GDF15 promotes simultaneous astrocyte remodeling and tight junction strengthening at the blood–brain barrier

Perivascular astrocyte processes (PAP) surround cerebral endothelial cells (ECs) and modulate the strengthening of tight junctions to influence blood–brain barrier (BBB) permeability. Morphologically altered astrocytes may affect barrier properties and trigger the onset of brain pathologies. However, astrocyte-dependent mediators of these events remain poorly studied. Here, we show a pharmacologically driven elevated expression and release of growth/differentiation factor 15 (GDF15) in rat primary astrocytes and cerebral PAP. GDF15 has been shown to possess trophic properties for motor neurons, prompting us to hypothesize similar effects on astrocytes. Indeed, its increased expression and release occurred simultaneously to morphological changes of astrocytes in vitro and PAP, suggesting modulatory effects of GDF15 on these cells, but also neighboring EC. Administration of recombinant GDF15 was sufficient to promote astrocyte remodeling and enhance barrier properties between ECs in vitro, whereas its pharmacogenetic abrogation prevented these effects. We validated our findings in male high anxiety-related behavior rats, an animal model of depressive-like behavior, with shrunk PAP associated with reduced expression of the junctional protein claudin-5, which were both restored by a pharmacologically induced increase in GDF15 expression. Thus, we identified GDF15 as an astrocyte-derived trigger of astrocyte process remodeling linked to enhanced tight junction strengthening at the BBB.     

Ageusia and anosmia,a common sign of COVID-19? A case series from four countries

Journal of NeuroVirology - Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the...     

Allogeneic stem cell transplantation in AML with t(6;9)(p23;q34);DEK-NUP214 shows a favourable outcome when performed in first complete remission

Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a poor-risk entity, commonly associated with FLT3-ITD (internal tandem duplication). Allogeneic stem-cell tranplantation (allo-SCT) is recommended, although studies analysing the outcome of allo-SCT in this setting are lacking. We selected 195 patients with t(6;9) AML, who received a first allo-SCT between 2000 and 2016 from the EBMT (European Society for Blood and Marrow Transplantation) registry. Disease status at time of allo-SCT was the strongest independent prognostic factor, with a two-year leukaemia-free survival and relapse incidence of 57% and 19% in patients in CR1 (first complete remission), 34% and 33% in CR2 (second complete remission), and 24% and 49% in patients not in remission, respectively (P < 0·001). This study, which represents the largest one available in t(6;9) AML, supports the recommendation to submit these patients to allo-SCT in CR1.     

Abdominale Migräne im Kindesalter – eine wichtige Komponente des weiten Migränespektrums

Monatsschrift Kinderheilkunde -     

Evaluation of low-viscosity bulk-fill composites regarding marginal and internal adaptation

This study aimed at evaluating the marginal and internal adaptation of low-viscosity bulk-fill composites to enamel and dentin using a self-etch or an etch-and-rinse adhesive without and with artificial ageing. Hundred and twenty-eight MOD cavities in extracted molars were assigned to eight groups (n = 16), restored with the adhesives OptiBond FL (OFL) or Xeno V+ (X) and two low-viscosity bulk-fill composites SDR or x-tra base, covered with Premise. Tetric EvoCeram Bulk Fill and Premise served as a control. n = 8 per group were subjected to prolonged water storage (180 days) and thermocycling (2500×). Scanning electron microscopy was used to determine marginal gaps (MG) and interfacial adhesive defects (IAD). There were no significant differences between composite types in 44 out of 48 (MG) or 43/48 (IAD) comparisons. More MG were observed with X than with OFL (14 out of 16 comparisons, two significant), while in 16 of 16 comparisons with X more IAD were observed (14 significant). After artificial ageing, MG generally increased (9/16 significant), compared to IAD (one significant). The performance of the investigated composite types concerning the integrity of the tooth-composites interface was comparable. Compared to the 1-step self-etch system, the bond with the 3-step etch-and-rinse adhesive was raised.