ABSTRACT
OBJECTIVE: Individuals with Dravet syndrome (DS) exhibit progressive gait disturbance. No quantitative studies have been conducted to evaluate the effectiveness of medication for gait disturbance. Therefore, the aim of this study was to evaluate the effectiveness of levodopa for pathological gait in people with DS using three-dimensional gait analysis (3DGA). METHODS: Nine individuals with DS, ages 6-20 years, participated in a crossover study of levodopa and were randomly assigned to the levodopa precedence or no levodopa precedence group. Levodopa/carbidopa hydrate was prescribed at a dose of 5 mg/kg/day (body weight <60 kg) or 300 mg/day (body weight ≥60 kg). The medication was taken for 4-6 weeks (4-week washout period). 3DGA was performed three times before the study, with and without levodopa. A mixed-effects model was used to evaluate the effectiveness of levodopa. The primary outcome was the change in the Gait Deviation Index (GDI). In addition, spatiotemporal gait parameters, 6-minute walking distance (6MD), and balance were evaluated. The correlation between the effectiveness of levodopa and age or gait performance before starting levodopa was analyzed. RESULTS: Levodopa improved the GDI by 4.2 points, (p = .029), 6MD by 52 m (p = .002), and balance test result by 4.1 mm (p = .011) in participants with DS. No severe adverse events were observed, with the exception of one participant, who exhibited fever and consequently stopped taking levodopa. Levodopa was more effective in younger participants with a higher baseline gait performance. SIGNIFICANCE: Our randomized crossover trial showed that levodopa has the potential to improve gait disturbance in people with DS.
Subject(s)
Cross-Over Studies , Epilepsies, Myoclonic , Gait Disorders, Neurologic , Levodopa , Humans , Levodopa/therapeutic use , Male , Female , Adolescent , Young Adult , Child , Gait Disorders, Neurologic/drug therapy , Gait Disorders, Neurologic/etiology , Epilepsies, Myoclonic/drug therapy , Gait Analysis , Treatment Outcome , Carbidopa/therapeutic use , Gait/drug effects , Drug CombinationsABSTRACT
INTRODUCTION: Axons of magnocellular neurosecretory cells project from the hypothalamus to the posterior lobe (PL) of the pituitary. In the PL, a wide perivascular space exists between the outer basement membrane (BM), where nerve axons terminate, and the inner BM lining the fenestrated capillaries. Hypothalamic axon terminals and outer BMs in the PL form neurovascular junctions. We previously had found that collagen XIII is strongly localized in the outer BMs. In this study, we investigated the role of collagen XIII in the PL of rat pituitaries. METHODS: We first studied the expression of Col13a1, the gene encoding the α1 chains of collagen XIII, in rat pituitaries via quantitative real-time polymerase chain reaction and in situ hybridization. We observed the distribution of COL13A1 in the rat pituitary using immunohistochemistry and immunoelectron microscopy. We examined the expression of Col13a1 and the distribution of COL13A1 during the development of the pituitary. In addition, we examined the effects of water deprivation and arginine vasopressin (AVP) signaling on the expression of Col13a1 in the PL. RESULTS: Col13a1 was expressed in NG2-positive pericytes, and COL13A1 signals were localized in the outer BM of the PL. The expression of Col13a1 was increased by water deprivation and was regulated via the AVP/AVPR1A/Gαq/11 cascade in pericytes of the PL. CONCLUSION: These results suggest that pericytes surrounding fenestrated capillaries in the PL secrete COL13A1 and are involved in the construction of neurovascular junctions. COL13A1 is localized in the outer BM surrounding capillaries in the PL and may be involved in the connection between capillaries and axon terminals.
Subject(s)
Collagen Type XIII , Animals , Rats , Male , Collagen Type XIII/metabolism , Neurosecretory Systems/metabolism , Arginine Vasopressin/metabolism , Rats, Wistar , Pituitary Gland, Posterior/metabolism , Pituitary Gland/metabolism , Pericytes/metabolism , Basement Membrane/metabolismABSTRACT
NHE5, an isoform of the Na+/H+ exchanger (NHE) protein, is an ion-transporting membrane protein that regulates intracellular pH and is highly expressed in colorectal adenocarcinoma. Therefore, we hypothesized that NHE5 inhibitors can be used as anticancer drugs. However, because NHE1 is ubiquitously expressed in all cells, it is extremely important to demonstrate its selective inhibitory activity against NHE5. We used amiloride, an NHE non-selective inhibitor, as a lead compound and created UTX-143, which has NHE5-selective inhibitory activity, using a structure-activity relationship approach. UTX-143 showed selective cytotoxic effects on cancer cells and reduced the migratory and invasive abilities of cancer cells. These results suggest a new concept wherein drugs exhibit cancer-specific cytotoxic effects through selective inhibition of NHE5 and the possibility of UTX-143 as a lead NHE5-selective inhibitor.
Subject(s)
Amiloride , Sodium , Amiloride/pharmacology , Sodium/metabolism , Sodium-Hydrogen Exchangers/metabolism , Membrane Proteins/metabolism , Hydrogen , Hydrogen-Ion ConcentrationABSTRACT
A 70s man underwent minimally invasive esophagectomy and gastric conduit reconstruction via the posterior mediastinal route for early esophageal cancer 5 years ago. Three days prior to hospital visit, he presented with abdominal fullness, left chest pain, and vomiting. A CT revealed a postoperative hiatal hernia, and emergency surgery was performed laparoscopically. The laparoscopic findings showed that the transverse colon had prolapsed into the left thoracic cavity through the esophageal hiatus on the left side of the gastric conduit. The transverse colon had no sign of necrosis. The diaphragmatic defect was closed with unabsorbable suture. Increased bowel motility due to postoperative fat loss in the mesentery and intra-abdominal pressure are thought to be causes of the hernia. In addition, decreased adhesion formation due to endoscopic surgery may be a contributing factor. Although there is no unanimous opinion regarding the suture fixation of the conduit to the diaphragm after esophagectomy, it should be performed to prevent a herniation. Postoperative hiatal hernia occurs more than 5 years after the surgery is relatively rare, but its occurrence should be noted.
Subject(s)
Esophagectomy , Hernia, Hiatal , Humans , Male , Diaphragm , Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Hernia, Hiatal/etiology , Hernia, Hiatal/surgery , Laparoscopy , AgedABSTRACT
The usefulness of greyscale (GS) in salivary gland ultrasonography for Sjögren's syndrome (SS) has been established; however, limited information is currently available on power Doppler signals (PDs), and changes after treatment remain unknown. PDs are considered to represent glandular inflammation, which indicates the worsening of GS in later years. We examined the changes in PDs in three immunosuppressant-treated SS patients. PDs decreased, along with GS and markers of disease activity, after treatment. PDs have the potential to provide insights into glandular inflammation in real time; however, large-scale studies on their clinical usefulness are needed.
Subject(s)
Salivary Glands , Sjogren's Syndrome , Ultrasonography, Doppler , Humans , Sjogren's Syndrome/diagnostic imaging , Sjogren's Syndrome/drug therapy , Female , Salivary Glands/diagnostic imaging , Middle Aged , Aged , Male , Immunosuppressive Agents/therapeutic useABSTRACT
Background: Multiple needle punctures during central venous line insertion can lead to serious complications. Needle deterioration owing to repeated punctures may be a major cause. We hypothesized that there is an optimal bevel angle for a back-cut point needle that is resistant to deterioration. In this study, we examined the effect of bevel angle differences in a back-cut point needle on needle tip deterioration caused by multiple punctures. Methods: The resin target was punctured perpendicularly using back-cut point needles with three bevel angles (15°, 17°, and 19°; n=8 for each angle) at a speed of 200 mm/min. The same needle was used for ten consecutive punctures at different locations on the target. The force applied to the needle was recorded as puncture force. The puncture force waveform is bimodal. The second peak values, which formed the maximum values of puncture force, were the focus of the main analysis. We considered a 5% elevation from the first to the 10th puncture force as needle deterioration, and the average slope value of the regression line between the puncture number and puncture force was used. When the upper limit of the 95% confidence interval (CI) of the slope value was less than 0.008889, the needle was considered to be resistant to deterioration. Results: The slopes of the second peak values during 10 consecutive punctures for each bevel angle (15°, 17°, 19°) were 0.003011 ± 0.01085 [-0.006056, 0.012077], 0.006116±0.007431 [-0.000096, 0.012328], and 0.001515 ± 0.005783 [-0.003320, 0.006349], respectively (mean ± standard deviation [95% CI]). Only the 19° angle needle had a smaller upper limit of the 95% CI for a slope value of 0.008889. Conclusion: The 19° bevel angle back-cut point needle was more resistant to deterioration than the 15° and 17° angle needles were.
ABSTRACT
Circadian rhythms are indispensable intrinsic programs that regulate the daily rhythmicity of physiological processes, such as feeding and sleep. The cricket has been employed as a model organism for understanding the neural mechanisms underlying circadian rhythms in insects. However, previous studies measuring rhythm-controlled behaviours only analysed locomotive activity using seesaw-type and infrared sensor-based actometers. Meanwhile, advances in deep learning techniques have made it possible to analyse animal behaviour and posture using software that is devoid of human bias and does not require physical tagging of individual animals. Here, we present a system that can simultaneously quantify multiple behaviours in individual crickets - such as locomotor activity, feeding, and sleep-like states - in the long-term, using DeepLabCut, a supervised machine learning-based software for body keypoints labelling. Our system successfully labelled the six body parts of a single cricket with a high level of confidence and produced reliable data showing the diurnal rhythms of multiple behaviours. Our system also enabled the estimation of sleep-like states by focusing on posture, instead of immobility time, which is a conventional parameter. We anticipate that this system will provide an opportunity for simultaneous and automatic prediction of cricket behaviour and posture, facilitating the study of circadian rhythms.
Subject(s)
Behavior, Animal , Circadian Rhythm , Gryllidae , Posture , Animals , Posture/physiology , Gryllidae/physiology , Sleep/physiology , Software , LocomotionABSTRACT
The introduction of exogenous particles into plants has promising applications in agriculture and biotechnology. Nanoparticles can be transported into plants through foliar application or root uptake. However, both methods have limitations in terms of the size of the particles (<40 nm) that can be transported due to the barriers of the cell wall and cuticle. In the present study, we proposed a novel method to deliver particles of up to 110 nm into plants by cutting the stem of tomato seedlings. We demonstrated for the first time, using water-insoluble silica colloids, that not only nanoparticles but also submicron particles can be transported toward the leaves when the plant stem is used as the entry point of particles. Thirty-five-day-old tomato seedlings were used as the target plants. When the cut stem seedlings were immersed in the colloidal particle suspension for up to 24 h, significant particle accumulation was observed in the nodes and leaves. The relatively low particle concentrations (10 mg/L) allowed effective transport throughout the plants. Silica particles with average diameters of 10 nm and 110 nm were both well transported and moved through the stem. Even after the particles entered the plant, adventitious roots were formed, resulting in the formation of whole plants with roots, stems, and leaves. This method can be applied not only to tomatoes but also to other food crops for various applications in plant biotechnology.
Subject(s)
Solanum lycopersicum , Seedlings , Water , Plant Stems , Silicon Dioxide , Plant RootsABSTRACT
We describe a setup for time- and angle-resolved photoemission spectroscopy with wavelength-tunable excitation and an extreme ultraviolet probe. It is enabled by using the 10 kHz twin Ti:sapphire amplifiers seeded by the common Ti:sapphire oscillator. The typical probe energy is 21.7 eV, and the wavelength of the pump excitation is tuned between 2400 and 1200 nm by using the optical parametric amplifier. The spectral width of the extreme ultraviolet probe is 53 meV, and the time resolution is dependent on the wavelength for the pump, better than 60 fs for the pump energy >0.7 eV. This system enables the pump energy to be matched with a specific interband transition and to probe a wider energy-momentum space. We present the results for the prototypical materials of highly oriented pyrolytic graphite and Bi2Se3 to show the performance of our system.
ABSTRACT
Primary racemose hemangioma of the bronchial artery (RHBA) is a rare congenital condition characterized by enlarged and convoluted bronchial arteries, often forming fistulas between the pulmonary artery or vein. Herein, we report a case of balloon-assisted embolization using N-butyl-2-cyanoacrylate (NBCA) performed for a primary RHBA in an asymptomatic 57-year-old woman. There were 2 tortuous and dilated branches of the right bronchial artery (RBA) (arising from the left subclavian artery and the descending thoracic aorta) which merged in the right pulmonary hilar region, forming multiple aneurysms that short-circuited the right pulmonary artery. Embolization was performed via the RBA arising from the subclavian artery using a triaxial system (a 5-Fr guiding catheter, a 2.7-Fr microballoon catheter, and a 1.9-Fr microcatheter). The guiding catheter was inserted into the peripheral side of the RBA using the microballoon catheter as an anchor; the balloon was slightly inflated and advanced further into the peripheral side using blood flow. The microcatheter was inserted as close to the aneurysms as possible and embolization was done using an NBCA-iodized oil mixture under blood flow control by the microballoon catheter. Bronchial artery embolization is the treatment of choice for primary RHBA because of the risk of rupture, and balloon-assisted techniques can help guide the catheter distally while also controlling blood flow.
ABSTRACT
Taraxacum albidum, a perennial herb of the Asteraceae family, exhibits both tetraploid and pentaploid in Japan. This study sequenced and characterized the complete chloroplast genome of T. albidum, revealing a 151,451 bp sequence with a typical quadripartite structure, comprising one large single-copy (LSC) region of 84,052 bp, one small single-copy (SSC) region of 18,541 bp, and two inverted repeat (IR) regions, IRa and IRb, each 24,429 bp in length. The chloroplast genome, excluding duplicates, contained 113 unique genes, including 79 protein-coding genes, 30 transfer RNA genes, and four ribosomal RNA genes. The GC content of this genome was 37.7%. Phylogenetic analysis revealed that T. albidum is most closely related to T. mongolicum, with the chloroplast genome sequences being nearly identical, differing by only one nucleotide. These findings suggest that the maternal lineage of T. albidum likely originates from T. mongolicum or its closely related species.
ABSTRACT
BACKGROUND: Various factors contribute to the development of infection-related acute encephalopathy (AE) in children, such as infectious agents and chronic underlying disorders. We studied underlying disorders in children with AE to identify predisposing factors of AE. METHODS: We investigated underlying disorders or past histories in patients with two types of AE from the database in the Tokai area of Japan between 2009 and 2022: 204 patients with AE with reduced subcortical diffusion (AED) and 137 with clinically mild encephalopathy with a reversible splenial lesion (MERS). We compared them with 89 patients with acute disseminated encephalomyelitis (ADEM) to clarify the specific disorders in the two AE types. RESULTS: The prevalence of underlying disorders in AED (34%, 70 patients) was significantly higher than that in ADEM (12%, 11 patients) (P < 0.01). The prevalence of underlying disorders in MERS was 23% (32 patients). The underlying disorders included seizure disorders, premature birth, genetic/congenital disorders, and endocrine/renal diseases. In patients with seizure disorders in AED, five patients (18%) had Dravet syndrome and four (15%) had West syndrome, whereas none with MERS had these syndromes. Twenty-five (12%) of 204 patients with AED, three (2%) with MERS, and one (1%) with ADEM were preterm or low birth weight. CONCLUSIONS: The high prevalence of seizure disorders suggests that seizure susceptibility is an important predisposing factor in AED. Premature birth also has an impact on the development of AED. Caution is required regarding the development of AE in patients with chronic seizure disorders or premature birth.
Subject(s)
Brain Diseases , Humans , Male , Female , Child, Preschool , Infant , Child , Brain Diseases/epidemiology , Brain Diseases/etiology , Brain Diseases/complications , Adolescent , Japan/epidemiology , Prevalence , Infant, Newborn , Encephalomyelitis, Acute Disseminated/epidemiology , Encephalomyelitis, Acute Disseminated/etiology , Encephalomyelitis, Acute Disseminated/complicationsABSTRACT
BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.
Subject(s)
Cough-Variant Asthma , Gastroesophageal Reflux , Humans , Chronic Cough , Japan/epidemiology , Prevalence , Quality of Life , Cough/epidemiology , Cough/etiology , Cough/diagnosis , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/epidemiology , Chronic DiseaseABSTRACT
The authors sequenced the complete mitochondrial (mt) genomes of the band-legged ground cricket (Dianemobius fascipes nigrofasciatus Matsumura, 1904) and a temperate form of the lawn ground cricket (Polionemobius taprobanensis Walker, 1869), collected in Japan. The length of the mt genome sequences was 15,354 bp in D. fascipes nigrofasciatus and 16,063 bp in P. taprobanensis. Annotation of the mt genome sequences revealed 13 protein-coding genes, two rRNA genes, and 22 tRNA genes. The orientation of the genes was the same as in other Grylloidea species, and the order was the same as in other Trigonidiidae species. In our phylogenetic analysis, D. fascipes nigrofasciatus formed a clade with D. fascipes collected in China, and the temperate form of P. taprobanensis formed a clade with P. taprobanensis collected in China. Comparison of the numbers of positions with different amino acid residues encoded by the protein-coding genes implied the separate species status of each member of each of the two pairs of ground crickets. The mt genome sequences of D. fascipes nigrofasciatus and P. taprobanensis will contribute to phylogenetic and taxonomic studies of the Trigonidiidae.
ABSTRACT
Cardiac metabolism is deranged in heart failure, but underlying mechanisms remain unclear. Here, we show that lysine demethylase 8 (Kdm8) maintains an active mitochondrial gene network by repressing Tbx15, thus preventing dilated cardiomyopathy leading to lethal heart failure. Deletion of Kdm8 in mouse cardiomyocytes increased H3K36me2 with activation of Tbx15 and repression of target genes in the NAD+ pathway before dilated cardiomyopathy initiated. NAD+ supplementation prevented dilated cardiomyopathy in Kdm8 mutant mice, and TBX15 overexpression blunted NAD+-activated cardiomyocyte respiration. Furthermore, KDM8 was downregulated in human hearts affected by dilated cardiomyopathy, and higher TBX15 expression defines a subgroup of affected hearts with the strongest downregulation of genes encoding mitochondrial proteins. Thus, KDM8 represses TBX15 to maintain cardiac metabolism. Our results suggest that epigenetic dysregulation of metabolic gene networks initiates myocardium deterioration toward heart failure and could underlie heterogeneity of dilated cardiomyopathy.
ABSTRACT
Sarcolipin is a transmembrane protein expressed in the sarco/endoplasmic reticulum of skeletal and atrial muscles in large animals. Sarcolipin plays crucial roles in heat production through modifying the function of sarco/endoplasmic reticulum Ca2+ ATPase, thereby being involved in thermogenesis and systemic metabolism. In skeletal muscle, endoplasmic reticulum (ER) stress has been implicated in several conditions, such as insulin resistance, muscle diseases, and hypo/hyper-contraction. Here, we investigated the effect of ER stress on sarcolipin expression in skeletal muscle cells, C2C12 myotubes. First, gene expression of sarcolipin was confirmed in the cells during myogenesis. Then, ER stress was induced in C2C12 myotubes by treatment with tunicamycin or thapsigargin. Sarcolipin messenger RNA (mRNA) and protein expression were significantly reduced by ER stress induction. The reduction was independent of inositol-requiring element 1 (IRE1), which is activated by ER stress and has potent endonuclease activity, when evaluated by treatment with an IRE1 inhibitor, 4μ8C. On the other hand, sarcolipin mRNA stability was reduced under the ER stress when evaluated by treatment with actinomycin D. In conclusion, these results show that ER stress represses sarcolipin expression due to changes in mRNA stability in C2C12