Results of Musculoskeletal Examinations in Elementary School Students and its Challenges

　児童生徒の運動に関連した現代的健康課題として，運動不足に伴う肥満などの生活習慣病と運動過多に伴う四肢および脊柱のスポーツ傷害が指摘されている。「運動器の10 年」日本委員会1）は，運動器疾患の罹患率を，６～７％と報告しており，「過度な運動，スポーツによる運動器疾患・障害を抱える子どももみられる状況」と指摘している。その流れを受けて，学校保健安全法施行規則の一部改正により検診項目に「運動器」が加えられ，平成28 年度より幼稚園から高等学校までの学校において運動器検診が義務化された。この検診を通じて，運動器疾患の早期発見やスポーツ障害を予防することが目指されている。しかし，平成23年の文部科学省の調査によると内科検診で運動器の検診している学校は，3.2 ～ 4.7％であり多くの学校で運動器検診は，これまで実施されていない。本研究は，平成27 年度に，義務実施に先行して小学校において運動器検診を行い，実施上の問題点や児童の運動器の現状を明らかにした

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Results of Musculoskeletal Examinations in Elementary School Students and its Challenges

　児童生徒の運動に関連した現代的健康課題として，運動不足に伴う肥満などの生活習慣病と運動過多に伴う四肢および脊柱のスポーツ傷害が指摘されている。「運動器の10 年」日本委員会1）は，運動器疾患の罹患率を，６～７％と報告しており，「過度な運動，スポーツによる運動器疾患・障害を抱える子どももみられる状況」と指摘している。その流れを受けて，学校保健安全法施行規則の一部改正により検診項目に「運動器」が加えられ，平成28 年度より幼稚園から高等学校までの学校において運動器検診が義務化された。この検診を通じて，運動器疾患の早期発見やスポーツ障害を予防することが目指されている。しかし，平成23年の文部科学省の調査によると内科検診で運動器の検診している学校は，3.2 ～ 4.7％であり多くの学校で運動器検診は，これまで実施されていない。本研究は，平成27 年度に，義務実施に先行して小学校において運動器検診を行い，実施上の問題点や児童の運動器の現状を明らかにした

Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat.

Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction

Possible Involvement of Opa-Interacting Protein 5 in Adipose Proliferation and Obesity

<div><p>Obesity is an epidemic matter increasing risk for cardiovascular diseases and metabolic disorders such as type 2 diabetes. We recently examined the association between visceral fat adiposity and gene expression profile of peripheral blood cells in human subjects. In a series of studies, Opa (Neisseria gonorrhoeae opacity-associated)-interacting protein 5 (OIP5) was nominated as a molecule of unknown function in adipocytes and thus the present study was performed to investigate the role of OIP5 in obesity. Adenovirus overexpressing Oip5 (Ad-Oip5) was generated and infected to 3T3-L1 cells stably expressing Coxsackie-Adenovirus Receptor (CAR-3T3-L1) and to mouse subcutaneous fat. For a knockdown experiment, siRNA against Oip5 (Oip5-siRNA) was introduced into 3T3-L1 cells. Proliferation of adipose cells was measured by BrdU uptake, EdU-staining, and cell count. Significant increase of Oip5 mRNA level was observed in obese white adipose tissues and such increase was detected in both mature adipocytes fraction and stromal vascular cell fraction. Ad-Oip5-infected CAR-3T3-L1 preadipocytes and adipocytes proliferated rapidly, while a significant reduction of proliferation was observed in Oip5-siRNA-introduced 3T3-L1 preadipocytes. Fat weight and number of adipocytes were significantly increased in Ad-Oip5-administered fat tissues. Oip5 promotes proliferation of pre- and mature-adipocytes and contributes adipose hyperplasia. Increase of Oip5 may associate with development of obesity.</p></div

A Novel Role for Adipose Ephrin-B1 in Inflammatory Response

<div><p>Aims</p><p>Ephrin-B1 (<i>EfnB1</i>) was selected among genes of unknown function in adipocytes or adipose tissue and subjected to thorough analysis to understand its role in the development of obesity.</p> <p>Methods and Results</p><p><i>EfnB1</i> mRNA and protein levels were significantly decreased in adipose tissues of obese mice and such reduction was mainly observed in mature adipocytes. Exposure of 3T3-L1 adipocytes to tumor necrosis factor-α (TNF-α) and their culture with RAW264.7 cells reduced EFNB1 levels. Knockdown of adipose EFNB1 increased monocyte chemoattractant protein-1 (<i>Mcp-1</i>) mRNA level and augmented the TNF-α-mediated THP-1 monocyte adhesion to adipocytes. Adenovirus-mediated adipose EFNB1-overexpression significantly reduced the increase in <i>Mcp-1</i> mRNA level induced by coculture of 3T3-L1 adipocytes with RAW264.7 cells. Monocyte adherent assay showed that adipose EfnB1-overexpression significantly decreased the increase of monocyte adhesion by coculture with RAW264.7 cells. TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was reduced by EFNB1-overexpression.</p> <p>Conclusions</p><p>EFNB1 contributes to the suppression of adipose inflammatory response. In obesity, reduction of adipose EFNB1 may accelerate the vicious cycle involved in adipose tissue inflammation.</p> </div

Expression of Ephrin-B1 in obese adipose tissue.

<p>A, Tissue distribution of Ephrin-B1 mRNA. Experiments were conducted in C57BL/6N mice under 12 hrs-fasting state at 12 weeks of age. B, Changes in adipose Ephrin-B1 mRNA level under high-fat/high-sucrose (HF/HS) diet. C57BL/6N mice were fed normal chaw diet (Cont) or HF/HS from 8 to 16 weeks of age. n=3 for each group. C, Adipose Ephrin-B1 mRNA levels in obese model mice. Ephrin-B1 mRNA level in WAT was examined in C57BL/6N (B6) and ob/ob (ob) mice at 8 and 16 weeks of age, respectively. n=6 for each group. D, Changes in adipose Ephrin-B1 protein level in mice of the obese model. Immunoblotting was performed using WAT of 16-week-old B6 and ob mice. Relative protein level (Ephrin-B1/α-tubulin) was calculated by densitometry. n=6 for each group. E, Ephrin-B1 mRNA level in fractionated WAT. WAT of 16-week-old B6 and ob mice was separated into mature adipocytes fraction (MAF) and stromal vascular fraction (SVF) as described in Materials and Methods section. n=5-6 for each group. <i>EfnB1</i> and EFNB1, Ephrin-B1; WAT, white adipose tissue; BAT, brown adipose tissue; DIO, diet-induced obesity; B6, C57BL/6J mice; ob, <i>ob/ob</i> mice; MAF, mature adipocytes fraction; SVF, stromal vascular fraction. Values are mean±SD. *<i>P</i><0.05; **<i>P</i><0.01; ***<i>P</i><0.001.</p

Effect of Oip5 overexpression on adipocytes proliferation.

<p>Adenovirus expressing β-galactosidase (βgal) or Oip5 was infected in Coxsackie-Adenovirus Receptor (CAR)-3T3-L1 adipocytes as described in Materials and Methods section. A, Oip5 mRNA level of the adenovirus-infected CAR-3T3-L1 adipocytes at 24 and 72 hrs after reseeding. B, Number of the adenovirus-infected CAR-3T3-L1 adipocytes at 24 hrs and 72 hrs after reseeding. C, Quantification of oil red O staining of the adenovirus-infected CAR-3T3-L1 adipocytes at 24 and 72 hrs after reseeding. D, Oil red O staining images of the adenovirus-infected CAR-3T3-L1 adipocytes at 24 and 72 hrs after reseeding. Oip5, Opa-interacting protein 5; βgal, β-galactosidase. Values are mean ± SE; n = 6 for each group. *<i>P</i><0.05;***<i>P</i><0.001.</p

Analysis of adipose tissue temperature in mice.

<p>Telemetric recording of spontaneous locomotor activity (A) and epididymal fat temperature (B) was performed in C57BL/6N (B6) and <i>ob/ob</i> (<i>ob</i>) mice at 10 weeks of age. C, Comparison of rectal and adipose tissue temperature in B6 and <i>ob</i> mice. In panels A and B, n = 2 per group. In panel C, n = 4 per group. Values are mean ± SEM. *P<0.05. #P<0.05, ##P<0.01, compared to B6 in each group.</p

Effect of several factors on Per1 mRNA level in 3T3-L1 adipocytes.

<p>A, Changes in Per1 mRNA level during 3T3-L1 adipocyte differentiation. n = 3–6 per group. B, Effects of H₂O₂ and tumor necrosis factor-α (TNF-α) on Per1 mRNA level. 3T3-L1 adipocytes were treated with or without 10 ng/mL of TNF-α and 50 µM of H₂O₂ for 24 hours on days 9 and 21. n = 3 per group. C, Effect of S100A8 and LPS on Per1 mRNA level in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with or without S100A8 and lipopolysaccharide (LPS) at the indicated concentrations for 24 hours. n = 4 per group. Values are mean ± SEM. *P<0.05, compared to Day 0.</p