Showing papers by "Hiroshi Yamaguchi published in 2022"

Hyperexcitable arousal circuits drive sleep instability during aging

Abstract: Sleep quality declines with age; however, the underlying mechanisms remain elusive. We found that hyperexcitable hypocretin/orexin (Hcrt/OX) neurons drive sleep fragmentation during aging. In aged mice, Hcrt neurons exhibited more frequent neuronal activity epochs driving wake bouts, and optogenetic activation of Hcrt neurons elicited more prolonged wakefulness. Aged Hcrt neurons showed hyperexcitability with lower KCNQ2 expression and impaired M-current, mediated by KCNQ2/3 channels. Single-nucleus RNA-sequencing revealed adaptive changes to Hcrt neuron loss in the aging brain. Disruption of Kcnq2/3 genes in Hcrt neurons of young mice destabilized sleep, mimicking aging-associated sleep fragmentation, whereas the KCNQ-selective activator flupirtine hyperpolarized Hcrt neurons and rejuvenated sleep architecture in aged mice. Our findings demonstrate a mechanism underlying sleep instability during aging and a strategy to improve sleep continuity. Description Aging and sleep disruption In humans, the deterioration of sleep quality during aging is one of the most prevalent complaints. In an animal model, Li et al. found that aging correlated with enhanced spontaneous activity of wake-promoting brain areas during sleep (see the Perspective by Jacobson and Hoyer). Hypocretin-expressing neurons were more active during sleep, raising the chances of brief arousals and thus causing sleep to be more fragmented. The excitability of hypocretin neurons in aged brain tissue was heightened, possibly because of decreased expression of a subpopulation of potassium channels. Aging-related sleep fragmentation may therefore be due to altered intrinsic excitability of arousal-promoting neurons. —PRS Down-regulation of potassium channels causes hyperexcitability of hypocretin neurons and leads to age related fragmentation of sleep. INTRODUCTION Sleep destabilization is strongly associated with aging and cognitive function decline. Despite sleep fragmentation being central to the most prevalent complaints of sleep problems in elderly populations, the mechanistic underpinnings of sleep instability remain elusive. Fragmented sleep during aging has been observed across species, indicating conserved underlying mechanisms across the phylogenetic tree. Therefore, understanding why the aging brain fails to consolidate sleep may shed light on translational applications for improving the sleep quality of aged individuals. RATIONALE We hypothesized that the decline in sleep quality could be due to malfunction of the neural circuits associated with sleep/wake control. It has been established that hypocretin/orexin (Hcrt/OX) neuronal activity is tightly associated with wakefulness and initiates and maintains the wake state. In this study, we investigated whether the intrinsic excitability of Hcrt neurons is altered, leading to a destabilized control of sleep/wake states during aging. RESULTS Aged mice exhibited sleep fragmentation and a significant loss of Hcrt neurons. Hcrt neurons manifested a more frequent firing pattern, driving wake bouts and disrupting sleep continuity in aged mice. Aged Hcrt neurons were capable of eliciting more prolonged wake bouts upon optogenetic stimulations. These results suggested that hyperexcitability of Hcrt neurons emerges with age. Patch clamp recording in genetically identified Hcrt neurons revealed distinct intrinsic properties between the young and aged groups. Aged Hcrt neurons were hyperexcitable with depolarized membrane potentials (RMPs) and a smaller difference between RMP and the firing threshold. Aged Hcrt neurons expressing ChR2-eYFP were more sensitive to optogenetic stimulations, with a smaller-amplitude attenuation upon repetitive light pulse stimulations. More spikelets were generated in aged Hcrt neurons upon current injections. Recording from non-Hcrt neurons postsynaptic to Hcrt neurons revealed that optogenetic stimulation of Hcrt neurons expressing ChR2-eYFP reliably evoked time-locked postsynaptic currents (PSCs) after optogenetic stimulation more often in the aged group. Aged Hcrt neurons were characterized with a functional impairment of repolarizing M-current mediated by KCNQ2/3 channels and an anatomical loss of KCNQ2, revealed with array tomography at ultrastructural resolution. Single-nucleus RNA-sequencing (snRNA-seq) revealed molecular adaptions, including up-regulated prepro-Hcrt mRNA expression and a smaller fraction of Kcnq family subtypes Kcnq1/2/3/5 in aged Hcrt neurons. CRISPR/SaCas9–mediated disruption of Kcnq2/3 genes selectively in Hcrt neurons was sufficient to recapitulate the aging-associated sleep fragmentation trait in young mice. Pharmacological augmentation of M-current repolarized the RMP, suppressed spontaneous firing activity in aged Hcrt neurons, and consolidated sleep stability in aged mice. Sleep fragmentation in a narcolepsy mouse model with genetic ablation of Hcrt neurons at young ages manifested a mechanism other than hyperexcitable arousal-promoting Hcrt neurons that drives sleep fragmentation during healthy aging. CONCLUSION Our data indicate that emerging hyperexcitability of arousal-promoting Hcrt neurons is strongly associated with fragmented sleep in aged mice, which display a lowered sleep-to-wake transition threshold defined for Hcrt neuronal activity. We have demonstrated that the down-regulation of KCNQ2/3 channels compromising repolarization drives Hcrt neuronal hyperexcitability, which leads to sleep instability during aging. Pharmacological remedy of sleep continuity through targeting KCNQ2/3 channels in aged mice confers a potential translational therapy strategy for improving sleep quality in aged individuals. Hyperexcitable Hcrt neurons drive sleep instability during aging. Elevated excitability of Hcrt neurons with depolarized RMPs and adaptive up-regulation of prepro-Hcrt mRNA expression converge to drive sleep/wake instability in the aged brain with substantial Hcrt neuron loss. Hyperexcitable aged Hcrt neurons express functional impairment of KCNQ2/3 channel–mediated M-current and an anatomical loss of KCNQ2, compromising the neurons to repolarize.

On-Chip Coherent Transduction between Magnons and Acoustic Phonons in Cavity Magnomechanics

Abstract: Magnons, namely spin waves, are collective spin excitations in ferromagnets, and their control through coupling with other excitations is a key technology for future hybrid spintronic devices. Although strong coupling has been demonstrated with microwave photonic structures, an alternative approach permitting high density integration and minimized electromagnetic crosstalk is required. Here we report a planar cavity magnomechanical system, where the cavity of surface acoustic waves enhances the spatial and spectral power density to thus implement magnon-phonon coupling at room temperature. Excitation of spin-wave resonance involves significant acoustic power absorption, whereas the collective spin motion reversely exerts a back-action force on the cavity dynamics. The cavity frequency and quality-factor are significantly modified by the back-action effect, and the resultant cooperativity exceeds unity, suggesting coherent interaction between magnons and phonons. The demonstration of a chip-scale magnomechanical system paves the way to the development of novel spin-acoustic technologies for classical and quantum applications.

Visualization and Measurement of Swirling Flow of Dry Ice Particles in Cyclone Separator-Sublimator

Abstract: The dry ice sublimation process of carbon dioxide (CO2) is a unique, environmentally friendly technology that can achieve a temperature of −56 °C or lower, which is a triple point of CO2 in CO2 refrigeration systems. In this study, a cyclone separator-evaporator was proposed to separate dry ice particles in an evaporator. As an initial step before introducing the cyclone separator-evaporator into an actual refrigeration system, a prototype cyclone separator-evaporator was constructed to visualize dry ice particles in a separation chamber. A high-speed camera was used to visualize the non-uniform flow of dry ice particles that repeatedly coalescence and collision in a swirl section. Consequently, the dry ice particle size and the circumferential and axial velocities of dry ice were measured. The results show that the equivalent diameter of the most abundant dry ice particles in the cyclone separation chamber is 2.0 mm. As the inner diameter of the separation section decreases, dry ice particles coalesce and grow from an equivalent diameter of 4 mm to a maximum of 40 mm. In addition, the comparison of the experimental and simulation results shows that the drag force due to CO2 gas flow is dominant in the circumferential velocity of dry ice particles.

Free-access optomechanical liquid probes using a twin-microbottle resonator

Abstract: Cavity optomechanics provides high-performance sensor technology, and the scheme is also applicable to liquid samples for biological and rheological applications. However, previously reported methods using fluidic capillary channels and liquid droplets are based on fixed-by-design structures and therefore do not allow an active free access to the samples. Here, we demonstrate an alternate technique using a probe-based architecture with a twin-microbottle resonator. The probe consists of two microbottle optomechanical resonators, where one bottle (for detection) is immersed in liquid and the other bottle (for readout) is placed in air, which retains excellent detection performance through the high optical Q (~107) of the readout bottle. The scheme allows the detection of thermomechanical motion of the detection bottle as well as optomechanical drive and frequency tracking with a phase-locked loop. This technique could lead to in situ metrology at the target location in arbitrary media and could be extended to ultrasensitive biochips and rheometers.

Prospects of the potential strategies to improve the efficacy of anti‐PD‐1/PD‐L1 therapy

Abstract: PD-1 is an immune-checkpoint regulator in T cells that transduces an inhibitory signal and inactivates T cells, while PD-L1 is the PD-1 ligand expressed in various cell types, including antigen- presenting cells (APCs) and cancer cells. The PD-L1/PD-1 a key role in the immune escape of cancer cells, and inhibitory monoclonal antibodies (mAbs) against PD-1 or PD-L1 are currently used for treatment of a wide variety of cancer types. These checkpoint inhibitors (ICIs) drastic therapeutic effects on a subset of patients and have revolu-tionized cancer therapy. However, the overall response rates are far from satisfactory due to intrinsic and acquired resistance. Therefore, in order to unnecessary the response

Maximum Spreading of Impacting Ferrofluid Droplets under the Effect of Nonuniform Magnetic Field.

Abstract: This article investigates the maximum spreading of ferrofluid droplets impacting on a hydrophobic surface under nonuniform magnetic fields. A generalized model for scaling the maximum spreading is developed. It is observed that, if the magnetic field strength is zero, a ferrofluid droplet not only demonstrates similar spreading dynamics as the water droplet but also obeys the same scaling law for the maximum spreading factor. Therefore, this article emphasizes the effects of magnetic field strength. In this regard, a dimensionless parameter (Nm) is introduced as the ratio between inertial force and Kelvin force, with an assumption that the kinetic energy mainly transforms to thermal energy. This parameter allows us to rescale all experimental data on a single curve with the Padé approximant, which is applicable to a wide range of impact velocities and magnetic field strengths.

Scalable Low-Latency Inter-FPGA Networks

Abstract: A cutting-edge FPGA card can be equipped with many high-bandwidth I/Os by means of high-density optical integration, e.g., onboard Si-photonics transceivers, to provide high network bandwidth for memory-to-memory inter-FPGA communication. This study presents its scalable switchless net-work architecture by exploiting an indirect path, consisting of two one-hop paths, for enabling a diameter-2 network topology. It then takes a Kautz network topology with a diameter of two for connecting d(d + 1) FPGAs with a degree of $d$, which is close to the theoretical upper bound. The Kautz network topologies have bi-directional links and uni-directional links which form triangles. Uni-directional links introduce difficulty in avoiding channel buffer overflow because the existing link-level flow control assumes a bi-directional link. This study presents an indirect flow control along a uni-directional triangle embedded in the Kautz network topology. It then develops a combination of unicasts that forms multi-port collective communications to mitigate the influence of the startup latency on the execution time. Since a high-degree FPGA card introduces difficulty in storing many I/O ports at the panel of a 1- U compute server, we propose using WDM (Wavelength Division Multiplexing) as an alternative and present its efficient mapping onto arrayed waveguide grating (AWG). The required number of wavelengths becomes d on d+ 1 AWG equipments. Based on our experimental results with OPTWEB of custom Stratix10 FPGA cards, SimGrid simulation results show that our collective communication is 7 × faster than that of Dragonfly with 272 FPGAs.

Functional Interaction Between GABAergic Neurons in the Ventral Tegmental Area and Serotonergic Neurons in the Dorsal Raphe Nucleus

Abstract: GABAergic neurons in the ventral tegmental area (VTA) have brain-wide projections and are involved in multiple behavioral and physiological functions. Here, we revealed the responsiveness of Gad67+ neurons in VTA (VTAGad67+) to various neurotransmitters involved in the regulation of sleep/wakefulness by slice patch clamp recording. Among the substances tested, a cholinergic agonist activated, but serotonin, dopamine and histamine inhibited these neurons. Dense VTAGad67+ neuronal projections were observed in brain areas regulating sleep/wakefulness, including the central amygdala (CeA), dorsal raphe nucleus (DRN), and locus coeruleus (LC). Using a combination of electrophysiology and optogenetic studies, we showed that VTAGad67+ neurons inhibited all neurons recorded in the DRN, but did not inhibit randomly recorded neurons in the CeA and LC. Further examination revealed that the serotonergic neurons in the DRN (DRN5–HT) were monosynaptically innervated and inhibited by VTAGad67+ neurons. All recorded DRN5–HT neurons received inhibitory input from VTAGad67+ neurons, while only one quarter of them received inhibitory input from local GABAergic neurons. Gad67+ neurons in the DRN (DRNGad67+) also received monosynaptic inhibitory input from VTAGad67+ neurons. Taken together, we found that VTAGad67+ neurons were integrated in many inputs, and their output inhibits DRN5–HT neurons, which may regulate physiological functions including sleep/wakefulness.

Targeting the ALK–CDK9-Tyr19 kinase cascade sensitizes ovarian and breast tumors to PARP inhibition via destabilization of the P-TEFb complex

Abstract: Abstract Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated promising clinical activity in multiple cancers. However, resistance to PARP inhibitors remains a substantial clinical challenge. In the present study, we report that anaplastic lymphoma kinase (ALK) directly phosphorylates CDK9 at tyrosine-19 to promote homologous recombination (HR) repair and PARP inhibitor resistance. Phospho-CDK9-Tyr19 increases its kinase activity and nuclear localization to stabilize positive transcriptional elongation factor b and activate polymerase II-dependent transcription of HR-repair genes. Conversely, ALK inhibition increases ubiquitination and degradation of CDK9 by Skp2, an E3 ligase. Notably, combination of US Food and Drug Administration-approved ALK and PARP inhibitors markedly reduce tumor growth and improve survival of mice in PARP inhibitor-/platinum-resistant tumor xenograft models. Using human tumor biospecimens, we further demonstrate that phosphorylated ALK (p-ALK) expression is associated with resistance to PARP inhibitors and positively correlated with p-Tyr19-CDK9 expression. Together, our findings support a biomarker-driven, combinatorial treatment strategy involving ALK and PARP inhibitors to induce synthetic lethality in PARP inhibitor-/platinum-resistant tumors with high p-ALK–p-Tyr19-CDK9 expression.

Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates.

Abstract: Triple-negative breast cancer (TNBC) is well-known as the most aggressive subtype of breast cancer. Because TNBC does not express Her2, estrogen receptor, and progesterone receptors, there had been no effective U.S. Food and Drug Administration-approved targeted therapy for it until PARP inhibitors and two PD-1/PD-L1 monoclonal antibodies were approved for treatment of TNBC. Most recently, an antibody-drug conjugate (ADC), called sacituzumab govitecan (SG), was approved for the treatment of TNBC patients previously received chemotherapy with advanced disease. SG consists of an anti-trophoblast cell-surface antigen 2 (Trop2) antibody conjugated with a topoisomerase I inhibitor, SN-38, which is diffused out of the targeted Trop2 positive cancer cells and induces the bystander killing effect on surrounding cells regardless of their Trop2 expression status. In the Phase III clinical trial, TNBC patients treated with SG showed significantly longer progression-free and overall survival compared to those who were received chemotherapy. In the present review, we summarized the cellular function and signaling of Trop2, the mechanism of action of SG, and the clinical trials of SG that led to its quick approval for TNBC. In addition, we introduced the current ongoing clinical trials of SG as well as another Trop2 ADC, which has potential to overcome some disadvantages of SG.

Biomarkers beyond BRCA: promising combinatorial treatment strategies in overcoming resistance to PARP inhibitors

Abstract: Abstract Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) exploit the concept of synthetic lethality and offer great promise in the treatment of tumors with deficiencies in homologous recombination (HR) repair. PARPi exert antitumor activity by blocking Poly(ADP-ribosyl)ation (PARylation) and trapping PARP1 on damaged DNA. To date, the U.S. Food and Drug Administration (FDA) has approved four PARPi for the treatment of several cancer types including ovarian, breast, pancreatic and prostate cancer. Although patients with HR-deficient tumors benefit from PARPi, majority of tumors ultimately develop acquired resistance to PARPi. Furthermore, even though BRCA1/2 mutations are commonly used as markers of PARPi sensitivity in current clinical practice, not all patients with BRCA1/2 mutations have PARPi-sensitive disease. Thus, there is an urgent need to elucidate the molecular mechanisms of PARPi resistance to support the development of rational effective treatment strategies aimed at overcoming resistance to PARPi, as well as reliable biomarkers to accurately identify patients who will most likely benefit from treatment with PARPi, either as monotherapy or in combination with other agents, so called marker-guided effective therapy (Mget). In this review, we summarize the molecular mechanisms driving the efficacy of and resistance to PARPi as well as emerging therapeutic strategies to overcome PARPi resistance. We also highlight the identification of potential markers to predict PARPi resistance and guide promising PARPi-based combination strategies.

Influence of SiC epitaxial wafer quality on yield of 1.2kV SiC-DMOSFETs

Abstract: This work presents the influence of SiC epitaxial wafer quality on yield of 1.2kV SiC-DMOSFETs. Various wafer quality indicators were estimated by an integrated wafer quality evaluation system. SiC-DMOSFETs were fabricated on six 100 mm 4H-SiC epitaxial wafers. We show that the yield of SiC-DMOSFETs is related to threading screw dislocation density, defect density and bunched-steps length density evaluated by an integrated wafer quality evaluation system. A one-to-one analysis of multiple inspection data for SiC epitaxial defects and wafer-level electrical test results reveals the main factors in the yield of SiC- MOSFETs.

Behavior of Shockley-Type Stacking Faults in SiC Superjunction MOSFET under Body Diode Current Stress

Abstract: We evaluated stacking faults expanding by body diode current stress in the SiC Semi-SJ MOSFET for the first time. It was found that body diode degradation of the SJ MOSFETs tends to be smaller than that of conventional Non-SJ MOSFETs. Detailed crystal evaluations revealed that the stacking faults did not expand into the SJ structure. It is assumed that the expansion stops due to low carrier densities. The result suggests that the SJ device has a high potential as a device for suppressing the body diode degradation.

Serum cardiac troponin I is a candidate biomarker for cardiomyopathy in Duchenne and Becker muscular dystrophies

Abstract: Serum cardiac troponin I (cTnI), its relation to cardiomyopathy, and the contribution of the ACTN3 genotype to serum levels of cTnI in Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) remain unknown. In this study we aimed to reveal the characteristics of cTnI, assess whether cTnI is a biomarker for cardiomyopathy in these dystrophinopathies, and evaluate the contribution of the ACTN3 genotype to the serum levels of cTnI in DMD patients.

A Kuramoto Network in a Single Nonlinear Microelectromechanical Device

Abstract: This work presents a frequency multiplexed 3-limit cycles network in a multimode microelectromechanical nonlinear resonator. The network is composed of libration limit cycles and behaves in an analogous manner to a phase oscillator network. The libration limit cycles, being of low frequency, interact through the stress tuning of the resonator, and result in an all-to-all coupling that can be described by a Kuramoto model. Beyond the typically present cubic nonlinearity the modes in question do not require any special frequency ratios. Thus an interconnect free Kuramoto network is established within a single physical device without the need for electrical or optical coupling mechanisms between the individual elements.

Phononic Crystal Cavity Magnomechanics

Abstract: Establishing a way to control magnetic dynamics and elementary excitations (magnons) is crucial to fundamental physics and the search for novel phenomena and functions in magnetic solid-state systems. Electromagnetic waves have been developed as means of driving and sensing in magnonic and spintronics devices used in magnetic spectroscopy, non-volatile memory, and information processors. However, their millimeter-scale wavelengths and undesired cross-talk have limited operation efficiency and made individual control of densely integrated magnetic systems difficult. Here, we utilize acoustic waves (phonons) to control magnetic dynamics in a miniaturized phononic crystal micro-cavity and waveguide architecture. We demonstrate acoustic pumping of localized ferromagnetic magnons, where their back-action allows dynamic and mode-dependent modulation of phononic cavity resonances. The phononic crystal platform enables spatial driving, control and read-out of tiny magnetic states and provides a means of tuning acoustic vibrations with magnons. This alternative technology enhances the usefulness of magnons and phonons for advanced sensing, communications and computation architectures that perform transduction, processing, and storage of classical and quantum information.

Double-Gate Vectorial Frequency Control in Piezoresistive Nanowire Electromechanical Devices

Abstract: Vacuum-gap and orthogonally aligned double-gate geometry is employed in a nanowire-based electromechanical resonator device to independently control two nearly degenerate orthogonal vibration modes. In the device, piezoresistance is the dominant mechanism of motion-induced conductance variation, which provides an efficient scheme for the self-transduction of vibrational motion into an electric signal. Two simultaneously applied gate voltages induce an opposite combined effect on the frequency shift between two vibration modes, which is well explained by model calculations. Using the opposite double-gate effect, we demonstrate vectorial control of two mode frequencies, which is not possible with single-gate geometry.

Direct electrospray patterning deposition for flexible organic devices

Abstract: Organic electronic devices are attracting much attention because of their ease of thin-film processing such as inkjet printing. In general, the electrospray deposition (ESD) method is useful for forming uniform thin films. In the present study, we propose a new direct-patterning ESD method in which an electric field is applied between a syringe needle and a patterned counter electrode. Patterned organic semiconductor films were formed on flexible insulator substrates overlying the counter electrodes. In addition, we show that the width of the patterned organic film could be controlled by varying the applied electric field between the syringe needle and counter electrode.

Development of Carbon Fiber-Reinforced/Silicon Carbide Composites by Film Boiling Method

Abstract: Film boiling is one of the heat transfer phenomena in which a liquid phase boils and the vapor film covers a solid phase to maintain steady heat transfer when the heat flux from the solid phase to the liquid phase is large. When a carbon fiber is used as a solid phase and an organic solvent is used as a liquid phase and a solid-liquid interface is heated to a high temperature, film boiling occurs, the vapor phase derived from the organic solvent is formed in the carbon fiber, and pyrolytic carbon can be rapidly deposited onto the carbon fiber from the vapor phase. Characteristics of this formation technology include shortening process time, densification of generated carbon, and remarkable graphitization property. In this study, the authors examined a manufacturing method of carbon fiber reinforced/silicon carbide composite material using this film boiling phenomenon.

Structural insights into EphA4 unconventional activation from prediction of the EphA4 and its complex with ribonuclease 1.

Abstract: It has been shown that several ribonuclease (RNase) A superfamily proteins serve as ligands of receptor tyrosine kinases (RTKs), representing a new concept for ligand/receptor interaction. Moreover, recent studies indicate high clinical values for this type of ligand/RTK interactions. However, there is no structural report for this new family of ligand/receptor. In an attempt to understand how RNase and RTK may interact, we focused on the RNase1/ephrin type-A receptor 4 (EphA4) complex and predicted their structure by using the state-of-the-art machine learning method, AlphaFold and its derivative method, AF2Complex. In this model, electrostatic force plays an essential role for the specific ligand/receptor interaction. We found the R39 of RNase1 is the key residue for EphA4-binding and activation. Mutation on this residue causes disruption of an essential basic patch, resulting in weaker ligand-receptor association and leading to the loss of activation. By comparing the surface charge distribution of the RNase A superfamily, we found the positively charged residues on the RNase1 surface is more accessible for EphA4 forming salt bridges than other RNases. Furthermore, RNase1 binds to the ligand-binding domain (LBD) of EphA4, which is responsible for the traditional ligand ephrin-binding. Our model reveals the location of RNase1 on EphA4 partially overlaps with that of ephrin-A5, a traditional ligand of EphA4, suggesting steric hindrance as the basis by which the ephrin-A5 precludes interactions of RNase1 with EphA4. Together, our discovery of RNase1/EphA4 interface provides a potential treatment strategy by blocking the RNase1-EphA4 axis.

Successful management of a congenital portosystemic shunt using coil-in-plug embolization: A case report

Abstract: A 20-year-old man was referred to pediatrics for hyperbilirubinemia and mental retardation. Abdominal ultrasonography findings were indicative of a portosystemic shunt, and as a shunt between the left branch of the portal vein and inferior vena cava was confirmed by abdominal computed tomography, he was diagnosed with patency of the venous duct. We decided to perform shunt embolization using IVR, but as the shunt diame-ter had expanded like a funnel, its embolization was performed using a plug-and -metal coil, which led to an im-provement in hepatic reserve and blood ammonia levels postprocedure. Surgical ligation has been typically used in the management of portosystemic shunts, but as it is highly invasive, shunt embolization by IVR has become prevalent in recent years. Here we describe stable embolization using the IVR technique.

Behavioral Therapy for Children with Avoidant/Restrictive Food Intake Disorder Dependent on Tube or Oral Enteral Nutrient Formula: A Feasibility Study.

Abstract: In children with eating disorders, nutritional status and growth may depend on enteral nutrient formula. Ultimately, its goal is to introduce or reintroduce oral feeding. Japanese research on the treatment of tube or oral formula-dependent children is scarce. This study determined the feasibility of behavioral therapy for children with avoidant/restrictive food intake disorder and dependency on the tube or oral enteral nutrient formula in Japan. Medical records of children diagnosed with this disorder, dependent on the tube or oral enteral nutrient formula and who had received behavioral therapy intervention to withdraw from the formula were retrospectively investigated. We collected their characteristics at first visit and the caloric percentage from oral food intake six months after starting the treatment. In total, four patients (age range: 2-5 years) participated in this study. The feeding routes employed before the intervention were a nasogastric tube for one patient, a gastrostomy bottom for the other patient, and oral formula for the remaining patients (i.e., two children). At the sixth month of the behavioral treatment, none of the patients needed the formula, and the caloric percentage of required nutrition from oral food intake was 100%. Our data demonstrate that this behavioral therapy is feasible for children with avoidant/restrictive food intake disorder dependent on the tube or oral formula in Japan.