Search

Background: Mutations in MPV17 cause the autosomal recessive disorder mitochondrial DNA depletion syndrome 6 (MTDPS6), also called Navajo neurohepatopathy (NNH). Clinical features of MTDPS6 is infantile onset of progressive liver failure with seldom development of progressive neurologic involvement.Methods: Whole exome sequencing (WES) was performed to isolate the causative gene of two unrelated neuropathy patients (9 and 13 years of age) with onset of the syndrome. Clinical assessments and biochemical analysis were performed.Results: A novel homozygous mutation (p.R41Q) in MPV17 was found by WES in both patients. Both showed axonal sensorimotor polyneuropathy without liver and brain involvement, which is neurophysiologically similar to axonal Charcot-Marie-Tooth disease (CMT). A distal sural nerve biopsy showed an almost complete loss of the large and medium-sized myelinated fibers compatible with axonal neuropathy. An in vitro assay using mouse motor neuronal cells demonstrated that the abrogation of MPV17 significantly affected cell integrity. In addition, the expression of the mutant protein affected cell proliferation. These results imply that both the loss of normal function of MPV17 and the gain of detrimental effects of the mutant protein might affect neuronal function.Conclusion: We report a novel homozygous mutation in MPV17 from two unrelated patients harboring axonal sensorimotor polyneuropathy without hepatoencephalopathy. This report expands the clinical spectrum of diseases caused by mutations of MPV17, and we recommend MPV17 gene screening for axonal peripheral neuropathies. [ABSTRACT FROM AUTHOR]

Background: Mutations in the Pleckstrin homology domain-containing, family G member 5 (PLEKHG5) gene has been reported in a family harboring an autosomal recessive lower motor neuron disease (LMND). However, the PLEKHG5 mutation has not been described to cause Charcot-Marie-Tooth disease (CMT). Methods: To identify the causative mutation in an autosomal recessive intermediate CMT (RI-CMT) family with childhood onset, whole exome sequencing (WES), histopathology, and lower leg MRIs were performed. Expression and activity of each mutant protein were analyzed. Results: We identified novel compound heterozygous (p.Thr663Met and p.Gly820Arg) mutations in the PLEKHG5 gene in the present family. The patient revealed clinical manifestations of sensory neuropathy. Fatty replacements in the distal lower leg muscles were more severe than in the thigh muscles. Although the symptoms and signs of this patient harboring slow nerve conduction velocities suggested the possibility of demyelinating neuropathy, a distal sural nerve biopsy was compatible with axonal neuropathy. Immunohistochemical analysis revealed that the patient has a low level of PLEKHG5 in the distal sural nerve and an in vitro assay suggested that the mutant proteins have a defect in activating the NF-κB signaling pathway. Conclusions: This study identifies compound heterozygous PLEKHG5 mutations as the cause of RI-CMT. We suggest that PLEKHG5 might play a role in the peripheral motor and sensory nervous system. This study expands the phenotypic spectrum of PLEKHG5 mutations [ABSTRACT FROM AUTHOR]

Background: Although graft extrusion is of concern after meniscal allograft transplantation (MAT), the correlation between extrusion and clinicoradiological outcomes remains unclear. Hypothesis: Patients with graft extrusion after MAT have worse clinical outcomes and greater arthritic change than those without graft extrusion. Study Design: Cohort study; Level of evidence, 3. Methods: Forty-three patients underwent MAT between 1999 and 2004. Grafts were classified as either nonextruded (<3 mm) or extruded (≥3 mm) according to 1-year postoperative magnetic resonance imaging (MRI) findings. The mean patient age at the time of surgery was 33.5 years (range, 17-43 years), and themean follow-up period was 5.1 years (range, 3.5-8.3 years). The Lysholm score was used to evaluate knee function. In addition, preoperative and postoperative (final follow-up) measurements were taken to determine the absolute and relative (affected side/normal side) joint space width (JSW) on a standing 45° flexion posteroanterior view. Results: Magnetic resonance imaging at 1 year showed the mean graft subluxation was 3.03±0.872 mm across all patients. Twenty-six knees (60%) were classified as nonextruded and 17 (40%) as extruded. No statistical difference was found between these 2 groups regarding Lysholm score improvement after MAT. Overall, absolute and relative JSWs were slightly narrower postoperatively compared with preoperatively across all patients (mean absolute difference, 0.283 mm; mean relative difference; 4.79%; P<.001). However, extruded and nonextruded knees were similar in terms of absolute (P = .764) and relative (P = .482) JSW after MAT. The amount of extrusion did not correlate with Lysholm score or the relative difference between preoperative and postoperative JSW across all patients or in either group. Conclusion: Joint space width was slightly narrower after MAT. Extrusion had no effect on 5-year clinical or radiological outcomes. [ABSTRACT FROM AUTHOR]

Effect of tension coating on iron loss has been investigated as a function of excitation induction and frequency in thin-gauged 3% silicon steel sheets and iron loss after tension coating has been evaluated by loss separation method. In order to additionally reduce iron loss, tension coating without forsterite base coating was applied on surfaces of the thin grain-oriented sheets. Reduction in total loss due to the tension coating results from combination of hysteresis loss and anomalous loss, but the latter plays a major role in the loss reduction. The coated sheets show a maximum iron loss reduction of 18% at an excitation induction of 1.0 T and an excitation frequency of 60 Hz. [ABSTRACT FROM AUTHOR]

Effects of bulk content of sulfur on final texture and magnetic induction have been investigated in 3% silicon iron strips. Within the tested range of sulfur content from 11 to 92 ppm, too high or low sulfur contents resulted in a poor magnetic induction arising from no or a limited {110} texture. A weak {110} texture at a high sulfur content is due to the prolonged time period of {100} or {111} grain growth. Despite the shortened time period of selective growth of {100} or {111} grains, also the weak {110} texture at a low sulfur content is probably attributed to a weak grain boundary pinning effect of the weakly segregated sulfur. A moderate sulfur content provides an appropriate pinning effect enough to suppress {100} or {111} selective growth, finally resulting in a sharp {110} texture. [ABSTRACT FROM AUTHOR]

Varying circumstances call for various types of donor hepatectomy. We report here on an unusual type of donor hepatectomy, right posterior segmentectomy. A 46-year-old sister of the recipient was the donor. Her preoperative CT showed that the right anterior portal vein originated from the umbilical portion of the left portal vein. Intraoperative cholangiography revealed that the right posterior hepatic duct joined the common hepatic duct in the extrahepatic area. Right posterior segmentectomy was performed without transfusion in the donor. The postoperative course proceeded favorably in both donor and recipient until postoperative day 41, when the recipient unexpectedly expired as a result of cerebral hemorrhage. The donor was discharged with good liver function. We can conclude that the right posterior segment of the donor can be used as a graft, when the volume of left liver is not enough for both donor and recipient, or the vascular structures favor right posterior segmentectomy. [ABSTRACT FROM AUTHOR]

Osmotic demyelination syndrome (ODS) is an acute demyelinating disorder characterized by the loss of myelin in the center of the basis pons, defined as central pontine myelinolysis (CPM), and demyelination in locations outside the pons, defined as extrapontine myelinolysis (EPM). ODS including CPM and EPM is mainly caused by rapid correction of hyponatremia. However, there are several reports of ODS in medical conditions such as malnutrition; alcoholism; liver transplantation; malignancy; sepsis; and electrolyte imbalance including hypernatremia, hypokalemia, hypophosphatemia, and chronic illness. ODS caused by rapid correction of hyperammonemia or continuous hyperbilirubinemia without sodium fluctuations has rarely been reported. Because ODS may be irreversible, prevention is crucial. Herein, we report a case of ODS secondary to rapid correction of hyperammonemia and continuous hyperbilirubinemia.

The interfacial contact area between the fuel and oxidizer components plays an important role in determining the combustion reactivity of nanothermite composites. In addition, the development of compact and reliable ignition methods can extend the applicability of nanothermite composites to various thermal engineering fields. In this study we report the development of a micro-chip initiator with controlled combustion reactivity using concepts usually applied to microelectromechanical systems (MEMS) and simple nanofabrication processes. The nanothermite composites fabricated in this study consisted of aluminum nanoparticles (Al NPs) as the fuel and copper oxide nanoparticles (CuO NPs) as the oxidizer accumulated on a silicon oxide substrate with a serpentine-shaped gold (Au) electrode. The micro-chip initiator rapidly ignited and exploded when minimal current was supplied. The effects of stacking structures of Al and CuO-based multilayers on the combustion properties were systematically investigated in terms of the pressurization rate, peak explosion time, and heat flow. Pressurization rates of 0.004–0.025 MPa μs−1 and heat flows of 2.0–3.8 kJ g−1 with a commonly fast response time of less than 20 ms could be achieved by simply changing the interfacial structures of the Al and CuO multilayers. The controllability of combustion reactivity of micro-chip initiator can be made for general nanothermite composites composed of Al and various metal oxides (e.g. Fe2O3, CuO, KMnO4, etc). The micro-chip initiator fabricated in this study was reliable, compact, and proved to be a versatile platform, exhibiting controlled combustion reactivity and fast response time, which could be used for various civilian and military thermal engineering applications, such as in initiators and propulsion, welding, and ordinance systems. [ABSTRACT FROM AUTHOR]

The electrons, accelerated by the laser ponderomotive force and subsequent plasma wakefields, radiate broadband emission continuously along the laser propagation direction, resulting in multi-mJ THz radiation in the far field.

Abstract Charcot–Marie–Tooth disease (CMT) is the most common hereditary peripheral neuropathy. Mutations in the neurofilament light polypeptide (NEFL) gene produce diverse clinical phenotypes, including demyelinating (CMT1F), axonal (CMT2E), and intermediate (CMTDIG) neuropathies. From 2005 to 2020, 1,143 Korean CMT families underwent gene sequencing, and we investigated the clinical, genetic, and neuroimaging spectra of NEFL‐related CMT patients. Ten NEFL mutations in 17 families (1.49%) were identified, of which three (p.L312P, p.Y443N, and p.K467N) were novel. Eight de novo cases were identified at a rate of 0.47 based on a cosegregation analysis. The age of onset was ≤3 years in five cases (13.5%). The patients revealed additional features including delayed walking, ataxia, dysphagia, dysarthria, dementia, ptosis, waddling gait, tremor, hearing loss, and abnormal visual evoked potential. Signs of ataxia were found in 26 patients (70.3%). In leg MRI analyses, various degrees of intramuscular fat infiltration were found. All compartments were evenly affected in CMT1F patients. The anterior and anterolateral compartments were affected in CMT2E, and the posterior compartment was affected in CMTDIG. Thus, NEFL‐related CMT patients showed phenotypic heterogeneities. This study's clinical, genetic, and neuroimaging results could be helpful in the evaluation of novel NEFL variants and differential diagnosis against other CMT subtypes.

Objective: To investigate the therapeutic effects of mechanical inspiration and expiration exercise using mechanical cough assist on velopharyngeal incompetence in patients with subacute stroke. Design: Pilot, randomized controlled study. Setting: University-based rehabilitation centre. Subjects: Thirty-six patients with subacute stroke diagnosed with velopharyngeal incompetence by videofluoroscopic swallowing study. Methods: Subjects were randomly assigned to 2 groups. The study group received conventional dysphagia therapy and additional mechanical inspiration and expiration exercise. The control group received conventional dysphagia therapy only. Swallowing function was evaluated according to the American Speech-Language-Hearing association scale, functional dysphagia score, and the penetration aspiration scale, based on the videofluoroscopic swallowing study. Coughing function was measured using peak cough flow. Results: Eighteen patients in each group completed the protocol and were analysed. After treatment, the study group showed significant improvement in functional dysphagia score with regard to nasal penetration degree. Comparing the treatment effect between the 2 groups, nasal penetration degree and peak cough flow showed greater improvement in the study group. Conclusion: Mechanical inspiration and expiration exercise had a therapeutic effect on velopharyngeal incompetence in subacute stroke patients with dysphagia. This therapy is easy to provide clinically and could be a useful therapeutic strategy for velo-pharyngeal incompetence with dysphagia in patients with stroke.

Abstract Understanding the water sorption behavior of protein powders is important in applications such as the preservation of protein-based pharmaceuticals. Most globular proteins exhibit a characteristic sigmoidal water adsorption isotherm at ambient conditions. However, it is not well understood how water sorption behavior is influenced by intrinsic factors that are related to structural properties of proteins. We investigate computationally how structural constraints on proteins influence the water sorption isotherms of amorphous protein powders. Specifically, we study the effects of non-local disulfide linkages and backbone connectivity using pheromone ER-23 and lysozyme as model proteins. We find that non-local disulfide linkages can significantly restrict structural changes during hydration and dehydration, and this in turn greatly reduces the extent of hysteresis between the adsorption and desorption branches. Upon removing the backbone connectivity by breaking all peptide bonds in lysozyme, we find that the hysteresis shifts towards the lower humidity regime, and the water uptake capacity is significantly enhanced. We attribute these changes to the higher aggregation propensity of the constraint-free amino acids in dehydrated condition, and the formation of a spanning water network at high hydration levels.

Charcot–Marie–Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the GNB4 gene cause dominant intermediate CMT type F (CMTDIF). The aim of this study is to investigate phenotypic heterogeneities and characteristics of CMT patients with GNB4 mutations. We enrolled 1143 Korean CMT families and excluded 344 families with a PMP22 duplication. We further analyzed the 799 remaining families to find their GNB4 mutations using whole-exome sequencing (WES). We identified two mutations (p.Gly77Arg and p.Lys89Glu) in three families, among which a heterozygous p.Gly77Arg mutation was novel. In addition, a significant uncertain variant (p.Thr177Asn) was observed in one family. The frequency of the GNB4 mutation in the Korean population is 0.38% in PMP22 duplication-negative families. All three families showed de novo mutation. Electrophysiological findings regarding the p.Lys89Glu mutation showed that the motor nerve conduction velocity (MNCV) of the median nerve was markedly reduced, indicating demyelinating neuropathy, and sural nerve biopsy revealed severe loss of myelinated axons with onion bulb formation. Lower extremity Magnetic Resonance Imaging (MRI) demonstrated relatively more severe intramuscular fat infiltrations in demyelinating type (p.Lys89Glu mutation) patients compared to intermediate type (p.Gly77Arg mutation) patients. The anterolateral and superficial posterior compartment muscles of the distal calf were preferentially affected in demyelinating type patients. Therefore, it seems that the investigated GNB4 mutations do cause not only the known intermediate type but also demyelinating-type neuropathy. We first presented three Korean families with GNB4 mutations and found phenotypic heterogeneities of both intermediate and demyelinating neuropathy. We suggest that those findings are useful for the differential diagnosis of CMT patients with unknown GNB4 variants.