Relationship between daily rated depression symptom severity and the retrospective self-report on PHQ-9 : A prospective ecological momentary assessment study on 80 psychiatric outpatients

Peer reviewe

GP participation in increasing uptake in a national bowel cancer screening programme: the PEARL project

Policy Research Unit (PRU) in Cancer Awareness, Screening and Early BRITISH JOURNAL OF CANCER The PEARL project The PRU receives funding for a research programme from the Department of Health Policy Research Programm

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

Relationship between daily rated depression symptom severity and the retrospective self-report on PHQ-9 : A prospective ecological momentary assessment study on 80 psychiatric outpatients

Peer reviewe

Disc herniations in astronauts: What causes them, and what does it tell us about herniation on earth?

PURPOSE: Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities. METHODS: The authors performed a narrative literature review of the possible mechanisms, and conducted a survey within the team to prioritize research and prevention approaches. RESULTS AND CONCLUSIONS: Based on literature review the most likely cause for lumbar IVD herniations was concluded to be swelling of the IVD in the unloaded condition during spaceflight. For the cervical IVDs, the knowledge base is too limited to postulate a likely mechanism or recommend approaches for prevention. Basic research on the impact of (un)loading on the cervical IVD and translational research is needed. The highest priority prevention approach for the lumbar spine was post-flight care avoiding activities involving spinal flexion, followed by passive spinal loading in spaceflight and exercises to reduce IVD hyper-hydration post-flight

Cervical spine and muscle adaptation after spaceflight and relationship to herniation risk:protocol from 'Cervical in Space' trial

BACKGROUND: Astronauts have a higher risk of cervical intervertebral disc herniation. Several mechanisms have been attributed as causative factors for this increased risk. However, most of the previous studies have examined potential causal factors for lumbar intervertebral disc herniation only. Hence, we aim to conduct a study to identify the various changes in the cervical spine that lead to an increased risk of cervical disc herniation after spaceflight. METHODS: A cohort study with astronauts will be conducted. The data collection will involve four main components: a) Magnetic resonance imaging (MRI); b) cervical 3D kinematics; c) an Integrated Protocol consisting of maximal and submaximal voluntary contractions of the neck muscles, endurance testing of the neck muscles, neck muscle fatigue testing and questionnaires; and d) dual energy X-ray absorptiometry (DXA) examination. Measurements will be conducted at several time points before and after astronauts visit the International Space Station. The main outcomes of interest are adaptations in the cervical discs, muscles and bones. DISCUSSION: Astronauts are at higher risk of cervical disc herniation, but contributing factors remain unclear. The results of this study will inform future preventive measures for astronauts and will also contribute to the understanding of intervertebral disc herniation risk in the cervical spine for people on Earth. In addition, we anticipate deeper insight into the aetiology of neck pain with this research project. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00026777. Registered on 08 October 2021. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05684-0

A population-specific HTR2B stop codon predisposes to severe impulsivity

Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission