Objective
Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination—known as infantile convulsions and paroxysmal choreoathetosis (ICCA)—are related ...autosomal dominant diseases. PRRT2 (proline‐rich transmembrane protein 2 gene) has been identified as the major gene in all 3 conditions, found to be mutated in 80 to 90% of familial and 30 to 35% of sporadic cases.
Methods
We searched for the genetic defect in PRRT2‐negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed cliniconeurophysiological workup.
Results
In 3 families with a total of 16 affected members, we identified the same, cosegregating heterozygous missense mutation (c.4447G>A; p.E1483K) in SCN8A, encoding a voltage‐gated sodium channel. A founder effect was excluded by linkage analysis. All individuals except 1 had normal cognitive and motor milestones, neuroimaging, and interictal neurological status. Fifteen affected members presented with afebrile focal or generalized tonic–clonic seizures during the first to second year of life; 5 of them experienced single unprovoked seizures later on. One patient had seizures only at school age. All patients stayed otherwise seizure‐free, most without medication. Interictal electroencephalogram (EEG) was normal in all cases but 2. Five of 16 patients developed additional brief paroxysmal episodes in puberty, either dystonic/dyskinetic or “shivering” attacks, triggered by stretching, motor initiation, or emotional stimuli. In 1 case, we recorded typical PKD spells by video‐EEG‐polygraphy, documenting a cortical involvement.
Interpretation
Our study establishes SCN8A as a novel gene in which a recurrent mutation causes BFIS/ICCA, expanding the clinical–genetic spectrum of combined epileptic and dyskinetic syndromes. ANN NEUROL 2016;79:428–436
“Node-RADS” addresses the lack of consensus in the radiologic assessment of lymph node involvement by cancer and meets the increasing demand for structured reporting on the likelihood of disease ...involvement. Node Reporting and Data System 1.0 (Node-RADS) systematically classifies the degree of suspicion of lymph node involvement based on the synthesis of established imaging findings. Straightforward definitions of imaging findings for two proposed scoring categories “size” and “configuration” are combined into assessment categories between 1 (“very low likelihood”) and 5 (“very high likelihood”). This scoring system is suitable for assessing likely involvement of lymph nodes on CT and MRI scans. It can be applied at any anatomical site, and to regional and non-regional lymph nodes in relation to a primary tumor location. Node-RADS will improve communication with referring physicians and promote the consistency of reporting for primary staging and in response assessment settings.
Key Points
• Node-RADS standardizes reporting of possible cancer involvement of regional and distant lymph nodes on CT and MRI.
• Node-RADS proposes the scoring categories “size” and “configuration” for assigning the 5-point Node-RADS score from 1 (“very low likelihood”) to 5 (“very high likelihood”).
• Node-RADS aims to increase consensus among radiologists for primary staging and in response assessment settings.
Background
The prevalence of allergic rhinitis is high, but the role of environmental factors remains unclear. We examined cohort‐specific and combined associations of residential greenness with ...allergic rhinitis and aeroallergen sensitization based on individual data from Swedish (BAMSE), Australian (MACS), Dutch (PIAMA), Canadian (CAPPS and SAGE), and German (GINIplus and LISAplus) birth cohorts (n = 13 016).
Methods
Allergic rhinitis (doctor diagnosis/symptoms) and aeroallergen sensitization were assessed in children aged 6–8 years in six cohorts and 10–12 years in five cohorts. Residential greenness was defined as the mean Normalized Difference Vegetation Index (NDVI) in a 500‐m buffer around the home address at the time of health assessment. Cohort‐specific associations per 0.2 unit increase in NDVI were assessed using logistic regression models and combined in a random‐effects meta‐analysis.
Results
Greenness in a 500‐m buffer was positively associated with allergic rhinitis at 6–8 years in BAMSE (odds ratio = 1.42, 95% confidence interval 1.13, 1.79) and GINI/LISA South (1.69 1.19, 2.41) but inversely associated in GINI/LISA North (0.61 0.36, 1.01) and PIAMA (0.67 0.47, 0.95). Effect estimates in CAPPS and SAGE were also conflicting but not significant (0.63 0.32, 1.24 and 1.31 0.81, 2.12, respectively). All meta‐analyses were nonsignificant. Results were similar for aeroallergen sensitization at 6–8 years and both outcomes at 10–12 years. Stratification by NO2 concentrations, population density, an urban vs rural marker, and moving did not reveal consistent trends within subgroups.
Conclusion
Although residential greenness appears to be associated with childhood allergic rhinitis and aeroallergen sensitization, the effect direction varies by location.
A growing subset of Type Ia supernovae (SNe Ia) shows evidence via narrow emission lines for unexpected interaction with a dense circumstellar medium (SNe IIn/Ia–CSM). The precise nature of the ...progenitor, however, remains debated owing to spectral ambiguities arising from a strong contribution from the CSM interaction. Late-time spectra offer potential insight if the post-shock cold, dense shell becomes sufficiently thin and/or the ejecta begin to cross the reverse shock. To date, only a few high-quality spectra of this kind exist. Here we report on the late-time optical and infrared spectra of the SNe Ia–CSM 2012ca and 2013dn. These SNe Ia–CSM spectra exhibit low Fe iii/Fe ii ratios and strong Ca ii at late epochs. Such characteristics are reminiscent of the super-Chandrasekhar-mass candidate SN 2009dc, for which these features suggested a low-ionization state due to high densities, although the broad Fe features admittedly show similarities to the blue ‘quasi-continuum’ observed in some core collapse SNe Ibn and IIn. Neither SN 2012ca nor any of the other SNe Ia–CSM in this paper show evidence for broad oxygen, carbon, or magnesium in their spectra. Similar to the interacting Type IIn SN 2005ip, a number of high-ionization lines are identified in SN 2012ca, including S iii, Ar iii, Ar x, Fe viii, Fe x, and possibly Fe xi. The total bolometric energy output does not exceed 1051 erg, but does require a large kinetic-to-radiative conversion efficiency. All of these observations taken together suggest that SNe Ia–CSM are more consistent with a thermonuclear explosion than a core collapse event, although detailed radiative transfer models are certainly necessary to confirm these results.
A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages ...could result from interactions with the companion during the common-envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 ± 0.59 kiloparsecs from the Sun.
Treatment with the phencyclidine derivative ketamine, a non-competitive
N-methyl-
d-aspartate receptor antagonist and a well known anesthetic, has recently been introduced to mimic schizophrenia in ...animals. Using rats repeatedly treated with sub-anesthetic doses we demonstrate in the hippocampal formation the cellular distribution patterns of proteins being relevant to the pathogenesis of schizophrenia. Compared with controls an increase in the density of reduced nicotinamide adenine dinucleotide phosphate diaphorase-, neuronal nitric oxide synthase- and cFOS-positive hippocampal interneurons was found, whereas the density of parvalbumin expressing cells was decreased. Our experiments show that repeated injections of sub-anesthetic doses of ketamine induce significant changes in the nitrergic and GABAergic system which, in part, resemble those described in postmortem brains of human schizophrenics indicating that sub-chronic treatment with sub-anesthetic doses of ketamine might be a useful animal model to study schizophrenia.
Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel ...running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed that NK cells were mobilized by epinephrine, and blockade of β-adrenergic signaling blunted training-dependent tumor inhibition. Moreover, epinephrine induced a selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies blunted training-induced tumor suppression, intratumoral NK cell infiltration, and NK cell activation. Together, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth.
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•Exercise reduces tumor incidence and growth in several mouse models•Exercise increases NK cell infiltration, thereby controlling tumor growth•Epinephrine mobilizes NK cells and β-blockade blunts the tumor suppression•Exercise-induced muscle-derived IL-6 is involved in NK cell redistribution
The beneficial effects of exercise are countless. Pedersen et al. now link exercise, cancer, and immunity and reveal that exercise decreases tumor incidence and growth by over 60% across several mouse tumor models through a direct regulation of NK cell mobilization and trafficking in an epinephrine- and IL-6-dependent manner.
Dupuytren's disease (DD) is a progressive fibromatosis that causes the formation of nodules and cords in the palmar aponeurosis leading to flexion contracture of affected fingers. The ...etiopathogenesis is multifactorial with a strong genetic predisposition. It is the most frequent genetic disorder of connective tissues. We have collected clinical data from 736 unrelated individuals with DD who underwent surgical treatment from Germany and Switzerland. We evaluated a standardised questionnaire, assessed the importance of different risk factors and compared subgroups with and without positive family history. We found that family history clearly had the strongest influence on the age at first surgery compared to environmental factors, followed by male sex. Participants with a positive family history were on average 55.9 years of age at the first surgical intervention, 5.2 years younger than probands without known family history (p = 6.7 × 10−8). The percentage of familial cases decreased with age of onset from 55% in the 40–49 years old to 17% at age 80 years or older. Further risk factors analysed were cigarettes, alcohol, diabetes, hypertension, and epilepsy. Our data pinpoint the importance of genetic susceptibility for DD, which has long been underestimated.
Interleukin 1β (IL-1β) is an important inflammatory mediator of type 2 diabetes. Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas ...during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1β. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1β production in vitro. Processing of IL-1β initiated by IAPP first required priming, a process that involved glucose metabolism and was facilitated by minimally oxidized low-density lipoprotein. Finally, mice transgenic for human IAPP had more IL-1β in pancreatic islets, which localized together with amyloid and macrophages. Our findings identify previously unknown mechanisms in the pathogenesis of type 2 diabetes and treatment of pathology caused by IAPP.
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