Liver-specific Lxr inhibition represses reverse cholesterol transport in cholesterol-fed mice.

BACKGROUND AND AIMS: High density lipoprotein (HDL) exerts an anti-atherosclerotic effect via reverse cholesterol transport (RCT). Several phases of RCT are transcriptionally controlled by Liver X receptors (Lxrs). Although macrophage Lxrs reportedly promote RCT, it is still uncertain whether hepatic Lxrs affect RCT in vivo. METHODS: To inhibit Lxr-dependent pathways in mouse livers, we performed hepatic overexpression of sulfotransferase family cytosolic 2B member 1 (Sult2b1) using adenoviral vector (Ad-Sult2b1). Ad-Sult2b1 or the control virus was intravenously injected into wild type mice and Lxrα/ß double knockout mice, under a normal or high-cholesterol diet. A macrophage RCT assay and an HDL kinetic study were performed. RESULTS: Hepatic Sult2b1 overexpression resulted in reduced expression of Lxr-target genes - ATP-binding cassette transporter G5/G8, cholesterol 7α hydroxylase and Lxrα itself - respectively reducing or increasing cholesterol levels in HDL and apolipoprotein B-containing lipoproteins (apoB-L). A macrophage RCT assay revealed that Sult2b1 overexpression inhibited fecal excretion of macrophage-derived 3H-cholesterol only under a high-cholesterol diet. In an HDL kinetic study, Ad-Sult2b1 promoted catabolism/hepatic uptake of HDL-derived cholesterol, thereby reducing fecal excretion. Finally, in Lxrα/ß double knockout mice, hepatic Sult2b1 overexpression increased apoB-L levels, but there were no differences in HDL levels or RCT compared to the control, indicating that Sult2b1-mediated effects on HDL/RCT and apoB-L were distinct: the former was Lxr-dependent, but not the latter. CONCLUSIONS: Hepatic Lxr inhibition negatively regulates circulating HDL levels and RCT by reducing Lxr-target gene expression.

Differences in walking and running parameters in elementary school students with and without backpacks.

BACKGROUND: Backpack syndrome (BS) is a term used to describe symptoms such as shoulder and back pain that are believed to be caused by carrying a backpack. Few studies have investigated the changes in walking and running parameters with and without backpacks. OBJECTIVE: The present study aimed to investigate the differences in walking and running parameters with and without backpacks in primary school children with and without BS. METHODS: This cross-sectional study included 51 children (average age 9.3 years, 6- 12 years). Two questions were asked beforehand: whether the respondents had shoulder or back pain when going to school and present; those who answered that they had pain in both cases were defined as the BS group, while the others were the control group. Walking and running at comfortable speeds and walking and running with a 6 kg backpack on their backs were measured. RESULTS: During walking, there were main effects for speed, cadence, and strike angle with and without the backpack, but no interactions were identified for any of the parameters. In running, however, there were main effects for speed, stride length, strike angle, and lift-off angle, and an interaction effect was observed for speed and stride length. CONCLUSIONS: During walking, carrying a 6 kg backpack increased cadence and walking speed. During running, carrying a backpack caused a decrease in stride length and running speed in the BS group, whereas there was no change in the control group, suggesting that the control and BS groups may respond differently.

A New Case of Abetalipoproteinemia Caused by Novel Compound Heterozygote Mutations in the MTTP Gene without Fat or Vitamin Malabsorption.

Abetalipoproteinemia (ABL) is a rare disease characterized by extremely low apolipoprotein B (apoB)-containing lipoprotein levels, dietary fat, and fat-soluble vitamin malabsorption, leading to gastrointestinal, neuromuscular, and ophthalmological symptoms. We herein report a case of ABL with novel compound heterozygous mutations in the microsomal triglyceride transfer protein gene (c.1686_1687del [p.Ser563TyrfsTer10] and c.1862T>C [p.Ile621Thr]), identified via panel sequencing. Although the patient had extremely reduced low-density lipoprotein cholesterol levels and a fatty liver, he did not exhibit other typical complications. Furthermore, unlike typical ABL, this patient had a preserved apoB-48 secretion and increased concentrations of high-density lipoprotein cholesterol, which may account for the normal serum fat-soluble vitamin levels.

Surgical Outcomes of Full Endoscopic Posterior Cervical Foraminotomy for Proximal Cervical Spondylotic Amyotrophy.

STUDY DESIGN: Retrospective analysis of case series. PURPOSE: This study aimed to clarify the effects of full endoscopic posterior cervical foraminotomy (FPCF) on cervical spondylotic amyotrophy (CSA). OVERVIEW OF LITERATURE: The method for decompressing the ventral nerve root and anterior horn (AH) in CSA is controversial. METHODS: Patients without myelopathy who underwent FPCF for proximal CSA between 2017 and 2022 were analyzed. The outcome measure was the results of the manual muscle testing (MMT) of the deltoid and biceps. Preoperative nerve root and AH compression were evaluated by magnetic resonance imaging. The intervertebral foramen morphology and bony decompression extent were evaluated by computed tomography. RESULTS: FPCF was performed at the C4/5 level and at the C4/5 and C5/6 levels in 14 and 11 patients, respectively. The width of the narrowest intervertebral foramen was significantly narrower on the affected side than on the healthy side at the C4/5 (2.5 mm vs. 3.6 mm) and operated C5/6 (1.9 mm vs. 3.1 mm) levels. AH compression occurred at the C4/5 and C5/6 levels in 28% and 21% of the patients, respectively. Bony decompression was performed laterally beyond the narrowest foramen at the C4/5 and C5/6 levels in 96% and 91% of the patients, respectively. Compared with patients without AH compression, in those with AH compression, the lamina was resected medially by an average of >1.7 mm and >3.6 mm at the C4/5 and C5/6 levels, respectively. Furthermore, 76% and 81% of the facet joint surfaces were preserved at the C4/5 and C5/6 levels, respectively. Postoperative MMT grade improvement was excellent, good, and fair in 64%, 20%, and 16% of the patients, respectively. CONCLUSIONS: FPCF was effective for treating proximal CSA.

Differences in the center of pressure movement during standing with running shoes of different constructions: A cross-sectional study.

Purpose: This study examined the differences in the center of pressure movement in a one-leg standing position with bare feet, thin-soled shoes, and thick-soled shoes. Methods: In total, 21 male university students participated in this study. The task involved standing on one leg with the dominant foot for 30 s, and the center of pressure movement was measured using a grab coder (G-620; ANIMA, Tokyo, Japan). Three shoe-wearing states, including bare feet, thin-soled shoes, and thick-soled shoes, with the eyes closed and open in each condition. Statistical analysis was performed, with the significance level set as 5%. Results: In the multiple comparison results, the anteroposterior (AP) locus length, AP locus length per second, and maximum amplitude in the AP direction were significantly larger with thick-soled shoes than with bare feet in the closed eyes state. The locus length per unit area was significantly smaller with the thick-soled shoes than with the barefoot condition. Other items did not differ significantly between the shoe-wearing states. Conclusion: Thick-soled shoes caused a greater center of pressure movement in the AP direction in the static one-leg standing position than did the barefoot state. Our findings suggest that the condition with thick-soled shoes was more unstable in static environments.

Video-based e-learning program for schoolteachers to support children of parents with mental illness: a cluster randomized trial.

BACKGROUND: Some children of parents with mental illness need support. This study aimed to develop and test the effectiveness of an e-learning program for training elementary schoolteachers to support children of parents with mental illness. METHODS: The program, which included a 30-min video-based e-learning program, aimed to help schoolteachers gain basic knowledge about mental illness and children of parents with mental illness, recognize children in need of support, and gain confidence in supporting them. A school-based cluster randomized controlled trial was conducted, and the schools were randomly divided into intervention and control groups. The teachers at these schools signed up for the program and participated individually. The outcome measures for the schoolteachers were evaluated at three time points: baseline (T1), post (T2), and one month later (T3). Along with the Sense of Coping Difficulty subscale (primary outcome measure), the following self-developed outcome measures were used: actual behaviors and attitude toward supporting children, knowledge, and self-assessment of program goals achievement. The Sense of Coping Difficulty subscale results at T3 were compared between the groups. Effectiveness over time was assessed for all the outcome measures. The interaction between baseline and intervention effects on the Sense of Coping Difficulty subscale was analyzed. As a part of the process evaluation, open-ended text responses were analyzed qualitatively. RESULTS: Baseline responses were collected from 87 participants in the intervention group and 84 in the control group. The total score of the Sense of Coping Difficulty subscale at T3 was significantly lower in the intervention group than in the control group (p = 0.007). Over time, a significant effect was observed on the Sense of Coping Difficulty subscale, actual behavior, knowledge of onset timing and probability of onset, and achievement of all program goals. Exploratory analysis was particularly effective for those who encountered a high level of difficulty in supporting children. The participants' text responses indicated that they planned to look carefully at children's backgrounds and stay close to them in the future. CONCLUSIONS: The program was effective for schoolteachers in supporting children of parents with mental illness. TRIAL REGISTRATION: UMIN000045483; 14/09/2021.

HDL Functions-Current Status and Future Perspectives.

Cardiovascular disease (CVD) is the leading cause of death in Western countries. A low HDL-C is associated with the development of CVD. However, recent epidemiology studies have shown U-shaped curves between HDL-C and CVD mortality, with paradoxically increased CVD mortality in patients with extremely high HDL-C levels. Furthermore, HDL-C raising therapy using nicotinic acids or CETP inhibitors mostly failed to reduce CVD events. Based on this background, HDL functions rather than HDL-C could be a novel biomarker; research on the clinical utility of HDL functionality is ongoing. In this review, we summarize the current status of HDL functions and their future perspectives from the findings of basic research and clinical trials.

Two Cases of Acquired High-Density Lipoprotein Deficiency with Immunoglobulin G4-Related Lecithin-Cholesterol Acyltransferase Autoantibody.

Lecithin-cholesterol acyltransferase (LCAT) plays a significant role in the progression from premature to mature high-density lipoprotein (HDL) in circulation. Consequently, primary or secondary LCAT deletion or reduction naturally results in low serum HDL cholesterol levels. Recently, rare cases of acquired HDL deficiency with LCAT autoantibodies have been reported, mainly from Japan, where LCAT autoantibodies of immunoglobulin G (IgG) caused the HDL deficiency. Here to our knowledge, we report for the first time two cases of acquired HDL deficiency caused by IgG4 linked LCAT autoantibodies with or without a high serum IgG4 level. Furthermore, these cases can extend to a new concept of "IgG4 autoimmune disease" from the viewpoint of verifying the serum autoantibody and/or renal histopathology.

Histological finding of maternal antibody-associated congenital heart block accompanied by large atrial septal defect and severe cardiac dysfunction.

Cardiac dysfunction commonly occurs in congenital heart block associated with maternal anti-SSA antibodies, especially after pacemaker implantation. We report the case of a 4-year-old girl with antibody-associated congenital heart block and a large secundum atrial septal defect who presented with significant cardiac dysfunction 4 years after pacemaker implantation. Histological findings were useful for determining the course of treatment and perioperative risk of intracardiac repair.

Effects of Dietary Education Program for the Japan Diet on Cholesterol Efflux Capacity: A Randomized Controlled Trial.

AIM: Improving cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) has been regarded as a novel target for preventing cardiovascular disease. HDL reportedly has antioxidant properties which may contribute to its functions. We investigated changes in CEC with intake of the Japan Diet (JD) recommended by the Japan Atherosclerosis Society and the relationship of these changes to serum antioxidant concentrations. METHODS: A randomized parallel controlled clinical trial on JD intake was performed in Japanese patients with dyslipidemia. Ninety-eight participants were randomly divided into the JD (n=49) or the partial JD (PJD) (n=49) group. Nutrition education, based on each diet at baseline and at 3 months, was provided and the participants were followed up for 6 months. RESULTS: Mean CEC was 1.05 in total and correlated positively with HDL-cholesterol (p＜0.001) at baseline. CEC did not change while oxygen radical absorbance capacity (ORAC) was decreased in both groups (p＜0.001). Although serum total carotenoid increased in both groups, serum α-tocopherol decreased in the JD group as compared to the PJD group (p＜0.05). CEC correlated positively with HDL ORAC at baseline (p=0.021) and with serum total carotenoid at 3 and 6 months (p=0.005, 0.035). Changes in CEC correlated positively with changes in HDL ORAC at 3 months and serum total tocopherol at 3 and 6 months (p＜0.001). CONCLUSION: CEC was not changed by JD education in Japanese patients with dyslipidemia who already had normal CEC at baseline. CEC was suggested to be positively associated with serum α- and γ-tocopherol and HDL ORAC.

Effects of posture and lower limb muscle strength on the results of the Star Excursion Balance Test.

[Purpose] This study aimed to clarify the relationship between the distance measurements in the Star Excursion Balance Test and participants' posture and lower limb muscle strength. [Participants and Methods] Nine healthy male college students participated in this study. Star Excursion Balance Test distance was measured in both lower limbs by performing anterior, posterolateral, and posteromedial trials; measuring the maximum reach; and performing three-dimensional motion analysis to determine the posture at maximum reach. Isokinetic muscle strength for knee flexion/extension, hip flexion/extension, and hip adduction/abduction were measured using an isokinetic machine. [Results] The hip extension strength, reach side ankle dorsiflexion angles, stance side knee flexion, reach side knee flexion, and knee flexion strength were selected as significant explanatory variables in the anterior direction. For the posteromedial direction, hip adduction and hip extension strength, reach side hip flexion angle, and stance side hip flexion angle were selected. For the posterolateral direction, reach side knee flexion angle and stance side ankle dorsiflexion, knee flexion strength and reach side hip flexion angle were selected. [Conclusion] The related factors differed between the dominant and non-dominant legs even in the same reach direction.

Crucial involvement of catecholamine neurotransmission in postoperative nausea and vomiting: Whole-transcriptome profiling in the rat nucleus of the solitary tract.

The genetic mechanisms of postoperative nausea and vomiting (PONV) and the involvement of the catecholamine system in the brain have not been elucidated. Eating kaolin clay as a type of pica has been examined as an alternative behavior to emesis. Here, we evaluated changes in whole-transcriptome analysis in the nucleus of the solitary tract (NTS) in a rat pica model as a surrogate behavior of PONV to elucidate the molecular genetic mechanisms of the development of PONV and the involvement of the catecholamine system in the NTS. First, kaolin pica behaviors were investigated in 71 female Wistar rats following isoflurane anesthesia, surgical insult or morphine administration. Multiple linear regression analysis showed that 3 mg/kg morphine increased kaolin intake by 2.8 g (P = 0.0002). Next, total RNA and protein were extracted from the dissected NTS, and whole-transcriptome sequencing (RNA-seq) was performed to identify PONV-associated genes and to verify the involvement of the catecholamine system. The gene expression levels of tyrosine hydroxylase and dopamine beta-hydroxylase in the catecholamine biosynthesis pathway decreased significantly in the PONV model. Release of noradrenaline, a catecholamine pathway end product, may have increased at the synaptic terminal of the NTS neuron after pica behavior. Systematic administration of α2 adrenergic receptor agonists after surgery reduced kaolin intake from 3.2 g (control) to 1.0 g (P = 0.0014). These results indicated that catecholamine neurotransmission was involved in the development of PONV in the NTS.

Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study.

BACKGROUND: Genetic factors such as single-nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study was to identify SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. METHODS: Associations between 659,636 SNPs and the incidence of PONV 24 h after surgery in a limited sample of 24 female patients were assessed using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. RESULTS: The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). CONCLUSIONS: We identified a novel SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. TRIAL REGISTRATION: This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903 , date of registration: June 27, 2016, retrospectively registered.

Synthesis and biological activity of a novel fungicide, flutianil.

Flutianil was discovered as a novel fungicide chemically characterized as a cyano-methylene thiazolidine. This chemical showed particularly high fungicidal activities against powdery mildew on various crops. Optimization of the fungicidal performance of the series of synthesized chemicals finally led to the identification of flutianil, which could control powdery mildew diseases. In this report, details of the structure-activity relationships from the lead compound to flutianil are described.

The relationship between the deep squat movement and the hip, knee and ankle range of motion and muscle strength.

[Purpose] We examined and clarified the relationship between the maximum squat depth and the range of motion of the ankle, knee, and hip joints, and the knee and hip muscle strength. [Participants and Methods] Nine healthy males participated in this study and performed a deep squat with the upper extremities raised; the movement was analyzed by two-dimensional motion analysis. We measured the ankle dorsiflexion, hip flexion, and knee flexion ranges of motion, as well as the knee extension and hip flexion muscle strengths and analyzed the relationship between the squatting motion, the range of motion, and the muscle strength of each joint. [Results] The right ankle dorsiflexion range of motion was a significant predictor of the ankle dorsiflexion angle on both sides. The right knee flexion range of motion was a significant predictor of the knee flexion angle, and the left knee flexion range of motion was a significant predictor of the trunk anterior tilt angle on both sides. The right ankle dorsiflexion range of motion was a significant predictor of the right hip flexion angle and vice versa. [Conclusion] This study reveals that movement on one side affects contralateral movement, which is important when evaluating the deep squat motion as a functional test.

Analysis of lower extremity side-reaching motion in junior high school baseball players.

[Purpose] The aim of this study was to clarify the movement pattern of the pelvis and trunk of junior high school baseball players based on the lateral reach motion of the lower limb, which is related to poor pitching movement. [Participants and Methods] Twenty-five male students belonging to a baseball club participated in this study. Each participant performed the lower limb side reach movement in the standing position, during which the movements of the knee joint, hip joint, pelvis, and trunk were analyzed. [Results] A significant correlation was found between reach distance and reach leg hip abduction, supporting leg hip abduction, trunk side bending, and trunk tilt. We found a significant correlation between reach leg hip abduction and pelvic tilt and trunk side bending and between supporting leg hip abduction and pelvic tilt, knee valgus, and trunk side bending. Furthermore, we found a significant correlation between knee valgus and lower leg tilt and trunk tilt and between trunk side bending and pelvic tilt. [Conclusion] This study suggests that in the standing position movement at this age, the hip and trunk movements are related to and affect performance.

Summary of Toxicity Studies with Flutianil.

We have evaluated the toxicity of flutianil, which was developed by OAT Agrio. Flutianil shows low toxicity, no carcinogenicity, no reproductive toxicity, and no genotoxicity. Based on these results, the ADI of flutianil has been set at 2.4 mg/kg bw/day with a safety factor of 100.