The relationship between structural properties of frontal cortical regions and response inhibition in 6-14-year-old children.

Development of attentional skills and inhibitory control rely on maturational changes in the brain across childhood and youth. However, both brain anatomy and different components of attention and inhibition show notable individual variation. Research on ADHD and inhibitory training and control have shown that variations in the thickness and surface area of particularly inferior cortical structures are associated with attentional control.

Divergent auditory activation in relation to inhibition task performance in children and adults.

Adults and children show remarkable differences in cortical auditory activation which, in children, have shown relevance for cognitive performance, specifically inhibitory control. However, it has not been tested whether these differences translate to functional differences in response inhibition between adults and children. We recorded auditory responses of adults and school-aged children (6-14 years) using combined magneto- and electroencephalography (M/EEG) during passive listening conditions and an auditory Go/No-go task.

How salience enhances inhibitory control: An analysis of electro-cortical mechanisms.

Stop-signal tasks (SSTs) combined with human electro-cortical recordings (Event-Related Potentials, ERPs) have revealed mechanisms associated with successful stopping (relative to failed), presumably contributing to inhibitory control. The corresponding ERP signatures have been labeled stop N1 (+/- 100-ms latency), stop N2 (200 ms), and stop P3 (160-250 ms), and argued to reflect more sensory-specific (N1) versus more generic (N2, P3) mechanisms. However, stop N1 and stop N2, as well as latencies of stop-P3, appear to be quite inconsistent across studies.

Improvement of microangiopathy after haematopoietic stem cell transplantation in systemic sclerosis.

Objectives: Haematopoietic stem cell transplantation (HSCT) is a treatment option for patients with severe systemic sclerosis (SSc), but the efficacy of the procedure in remodelling the nailfold microvascular array is largely unknown. Therefore, this study aimed to evaluate the effect of HSCT on microangiopathy assessed through nailfold capillaroscopy (NC) and to compare the results with findings in patients receiving conventional immunosuppression.

Methods: We included SSc patients with severe SSc and whose pre- and post-treatment NC images were available.

Activity level in left auditory cortex predicts behavioral performance in inhibition tasks in children.

Sensory processing during development is important for the emerging cognitive skills underlying goal-directed behavior. Yet, it is not known how auditory processing in children is related to their cognitive functions. Here, we utilized combined magneto- and electroencephalographic (M/EEG) measurements in school-aged children (6-14y) to show that child auditory cortical activity at ∼250 ms after auditory stimulation predicts the performance in inhibition tasks.

Identification of Risk Factors for COVID-19 Hospitalization in Patients With Anti-Rheumatic Drugs: Results From a Multicenter Nested Case Control Study.

Patients with inflammatory rheumatic diseases (IRDs) do not have an increased risk for coronavirus disease 2019 (COVID-19) compared with the general population. However, it remains uncertain whether subgroups of patients with IRD using different immunosuppressive antirheumatic drugs carry a higher risk for severe COVID-19 compared with other patients with IRD. The aim of this study is to identify risk factors for severe COVID-19, requiring hospitalization in patients with IRD.

A phase I clinical trial to study the safety of treatment with tipifarnib combined with bortezomib in patients with advanced stages of myelodysplastic syndrome and oligoblastic acute myeloid leukemia.

Purpose: To determine the safety of tipifarnib in combination with escalating doses of bortezomib and to determine the maximum tolerated dose in patients with untreated high-risk MDS and oligoblastic acute myeloid leukemia, who were not eligible for intensive therapy.

Experimental Design: In a "3 + 3″ design, patients received fixed doses of tipifarnib 200 mg bid (days 1-21) and escalating doses of bortezomib (days 8, 15, 22) every 4 weeks in 4-6 cycles.

Results: The combination was tolerated well by the 11 patients in this study without reaching the maximum tolerated dose.

Predictive factors for treatment-related mortality and major adverse events after autologous haematopoietic stem cell transplantation for systemic sclerosis: results of a long-term follow-up multicentre study.

Background: Autologous haematopoietic stem cell transplantation (HSCT) improves survival in systemic sclerosis (SSc) with poor prognosis, but is hampered by treatment-related mortality (TRM).

Objective: To evaluate event-free survival (EFS), TRM, response to treatment, disease progression and patient characteristics associated with events.

Methods: All patients treated with HSCT for SSc in The Netherlands until 2017 (n=92) were included.

Left hemisphere enhancement of auditory activation in language impaired children.

Specific language impairment (SLI) is a developmental disorder linked to deficient auditory processing. In this magnetoencephalography (MEG) study we investigated a specific prolonged auditory response (N250m) that has been reported predominantly in children and is associated with level of language skills. We recorded auditory responses evoked by sine-wave tones presented alternately to the right and left ear of 9-10-year-old children with SLI (n = 10) and children with typical language development (n = 10).

Functionally active NKG2A-expressing natural killer cells are elevated in rheumatoid arthritis patients compared to psoriatic arthritis patients and healthy donors.

Objectives: Natural killer cell receptors (NKR) have been implicated in rheumatoid (RA) and psoriatic arthritis (PsA) pathogenesis. To gain more insight into their role, we characterised NKR (co-)expression patterns on NK and T cells and NK cell function in RA and PsA.

Methods: The frequency of NK and T cells expressing killer like immunoglobulin (KIR) and NKG2 receptors and natural cytotoxicity receptors was assessed by 10-colour flow cytometry in peripheral blood of 23 RA, 12 PsA patients and 18 healthy donors (HD).

Neutrophil activation and nucleosomes as markers of systemic inflammation in paroxysmal nocturnal hemoglobinuria: effects of eculizumab.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis and a high risk of life-threatening venous and arterial thrombosis. Uncontrolled complement activation and the release of cell-free heme may result in systemic inflammation, neutrophil activation, and the release of procoagulant neutrophilic proteases. Eculizumab, an antibody to complement factor C5, inhibits hemolysis and reduces thrombotic risk.

Alterations in markers of coagulation and fibrinolysis in patients with Paroxysmal Nocturnal Hemoglobinuria before and during treatment with eculizumab.

Background: Paroxysmal Nocturnal Hemoglobinuria is characterized by complement-mediated hemolysis and an increased thrombosis risk. Eculizumab, an antibody to complement factor C5, reduces thrombotic risk via unknown mechanisms. Clinical observations suggest that eculizumab has an immediate effect.

Induction of myelodysplasia by myeloid-derived suppressor cells.

Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors.

Mechanisms and clinical implications of thrombosis in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease characterized by a clone of blood cells lacking glycosyl phosphatidylinositol (GPI)-anchored proteins at the cell membrane. Deficiency of the GPI-anchored complement inhibitors CD55 and CD59 on erythrocytes leads to intravascular hemolysis upon complement activation. Apart from hemolysis, another prominent feature is a highly increased risk of thrombosis.

T cells expressing the activating NK-cell receptors KIR2DS4, NKG2C and NKG2D are elevated in paroxysmal nocturnal hemoglobinuria and cytotoxic toward hematopoietic progenitor cell lines.

Objective: To investigate the presence of T cells with natural killer cell receptors (NKR) in paroxysmal nocturnal hemoglobinuria (PNH), and their potential involvement in clonal expansion of glycosylphosphatidylinositol (GPI)-deficient hematopoietic stem cells by selective immune attack to normal and not GPI-deficient hematopoietic stem cells.

Materials And Methods: By flow cytometry, the frequency and number of T cells expressing NKR was evaluated in 39 PNH patients and compared to healthy controls. Elevated T cell subsets in PNH were assessed for differential cytotoxic lysis of GPI(+) and GPI(-) CD34(+) hematopoietic progenitor cell lines.