Molecular Phylogeny of OVOL Genes Illustrates a Conserved C2H2 Zinc Finger Domain Coupled by Hypervariable Unstructured Regions

OVO-like proteins (OVOL) are members of the zinc finger protein family and serve as transcription factors to regulate gene expression in various differentiation processes. Recent studies have shown that OVOL genes are involved in epithelial development and differentiation in a wide variety of organisms; yet there is a lack of comprehensive studies that describe OVOL proteins from an evolutionary perspective. Using comparative genomic analysis, we traced three different OVOL genes (OVOL1-3) in vertebrates. One gene, OVOL3, was duplicated during a whole-genome-duplication event in fish, but only the copy (OVOL3b) was retained. From early-branching metazoa to humans, we found that a core domain, comprising a tetrad of C2H2 zinc fingers, is conserved. By domain comparison of the OVOL proteins, we found that they evolved in different metazoan lineages by attaching intrinsically-disordered (ID) segments of N/C-terminal extensions of 100 to 1000 amino acids to this conserved core. These ID regions originated independently across different animal lineages giving rise to different types of OVOL genes over the course of metazoan evolution. We illustrated the molecular evolution of metazoan OVOL genes over a period of 700 million years (MY). This study both extends our current understanding of the structure/function relationship of metazoan OVOL genes, and assembles a good platform for further characterization of OVOL genes from diverged organisms

NMDA-receptor antibodies alter cortical microcircuit dynamics

NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities-or even seizures-is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in pediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab-related changes render microcircuitry critically susceptible to overt EEG paroxysms when these key parameters are changed, even though the same parameter fluctuations are tolerated in the in silico model of the control condition. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures

Objective: We aimed to describe the extent of neurodevelopmental impairments andidentify the genetic etiologies in a large cohort of patients with epilepsy with myoclonicatonic seizures (MAE).Methods: We deeply phenotyped MAE patients for epilepsy features, intellectualdisability, autism spectrum disorder, and attention-deficit/hyperactivity disorderusing standardized neuropsychological instruments. We performed exome analysis(whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets toidentify genetic etiologies.Results: We analyzed 101 patients with MAE (70% male). The median age of seizureonset was 34 months (range = 6-72 months). The main seizure types were myoclonicatonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absencein 60%, and tonic seizures in 19% of patients. We observed intellectual disability in62% of patients, with extremely low adaptive behavioral scores in 69%. In addition,24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivitysymptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, includingfive previously published patients. These were pathogenic genetic variants inSYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2,SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three newcandidate genes, ASH1L, CHD4, and SMARCA2 in one patient each.Significance: MAE is associated with significant neurodevelopmental impairment.MAE is genetically heterogeneous, and we identified a pathogenic genetic etiologyin 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestationof several etiologies rather than a discrete syndromic entity

Morphological and Morphometric study of Glenoid Cavity and it’s Clinical Application in Western Rajasthan Population

Background: Glenoid cavity (GC) is a shallow, concave and oval fossa at superolateral border of scapula and form glenohumeral joint with scapula. There is a notch present on its anterosuperior part which gives its different shape. When this glenoid notch is indistinct its shape is pear shaped, when it is distinct it looks like inverted comma shape and when it is absent its oval shape. Understanding morphometric and morphological variation of GC plays an important role for surgeon while designing and fitting of glenoid component for total shoulder arthroplasty. Aims: A morphometric study of the glenoid cavity of 120 adult dry human scapulae in Western Rajasthan Population was done to evaluate the shape and various diameters of the GC. Material and methods: 120 dry scapulae (60 Right and 60 Left) of unknown sex, were taken for the study. Damaged bones were excluded from the study. Supero-Inferior Diameter (SI-D), Antero-Posterior Diameters (AP-D1 and AP-D2) of both sides were analysed and compared by unpaired t-test. Results: Most common shape of GC was pear shaped (45.83%) followed by oval shape (35%). Least common shape was inverted comma shape (19.16%). Difference in mean SI-D of both sides were statistically insignificant while AP-D1 and AP-D2 were found statistically significant. Mean Glenoid Cavity Index on right and left sides were 64.57 ± 6.91% and 68.33 ± 6.29% respectively. Conclusions: The above study helps Orthopedicians in shoulder dislocation, fractures and treating shoulder pathological conditions like glenohumeral instability and rotator cuff pathology

Development, evaluation and implementation of video-EEG telemetry at home

AbstractPurposeTo describe the development and implementation of video EEG telemetry (VT) in the patient's home (home video telemetry, HVT) in a single centre.MethodsHVT met the UK Medical Research Council definition of a complex intervention, and we used its guidance to evaluate the process of piloting, evaluating, developing and implementing this new clinical service. The first phase was a feasibility study, comparing inpatient VT (IVT) with HVT in a test–retest design (n=5), to assess data quality and yield of clinically relevant events. The second phase was a pre-implementation study (n=8), to examine acceptability and satisfaction as well as the costs of IVT and HVT. Subsequently, we implemented the service, and reviewed the outcomes of the first 34 patients.ResultsThe feasibility study found no difference in the quality of recording or clinical yield between IVT and HVT. The pre-implementation study showed excellent patient satisfaction. We also discuss the findings of the main stakeholder survey (consultants and technicians). Our economic modelling demonstrates a clear financial superiority of HVT over IVT.ConclusionOur findings show that diagnostic HVT for seizure classification and polysomnographies can be carried out safely in the patients’ home and poses no security risks for staff. HVT can be effectively integrated into an existing tertiary care service as a routine home or community-based procedure. We hope to encourage other clinical neurophysiology departments and epilepsy centres to take advantage of our experience and consider adopting and implementing HVT, with the aim of a nationwide coverage

Past, Present and Future of Home video-electroencephalographic telemetry:A review of the development of in-home video-electroencephalographic recordings

Video-electroencephalographic (EEG) monitoring is an essential tool in epileptology, conventionally carried out in a hospital epilepsy monitoring unit. Due to high costs and long waiting times for hospital admission, coupled with technological advances, several centers have developed and implemented video-EEG monitoring in the patient's home (home video-EEG telemetry [HVET]). Here, we review the history and current status of three general approaches to HVET: (1) supervised HVET, which entails setting up video-EEG in the patient's home with daily visiting technologist support; (2) mobile HVET (also termed ambulatory video-EEG), which entails attaching electrodes in a health care facility, supplying the patient and carers with the hardware and instructions, and then asking the patient and carer to set up recording at home without technologist support; and (3) cloud-based HVET, which adds to either of the previous models continuous streaming of video-EEG from the home to the health care provider, with the option to review data in near real time, troubleshoot hardware remotely, and interact remotely with the patient. Our experience shows that HVET can be highly cost-effective and is well received by patients. We note limitations related to long-term electrode attachment and correct camera placing while the patient is unsupervised at home, and concerns related to regulations regarding data privacy for cloud services. We believe that HVET opens significant new opportunities for research, especially in the field of understanding the many influences in seizure occurrence. We speculate that in the future HVET may merge into innovative new multisensor approaches to continuously monitoring people with epilepsy

Unraveling the role of chitosan for nasal drug delivery systems: A review

The discipline of nanoscience has made enormous strides in the recent two decades. The researchers in the field of nanomedicine have been looking into using natural biodegradable polymeric nano-colloids for targeted drug delivery, due to their high levels of bioavailability, biocompatibility, enhanced permeability, better retention time, safety, and less toxicity. The nasal cavity has been considered as an efficient route with great potential for the management of local and systemic diseases like asthma, pneumonia, Alzheimer's disease, etc. Chitosan (CS), a natural polymer, along with its greater efficacy and less toxicity, makes it an attractive candidate for nasal administration. This review has focused on the limitations that might arise when using the nasal route and how CS can play a mechanistic role in helping with these complications when using the nasal drug delivery system. The major revelation from this article is to summarize the various formulations and innovation of CS-loaded nano colloids, such as nanoparticles, liposomes, hydrogels, in situ gel, etc. The preclinical study and various patents published also concluded that the intranasal delivery of CS-loaded nanocolloids have wide potential to manage various neurodegenerative, respiratory, cardiovascular, etc. disorders