A new insight into sentence comprehension : the impact of word associations in sentence processing as shown by invasive EEG recording

The effect of word association on sentence processing is still a matter of debate. Some studies observe no effect while others found a dependency on sentence congruity or an independent effect. In an attempt to separate the effects of sentence congruity and word association in the spatio-temporal domain, we jointly recorded scalp- and invasive-EEG (iEEG). The latter provides highly localized spatial (unlike scalp-EEG) and high temporal (unlike fMRI) resolutions. We recorded scalp- and iEEG in three patients with refractory epilepsy. The stimuli consisted of 280 sentences with crossed factors of sentence congruity and within sentence word-association. We mapped semantic retrieval processes involved in sentence comprehension onto the left temporal cortex and both hippocampi, and showed for the first time that certain localized regions participate in the processing of word association in sentence context. Furthermore, simultaneous recording of scalp- and iEEG gave us a direct overview of signal change due to its propagation across the head tissues

Cervical high-intensity intramedullary lesions in achondroplasia:Aetiology, prevalence and clinical relevance

In achondroplastic patients with slight complaints of medullary compression the cervical spinal cord regularly exhibits an intramedullary (CHII) lesion just below the craniocervical junction with no signs of focal compression on the cord. Currently, the prevalence of the lesion in the general achondroplastic population is studied and its origin is explored. Eighteen achondroplastic volunteers with merely no clinical signs of medullary compression were subjected to dynamic magnetic resonance imaging (MRI). The presence of a CHII lesion and craniocervical medullary compression in flexed and retroflexed craniocervical positions was explored. Several morphological characteristics of the craniocervical junction, possibly related to compression on the cord, were assessed. A CHII lesion was observed in 39% of the subjects and in only one of these was compression at the craniocervical junction present. Consequently, no correlation between the CHII lesion and compression could be established. None of the morphological characteristics demonstrated a correlation with the CHII lesion, except thinning of the cord at the site of the CHII lesion. CHII lesions are a frequent finding in achondroplasia, and are generally unaccompanied by clinical symptoms or compression on the cord. Further research focusing on the origin of CHII lesions and their clinical implications is warranted. aEuro cent MRI now reveals exquisite detail of the cervical spinal cord. aEuro cent Cervical cord lesions are observed in one third of the achondroplastic population. aEuro cent These lesions yield high signal intensity on T2 weighted MRI. aEuro cent They are generally unaccompanied by clinical symptoms or cord compression. aEuro cent Their aetiology is unclear and seems to be unrelated to mechanical causes

A diet rich in unsaturated fatty acids prevents progression toward heart failure in a rabbit model of pressure and volume overload

Background-During heart failure (HF), cardiac metabolic substrate preference changes from fatty acid (FA) toward glucose oxidation. This change may cause progression toward heart failure. We hypothesize that a diet rich in FAs may prevent this process, and that dietary 3-FAs have an added antiarrhythmic effect based on action potential (AP) shortening in animals with HF. Methods and Results-Rabbits were fed a diet containing 1.25% (w/w) high oleic sunflower oil (HF-9, N 11), 1.25% fish oil (HF-3, N11), or no supplement (HF-control, N8). Subsequently, HF was induced by volume and pressure overload. After 4 months, HF-parameters were assessed, electrocardiograms were recorded, and blood and ventricular tissue were collected. Myocytes were isolated for patch clamp or intracellular Ca2-recordings to study electrophysiologic remodeling and arrhythmogenesis. Both the HF-9 and the HF-3 groups had larger myocardial FA oxidation capacity than HF control. The HF-3 group had significantly lower mean ( SEM) relative heart and lung weight (3.3-0.13 and 3.2-0.12 g kg 1, respectively) than HF control (4.8-0.30 and 4.5-0.23), and shorter QTc intervals (167-2.6 versus 182-6.4). The HF-9 also displayed a significantly reduced relative heart weight (3.6-0.26), but had similar QTc (179-4.3) compared with HF control. AP duration in the HF-3 group was 20% shorter due to increased Ito1 and IK1 and triggered activity, and Ca2-aftertransients were less than in the HF-9 group. Conclusions-Dietary unsaturated FAs started prior to induction of HF prevent hypertrophy and HF. In addition, fish oil FAs prevent HF-induced electrophysiologic remodeling and arrhythmias. © 2012 American Heart Association, Inc

Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: A systematic review and meta-analysis

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/)Aims:The value of elective coronary revascularisation plus medical therapy over medical therapy alone in managing stable patients with coronary artery disease is debated. We reviewed all trials comparing the two strategies in this population. Methods and results:From inception through November 2020, Medline, Embase, Google Scholar and other databases were searched for randomised trials comparing revascularisation to medical therapy alone in clinically stable coronary artery disease patients. Treatment effects were measured by rate ratios (RR) with 95% confidence intervals using random-effects models. Cardiac mortality was the prespecified primary endpoint. Spontaneous myocardial infarction (MI) and its association with cardiac mortality were secondary endpoints. Further endpoints included all-cause mortality, any MI and stroke. Longest follow-up data were abstracted. The study is registered with PROSPERO (CRD42021225598). Twenty-five trials involving 19,806 patients (10,023 randomised to revascularisation plus medical therapy and 9,783 to medical therapy alone) were included. Compared to medical therapy alone, revascularisation was associated with a lower risk of cardiac death (RR 0.79 [0.67-0.93], p<0.01) and spontaneous MI (RR 0.74 [0.64-0.86], p<0.01). By meta-regression, the cardiac death risk reduction after revascularisation, compared to medical therapy alone, was linearly associated with follow-up duration (RR per 4-year follow-up: 0.81 [0.69-0.96], p=0.008) and spontaneous MI absolute difference (p=0.01). Trial sequential and sensitivity analyses confirmed the reliability of the cardiac mortality findings. All cause mortality (0.94 [0.87-1.01], p=0.11), any MI (p=0.14) and stroke risk (p=0.30) did not differ significantly between strategies. Conclusion:In stable coronary artery disease patients, randomisation to elective coronary revascularisation plus medical therapy led to reduced cardiac mortality compared to medical management alone. The cardiac survival benefit after revascularisation improved with longer follow-uptimes and was associated with fewer spontaneous MIs.Peer reviewedFinal Published versio

Usefulness of High-Sensitivity Cardiac Troponin T to Predict Long-Term Outcome in Patients with Hypertrophic Cardiomyopathy

Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity in confirmative data. We performed a prospective, prespecified 5-year follow-up cohort study of 135 HC patients who participated in a national multicenter project and underwent clinical evaluation, MRI (cine, LGE and T2-weighted imaging) and biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide of Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up was systematically performed for the primary endpoint: a composite of sudden cardiac death, heart failure related death, stroke-related death, heart failure hospitalization, hospitalization for stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, and progression to NYHA class III-IV. Elevated hs-cTnT was present in 33 of 135 (24%) HC patients. During a median follow-up of 5.0 years (IQR: 4.9-5.1) 18 patients reached the primary endpoint. Using Cox regression analysis, elevated hs-cTnT was univariately associated with the primary endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, previous non-sustained VT, reduced LV ejection fraction (&lt;50%) and CICP were associated with the primary endpoint. In multivariable analysis, elevated hs-cTnT remained independently associated with outcome (aHR: 4.7 (95%CI: 1.8-12.6, p = 0.002). In conclusion, this 5-year follow-up study is the first to prospectively confirm the association of elevated hs-cTnT and adverse outcomes. In addition to established clinical variables, cTn seems the biomarker of interest to further improve risk prediction in HC, which should be evaluated in larger prospective registries.</p

Identification of a Novel Genomic Island Associated with vanD-Type Vancomycin Resistance in Six Dutch Vancomycin-Resistant Enterococcus faecium Isolates

Genomic comparison of the first six Dutch vanD-type vancomycin-resistant Enterococcus faecium (VRE) isolates with four vanD gene clusters from other enterococcal species and anaerobic gut commensals revealed that the vanD gene cluster was located on a genomic island of variable size. Phylogenetic inferences revealed that the Dutch VRE isolates were genetically not closely related and that genetic variation of the vanD-containing genomic island was not species specific, suggesting that this island is transferred horizontally between enterococci and anaerobic gut commensals.Peer reviewe

High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins

Introduction: Takayasu arteritis (TA) and giant cell arteritis (GCA) are large vessel vasculitides (LVV) that usually present as granulomatous inflammation in arterial walls. High mobility group box 1 (HMGB1) is a nuclear protein that acts as an alarmin when released by dying or activated cells. This study aims to evaluate whether serum HMGB1 can be used as a biomarker in LVV. Methods: Twenty-nine consecutive TA patients with 29 healthy controls (HC) were evaluated in a cross-sectional study. Eighteen consecutive GCA patients with 16 HC were evaluated at the onset of disease and some of them during follow-up. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. Results: In GCA patients at disease onset mean serum HMGB1 levels did not differ from HC (5.74 +/- 4.19 ng/ml vs. 4.17 +/- 3.14 ng/ml; p = 0.230). No differences in HMGB1 levels were found between GCA patients with and without polymyalgia rheumatica (p = 0.167), ischemic manifestations (p = 0.873), systemic manifestations (p = 0.474) or relapsing disease (p = 0.608). During follow-up, no significant fluctuations on serum HMGB1 levels were observed from baseline to 3 months (n = 13) (p = 0.075), 12 months (n = 6) (p = 0.093) and at the first relapse (n = 4) (p = 0.202). Serum HMGB1 levels did not differ between TA patients and HC [1.19 (0.45-2.10) ng/ml vs. 1.46 (0.89-3.34) ng/ml; p = 0.181] and no difference was found between TA patients with active disease and in remission [1.31 (0.63-2.16) ng/ml vs. 0.75 (0.39-2.05) ng/ml; p = 0.281]. HMGB1 levels were significantly lower in 16 TA patients on statins compared with 13 patients without statins [0.59 (0.29-1.46) ng/ml vs. 1.93 (0.88-3.34) ng/ml; p = 0.019]. Age was independently associated with higher HMGB1 levels regardless of LVV or control status. Conclusions: Patients with TA and GCA present similar serum HMGB1 levels compared with HC. Serum HMGB1 is not useful to discriminate between active disease and remission. In TA, use of statins was associated with lower HMGB1 levels. HMGB1 is not a biomarker for LVV

Exploring the Correlation Between Fibrosis Biomarkers and Clinical Disease Severity in PLN p.Arg14del Patients

Background: Pathogenic variants in phospholamban (PLN, like p. Arg14del), are found in patients diagnosed with arrhythmogenic (ACM) and dilated cardiomyopathy (DCM). Fibrosis formation in the heart is one of the hallmarks in PLN p.Arg14del carriers. During collagen synthesis and breakdown, propeptides are released into the circulation, such as procollagen type I carboxy-terminal propeptide (PICP) and C-terminal telopeptide collagen type I (ICTP). Aim: To investigate if PICP/ICTP levels in blood are correlative biomarkers for clinical disease severity and outcome in PLN p.Arg14del variant carriers. Methods: Serum and EDTA blood samples were collected from 72 PLN p.Arg14del carriers (age 50.5 years, 63% female) diagnosed with ACM (n = 12), DCM (n = 14), and preclinical variant carriers (n = 46). PICP levels were measured with an enzyme-linked immune sorbent assay and ICTP with a radio immuno-assay. Increased PICP/ICTP ratios suggest a higher collagen deposition. Clinical data including electrocardiographic, and imaging results were adjudicated from medical records. Results: No correlation between PICP/ICTP ratios and late gadolinium enhancement (LGE) was found. Moderate correlations were found between the PICP/ICTP ratio and end-diastolic/systolic volume (both r(s) = 0.40, n = 23, p = 0.06). PICP/ICTP ratio was significantly higher in patients with T wave inversion (TWI), especially in leads V4–V6, II, III, and aVF (p < 0.022) and in patients with premature ventricular contractions (PVCs) during an exercise tolerance test (p = 0.007). Conclusion: High PICP/ICTP ratios correlated with clinical parameters, such as TWI and PVCs. Given the limited size and heterogeneity of the patient group, additional studies are required to substantiate the incremental prognostic value of these fibrosis biomarkers in PLN p.Arg14del patients

Barriers to and Facilitators of Sustained Employment:A Qualitative Study of Experiences in Dutch Patients With CKD

Rationale & Objective: Although patients with chronic kidney disease (CKD) are at risk for work disability and loss of employment, not all experience work disruption. We aimed to describe the barriers to and facilitators of sustained employment experienced by Dutch patients with CKD. Study Design: Qualitative study using semi-structured interviews. Setting & Participants: 27 patients with CKD glomerular filtration rate categories 3b-5 (G3b-G5) from 4 nephrology outpatient clinics in The Netherlands. Analytical Approach: Content analyses with constant comparison of interview data based on the International Classification of Functioning, Disability and Health framework. Results: Participants were 6 patients with CKD G3b-G4, 8 patients receiving maintenance dialysis, and 13 patients with functioning kidney transplants. We identified health-related barriers (symptoms, physical toll of dialysis/transplantation, limited work capacity) and facilitators (few physical symptoms, successful posttransplantation recovery, absence of comorbidities, good physical condition), personal barriers (psychological impact, limited work experience) and facilitators (positive disposition, job satisfaction, work attitude, person-job fit), and environmental barriers and facilitators. Environmental barriers were related to nephrology care (waiting time, use of a hemodialysis catheter) and work context (reorganization, temporary contract, working hours, physical demands); environmental facilitators were related to nephrology care (personalized dialysis, preemptive transplant), work context (large employer, social climate, job requiring mental rather than physical labor, flexible working hours, adjustment of work tasks, reduced hours, remote working, support at work, peritoneal dialysis exchange facility), and support at home. Occupational health services and social security could be barriers or facilitators. Limitations: The study sample of Dutch patients may limit the transferability of these findings to other countries. Conclusions: The wide range of barriers and facilitators in all International Classification of Functioning, Disability and Health components suggests great diversity among patients and their circumstances. These findings underline the importance of personalized nephrology and occupational health care as well as the importance of individually tailored workplace accommodations to promote sustained employment for patients with CKD

Exercise and myocardial injury in hypertrophic cardiomyopathy

Objective: Troponin and high signal intensity on T2-weighted (HighT2) cardiovascular magnetic resonance imaging (CMRi) are both markers of myocardial injury in hypertrophic cardiomyopathy (HCM). The interplay between exercise and disease development remains uncertain in HCM. We sought to assess the occurrence of postexercise troponin rises and its determinants. Methods: Multicentre project on patients with HCM and mutation carriers without hypertrophy (controls). Participants performed a symptom limited bicycle test with hs-cTnT assessment pre-exercise and 6 hours postexercise. Pre-exercise CMRi was performed in patients with HCM to assess measures of hypertrophy and myocardial injury. Depending on baseline troponin (13 ng/L), a rise was defined as a >50% or >20% increase, respectively. Results: Troponin rises occurred in 18% (23/127) of patients with HCM and 4% (2/53) in mutation carriers (p=0.01). Comparing patients with HCM with and without a postexercise troponin rise, maximum heart rates (157±19 vs 143±23, p=0.004) and maximal wall thickness (20 mm vs 17 mm, p=0.023) were higher in the former, as was the presence of late gadolinium enhancement (85% vs 57%, p=0.02). HighT2 was seen in 65% (13/20) and 19% (15/79), respectively (p<0.001). HighT2 was the only independent predictor of troponin rise (adjusted odds ratio 7.9; 95% CI 2.7 to 23.3; p<0.001). Conclusions: Postexercise troponin rises were seen in about 20% of patients with HCM, almost five times more frequent than in mutation carriers. HighT2 on CMRi may identify a group of particularly vulnerable patients, supporting the concept that HighT2 reflects an active disease state, prone to additional injury after a short episode of high oxygen demand