Nascent polypeptide within the exit tunnel stabilizes the ribosome to counteract risky translation.

Continuous translation elongation, irrespective of amino acid sequences, is a prerequisite for living organisms to produce their proteomes. However, nascent polypeptide products bear an inherent risk of elongation abortion. For example, negatively charged sequences with occasional intermittent prolines, termed intrinsic ribosome destabilization (IRD) sequences, weaken the translating ribosomal complex, causing certain nascent chain sequences to prematurely terminate translation. Here, we show that most potential IRD sequences in the middle of open reading frames remain cryptic and do not interrupt translation, due to two features of the nascent polypeptide. Firstly, the nascent polypeptide itself spans the exit tunnel, and secondly, its bulky amino acid residues occupy the tunnel entrance region, thereby serving as a bridge and protecting the large and small ribosomal subunits from dissociation. Thus, nascent polypeptide products have an inbuilt ability to ensure elongation continuity.

Comparison of visual outcomes between medical treatment alone and Ahmed glaucoma valve implantation in Shiba dogs with primary angle closure glaucoma.

OBJECTIVE: The objective of the study was to evaluate visual outcomes between medical treatment alone (MED) and Ahmed glaucoma valve implantation (AGVI) in Shiba dogs with primary angle closure glaucoma (PACG). PROCEDURES: Records of 65 Shiba dogs (104 eyes) with PACG were retrospectively reviewed. Vision was assessed qualitatively using both the menace response and maze testing. The significance of age, sex, intraocular pressure (IOP), and duration of clinical signs (≤72 h or >72 h) at first presentation (V1) was assessed. Eyes with vision at V1 were divided into groups according to subsequent treatment method (MED versus AGVI), and vision as a survival outcome was compared between group by the Kaplan-Meier method. RESULTS: At V1, 65 eyes (62.5%) of 54 dogs had vision. There was no statistically significant difference in age or sex on the presence of vision at V1. Median IOP was higher in blind (52 mmHg) compared to sighted eyes (28 mmHg) (p < .001). Eyes presenting in ≤72 h of the onset of clinical signs were more likely to have vision (86.7%) compared to those presenting after 72 h (44.1%) (p < .001). By the Kaplan-Meier analysis, the cumulative visual retention rate was significantly higher with AGVI than with MED (69.2% vs. 7.7%; p < .01) at 12 months. The median time to visual loss was 39.9 months with AGVI vs. 1.7 months with MED. CONCLUSIONS: AGVI resulted in better visual outcomes than MED and should be considered in Shiba dogs with PACG that are visual at the time of presentation and suitable for surgery.

Effects of melatonin on dopaminergic neuron development via IP3-mediated mitochondrial Ca2+ regulation in autism spectrum disorder.

Melatonin entrainment of suprachiasmatic nucleus-regulating circadian rhythms is mediated by MT1 and MT2 receptors. Melatonin also has neuroprotective and mitochondrial activating effects, suggesting it may affect neurodevelopment. We studied melatonin's pharmacological effects on autism spectrum disorder (ASD) neuropathology. Deciduous tooth-derived stem cells from children with ASD were used to model neurodevelopmental defects and differentiated into dopaminergic neurons (ASD-DNs) with or without melatonin. Without melatonin, ASD-DNs had reduced neurite outgrowth, mitochondrial dysfunction, lower mitochondrial Ca2+ levels, and Ca2+ accumulation in the endoplasmic reticulum (ER) compared to control DNs from typically developing children-derived stem cells. Melatonin enhanced IP3-dependent Ca2+ release from ER to mitochondria, improving mitochondrial function and neurite outgrowth in ASD-DNs. Luzindole, an MT1/MT2 antagonist, blocked these effects. Thus, melatonin supplementation may improve dopaminergic system development in ASD by modulating mitochondrial Ca2+ homeostasis via MT1/MT2 receptors.

Evaluation of temperature-dependent fluctuations in skin microcirculation flow using a light-emitting diode based photoacoustic imaging device.

PURPOSE: Skin microvessels maintain temperature homeostasis by contracting and dilating upon exposure to changes in temperature. Under general anesthesia, surgical invasiveness, including incisions and coagulation, and the effects of anesthetics may cause variations in the threshold temperature, leading to the constriction and dilation of cutaneous blood vessels. Therefore, studies on skin microvascular circulation are necessary to develop appropriate interventions for complications during surgery. METHODS: We visualized and quantified skin microcirculatory fluctuations associated with temperature variations using a light-emitting diode photoacoustic imaging (LED-PAI) device. The hands of ten healthy volunteers were stressed with four different water temperatures [25℃ (Control), 15℃ (Cold1), 40℃ (Warm), and 15℃ (Cold2)]. The photoacoustic images of the fingers were taken under each condition, and the microvascular flow owing to temperature stress was quantified as the area of photoacoustic signal (S) in each image. The S values were compared with the variations in blood flow (Q) measured by laser Doppler flowmetry (LDF). RESULTS: The correlation between Q and S according to the 40 measurements was r = 0.45 (p＜0.01). In addition, the values of S under each stress condition were as follows: Scontrol = 10,826 ± 3364 pixels, Scold1 = 8825 ± 2484 pixels, Swarm = 13,369 ± 3001 pixels, and Scold2 = 8838 ± 1892 pixels; the differences were significant. The LDF blood flow (Q) showed similar changes among conditions. CONCLUSION: These findings suggest that the LED-PAI device could be an option for evaluating microcirculation in association with changes in temperature.

Temperature characteristics of K-Rb hybrid optically pumped magnetometers with different density ratios.

Optically pumped magnetometers (OPMs) that are equipped with hybrid cells of K and Rb have been studied for improving their sensitivity and biomagnetic field measurements. The densities of the two alkali metal atoms and their density ratio are especially important for hybrid OPMs. In this study, we fabricated five hybrid cells using different K and Rb atom densities and measured the output signal intensities by controlling their cell temperatures. The output signal intensity of OPMs has different temperature characteristics depending on the density ratios of K and Rb atoms. The densities of the two atoms at any temperature were estimated based on the Raoult's law, and we compared the experimental results with the calculated results based on the Bloch equations. Furthermore, the numerical calculations that were obtained based on the Bloch equation by incorporating a relaxation term due to the absorption of the probe beam exhibited good agreement with the experimental results. Finally, in case of nK/nRb = 4.85, it is estimated that a sensitivity of 1.6 fT/Hz1/2 can be achieved by increasing the temperature to 270 °C.

High-sensitivity multi-channel probe beam detector towards MEG measurements of small animals with an optically pumped K-Rb hybrid magnetometer.

Multi-channel measurements with fine spatial resolution will make magnetoencephalograms (MEGs) possible with small animals using optically pumped magnetometers (OPMs). Therefore, we fabricated a 20-channel probe-beam detector that uses a K-Rb hybrid OPM to increase the spatial resolution. First, we investigated the sensitivity of the detector using the multi-channel measurements and demonstrated that the detector had a fine sensitivity (10-20 fT/Hz1/2 at 10 Hz). Subsequently, we measured magnetic field distribution generated from a loop coil and compared those measurements with analytically calculated distributions. The measurements were in good agreement with the theoretical predictions. The experimental results indicate that our newly developed multi-channel OPM detector has sufficient performance specifications for MEG measurements.

A new application for the quantification of apoplastic redox radicals of plant roots using pre-fluorescent probe.

New application of fluorescence probe to detect apoplastic redox radicals from plant roots were sought. This probe can detect radicals selectively. Calibration curve for radicals was obtained using nitrogen monoxide as radical standard produced by NOC7. Apoplastic radicals released constitutively were quantified and the release rate was 60 µmol L-1 h-1. Oxidative burst triggered by chitin was distinguished from constitutive radical release.

Predictors of cognitive function in patients with hypothalamic hamartoma following stereotactic radiofrequency thermocoagulation surgery.

OBJECTIVE: To determine the predictors of cognitive function in patients with drug-resistant gelastic seizures (GS) related to hypothalamic hamartoma (HH) before and after stereotactic radiofrequency thermocoagulation surgery (SRT). METHODS: We studied 88 patients with HH who underwent SRT between October 1997 and December 2014. Patients received neuropsychological tests preoperatively and postoperatively. Based on the preoperative measures, patients were categorized as "high-functioning" (full-scale intelligence quotient [FSIQ] ≥70; n = 48) and "low-functioning" group (FSIQ <70; n = 40). Univariate and multivariate linear regression analyses determined the clinical, electroencephalography (EEG), and imaging factors associated with preoperative cognitive function as well as postoperative cognitive change. RESULTS: Eighty-seven patients (98.8%) were followed postoperatively for an average of 3.3 years, and 75 (85.2%) of them achieved GS remission at the last hospital visit. Neuropsychological performance was significantly improved after surgery in both groups. Multivariate linear regression analysis showed that a smaller HH size (p = 0.002) and a smaller number of antiepileptic drugs (p < 0.001) were preoperatively associated with better neuropsychological performance. Multivariate linear regression analysis showed that better postoperative improvement in cognition was associated with a shorter duration of epilepsy (p = 0.03). SIGNIFICANCE: Cognitive impairment related to epileptic encephalopathy may improve following SRT in substantial proportions of HH patients. Reduced improvement in postoperative cognitive function in patients with longer duration of epilepsy warrants further studies to determine if earlier SRT provides a greater chance of postoperative cognitive improvement in patients with HH.

Ca2+ -permeable AMPA receptors associated with epileptogenesis of hypothalamic hamartoma.

Hypothalamic hamartoma (HH), composed of neurons and glia without apparent cytologic abnormalities, is a rare developmental malformation in humans. Patients with HH often have characteristic medically refractory gelastic seizures, and intrinsic epileptogenesis within the lesions has been speculated. Herein we provide evidence to suggest that in HH neurons, Ca2+ permeability through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors is aberrantly elevated. In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues. In HH, however, these activities were clearly abolished by application of Joro Spider Toxin (JSTX), a specific inhibitor of the Ca2+ -permeable AMPA receptor. Consistent with these physiologic findings, the neuronal nuclei showed disappearance of adenosine deaminase acting on RNA 2 (ADAR2) immunoreactivity. Furthermore, examination of glutamate receptor 2 (GluA2) messenger RNA (mRNA) revealed that editing efficiency at the glutamine/arginine site was significantly low. These results suggest that neurons in HH may bear Ca2+ -permeable AMPA receptors due to dislocation of ADAR2.

Effects of Secreted Mast Cell Mediators on Retinal Pigment Epithelial Cells: Focus on Mast Cell Tryptase.

Numerous mast cells are present in the choroid, but the effects of mast cell mediators on retinal pigment epithelial (RPE) cells are not well understood. We investigated the influence of mast cell mediators on RPE cells in vitro, focusing on tryptase. Expression of receptors was examined by the reverse transcription polymerase chain reaction. We also assessed production of interleukin 8 and vascular endothelial growth factor (VEGF) after RPE cells were stimulated with mast cell mediators by using an antibody array and enzyme-linked immunosorbent assay. Furthermore, we investigated the influence of tryptase on RPE cell migration and integrity by the scratch assay and the transepithelial resistance. RPE cells expressed protease-activated receptor 2 (PAR2), histamine receptor 1, tumor necrosis factor-α (TNF-α) receptor 1, and CCR 1, 3, 4, 8, and 11. Tryptase, PAR2 agonists, histamine, and TNF-α all enhanced interleukin 8 production by RPE cells, while only tryptase enhanced VEGF production. Tryptase also enhanced expression of phosphorylated extracellular signal-regulated kinases 1/2, resulting in increased migration of RPE cells. However, tryptase did not alter epithelial integrity or the expression of zonula occludens-1 and junctional adhesion molecule-A by RPE cells. Mast cell mediators, especially tryptase, may influence RPE cell inflammation.

Comparison between indocyanine green angiography and fluorescein angiography in normal cats.

OBJECTIVE: To study a new approach to indocyanine green (ICG) angiography for contrasting the ocular fundus in cats. ANIMALS STUDIED: Six healthy laboratory cats. PROCEDURES: Fluorescein (FLUO) and ICG angiography were performed using an infrared-sensitive charged coupled device-equipped fundus camera on sedated cats. RESULTS: At 12.3 ± 3.4 s after ICG administration, the choroidal arteries could be seen extending radially from the optic disk. The choroidal veins became apparent at 16.2 ± 4.1 s alongside the choroidal arteries. Gradual fading of the choroidal vessels began 5.8 ± 1.5 min postdye administration and diffuse fluorescence of the fundus appeared. Diffuse fluorescence of the optic disk faded at about 18.8 ± 2.9 min. Mean arterial blood pressure at 1 and 3 min after ICG administration showed no significant change when compared to pre-administration (P > 0.05). However, 5 min (P = 0.054) and 10 min (P < 0.05) postadministration, a significant drop in blood pressure occurred. The time lapse between FLUO administration and its appearance in the ocular fundus was 15.7 ± 3.8 s. Retinal veins became apparent at 22.0 ± 3.6 s alongside retinal arteries. At 31.2 ± 4.1 s, full venous fluorescence was visualized throughout the entire fundus. CONCLUSIONS: While FLUO angiography shows only the retinal vessels, ICG angiography enabled visualization of the choroidal vasculature. ICG angiography provides clear resolution while remaining reliable and simple; thus, a combination of ICG and FLUO angiography shows promise as a diagnostic aid for clinical evaluation of various chorioretinal diseases in cats.

[A Case of a Stuck Bioprosthetic Mitral Valve Leaflet Diagnosed by Intraoperative Transesophageal Echocardiography: Suture Loop Jamming].

We present a case of a very rare complication of valvular surgery-suture loop jamming. A 77-year-old woman was admitted for surgical treatment of moderate aortic regurgitation, severe mitral regurgitation (MR) and severe tricuspid regur- gitation. She underwent mitral valve replacement (MVR) with porcine bioprosthetic valve and tricuspid annuloplasty by DeVega procedure. Before termination of cardiopulmonary bypass, transesophageal echocardiography (TEE) showed se- vere MR at the center of the bioprosthetic valve along the posterior left atrial wall In addition, echogenic fili- form structure which disturbed the movement of the leaflets was detected. The patient was placed on car- dioplegic arrest again and the heart was reopened, suture loop jamming around the stents of the biopros- thetic valve resulting in significant mitral regurgitation was diagnosed. The implanted bioprosthetic valve was removed and a new bioprosthetic valve was subse- quently re-implanted. Intraoperative TEE provided a visible assessment of mitral prosthetic valve dysfunction and we were immediately able to reach diagnosis of this rare and serious complication-suture loop jamming. Our case makes us recognize suture loop jamming as one of the complications of MVR.

Optimal densities of alkali metal atoms in an optically pumped K-Rb hybrid atomic magnetometer considering the spatial distribution of spin polarization.

An optically pumped K-Rb hybrid atomic magnetometer can be a useful tool for biomagnetic measurements due to the high spatial homogeneity of its sensor property inside a cell. However, because the property varies depending on the densities of potassium and rubidium atoms, optimization of the densities is essential. In this study, by using the Bloch equations of K and Rb and considering the spatial distribution of the spin polarization, we confirmed that the calculation results of spin polarization behavior are in good agreement with the experimental data. Using our model, we calculated the spatial distribution of the spin polarization and found that the optimal density of K atoms is 3 × 1019 m-3 and the optimal density ratio is nK/nRb ~ 400 to maximize the output signal and enhance spatial homogeneity of the sensor property.

[Anesthetic Management of a 69-year-old Patient with Eisenmenger Syndrome for Abdominoperineal Resection].

Although life expectancy of the patients with Eisenmenger syndrome (ES) is currently reported to be lower than 40 years, life span of the patients with ES may be extended because of development of medical care. According to recently reported middle-aged patients with ES undergoing non-cardiac surgeries, per-operative mortality and morbidity of the patients with ES undergoing non-cardiac surgeries may be lower than previously thought, and even elderly patients may be able to undergo major surgeries such as laparotomies for cancers. We described the anesthetic management of a 69-year-old patient with ES who had undergone abdominoperineal resection. In the anesthetic management it is important to maintain adequate blood volumne and systemic vascular resistance and this avoids increases of right-to-left shunt. Perioperative monitoring of pulmonary arterial pressure was useful for hemodynamic management. Good pain control and management of body temperature were also needed for a perioperative course with no adverse events. The appropriate anesthetic management of the 69-year-old patient with ES for abdominoperineal resection resulted in the successful perioperative course.

Noise reduction and signal-to-noise ratio improvement of atomic magnetometers with optical gradiometer configurations.

In the field of biomagnetic measurement, optically-pumped atomic magnetometers (OPAMs) have attracted significant attention. With the improvement of signal response and the reduction of sensor noise, the sensitivity of OPAMs is limited mainly by environmental magnetic noise. To reduce this magnetic noise, we developed the optical gradiometer, in which the differential output of two distinct measurement areas inside a glass cell was obtained directly via the magneto-optical rotation of one probe beam. When operating in appropriate conditions, the sensitivity was improved by the differential measurement of the optical gradiometer. In addition, measurements of the pseudo-magnetic noise and signal showed the improvement of the signal-to-noise ratio. These results demonstrate the feasibility of our optical gradiometer as an efficient method for reducing the magnetic noise.

[Anesthetic management for a patient with chronic expanding hematoma of the thorax associated with respiratory failure].

Chronic expanding hematoma (CEH) of the thorax is an intractable disease which induces long-standing growing hematoma after tuberculosis or thoracic surgery. It causes respiratory failure and heart failure by compressing the mediastinum. A 68-year-old man with a history of tuberculosis during childhood had suffered from progressive exertional dyspnea for 20 years. Because a huge hematoma occupying whole right thoracic cavity compressed the heart and the trachea to the left, he was scheduled for extrapleural pneumonectomy. Bronchial arterial embolization was performed preoperatively to prevent hemoptysis and reduce intraoperative blood loss. There was no problem in the airway management using a double lumen endotracheal tube. However, severe hypotension and a decrease in cardiac index were observed due to excessive bleeding, leading to total blood loss of 11,000 g. In addition, surgical manipulation caused abrupt severe hypotension. Monitoring of arterial pressure-based cardiac output and deep body temperature was useful for the hemodynamic management during the operation. The successful postoperative course resulted in remarkable improvement of Huge-Jones dyspnea criteria from IV to II. In the anesthetic management of CEH precautions should be taken against the excessive intraoperative bleeding and abrupt hemodynamic changes.

De novo proteinuria with pathological evidence of glomerulonephritis after everolimus induction.

A 68-year-old man who underwent living-unrelated kidney transplantation from his spousal donor was immunosuppressed with tacrolimus and mycophenolate mofetil. Despite his uneventful clinical course, protocol biopsy at 2 years post transplant showed de novo CNI tubulotoxicity despite low tacrolimus exposure. Everolimus was added in order to discontinue TACER. However, prominent proteinuria impeded continuation of everolimus since biopsy showed diffuse glomerular endocapillary proliferation without C4d deposition. No donor-specific antibody was detected. Pulse steroids were given and proteinuria returned to normal with histological reversal.

The orthopaedic effects of bone-anchored maxillary protraction in a beagle model.

SUMMARY BACKGROUND/OBJECTIVES: The purpose of this study was to establish an animal model of bone-anchored maxillary protraction (BAMP) and verify the effects of such treatment in this model. SUBJECTS/METHODS: Ten total immature (90-day-old) male beagle dogs were used. On Day -20, one miniplate per jaw quadrant was placed and secured with screws. From Day 0 to Day 60, miniplates in the dogs in the intermaxillary traction group (group T, n = 5) were loaded with coil springs. In the control group (group C, n = 5), the miniplates received no force. Every 20 days from Day -20, all dogs were assessed by measuring body weight, taking photographs, and acquiring standardized lateral cephalometric radiographs using a specially designed cephalostat. Cephalometric analyses were performed and the two groups compared. New bone formation was labelled by double-fluorochrome administration with calcein and tetracycline. Animals were sacrificed at Day 60, and bone sections of zygomaticomaxillary sutures were analysed using histomorphometry with fluorescence microscopy. Groups were compared with Mann-Whitney U-tests (P < 0.05). RESULTS: Cephalometric analysis indicated significant maxillary advancement and retroclination of maxillary incisors in group T, with concomitant significant posterior relocation of the condyles and proclination of the mandibular incisors. In histological analysis, vigorous bone apposition at the zygomaticomaxillary suture was only detected in group T. LIMITATIONS: Further histological studies would clarify the effects of BAMP on the mandible, especially on temporomandibular articulation. CONCLUSIONS/IMPLICATIONS: Our results, using this newly developed animal model, support the orthopaedic effects of BAMP.

[Anesthesia for pneumothorax surgery in a patient with type II chronic respiratory failure associated with inclusion body myositis].

A 40-year-old man was scheduled for video assisted thoracoscopic surgery due to pneumothorax. He had been diagnosed with inclusion body myositis and received nocturnal non-invasive positive pressure ventilation. Anesthesia was induced with propofol, remifentanil, and rocuronium, and maintained with propofol, remifentanil and fentanyl. The dosage of rocuronium was 10 mg. Although we administered neostigmine at the end of the operation and TOF ratio was over 90%, he was transported to the ICU with tracheal intubation because of poor spontaneous respiration. On POD 1, the tracheal tube was extubated and NPPV was administered again. Minitrach was inserted on POD 2, and he left the ICU on POD 4. Generally, in patients with myopathy the dose of muscle relaxant should be decreased in proportion to their muscle atrophy. Rocuronium 10 mg was administered in this case and we thought it could be antagonized by neostigmine, but extubation on the day of operation was impossible. We think this is not because of the residual effect of muscle relaxant, but because of decreases in pulmonary function. In this case, we expected long-term mechanical ventilation might be necessary, but he showed a good postoperative course owing to minimally invasive surgery, NPPV, and suctioning of sputum via Minitrach.

Importance of changes in abnormal muscle responses during microvascular decompression for hemifacial spasm.

Objective: To determine if compression sites of the facial nerve correlate with immediate postoperative outcomes in patients with hemifacial spasm (HFS), and if changes in the waveform of abnormal muscle response (AMR) during microvascular decompression (MVD) for HFS can predict the postoperative course. Methods: In this retrospective review, we evaluated 50 patients with HFS who underwent AMR monitoring during MVD. The ratios of amplitude and duration of AMR waveforms were computed by comparing baseline with final examinations. Vascular compression sites were categorized into four portions of the facial nerve. Postoperatively, we classified patients into two groups based on symptom relief as those whose symptoms disappeared immediately (DI group), and those whose symptoms disappeared gradually (DG group). Results: The compression sites significantly correlated with postoperative outcomes at discharge (p < 0.001) but not with outcomes after 6 months of MVD. Lower duration ratios of AMRs from the mentalis muscle were significantly associated with an increased chance of classification into the DI group based on the results of multivariate logistic regression analysis (p = 0.017). Conclusions: Relationship between compression sites and immediate outcomes could provide useful information to surgeons for predicting if symptoms will resolve over long term. Moreover, changes in AMRs recorded from the mentalis muscle could predict the postoperative course of HFS. Significance: These findings can help surgeons evaluate the changes in AMR amplitude and duration during MVD for HFS.