•Clinical features from the largest cohort of KCNQ2-DEE patients.•Comorbidities defined and collected with the collaboration of caregivers.•Patients divided by severity via cluster analysis ...regardless of epilepsy phenotype.•Groups with different severity had different epilepsy onset and course.•Report impact of disease on families beyond seizures to identify new outcomes.
Variants of KCNQ2 are associated with a wide spectrum of disorders, ranging from Self-limiting Neonatal Epilepsy (SelNE) to Early Onset Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Comorbidities associated with this end of the spectrum have been seldomly described and their impact on the life of patients and their families is yet to be investigated.
Collaborating with caregivers from different European family associations, we have developed a questionnaire aimed at investigating the onset and frequency of epileptic seizures, anti-seizure medications (ASM), hospitalizations, stages of development, and comorbidities.
Responses from 80 patients, 40 males, from 14 countries have been collected. Median age 7.6 years (4 months – 43.6 years). Of 76 epileptic patients (93.6%), 55.3% were seizure-free with a mean age at last seizure of 26.7 months. Among patients with active epilepsy, those older have a lower frequency of seizures (p > 0.05). We were able to identify three different clusters of varying severity (Mild, Severe, Profound), based on neurodevelopmental features and symptoms, excluding epilepsy. Patients in a higher severity cluster had a higher mean number of comorbidities, which had a higher impact on families. Notably, patients in different clusters presented different epilepsy onset and courses.
This study constitutes the most extensive data collection of patients with KCNQ2-DEE, with a focus on comorbidities in a wide age group. The participation of caregivers helps to define the impact of the disease on the lives of patients and families and can help identify new primary and secondary outcomes beyond seizures in future studies.
We investigated the role played by the right parietal lobe in object identification and the ability to interpret object orientation, using transcranial magnetic stimulation (TMS) to momentarily ...interfere with ongoing cortical activity. Short trains of TMS pulses (12 Hz) were applied to a site overlying the right intraparietal sulcus/inferior parietal lobe while subjects performed either object identification tasks (i.e., picture-word verification and categorizing objects as natural or manufactured) or object orientation judgment tasks (i.e., picture-arrow verification and deciding whether an object was rotated clockwise or counterclockwise). Across different tasks, right parietal TMS impaired orientation judgments, but facilitated object identification, compared to TMS applied to a brain vertex control site. These complementary findings demonstrate that the right parietal lobe—a region belonging to the dorsal visual stream—is critical for processing the spatial attributes of objects, but not their identity. The observed improvement in object recognition, however, suggests an indirect role for the right parietal lobe in object recognition. We propose that this involves the creation of a spatial reference frame for the object, which allows interaction with the object and the individuation of specific viewing instances.
An ongoing debate in the object recognition literature centers on whether the shape representations used in recognition are coded in an orientation-dependent or orientation-invariant manner. In this ...study, we asked whether the nature of the object representation (orientation-dependent vs orientation-invariant) depends on the information-processing stages tapped by the task.
We employed a repetition priming paradigm in which briefly presented masked objects (primes) were followed by an upright target object which had to be named as rapidly as possible. The primes were presented for variable durations (ranging from 16 to 350 ms) and in various image-plane orientations (from 0 degrees to 180 degrees, in 30 degrees steps). Significant priming was obtained for prime durations above 70 ms, but not for prime durations of 16 ms and 47 ms, and did not vary as a function of prime orientation. In contrast, naming the same objects that served as primes resulted in orientation-dependent reaction time costs.
These results suggest that initial processing of object identity is mediated by orientation-independent information and that orientation costs in performance arise when objects are consolidated in visual short-term memory in order to be reported.
An inductively coupled plasma−optical emission spectrometry method was optimized and validated for the determination of major elements (Ca, K, Mg, Na and P) in cultivated freshwater fish (rainbow ...trout
Oncorhynchus mykiss
). The method was validated by analysis of a Certified Reference Material, consisting in a frozen tissue homogenate from lake trout (
Salvelinus namaycush namaycush
). The linearity of this method was very good, as evidenced by the coefficients of correlation (
r
) for calibration graphs that were higher than 0.9999 in all cases and by linearity test (response factor <5% and relative calibration graph slope <2%). Accuracy, expressed as relative recovery (%) in comparison with certified concentration ranged from 100 to 109%, and precision, expressed as residual standard deviation (%) ranged from 1.2 to 6.5% (repeatability) and from 1.0 to 9.6% (reproducibility). The limit of quantification ranged from 4 ng/mL (Ca and Mg) to 203 ng/mL (P). The optimized method was applied to major element determination in skin and muscle samples from rainbow trout fillets.
We describe a patient from the 100,000 Genomes Project with a complex de novo structural variant within KMT2E leading to O'Donnell‐Luria‐Rodan syndrome. This case expands the mutational spectrum for ...this syndrome and highlights the importance of revisiting unsolved cases using better SV prioritisation tools and updated gene panels.
We investigated distractor processing in a dual-target rapid serial visual presentation (RSVP) task containing familiar objects, by measuring repetition priming from a priming distractor (PD) to ...Target 2 (T2). Priming from a visually identical PD was contrasted with priming from a PD in a different orientation from T2. We also tested the effect of attention on distractor processing, by placing the PD either within or outside the attentional blink (AB). PDs outside the AB induced positive priming when they were in a different orientation to T2 and no priming, or negative priming, when they were perceptually identical to T2. PDs within the AB induced positive priming regardless of orientation. These findings demonstrate (1) that distractors are processed at multiple levels of representation; (2) that the view-specific representations of distractors are actively suppressed during RSVP; and (3) that this suppression fails in the absence of attention. (Contains 4 footnotes and 8 figures.)
Abstract
Introduction
Distal embolization may compromise the results of primary angioplasty. Our aim is to analyze the influence of the speed of deflation of the stent delivery system on the ...myocardial blush ≥2 and on the ST-Segment resolution ≥70%.
Methods
From December 2016 to February 2019, all consecutive patients with ST-elevation myocardial infarction who underwent urgent coronary angiography at our institution who were susceptible of thrombectomy, IIB-IIIA inhibitors and direct stenting were randomized 1:1 to fast deflation of the stent delivery system (group 1, n=103) or to slow deflation at 1 atm/second (group 2, n=107). Pre- and postdilatation was not allowed per protocol. The primary outcomes were the myocardial blush ≥2 and the ST-Segment resolution ≥70% while the size of myocardial damage, ejection fraction at discharge and at 12 months and total and cardiovascular mortality at 12 months were the secondary outcomes. A multivariate analysis was performed to analyze the influence of the speed of deflation of the stent delivery system in both primary end-points in case of possible imbalances among groups despite the randomization.
Results
Both groups represented 47% of the 447 procedures of primary angioplasty performed in that period. Baseline characteristics of the whole cohort: female gender 46 (21.9%), age 59.5±10.6 years, diabetes 35 (16.7%), Killip class IV 5 (2.4%), total ischemic time 177.5 (124–275) minutes and door to balloon time 84 (66–120.5) minutes. There were not differences in clinical or angiographic characteristics between both groups, although there was a non-significant trend towards larger reference vessel diameter in the slow deflation group (2.74±0.42 vs. 2.86±0.47, p=0.07). The study was prematurely stopped with 50% of the calculated sample size due to futility. The primary endpoint of myocardial blush ≥2 occurred in 77 (74.7%) vs. 79 (75.2%), p=0.93 and ST-Segment resolution ≥70% in 54 (53.9%) vs. 59 (55.5%), p=0.75 in group 1 and 2, respectively, without differences in any of the secondary endpoints. The speed of deflation of the stent delivery system did not show any influence on the MB or ST-Segment resolution ≥70% in the multivariate analysis. Predictors of myocardial blush ≥2 were systolic blood pressure at admission, creatinine clearance <60 ml/min and maximal diameter postprocedure. Diabetes, previous infarction, left anterior descending, TIMI ≥2 before intervention, TIMI 3 after intervention and collateral supply grade ≥2 were predictors of ST segment resolution≥70% with an area under the curve of 0.71 (0.63–0.80) and 0.75 (0.68–0.82), respectively.
Conclusions
In our series, the speed of deflation of the stent delivery system in primary angioplasty did not modified the myocardial blush ≥2 or ST-Segment resolution ≥70% and neither showed any influence in clinical outcomes, size of myocardial infarction by biomarkers and ejection fraction.
Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Abbott Laboratories
This review provides a valuable source of information on the technological advances in near infrared absorption spectrometry area and its industrial applications, especially on the alimentary ...technology and environmental applications over biofuels.
In the second C4 article, contributors examine five issues, including timely access during the hospital discharge process, access to immunosuppressive medications for life after transplant, access to ...medications used for off‐label indications, access to drugs affected by drug shortages, and the patient perspective.
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