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Data-driven pupil response profiles as transdiagnostic readouts for the detection of neurocognitive functioning in affective and anxiety disorders.
Get PDFINTRODUCTION
Neurocognitive functioning is a relevant transdiagnostic dimension in psychiatry. As pupil size dynamics track cognitive load during a working memory task, we aimed to explore if this parameter allows to identify psychophysiological subtypes in healthy participants and patients with affective and anxiety symptomatology.
METHODS
Our sample consisted of 226 participants who completed the N-back task during simultaneous fMRI and pupillometry measurements. We used Latent Class Growth Modeling to identify clusters based on pupil size in response to cognitive load. In a second step, these clusters were compared on affective and anxiety symptom levels, performance in neurocognitive tests, and fMRI activity.
RESULTS
The clustering analysis resulted in two distinct pupil response profiles: one with a stepwise increasing pupil size with increasing cognitive load (reactive group), the other one with a constant pupil size across conditions (non-reactive group). A larger increase in pupil size was significantly associated with better performance in neurocognitive tests in executive functioning and sustained attention. Statistical maps of parametric modulation of pupil size during the N-back task showed the frontoparietal network in the positive and the default mode network in the negative contrast. The pupil response profile of the reactive group was associated with more thalamic activity, likely reflecting better arousal upregulation, and less deactivation of the limbic system.
CONCLUSION
To conclude, pupil measurements have the potential to serve as a highly sensitive psychophysiological readout for detection of neurocognitive deficits in the core domain of executive functioning adding to the development of valid transdiagnostic constructs in psychiatry
Prechoroidal Cleft Regression After Switch to Intravitreal Brolucizumab.
No full textINTRODUCTION
Prechoroidal cleft has been described as a negative prognostic biomarker in patients affected with neovascular age related macular degeneration (nAMD). This peculiar finding consists of a lenticular hyporeflective space located between an outward bowing of Bruch's membrane and the base of a fibrovascular retinal pigment epithelium detachment (PED). Previous studies have reported the partial or complete regression of prechoroidal clefts after treatment with anti-vascular endothelial growth factor (VEGF) injections.
CASE REPORT
To report a case of complete anatomical regression of an unresponsive prechoroidal cleft after switching to intravitreal Brolucizumab. The patient maintained cleft regression over time and no adverse events (i.e., RPE tears, intraocular inflammation) were observed during follow-up.
CONCLUSIONS AND IMPORTANCE
To our knowledge, this case report is the first to analyze the clinical efficacy of brolucizumab targeting prechoroidal clefts. Clinical implication and pathogenesis of prechoroidal clefts are yet to be fully elucidated
Efficacy and feasibility of pharmacoscopy-guided treatment for acute myeloid leukemia patients who have exhausted all registered therapeutic options.
No full textNot available
Association of atrial fibrillation with survival in patients with low-flow low-gradient aortic stenosis with preserved ejection fraction undergoing TAVI.
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There is limited evidence on the prognostic significance of atrial fibrillation (AF) in patients with low flow, low gradient aortic stenosis with preserved ejection fraction (LFLG-pEF AS). We aimed to evaluate the recovery of stroke volume after transcatheter aortic valve implantation (TAVI) and clinical outcomes in patients with LFLG-pEF AS stratified by presence or absence of AF.
METHODS AND RESULTS
In a prospective TAVI registry, patients with preserved left ventricular ejection fraction (LVEF ≥ 50%) were stratified according to flow-gradient status and presence of AF. Among 2 259 TAVI patients with preserved LVEF between August 2007 and June 2021, 765 had high-gradient AS (HG AS) and 444 had LFLG-pEF AS. AF was observed in 199 patients with HG AS (26.0%) and 190 patients with LFLG-pEF AS (42.8%). At 1 year, SVi was significantly improved in LFLG-pEF AS patients without AF, while SVi remained low in patients with AF (from 25.9 ± 8.5 mL/m2 to 37.2 ± 9.9 mL/m2 and from 26.8 ± 5.1 mL/m2 to 26.1 ± 9.1 mL/m2, respectively). LFLG-pEF AS patients with AF had an increased risk of 1-year all-cause mortality compared with those without AF (HRadjusted 2.57; 95% CI 1.44-4.59). LFLG-pEF AS patients without AF had similar mortality compared with HG AS patients without AF (HRadjusted 0.85; 95% CI 0.49-1.46).
CONCLUSIONS
Patients with LFLG-pEF AS and AF experienced no relevant recovery of stroke volume after TAVI, but a more than two-fold increased risk of death compared to patients with HG AS or LFLG-pEF AS without AF. Clinical Trial Registration: https://www.clinicaltrials.gov. NCT01368250
EEG Microstates in Social and Affective Neuroscience.
Get PDFSocial interactions require both the rapid processing of multifaceted socio-affective signals (e.g., eye gaze, facial expressions, gestures) and their integration with evaluations, social knowledge, and expectations. Researchers interested in understanding complex social cognition and behavior face a "black box" problem: What are the underlying mental processes rapidly occurring between perception and action and why are there such vast individual differences? In this review, we promote electroencephalography (EEG) microstates as a powerful tool for both examining socio-affective states (e.g., processing whether someone is in need in a given situation) and identifying the sources of heterogeneity in socio-affective traits (e.g., general willingness to help others). EEG microstates are identified by analyzing scalp field maps (i.e., the distribution of the electrical field on the scalp) over time. This data-driven, reference-independent approach allows for identifying, timing, sequencing, and quantifying the activation of large-scale brain networks relevant to our socio-affective mind. In light of these benefits, EEG microstates should become an indispensable part of the methodological toolkit of laboratories working in the field of social and affective neuroscience
DigiPrim – Status quo der Digitalisierung auf der Primarstufe.
Get PDFDieser Bericht präsentiert aktuelle und umfassende, stichprobenbasierte Erkenntnisse zum Stand der Digitalisierung in Schweizer Primarschulen. Basierend auf Befragungen von Schulleitungen und Eltern zwischen Mai und Juli 2022 zeigt sich eine grosse Heterogenität zwischen den Schulen hinsichtlich technischer Ausstattung, personeller Ressourcen und digitaler Schulkultur. Während viele Primarschulen bereits wichtige Vorbedingungen für die Nutzung digitaler Technologien erfüllen, stehen andere Primarschulen noch vor ganz grundlegenden Herausforderungen. Insbesondere zwischen den Sprachregionen zeigen sich systematische Unterschiede, während weitere Strukturmerkmale der Gemeinden und der Schulen nur vereinzelt mit Aspekten der Digitalisierung in Zusammenhang stehen. Digitale Geräte werden in der Mehrheit der Primarschulen bereits regelmässig im Unterricht eingesetzt, wobei unklar bleibt, wie genau dieser Einsatz aussieht
A comparative analysis of tie2-positive IVD progenitor cells in single-cell and bulk transcriptomics.
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Back pain and disability are often attributed to intervertebral disc (IVD) degeneration1, where current treatments are limited by an incomplete understanding of IVD biology. This study focuses on the Angiopoietin-1 receptor Tie2, which marks a progenitor cell subset in the nucleus pulposus (NP)2, crucial for repair and regeneration3,4. We aim to elucidate the transcriptomic profile of these Tie2-positive NP progenitor cells (NPPCs) to understand their role in IVD homeostasis and repair.
Methods:
We utilized single-cell and bulk RNA sequencing to characterize the transcriptomic profiles of Tie2-positive NPPCs from bovine and human IVDs.
For single-cell sequencing, reanalysis was conducted on the dataset published by Caliò et al. (2021)5, which included samples comprising pooled cells from three adjacent discs of either distal or proximal region of the bovine coccygeal tail of two biological replicates.
Single-cell suspension was obtained through enzymatic dissociation using Collagenase Type II. Library preparation followed the single-cell 3’-version-3-protocol6 and sequencing was performed on the Illumina NovaSeq platform. The sequencing data were aligned to the Bos taurus reference genome (UMD-v3.1 Release-92) from Ensembl. Post-sequencing analysis involved cell cluster identification using the Seurat package.
In parallel, bulk RNA sequencing was conducted on human IVD samples. Cells were isolated, and Tie2-positive cells were obtained by subsequent fluorescent activated cell sorting (FACS). These cells were subsequently expanded for one week. We compared Tie2-enriched samples from four healthy individuals, to Tie2-negative samples from three healthy individuals using the NovaSeq system. Differential expression analysis was carried out using DESeq2 to pinpoint marker genes specific to Tie2-enrichment. Furthermore, we performed Pearson correlation analysis contrasting the expression profiles of each identified single-cell cluster against the average profile of the Tie2-enriched samples, which facilitated the delineation of potential NPPC clusters.
Results:
We identified 14 distinct cell clusters (Fig. 1), underscoring NP cellular heterogeneity. Although not expressing a significant higher expression of the TEK gene, the gene for Tie2, Tie2-positive NPPCs exhibited a unique gene expression profile when compared to Tie2-negative cells, with specific marker genes identified. Through correlation analysis, these NPPCs were associated with specific clusters, suggesting a specialized “niche” in the IVD. Enrichment analysis indicated their involvement in tissue homeostasis and regeneration
Pitfalls in Valganciclovir Prophylaxis Dose Adjustment Based on Renal Function in Kidney Transplant Recipients.
Get PDFValganciclovir (VGC) is administered as prophylaxis to kidney transplant recipients (KTR) CMV donor (D)+/recipient (R)- and CMV R+ after thymoglobulin-induction (R+/TG). Although VGC dose adjustments based on renal function are recommended, there is paucity of real-life data on VGC dosing and associations with clinical outcomes. This is a retrospective Swiss Transplant Cohort Study-embedded observational study, including all adult D+/R- and R+/TG KTR between 2010 and 2020, who received prophylaxis with VGC. The primary objective was to describe the proportion of inappropriately (under- or over-) dosed VGC week-entries. Secondary objectives included breakthrough clinically significant CMV infection (csCMVi) and potential associations between breakthrough-csCMVi and cytopenias with VGC dosing. Among 178 KTR, 131 (73.6%) patients had ≥2 week-entries for the longitudinal data of interest and were included in the outcome analysis, with 1,032 VGC dose week-entries. Overall, 460/1,032 (44.6%) were appropriately dosed, while 234/1,032 (22.7%) and 338/1,032 (32.8%) were under- and over-dosed, respectively. Nineteen (14.5%) patients had a breakthrough-csCMVi, without any associations identified with VCG dosing (p = 0.44). Unlike other cytopenias, a significant association between VGC overdosing and lymphopenia (OR 5.27, 95% CI 1.71-16.22, p = 0.004) was shown. VGC prophylaxis in KTR is frequently inappropriately dosed, albeit without meaningful clinical associations, neither in terms of efficacy nor safety
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