The aqueous humor proteome of primary open angle glaucoma: An extensive review

Background: We reviewed the literature on the aqueous humor (AH) proteome of primary open angle glaucoma (POAG) patients in order to obtain deeper insight into the pathophysiology of POAG. Methods: We searched Pubmed and Embase up to May 2019 for studies that compared AH protein composition between POAG (cases) and cataract (controls). Untargeted studies (measuring the whole proteome, by LC-MS/MS) were divided into two subgroups depending on the type of surgery during which POAG AH was collected: glaucoma filtration surgery (subgroup 1) or cataract surgery (subgroup 2). We reanalyzed the raw data (subgroup 1) or combined the reported data (subgroup 2) to perform GO enrichment (GOrilla) and pathway analysis (Pathvisio). Results: Out of 93 eligible proteomic studies, seven were untargeted studies that identified 863 AH proteins. We observed 73 differentially expressed proteins in subgroup 1 and 87 differentially expressed proteins in subgroup 2. Both subgroups were characterized by activation of the acute immune response, dysregulation of folate metabolism and dysregulation of the selenium micronutrient network. For subgroup 1 but not for subgroup 2, proteins of the complement system were significantly enriched. Conclusion: AH proteome of POAG patients shows strong activation of the immune system. In addition, analysis suggests dysregulation of folate metabolism and dysregulation of selenium as underlying contributors. In view of their glaucoma surgery, POAG patients of subgroup 1 most likely are progressive whereas POAG patients in subgroup 2 most likely have stable POAG. The proteome difference between these subgroups suggests that the complement system plays a role in POAG progression

Rationalisatie van slaapmiddelen: een sisyfusarbeid?

Ondanks meerdere sensibilisatiecampagnes gedurende de afgelopen jaren blijft langdurig gebruik van slaapmiddelen een prevalent probleem. Gezien de snelle tolerantie voor het effect in combinatie met de bijwerkingen is langdurig gebruik veelal schadelijk voor de patiënt. Indien er geen andere mogelijkheid is dan het gebruik van slaapmiddelen, moet men de duur beperken tot twee weken en moet er systematisch getracht worden om bij langdurig gebruik deze middelen af te bouwen en finaal te stoppen. De afbouw van slaapmiddelen is een uitdaging gezien de psychologische en de fysieke afhankelijkheid aan deze middelen. De winst na afbouw treedt echter snel op. Bij het gebruik van deze geneesmiddelen bij ouderen is het risico op ongewenste effecten groter, met name een verminderd cognitief vermogen en verminderde motorische functies, met als gevolg een grotere kans op ongewenste sedatie, vallen en fracturen.status: publishe

SARS-CoV-2 infection causes prolonged cardiomyocyte swelling and inhibition of HIF1 alpha translocation in an animal model COVID-19

Recovered COVID-19 patients often display cardiac dysfunction, even after a mild infection. Most current histological results come from patients that are hospitalized and therefore represent more severe outcomes than most COVID-19 patients face. To overcome this limitation, we investigated the cardiac effects of SARS-CoV-2 infection in a hamster model. SARS-CoV-2 infected hamsters developed diastolic dysfunction after recovering from COVID-19. Histologically, increased cardiomyocyte size was present at the peak of viral load and remained at all time points investigated. As this increase is too rapid for hypertrophic remodeling, we found instead that the heart was oedemic. Moreover, cardiomyocyte swelling is associated with the presence of ischemia. Fibrin-rich microthrombi and pericyte loss were observed at the peak of viral load, resulting in increased HIF1α in cardiomyocytes. Surprisingly, SARS-CoV-2 infection inhibited the translocation of HIF1α to the nucleus both in hamster hearts, in cultured cardiomyocytes, as well as in an epithelial cell line. We propose that the observed diastolic dysfunction is the consequence of cardiac oedema, downstream of microvascular cardiac ischemia. Additionally, our data suggest that inhibition of HIF1α translocation could contribute to an exaggerated response upon SARS-CoV-2 infection