GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation : a potential neurogenetic pathway to panic disorder

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG - related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1,370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, p=3.3x10-8; rs191260602, p=3.9x10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2,547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3,845) and a case control sample with the categorical phenotype PD/AG (Ncombined =1,012) obtaining highly significant p-values also for GLRB single nucleotide variants rs17035816 (p=3.8x10-4) and rs7688285 (p=7.6x10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout-mice demonstrated an agoraphobic phenotype. In conjunction withthe clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, though functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.PostprintPeer reviewe

Küchenassistenzroboter für Seniorinnen und Senioren : Bedürfnisse, Akzeptanzfaktoren und Wirtschaftlichkeit

Hintergrund: Ältere Menschen wünschen sich möglichst lange unabhängig in der eigenen Wohnung leben zu können. Insbesondere das Arbeiten in der Küche stellt jedoch eine grosse Herausforderung dar. Im Rahmen eines interdisziplinären Projekts untersuchten Forschende der Zürcher Hochschule für angewandte Wissenschaften, der FH St. Gallen verschiedene Fragestellungen, die das Arbeiten älterer Menschen in der Küche betreffen. Das Projekt wurde von der Walder Stiftung finanziert und von Pro Senectute unterstützt. Ziele der Studie: Hauptziel der Studie war es festzustellen, ob ein Roboterarm eine sinnvolle und wirtschaftlich machbare Unterstützung für ältere Menschen in der Küche sein könnte. Dazu wurden folgende Fragestellungen untersucht: - Wie verändert sich die Bedeutung der Küche und des Kochens im Laufe des Lebens? - Welche Einschränkungen erfahren ältere Menschen während der Küchenarbeiten? - Unter welchen Bedingungen würden sie einen Roboterarm akzeptieren? - Wie gross ist das Marktpotential und welche Marktzugänge wären erfolgsversprechend? - Sind die Anforderungen der Personen und des Marktes technisch realisierbar? Methodik: Neben einer Literaturrecherche wurden eine Fokusgruppe und zwei Gruppeninterviews durchgeführt. Mit Hilfe einer Marktanalyse wurde die Wirtschaftlichkeit eines Roboterarms untersucht. Resultate: Die Bedeutung des Kochens verändert sich im Alter. Unterstützung wünschen sie die Teilnehmenden der Fokusgruppen insbesondere bei Tätigkeiten, die viel Kraft und Geschicklichkeit erfordern, die Mobilität betreffen und die unbeliebt und zeitaufwendig sind (z.B. Reinigungsarbeiten). In der Fokusgruppe konnte eine grundsätzliche Offenheit und Technikbereitschaft festgestellt werden. Besonders Menschen mit starken Einschränkungen eigenen sich hilfreiche Strategien an, um den Küchenalltag einfacher zu gestalten. Die Untersuchung der Wirtschaftlichkeit und technischen Machbarkeit ergab, dass der Einbau eines Roboterarms in bestehende Küchen aufgrund der Kosten, der hohen Erwartungen der Nutzenden und der meist kleinen Küchen wenig erfolgsversprechend ist. Für den Neubau altersgerechter Wohnungen könnte der Einbau von technischer Assistenz wie z.B. eines Roboterarms eher sinnvoll sein

Acute regulation of metabolic genes and insulin receptor substrates in the liver of mice by one single bout of treadmill exercise

Acute exercise performance represents a major metabolic challenge for the skeletal muscle, but also for the liver as the most important source of energy. However the molecular adaptation of the liver to one single bout of exercise is largely unknown. C57BL/6 mice performed a 60 min treadmill run at high aerobic intensity. Liver, soleus and white gastrocnemius muscle were removed immediately after exercise. The single bout of exercise resulted in a very rapid and pronounced induction of hepatic metabolic enzymes and regulators of metabolism or transcription: glucose-6-phosphatase (G6Pase; 3-fold), pyruvate dehydrogenase kinase-4 (PDK4; 4.8-fold), angiopoietin-like 4 (2.1-fold), insulin receptor substrate (IRS)-2 (5.1-fold), peroxisome proliferator activated receptor-γ coactivator 1α (PGC-1α; 3-fold). In soleus and white gastrocnemius muscle the up-regulation of IRS-2 and PDK4 was less pronounced compared with the liver and no significant induction of PGC-1α could be detected at this early time point. Activation of AMPK was found in both liver and white gastrocnemius muscle as phosphorylation of Thr-172. The induction of endogenous insulin secretion by a glucose load directly after the exercise bout resulted in a significantly higher PKB/Akt phosphorylation in the liver of exercised mice. The markedly enhanced IRS-2 protein amount, and presumably reduced serine/threonine phosphorylation of the IRS proteins induced by the acute exercise could be responsible for this enhanced action of insulin. In conclusion, acute exercise induced a rapid and pronounced transcriptional adaptation in the liver, and regulated hepatic IRS proteins leading to improved cellular insulin signal transduction

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: One-Year Follow-up.

BACKGROUND AND OBJECTIVES Declines in stroke admission, intravenous thrombolysis, and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the impact of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), intravenous thrombolysis (IVT), and mechanical thrombectomy over a one-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). METHODS We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, intravenous thrombolysis treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS There were 148,895 stroke admissions in the one-year immediately before compared to 138,453 admissions during the one-year pandemic, representing a 7% decline (95% confidence interval [95% CI 7.1, 6.9]; p<0.0001). ICH volumes declined from 29,585 to 28,156 (4.8%, [5.1, 4.6]; p<0.0001) and IVT volume from 24,584 to 23,077 (6.1%, [6.4, 5.8]; p<0.0001). Larger declines were observed at high volume compared to low volume centers (all p<0.0001). There was no significant change in mechanical thrombectomy volumes (0.7%, [0.6,0.9]; p=0.49). Stroke was diagnosed in 1.3% [1.31,1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82,2.97], 5,656/195,539) of all stroke hospitalizations. DISCUSSION There was a global decline and shift to lower volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared to the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. TRIAL REGISTRATION INFORMATION This study is registered under NCT04934020