Genomic analysis of “microphenotypes” in epilepsy Stanley, Kate; Hostyk, Joseph; Tran, Linh ...
American journal of medical genetics. Part A,
January 2022, 2022-01-00, 20220101, Letnik:
188, Številka:
1
Journal Article
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Large international consortia examining the genomic architecture of the epilepsies focus on large diagnostic subgroupings such as “all focal epilepsy” and “all genetic generalized epilepsy”. In ...addition, phenotypic data are generally entered into these large discovery databases in a unidirectional manner at one point in time only. However, there are many smaller phenotypic subgroupings in epilepsy, many of which may have unique genomic risk factors. Such a subgrouping or “microphenotype” may be defined as an uncommon or rare phenotype that is well recognized by epileptologists and the epilepsy community, and which may or may not be formally recognized within the International League Against Epilepsy classification system. Here we examine the genetic structure of a number of such microphenotypes and report in particular on two interesting clinical phenotypes, Jeavons syndrome and pediatric status epilepticus. Although no single gene reached exome‐wide statistical significance to be associated with any of the diagnostic categories, we observe enrichment of rare damaging variants in established epilepsy genes among Landau–Kleffner patients (GRIN2A) and pediatric status epilepticus patients (MECP2, SCN1A, SCN2A, SCN8A).
Defective primary ciliogenesis or cilium stability forms the basis of human ciliopathies, including Joubert syndrome (JS), with defective cerebellar vermis development. We performed a high-content ...genome-wide small interfering RNA (siRNA) screen to identify genes regulating ciliogenesis as candidates for JS. We analyzed results with a supervised-learning approach, using SYSCILIA gold standard, Cildb3.0, a centriole siRNA screen and the GTex project, identifying 591 likely candidates. Intersection of this data with whole exome results from 145 individuals with unexplained JS identified six families with predominantly compound heterozygous mutations in KIAA0586. A c.428del base deletion in 0.1% of the general population was found in trans with a second mutation in an additional set of 9 of 163 unexplained JS patients. KIAA0586 is an orthologue of chick Talpid3, required for ciliogenesis and Sonic hedgehog signaling. Our results uncover a relatively high frequency cause for JS and contribute a list of candidates for future gene discoveries in ciliopathies.
A full-term male newborn presented to us at the age of 2 weeks with left facial weakness that had started at the age of 4 days and steadily progressed over a 10-day period. Physical examination ...revealed a complete unilateral left peripheral facial nerve paralysis, with an erythematous dull and bulging left tympanic membrane. Computed tomography and magnetic resonance imaging were normal. The patient underwent left myringotomy and placement of a pneumatic equalization tube within 24 hours of presentation. He also received a 5-day course of prednisone and a 2-week course of antibiotics and acyclovir. Improvement of the facial paralysis was rapid, with near-complete resolution at the time of discharge home and complete resolution 6 weeks later. To our knowledge, this is the only reported case of acute otitis media with associated facial nerve palsy in a newborn during the first 2 weeks of life. (J Child Neurol 2005;20:452—454).
The acute pathophysiologic changes during hemiplegic spells and the long-term outcome of alternating hemiplegia remain obscure. In a 41-year-old male with familial alternating hemiplegia we found an ...increase in right frontal cerebral blood flow 3 h into a 5-h left hemiplegic episode. A repeat high-resolution brain SPECT study performed 26 h after the resolution of the left hemiplegia revealed normalization of the frontal blood flow accompanied by hyperperfusion in the right parietal lobe. An interictal SPECT scan several weeks later showed no asymmetries. Head CT and MRI scans were negative. Neuropsychologic assessment and neurologic examination revealed evidence of a diffuse disorder which predominantly involved the right hemisphere. To our knowledge, there are no previous correlative studies of serial high-resolution brain SPECT with MRI, or of detailed neuropsychologic assessment, in adult patients with such an advanced course of alternating hemiplegia of childhood.
Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence.
To develop a framework that characterizes the processes of ...development of living practice guidelines in health care.
First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders.
International.
Multidisciplinary group of 51 persons who have experience with guidelines.
Not applicable.
A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the organization's adoption of the living methodology as well as each specific guideline project. The production process consists of initiation, maintenance, and retirement phases. The reporting should cover the evidence surveillance time stamp, the outcome of reassessment of the body of evidence (when applicable), and the outcome of revisiting a recommendation (when applicable). The dissemination process may necessitate the use of different venues, including one for formal publication.
This study does not provide detailed or practical guidance for how the described concepts would be best implemented.
The framework will help guideline developers in planning, producing, reporting, and disseminating living guideline projects. It will also help research methodologists study the processes of living guidelines.
None.
Promising application prospects and excellent characteristics of metamaterials are currently under intensive research work all over the world. In this paper, novel wavelength selective metamaterial ...absorber based on 2D split rhombus grating is numerically proposed and analyzed. The suggested metamaterial absorber is made of molybdenum metals with dielectric spacer of Magnetic Florid (MgF
2
). The effects of the design parameters are studied to improve the absorption of the reported metamaterial absorber. Additionally, the inductor and capacitor (LC) model is investigated to understand the physics beyond the absorption of the studied design. The finite difference time domain method is used to obtain the modal analysis and absorption characteristics of the metamaterial structure. Perfect absorption is achieved through studied wavelength range from 300 to 20,000 nm with high photon-to-heat efficiency of 81.71% at 1000 K. The absorption enhancement is due to the coupling between the surface plasmon polariton, Fabry–Perot resonance, and magnetic polariton. It is also found that the achieved absorption is insensitive to the oblique incidence from θ = 0° to 60° for the transverse magnetic (TM) and transverse electric (TE) waves. Therefore, the suggested absorber has a good potential for using in solar energy harvesting and conversion systems.
The objectives of this study are to describe the characteristics of living systematic reviews (LSRs) and to understand their life cycles.
We conducted a comprehensive search up to April 2021 then ...selected articles and abstracted data in duplicate and independently. We undertook descriptive analyses and calculated delay in version update and delay since the last published version.
We included 76 eligible LSRs with a total of 279 eligible versions. The majority of LSRs was from the clinical field (70%), was COVID-19 related (63%), and had a funding source specified (62%). The median number of versions per LSR was 2 (interquartile range (IQR) 1–4; range 1–19). The median and IQR for the ratio of the actual period of update to the planned period of update was 1.12 (0.81; 1.71). Out of all reviews with a ‘planned period of update’ and at least one update (N = 19), eight LSRs (42%) had a period since last published version greater than 3 times the planned period of update. No LSR included a ‘retirement notice’ in their latest published version.
While most LSR complied with the planned period of producing updates, a substantive proportion lagged since their last update.
Because Kawasaki disease is a disorder characterized by lymphocyte activation and immune complex destruction of endothelial cells, we examined the effect of administration of high doses of ...intravenously administered immune globulin (IVIG) on a lymphocyte population with affinity for endothelial cells: the natural killer cells. We found that administration of high doses of IVIG resulted in a significant increase in the activity of natural killer cells and in the numbers of circulating CD16+ cells. Furthermore, a study of patients treated with IVIG for seizure disorders suggests that this effect of IVIG on circulating NK cells is not unique to patients with Kawasaki disease. The beneficial effect of IVIG in the treatment of Kawasaki disease may be due to the ability of IVIG to inhibit interaction between natural killer cells and endothelial cells.
A novel porous core photonic crystal fiber (PC-PCF) is suggested and analyzed for terahertz waveguiding. The PC-PCF has a TOPAS background material with suspended asymmetric slotted core. Therefore, ...high birefringence of 0.09 is achieved with small material absorption losses of 0.016 cm
−1
and 0.028 cm
−1
for the quasi transverse electric (TE) and quasi transverse magnetic (TM) modes, respectively at
f
= 1.5 THz. Additionally low bending losses of 2.63 × 10
–24
cm
−1
and 8.16 × 10
–36
cm
−1
are obtained for the quasi TE and quasi TM modes, respectively at 1.0 cm bending radius and
f
= 1.5 THz. Further, the PC-PCF has an ultra-flat low dispersion of 0.54
±
0.08 ps/THz/cm and 0.94
±
0.1
ps/THz/cm for the quasi TE and TM modes, respectively within the frequency range of 0.8–1.2 THz. Therefore, the reported SSCPCF has a strong potential for usage in the Terahertz regime.
In this paper, a new design of hybrid plasmonic photonic crystal (PhC) waveguide is proposed and analyzed at operating wavelength of 1550 nm. The suggested design consists of hybrid cylindrical core ...with periodic grating as a cladding region. The effective index (
n
eff
), propagation length (
L
p
), and normalized mode effective area (
A
eff
) of the supported modes are numerically investigated using full vectorial finite element method. The cladding geometry is tuned to obtain long propagation length with good field confinement. The reported plasmonic PhC with uniform grating achieves long propagation length and low propagation loss of 124 µm, and 0.035 dB/µm respectively. Further, the PhC with chirped cladding offers propagation length and low propagation loss of 162 µm, and 0.0268 dB/µm at λ = 1550 nm, respectively.
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