Effects of aging on cerebral oxygenation during working-memory performance: A functional near-infrared spectroscopy study

Contains fulltext : 102484.pdf (publisher's version ) (Open Access)Working memory is sensitive to aging-related decline. Evidence exists that aging is accompanied by a reorganization of the working-memory circuitry, but the underlying neurocognitive mechanisms are unclear. In this study, we examined aging-related changes in prefrontal activation during working-memory performance using functional Near-Infrared Spectroscopy (fNIRS), a noninvasive neuroimaging technique. Seventeen healthy young (21–32 years) and 17 healthy older adults (64–81 years) performed a verbal working-memory task (n-back). Oxygenated and deoxygenated hemoglobin concentration changes were registered by two fNIRS channels located over the left and right prefrontal cortex. Increased working-memory load resulted in worse performance compared to the control condition in older adults, but not in young participants. In both young and older adults, prefrontal activation increased with rising working-memory load. Young adults showed slight right-hemispheric dominance at low levels of working-memory load, while no hemispheric differences were apparent in older adults. Analysis of the time-activation curve during the high working-memory load condition revealed a continuous increase of the hemodynamic response in the young. In contrast to that, a quadratic pattern of activation was found in the older participants. Based on these results it could be hypothesized that young adults were better able to keep the prefrontal cortex recruited over a prolonged period of time. To conclude, already at low levels of working-memory load do older adults recruit both hemispheres, possibly in an attempt to compensate for the observed aging-related decline in performance. Also, our study shows that aging effects on the time course of the hemodynamic response must be taken into account in the interpretation of the results of neuroimaging studies that rely on blood oxygen levels, such as fMRI.11 p

G protein variation in respiratory syncytial virus group A does not correlate with clinical severity

Respiratory syncytial virus group A strain variations of 28 isolates from The Netherlands collected during three consecutive seasons were studied by ana

Update of the Preventive Antibiotics in Stroke Study (PASS): Statistical analysis plan

Background: Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were st

Het schrijven van RIKILT rapporten en wetenschappelijke artikelen

Dit rapport is samengesteld door de werkgroep "Herziening rapportindeling RIKILT en herzien door de werkgroep "RIKILT rapporten". Duidelijk ingedeelde rapporten, voorzien van een abstract, verhogen de leesbaarheid en de bekendheid. De aanbevelingen, die hier gegeven worden, zijn gebaseerd op internationale afspraken. Verder zijn er nog aanvullende richtlijnen gegeven voor zover dat nodig was, zodat dit rapport alle informatie bevat voor het schrijven van een RIKILT rapport. Voor het schrijven van wetenschappelijke artikelen is volstaan met het geven van richtlijnen. Doorgaans is het de regel dat ieder tijdschrift en/of iedere uitgever zijn eigen richtlijnen heeft, waaraan de schrijver zich moet houden

The diagnosis and treatment of invasive aspergillosis in Dutch haematology units facing a rapidly increasing prevalence of azole-resistance

Patients with haematological malignancies are at risk for invasive fungal diseases (IFD). A survey was conducted in all Dutch academic haematology centres on their current diagnostic, prophylactic and therapeutic approach towards IFD in the context of azole-resistance. In all 8 centres, a haematologist and microbiologist filled in the questionnaire that focused on different subgroups of haematology patients. Fungal prophylaxis during neutropaenia was directed against Candida and consisted of fluconazole and/or amphotericin B suspension. Mould-active prophylaxis was given to acute myeloid leukaemia patients during chemotherapy in 2 of 8 centres. All centres used azole prophylaxis in a subset of patients with graft-versus-host disease. A uniform approach towards the diagnosis and treatment of IFD and in particular azole-resistant Aspergillus fumigatus was lacking. In 2017, all centres agreed to implement a uniform diagnostic and treatment algorithm regarding invasive aspergillosis with a central role for comprehensive diagnostics and PCR-based detection of azole-resistance. This study (DB-MSG 002) will re-evaluate this algorithm when 280 patients have been treated. A heterogeneous approach towards antifungal prophylaxis, diagnosis and treatment was apparent in the Netherlands. Facing triazole-resistance, consensus was reached on the implementation of a uniform diagnostic approach in all 8 centres

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause lifethreatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

A mind-breaking cause of acute kidney injury

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Osteoblast differentiation of murine embryonic stem cells as a model to study the embryotoxic effect of compounds

The embryonic stem cell test (ESTc), in which the effect of chemical compounds on cardiomyocyte differentiation is evaluated, is one of the most studied in vitro alternatives for developmental toxicity testing. Because the assay readout is restricted to a single endpoint of differentiation, compounds that affect alternative differentiation pathways might be overlooked. It has therefore been suggested that the predictive value of the EST may be improved by including alternative differentiation endpoints. The aim of the present study was to evaluate the effect of five teratogenic compounds as well as one non-teratogenic compound on the differentiation of murine embryonic stem cells into osteoblasts (ESTo) and to compare results with those in the classical ESTc. We established an ESTo assay which proved robust, stable and reproducible. In this study, we showed that the evaluated compounds affected osteoblast differentiation both at the level of calcium concentrations in the culture as well as on multiple gene expression. Furthermore, we showed that the effect on calcium concentrations appeared to be primarily mediated by a general apoptotic effect and not by a specific effect on differentiation. The compounds tested showed little difference in their potency in the ESTo as compared to the ESTc. Before a definitive statement can be made regarding the added value of including an osteoblast differentiation endpoint into the EST, more compounds need to be evaluated