KCTD7-related progressive myoclonic epilepsy: Report of 42 cases and review of literature.

OBJECTIVE: KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort. METHODS: Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized. RESULTS: Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years). SIGNIFICANCE: This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.

A histone modification identifies a DNA element controlling slo BK channel gene expression in muscle.

The slo gene encodes the BK-type Ca(2+)-activated K(+) channels. In Drosophila, expression of slo is induced by organic solvent sedation (benzyl alcohol and ethanol), and this increase in neural slo expression contributes to the production of functional behavioral tolerance (inducible resistance) to these drugs. Within the slo promoter region, we observed that benzyl alcohol sedation produces a localized spike of histone acetylation over a 65-nucleotide (65-n) conserved DNA element called 55b. Changes in histone acetylation are commonly the consequence of transcription factor activity, and previously, a localized histone acetylation spike was used to successfully map a DNA element involved in benzyl alcohol-induced slo expression. To determine whether the 55b element was also involved in benzyl alcohol-induced neural expression of slo, we deleted it from the endogenous slo gene by homologous recombination. Flies lacking the 55b element were normal with respect to basal and benzyl alcohol-induced neural slo expression, the capacity to acquire and maintain functional tolerance, their threshold for electrically-induced seizures, and most slo-related behaviors. Removal of the 55b element did however increase the level of basal expression from the muscle/tracheal cell-specific slo core promoter and produced a slight increase in overall locomotor activity. We conclude that the 55b element is involved in control of slo expression from the muscle and tracheal-cell promoter but is not involved in the production of functional benzyl alcohol tolerance.

Synthesis of BF3 catalyzed Mannich derivatives with excellent ee from phenylpropanolamine, study of their antimicrobial activity and molecular docking.

Antimicrobial agents 4a-g and 5a-g with very good potency were synthesized with 100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components one pot Mannich reaction in good yields. Obtained compounds were characterized using spectral techniques. Antimicrobial study of these compounds revealed a good to very high potential activity against tested microbes when compared to standard antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds exhibited significant minimum inhibitory concentration (MIC) values against Gram positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e exhibited very high potent MIC values against tested twelve bacteria and three fungi when compared to control. When subjected to molecular docking, in silico studies revealed significant binding energies ranging from -7.06 to -8.90 kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90 kcal/mol, respectively.

Synthesis, antimicrobial and molecular docking studies of enantiomerically pure N-alkylated ß-amino alcohols from phenylpropanolamines.

Enantiomerically pure N-alkylated ß-amino alcohols 1a, 1a', 1c, 1c', 1d, 1d', 1e and 1e', with ee 100% have been synthesized from phenylpropanolamines 2. Effect of the neighboring chiral environment on the newly formed chiral center has been studied experimentally and concluded that the newly formed chiral center's absolute configuration is opposite to the adjacent (α- or ß-) chiral environment. The antimicrobial activity of the synthesized ß-amino alcohols were screened using in vitro disc diffusion method and variable antimicrobial activities were shown for 1a, 1a', 1c, 1c', 1d, 1d', 1e &1e' and amongst them 1d &1d' exhibited significant activity against bacteria and fungi. In silico studies revealed all the synthesized ß-amino alcohols 1a-e and 1a'-e' have shown good binding energies ranging from -7.38 to -6.09 kJ/mol towards the target receptor DNA topoisomerase IV and 1d' has shown maximum binding energy -7.38 kJ/mol.

Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line.

Novel dispirooxindole-pyrrolidine derivatives have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide generated from isatin and sarcosine with the dipolarophile 3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3-ylidene)propanenitrile, and also spiro compound of acenaphthenequinone obtained by the same optimized reaction condition. Synthesized compounds were evaluated for their antimicrobial activity and all the compounds shown significant activity. Anticancer activity was evaluated against A549 human lung adenocarcinoma cancer cell lines. Compounds 7b, 7g, 7i and 7r exhibit very good anticancer activity 62.96%, 62.03%, 67.67% and 60.22%, respectively, at the dose of 200µg/mL and compound 7i shows IC50 value in 50µg/mL.

Mitochondrial Complex I Deficiency Masquerading as Stroke-Like Episode Clinically and as Alexander Disease Radiologically Following Chicken Pox.

Mitochondrial disorders are a group of metabolic disorders with variable presentation and usually affect organs with high energy requirements like the brain, eye, and heart. Seventeen-month-old girl child presented with right hemiparesis and regression of milestones following chicken pox. Investigations showed elevated lactate, white matter signal changes in both periventricular and subcortical white matter with frontal predominance in the MRI of the brain, cardiomyopathy in the echocardiography, with complex I deficiency in respiratory enzyme assay in the muscle biopsy. A homozygous missense variant c.304C>T (p. Arg102Cys) in exon 5 of NDUFS8 gene (chr11:67800682C>T; NM_002496.4) was detected on whole exome sequencing with positive parental Sanger for the same gene. The child was started on a mitochondrial cocktail, ramipril, and frusemide. Mitochondrial complex deficiency should be considered in cases with stroke-like episodes, and predominant white matter involvement on imaging mimicking classical genetic leukodystrophy like Alexander disease.

Functional Properties of Grapefruit Seed Extract Embedded Blend Membranes of Poly(vinyl alcohol)/Starch: Potential Application for Antiviral Activity in Food Safety to Fight Against COVID-19.

The poly(vinyl alcohol) (PVA) and starch-based polymeric films with a ratio of 2:8 were prepared using solution casting followed by a solvent evaporation method. Four types of membranes with varied concentrations of grapefruit seed extract (GSE) i.e., 2.5-10 wt% was incorporated in the films. The prepared membranes were assessed for transparency test, mechanical properties, surface morphology, permeability test for O2, and antimicrobial properties. The PVA/starch-10% GSE loaded film showed excellent mechanical properties showing highest 1344 ± 0.7% elongation at break but poor optical transparency with 53.8% to 68.61%. The Scanning Electron Microscopic study reveals the good compatibility between the PVA, Starch, and GSE. The gas permeability test reveals that the prepared films have shown good resistance to the O2 permeability 0.0326-0.316 Barrer at 20 kg/cm2 feed pressure for the prepared membranes showing excellent performance. By adding the little amount of GSE into the PVA/starch blend membranes showed promising antimicrobial efficacy against MNV-1. For 4 h. incubation, PVA/starch blend membranes containing 2.5%, 5%, and 10% GSE caused MNV-1 reductions of 0.92, 1.89, and 2.27 log PFU/ml, respectively. Similarly, after 24 h, the 5% and 10% GSE membranes reduced MNV-1 titers by 1.90 and 3.26 log PFU/ml, respectively. Antimicrobial tests have shown excellent performance to resist microorganisms. The water uptake capacity of the membrane is found 72% for the PVA/starch pristine membrane and is reduced to 32% for the 10% GSE embedded membrane. Since the current pandemic situation due to COVID-19 occurred by SARSCOV2, the prepared GSE incorporated polymeric blend films are the rays of hope in the packaging of food stuff.

An Experimental and Simulation Study of the Active Camber Morphing Concept on Airfoils Using Bio-Inspired Structures.

Birds are capable of morphing their wings across different flight modes and speeds to improve their aerodynamic performance. In light of this, the study aims to investigate a more optimized solution compared to conventional structural wing designs. The design challenges faced by the aviation industry today require innovative techniques to improve flight efficiency and minimize environmental impact. This study focuses on the aeroelastic impact validation of wing trailing edge morphing, which undergoes significant structural changes to enhance performance as per mission requirements. The approach to design-concept, modeling, and construction described in this study is generalizable and requires lightweight and actively deformable structures. The objective of this work is to demonstrate the aerodynamic efficiency of an innovative structural design and trailing edge morphing concept compared to conventional wing-flap configurations. The analysis revealed that the maximum displacement at a 30-degree deflection is 47.45 mm, while the maximum stress is 21 MPa. Considering that the yield strength of ABS material is 41.14 MPa, this kerf morphing structure, with a safety factor of 2.5, can withstand both structural and aerodynamic loads. The analysis results of the flap and morph configurations showed a 27% efficiency improvement, which was confirmed through the convergence criteria in ANSYS CFX.

Enhanced O2/N2 separation by QuaternizedMatrimid/Multiwalled carbon nanotube mixed-matrix membrane.

The air separation (O2/N2) based on polymeric membranes is critical because it is more energy efficient than traditional methods. Dense polymeric membranes are now the main stay of industrial processes that generate oxygen and nitrogen enriched gas. Though, regular polymeric membranes often fall short of selective pressure demands because O2 and N2 gases have such comparable equivalent diameters. While polymer composites have their benefits, nanocomposite (NCs) allows for the production of high-performance barriers. Utilising Matrimid® 5218 (Matrimid) as the base framework and multiwall carbon nanotube (MWCNT) as the filler, a novel NCs for O2/N2 separation was developed. Both matrimid and MWCNTs were chemically modified quaternization and functionalizing the MWCNTs. The membranes were casted using solution casting with a combination of quaternized matrimid and functionalized multi-walled carbon nanotubes (f-MWCNT). When f-MWCNT was added to quaternized matrimid, it created interfacial compatibility, which increased O2/N2 selectivity and permeability by 65 % and 35 %, respectively. In the current study, increasing O2 diffusivity and O2/N2 solubility selectivity resulted in improved performance, this paves a way for manufacturing innovation.

Synthesis and Characterization of Microwave-Assisted Copolymer Membranes of Poly(vinyl alcohol)-g-starch-methacrylate and Their Evaluation for Gas Transport Properties.

Poly(vinyl alcohol) (PVA) is an excellent membrane-forming polymer and can be modified with potato starch and methyl acrylate monomers to obtain copolymers with improved physical and chemical properties. The study presents the synthesis of poly(vinyl alcohol)-g-starch-poly(methyl acrylate) PVA-g-St-g-PMA copolymers using microwave irradiation technique and potassium persulfate initiator. Solution casting and solvent evaporation methods were adopted for the fabrication of polyvinyl alcohol-g-starch-acrylamide composite membranes. The synthesized graft copolymer was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and thermal analysis. The modified nanocomposite membranes were showed very promising results with the parameters permeability and selectivity. The nanocomposite membranes exhibited the advantages of easy handling and reuse.

Biomimicking Nature-Inspired Design Structures-An Experimental and Simulation Approach Using Additive Manufacturing.

Whether it is a plant- or animal-based bio-inspiration design, it has always been able to address one or more product/component optimisation issues. Today's scientists or engineers look to nature for an optimal, economically viable, long-term solution. Similarly, a proposal is made in this current work to use seven different bio-inspired structures for automotive impact resistance. All seven of these structures are derived from plant and animal species and are intended to be tested for compressive loading to achieve load-bearing capacity. The work may even cater to optimisation techniques to solve the real-time problem using algorithm-based generative shape designs built using CATIA V6 in unit dimension. The samples were optimised with Rhino 7 software and then simulated with ANSYS workbench. To carry out the comparative study, an experimental work of bioprinting in fused deposition modelling (3D printing) was carried out. The goal is to compare the results across all formats and choose the best-performing concept. The results were obtained for compressive load, flexural load, and fatigue load conditions, particularly the number of life cycles, safety factor, damage tolerance, and bi-axiality indicator. When compared to previous research, the results are in good agreement. Because of their multifunctional properties combining soft and high stiffness and lightweight properties of novel materials, novel materials have many potential applications in the medical, aerospace, and automotive sectors.

Experimental and Computational Study of Mechanical and Thermal Characteristics of h-BN and GNP Infused Polymer Composites for Elevated Temperature Applications.

Polymer-based nanocomposites are being considered as replacements for conventional materials in medium to high-temperature applications. This article aims to discover the synergistic effects of reinforcements on the developed polymer-based nanocomposite. An epoxy-based polymer composite was manufactured by reinforcing graphene nanoplatelets (GNP) and h-boron nitride (h-BN) nanofillers. The composites were prepared by varying the reinforcements with the step of 0.1 from 0.1 to 0.6%. Ultrasonication was carried out to ensure the homogenous dispersion of reinforcements. Mechanical, thermal, functional, and scanning electron microscopy (SEM) analysis was carried out on the novel manufactured composites. The evaluation revealed that the polymer composite with GNP 0.2 by wt % has shown an increase in load-bearing capacity by 265% and flexural strength by 165% compared with the pristine form, and the polymer composite with GNP and h-BN 0.6 by wt % showed an increase in load-bearing capacity by 219% and flexural strength by 114% when compared with the pristine form. Furthermore, the evaluation showed that the novel prepared nanocomposite reinforced with GNP and h-BN withstands a higher temperature, around 340 °C, which is validated by thermogravimetric analysis (TGA) trials. The numerical simulation model is implemented to gather the synthesised nanocomposite's best composition and mechanical properties. The minor error between the simulation and experimental data endorses the model's validity. To demonstrate the industrial applicability of the presented material, a case study is proposed to predict the temperature range for compressor blades of gas turbine engines containing nanocomposite material as the substrate and graphene/h-BN as reinforcement particles.

Progressive retinal changes in pediatric multiple sclerosis.

Objectives To determine to what extent acute demyelinating episodes versus chronic degenerative phenomena drive retinal neuroaxonal damage in pediatric acquired demyelinating syndromes (ADS). Methods We acquired optical coherence tomography (OCT) data (follow-up range: 2 weeks - 5 years, at variable intervals from presentation) in pediatric participants who had multiple sclerosis (MS), monophasic ADS, or were healthy. Multivariable mixed effects models were used to assess the association of the number of demyelinating episodes (either optic neuritis [ON], or non-ON relapses) with changes in retinal nerve fiber layer (RNFL) or ganglion cell layer-inner plexiform layer (GCIPL) thickness. Results 64 OCT sans from 23 MS, and 33 scans from 12 monophasic ADS participants were compared with 68 scans from 62 healthy participants. The first ON episode had the biggest impact on RNFL or GCIPL thickness in monophasic ADS (RNFL: -7.9 µm, CI=5.5, p = 0.0056; GCIPL: -8.4 µm, CI=4.4, p = 0.0002) and MS (RNFL: -16 µm, CI = 3.7, p < 10-6; GCIPL: -15 µm, CI = 2.6, p < 10-6). Non-ON relapses were also associated with small but significant retinal thickness reductions in MS (RNFL: -2.6 µm/relapse, CI = 1.4, p = 0.0003; GCIPL: -2.8 µm/relapse, CI = 0.89, p < 10-6). MS participants showed progressive GCIPL thinning independent of acute demyelinating episodes (-2.7 µm/year, CI = 1.9, p = 0.0058). Conclusions We showed a prominent impact of early ON episodes on OCT measures of neuroaxonal structure in patients with ADS. We also demonstrated negative effects of non-ON relapses, and the presence of chronic retinal neurodegenerative changes, in youth with MS.

Influence of Solid Lubricant Addition on Friction and Wear Response of 3D Printed Polymer Composites.

In this study, acrylonitrile butadiene styrene (ABS) and graphite powder-a solid lubricant-were filled and characterized for friction and wear responses. The fused deposition modeling (FDM) technique was utilized to synthesize ABS-graphite composites. A twin-screw extrusion approach was employed to create the composite filament of graphite-ABS that is suitable for the FDM process. Three graphite particle ratios ranging from 0% to 5% were explored in the ABS matrix. The wear and friction properties of ABS composites were examined using a pin on disc tribometer at varied sliding velocities and weights. As a result of the graphite addition in the ABS matrix, weight losses for FDM components as well as a decreased coefficient of friction were demonstrated. Furthermore, as the graphite weight percentage in the ABS matrix grows the value of friction and wear loss decreases. The wear mechanisms in graphite filled ABS composites and ABS were extensively examined using scanning electron microscopy and confocal microscopy.

Mechanical Properties of PC-ABS-Based Graphene-Reinforced Polymer Nanocomposites Fabricated by FDM Process.

This experimental study investigates the mechanical properties of polymer matrix composites containing nanofiller developed by fused deposition modelling (FDM). A novel polymer nanocomposite was developed by amalgamating polycarbonate-acrylonitrile butadiene styrene (PC-ABS) by blending with graphene nanoparticles in the following proportions: 0.2, 0.4, 0.6, and 0.8 wt %. The composite filaments were developed using a twin-screw extrusion method. The mechanical properties such as tensile strength, low-velocity impact strength, and surface roughness of pure PC-ABS and PC-ABS + graphene were compared. It was observed that with the addition of graphene, tensile strength and impact strength improved, and a reduction in surface roughness was observed along the build direction. These properties were analyzed to understand the dispersion of graphene in the PC-ABS matrix and its effects on the parameters of the study. With the 0.8 wt % addition of graphene to PC-ABS, the tensile strength increased by 57%, and the impact resistance increased by 87%. A reduction in surface roughness was noted for every incremental addition of graphene to PC-ABS. The highest decrement was seen for the 0.8 wt % addition of graphene reinforcement that amounted to 40% compared to PC-ABS.

Analysis of the Effect of Parameters on Fracture Toughness of Hemp Fiber Reinforced Hybrid Composites Using the ANOVA Method.

In today's world, global warming has become a concern. To overcome this, we need to reduce the carbon footprints caused by the production of materials. Much of the time, this is equivalent to the same amount of CO2 emissions per tonne of production. This is a serious concern and needs to be overcome by identifying alternative materials to have as minimal a carbon footprint as possible. In this context, hemp fiber is by far the best natural fiber when compared to its peers. As per the survey conducted by the Nova institute, hemp has CO2 emissions of only 360 Kg/tonne, whereas jute has CO2 emissions of 550 Kg/tonne, kenaf 420 Kg/tonne, and flax 350 Kg/tonne. This paper presents an experimental study of the fracture toughness of hemp-reinforced hybrid composites (HRHC). The effect of the parameters on the fracture toughness behavior of HRHC is studied using the Taguchi technique. It uses different filler combinations with hemp fiber and epoxy. Hemp fiber is used as the reinforcement, epoxy resin is used as a matrix, and banana fiber, coconut shell powder, and sawdust are used as fillers. The experimental plan is prepared using an orthogonal array and analyzed using Minitab software. The obtained results were analyzed using ANOVA and main effects plots. It was observed that the fracture toughness increases with a decrease in thickness. The fracture toughness is affected by the fiber content in the range of 25%-35% and is also affected by the filler materials.

Investigation of Mechanical and Physical Properties of Big Sheep Horn as an Alternative Biomaterial for Structural Applications.

This paper investigates the physical and mechanical properties of bighorns of Deccani breed sheep native from Karnataka, India. The exhaustive work comprises two cases. First, rehydrated (wet) and ambient (dry) conditions, and second, the horn coupons were selected for longitudinal and lateral (transverse) directions. More than seventy-two samples were subjected to a test for physical and mechanical property extraction. Further, twenty-four samples were subjected to physical property testing, which included density and moisture absorption tests. At the same time, mechanical testing included analysis of the stress state dependence with the horn keratin tested under tension, compression, and flexural loading. The mechanical properties include the elastic modulus, yield strength, ultimate strength, failure strain, compressive strength, flexural strength, flexural modulus, and hardness. The results showed anisotropy and depended highly on the presence of water content more than coupon orientation. Wet conditioned specimens had a significant loss in mechanical properties compared with dry specimens. The observed outcomes were shown at par with results for yield strength of 53.5 ± 6.5 MPa (which is better than its peers) and a maximum compressive stress of 557.7 ± 5 MPa (highest among peers). Young's modulus 6.5 ± 0.5 GPa and a density equivalent to a biopolymer of 1.2 g/cc are expected to be the lightest among its peers; flexural strength 168.75 MPa, with lowest failure strain percentage of 6.5 ± 0.5 and Rockwell hardness value of 60 HRB, seem best in the class of this category. Simulation study identified a suitable application area based on impact and fatigue analysis. Overall, the exhaustive experimental work provided many opportunities to use this new material in various diversified applications in the future.

Sol-Gel Co-Precipitation Synthesis, Anticoagulant and Anti-Platelet Activities of Copper-Doped Nickel Manganite Nanoparticles.

Copper-substituted nickel manganites Ni(1-x)CuxMn2O4 (Ni-TCE-NPs) were produced by co-precipitation route (sol-gel) at room temperature. Ni(1-x)CuxMn2O4-Bio (NCB) NPs were studied by powder X-ray diffraction technique, scanning electron microscopy and Raman spectroscopy. XRD spectra authenticated the copper-doped nickel manganites' formation with particle size 23-28 nm. A significant decrease in the lattice parameter confirmed the doping of copper ions into the nickel manganites. Microscopy (SEM) was used to estimate the grain size, shape and uniformity, revealing the non-uniform agglomerated polygon and plate-like microstructure. The NCB-NPs showed anticoagulant activity by enhancing the coagulation time of citrated plasma of human beings. NCB-NPs with x = 0.35 and 0.45 have increased clotting time from control 133 ± 4 s to 401 ± 7 s and 3554 ± 80 s, respectively, and others around 134 s. Additionally NCB-NPs with x = 0.35, 0.45 inhibited the platelet aggregation by 80% and 92%, while remaining inhibited with only 30%. NCB-NPs did not show hemolytic activity in RBC cells intimate its non-toxic nature. Finally, NCB-NPs were non-toxic and known to exhibit anti-blood-clotting and antiplatelet activities, which can be used in the field of biomedical applications, especially as antithrombotic agents.

Nanoceramic Composites for Nuclear Radiation Attenuation.

The development of radiation attenuation materials with lean cross-sections is the need of the hour. However, the inherent threat of radiations accompanying these processes is of major concern. Thus, in an attempt to shield unnecessary radiations, several novel materials have been fabricated alongside the conventional materials available. Yet, there is a need for cost-effective, efficient shielding materials that have good mechanical strength and effective shielding properties. The present work investigates ceramic composite behaviors and radiation shielding capacity reinforced with lead oxide nano-powder. Developed nano-lead-based cement composites were subjected to mechanical tests to determine flexural and compressive strengths to check their suitability for structural applications. Further, the gamma attenuation test of the composites was conducted to determine their neutron absorption capacity. The addition of nano-leadoxide in the control beams was varied from 0.7 to 0.95 and 1 wt.% of the ceramic matrix. The percentage of nano-leadoxide that gives the best results in both enhanced properties and economic aspects was determined to be 0.6 wt.% of the cement.