Effect of adenoids and tonsil tissue on pediatric obstructive sleep apnea severity determined by computational fluid dynamics

Study objective: Obstructive sleep apnea (OSA) is a respiratory disorder caused by the obstruction of the upper airway during sleep. The most common cause of pediatric OSA is adenotonsillar hypertrophy. Adenotonsillectomy is the first-line treatment for pediatric OSA; however, OSA persists in a significant number of patients due, in part, to the method of evaluating enlarged adenoids and tonsil tissue (AT). The reason for these effects on OSA severity is not clear. This study aimed to establish a method to diagnose the need for adenoidectomy or tonsillectomy. Methods: Twenty-seven Japanese children (mean age 6.6 years) participated in this study, undergoing polysomnography and computed tomography examination. Pharyngeal airway morphology (AT size, volume, and cross-sectional area [CSA]) and pressure on the upper airway were evaluated at each site using computational fluid dynamic analysis. Results: Apnea hypopnea index (AHI) showed a strong linear association with maximum negative pressure (Pmax) (AHI = -0.055* Pmax -1.326, R2 = 0.805). The relationship between minimum CSA (CSAmin) and Pmax was represented by an inversely proportional fitted curve (Pmax = -4797/ CSAmin -5.1, R2 = 0.507). The relationship between CSAmin and AHI was also represented by an inversely proportional fitted curve (AHI = 301.6/ CSAmin 1.22, R2 = 0.680). Pmax greatly increased if CSAmin became ≤ 30 mm2. The negative pressure of each site increased when CSA measured ≤ 50 mm2. Conclusions: In children, when the CSA for each site is ≤ 50 mm2, AHI is likely to be elevated, and the patient may require tonsillectomy or adenoidectomy

A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease

Proximal tubular cells (PTCs) are crucial for maintaining renal homeostasis, and tubular injuries contribute to progression of diabetic kidney disease (DKD). However, the roles of visceral adipose tissue-derived serine protease inhibitor (vaspin) in the development of DKD is not known. We found vaspin maintains PTCs through ameliorating ER stress, autophagy impairment, and lysosome dysfunction in DKD. Vaspin-/- obese mice showed enlarged and leaky lysosomes in PTCs associated with increased apoptosis, and these abnormalities were also observed in the patients with DKD. During internalization into PTCs, vaspin formed a complex with heat shock protein family A (Hsp70) member 1 like (HSPA1L) as well as 78kDa glucose-regulated protein (GRP78). Both vaspin-partners bind to clathrin heavy chain and involve in the endocytosis. Notably, albumin-overload enhanced extracellular release of HSPA1L and overexpression of HSPA1L dissolved organelle stresses, especially autophagy impairment. Thus, vapsin/HSPA1L-mediated pathways play critical roles in maintaining organellar function of PTCs in DKD

AJK2011-04001 A FULL EULERIAN FINITE DIFFERENCE METHOD FOR HYPERELASTIC PARTICLES IN FLUID FLOWS

ABSTRACT A full Eulerian finite difference method has been developed for solving a dynamic interaction problem between Newtonian fluid and hyperelastic material. It facilitates to simulate certain classes of problems, such that an initial and neutral configuration of a multi-component geometry converted from voxel-based data is provided on a fixed Cartesian mesh. A solid volume fraction, which has been widely used for multiphase flow simulations, is applied to describing the multicomponent geometry. The temporal change in the solid deformation is described in the Eulerian frame by updating a left Cauchy-Green deformation tensor, which is used to express constitutive equations for incompressible hyperelastic materials. The present Eulerian approach is confirmed to well reproduce the material deformation in the lid-driven flow and the particle-particle interaction in the Couette flow computed by means of the finite element method. It is applied to a Poiseuille flow containing biconcave neo-Hookean particles. The deformation, the relative position and orientation of a pair of particles are strongly dependent upon the initial configuration. The increase in the apparent viscosity is dependent upon the developed arrangement of the particles. INTRODUCTION Numerical simulations of Fluid-Structure Interaction (FSI) problems would make it possible to predict the effect of a medical treatment and help one decide the treatment strategy in clinical practice. In particular, a blood flow simulation is expected to contribute to assisting the surgical planning of a cardiovascular disease and a brain aneurysm. Recently, there are growing expectations for its applications along with a progress in imaging and computational technologies. It is also expected to contribute to the field of life science, such as in the understanding of the very essence of life and the demonstration of pathological mechanisms. It is of great importance to develop numerical techniques suitable for the characteristics of body tissues, which are flexible and complicated in shape, when attempting to rationalize and to generalize the fluidstructure coupled analyses. The expectations include the further understandings of the micro/mesoscopic behavior of the flexibly deformable Red Blood Cells (RBCs) in plasma useful for evaluating the macroscopic blood rheology, and the thrombosis formation as aggregation of platelets, of which th

HBD1 protein with a tandem repeat of two HMG-box domains is a DNA clip to organize chloroplast nucleoids in Chlamydomonas reinhardtii

葉緑体核様体をコンパクトに折りたたむ「DNAクリップ」の発見 --ミトコンドリアとも共通する普遍的なしくみの解明--. 京都大学プレスリリース. 2021-05-12.Compaction of bulky DNA is a universal issue for all DNA-based life forms. Chloroplast nucleoids (chloroplast DNA–protein complexes) are critical for chloroplast DNA maintenance and transcription, thereby supporting photosynthesis, but their detailed structure remains enigmatic. Our proteomic analysis of chloroplast nucleoids of the green alga Chlamydomonas reinhardtii identified a protein (HBD1) with a tandem repeat of two DNA-binding high mobility group box (HMG-box) domains, which is structurally similar to major mitochondrial nucleoid proteins transcription factor A, mitochondrial (TFAM), and ARS binding factor 2 protein (Abf2p). Disruption of the HBD1 gene by CRISPR-Cas9–mediated genome editing resulted in the scattering of chloroplast nucleoids. This phenotype was complemented when intact HBD1 was reintroduced, whereas a truncated HBD1 with a single HMG-box domain failed to complement the phenotype. Furthermore, ectopic expression of HBD1 in the mitochondria of yeast Δabf2 mutant successfully complemented the defects, suggesting functional similarity between HBD1 and Abf2p. Furthermore, in vitro assays of HBD1, including the electrophoretic mobility shift assay and DNA origami/atomic force microscopy, showed that HBD1 is capable of introducing U-turns and cross-strand bridges, indicating that proteins with two HMG-box domains would function as DNA clips to compact DNA in both chloroplast and mitochondrial nucleoids

A full Eulerian finite difference approach for solving fluid-structure coupling problems

A new simulation method for solving fluid-structure coupling problems has been developed. All the basic equations are numerically solved on a fixed Cartesian grid using a finite difference scheme. A volume-of-fluid formulation (Hirt and Nichols (1981, J. Comput. Phys., 39, 201)), which has been widely used for multiphase flow simulations, is applied to describing the multi-component geometry. The temporal change in the solid deformation is described in the Eulerian frame by updating a left Cauchy-Green deformation tensor, which is used to express constitutive equations for nonlinear Mooney-Rivlin materials. In this paper, various verifications and validations of the present full Eulerian method, which solves the fluid and solid motions on a fixed grid, are demonstrated, and the numerical accuracy involved in the fluid-structure coupling problems is examined.Comment: 38 pages, 27 figures, accepted for publication in J. Comput. Phy

Development of an Oropharyngeal Scope with an Integrated Tongue Depressor: NTOP2013 Study

The oropharynx is examined with a light source such as an electric light, a penlight, or a forehead mirror based on an acquired visual field using a tongue depressor. However, it is extremely difficult to obtain objective and reproducible images of tissue within the pharynx required in recent years with these methods, and insufficient progress in the examination tools has been made. There is an increasing need to develop a method for display during oropharyngeal examination. We conducted the present study to develop a novel oropharyngeal endoscope as an objective observation method

Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17.

Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-γ-deficient and IL-17-deficient mice as donors. Infusion of IFN-γ(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-β expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD

EGUIDE project and treatment guidelines

Aim: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. Methods: Four hundred thirteen out of 461 psychiatrists attended two 1‐day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants’ clinical knowledge of the treatment guidelines using self‐completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants’ demographics and their clinical knowledge scores. Results: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. Conclusion: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants’ clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders

Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients

Objectives Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000–3000 years. Methods Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype. Results In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10–8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients’ gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout. Conclusions Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia

Modeling of the Thermal Behavior Inside a Bubble

Cavitation occurs by the sudden expansion and the volumetric oscillation of bubble nuclei in the water due to the ambient pressure change. The size of bubble nuclei is O(10mm) and the thermal damping effects on the bubble motion is dominant in comparison with the acoustic and viscous damping effects. Because the thermal damping effect strongly depends on the thermal phenomena inside the bubble, it is important to simulate the detailed thermal behavior inside the bubble. The full DNS (Matsumoto and Takemura (1994) and Takemura and Mastumoto (1994)) is the most useful method to obtain the detailed structure. However, since it requires a long computational time to conduct the full DNS, a simple modeling for the internal thermal behavior is required. As we have known that there are many simple models for calculating the bubble oscillation such as the Rayleigh-Plesset equation etc. Nevertheless, most of previous works have assumed the thermal process of content inside the bubble to be adiabatic or isothermal and have neglected the thermal damping effect. In the present study, a simple model of the thermal behavior inside a spherical bubble is developed coupling with the Rayleigh-Plesset equation. The behavior of a spherical bubble in an acoustic field is numerically obtained by the full DNS, the present model and the conventional ones under adiabatic and isothermal assumptions