrome type 2a (USH2a) patients.

Design: Cross-sectional study.

Participants: Fifty-six genetically confirmed Dutch patients with syndromic USH2a and 120 healthy controls.

A protein domain-oriented approach to expand the opportunities of therapeutic exon skipping for -associated retinitis pigmentosa.

Loss-of-function mutations in are among the most common causes of syndromic and non-syndromic retinitis pigmentosa (RP). We previously presented skipping of exon 13 as a promising treatment paradigm for -associated RP. However, RP-associated mutations are often private, and evenly distributed along the gene.

How negative affect does and does not lead to binge eating-The importance of craving and negative urgency in bulimia nervosa.

Studies suggest that negative affect (NA) can trigger binge eating (BE) in patients with bulimia nervosa (BN). Important factors in this relation between NA and BE could be craving (an intense desire for a BE episode) and negative urgency (the tendency to act rashly when NA is high). Therefore, this study wants to firstly explore the relations between NA, craving, rash action, and BE in daily life and secondly whether craving and rash action mediate the relationship between NA and BE.

Disruption of the gene in zebrafish reveals conserved functions in development of the craniofacial skeleton and the thyroid.

Mutations in the FOXE1 gene are implicated in cleft palate and thyroid dysgenesis in humans. To investigate whether zebrafish could provide meaningful insights into the etiology of developmental defects in humans related to FOXE1, we generated a zebrafish mutant that has a disruption in the nuclear localization signal in the foxe1 gene, thereby restraining nuclear access of the transcription factor. We characterized skeletal development and thyroidogenesis in these mutants, focusing on embryonic and larval stages.

The cumulative effect of chronic stress and depressive symptoms affects heart rate in a working population.

Background: Chronic stress and depressive symptoms have both been linked to increased heart rate (HR) and reduced HR variability. However, up to date, it is not clear whether chronic stress, the mechanisms intrinsic to depression or a combination of both cause these alterations. Subclinical cases may help to answer these questions.

Regulation of CD4 and CD8 T Cell Biology by Short-Chain Fatty Acids and Its Relevance for Autoimmune Pathology.

The gut microbiota encodes a broad range of enzymes capable of synthetizing various metabolites, some of which are still uncharacterized. One well-known class of microbiota-derived metabolites are the short-chain fatty acids (SCFAs) such as acetate, propionate, butyrate and valerate. SCFAs have long been considered a mere waste product of bacterial metabolism.

The neurobiological reward system and binge eating: A critical systematic review of neuroimaging studies.

Objective: Changes in reward processing are hypothesized to play a role in the onset and maintenance of binge eating (BE). However, despite an increasing number of studies investigating the neurobiological reward system in individuals who binge eat, no comprehensive systematic review exists on this topic. Therefore, this review has the following objectives: (1) identify structural and functional changes in the brain reward system, either during rest or while performing a task; and (2) formulate directions for future research.

Affinity purification of in vivo assembled whirlin-associated protein complexes from the zebrafish retina.

Mutations in WHRN lead to Usher syndrome type 2d or to non-syndromic hearing impairment. The WHRN-encoded gene product whirlin directly interacts with the intracellular regions of the other two Usher syndrome type 2-associated proteins, usherin and ADGRV1. In photoreceptor cells, this protein complex constitutes fibrous links between the periciliary membrane and the connecting cilium.

Scrutinizing pathogenicity of the USH2A c.2276 G > T; p.(Cys759Phe) variant.

The USH2A variant c.2276 G > T (p.(Cys759Phe)) has been described by many authors as a frequent cause of autosomal recessive retinitis pigmentosa (arRP).

Altering gene expression using antisense oligonucleotide therapy for hearing loss.

Hearing loss affects more than 430 million people, worldwide, and is the third most common chronic physical condition in the United States and Europe (GBD Hearing Loss Collaborators, 2021; NIOSH, 2021; WHO, 2021). The loss of hearing significantly impacts motor and cognitive development, communication, education, employment, and overall quality of life. The inner ear houses the sensory organs for both hearing and balance and provides an accessible target for therapeutic delivery.

Exhausted Heart Rate Responses to Repeated Psychological Stress in Women With Major Depressive Disorder.

Past research links depression and blunted cardiac vagal reactivity to chronic stress. Yet, to our knowledge no experiment investigates heart rate (variability) responses to a repeated laboratory stressor in patients with depression. Repeated exposure may provide valuable information on stress reactivity in depression.