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High-mobility group box 2, a chromatin-associated protein that interacts with deoxyribonucleic acid, is implicated in multiple biological processes, including gene transcription, replication, and repair. High-mobility group box 2 is expressed in several tissues, including the testis; however, its functional role is largely unknown. Here, we elucidated the role of high-mobility group box 2 in spermatogenesis. Paraffin-embedded testicular tissues were obtained from 8-week-old and 1-year-old wild-type and knock-out mice. Testis weight and number of seminiferous tubules were decreased, whereas atrophic tubules were increased in high-mobility group box 2-depleted mice. Immunohistochemistry revealed that atrophic tubules contained Sertoli cells, but not germ cells. Moreover, decreased cell proliferation and increased apoptosis were demonstrated in high-mobility group box 2-depleted mouse testis. To elucidate the cause of tubule atrophy, we examined the expression of androgen and estrogen receptors, and the results indicated aberrant expression of androgen receptor and estrogen receptor alpha in Sertoli and Leydig cells. Southwestern histochemistry detected decreased estrogen response element–binding sites in high-mobility group box 2-depleted mouse testis. High-mobility group box 1, which has highly similar structure and function as high-mobility group box 2, was examined by immunohistochemistry and western blotting, which indicated increased expression in testis. These findings indicate a compensatory increase in high-mobility group box 1 expression in high-mobility group box 2 knock-out mouse testis. In summary, depletion of high-mobility group box 2 induced aberrant expression of androgen receptor and estrogen receptor alpha, leading to decreased germ cell proliferation and increased apoptosis which resulted in focal seminiferous tubule atrophy.

The volume loss of skeletal muscle, including lumbar paravertebral muscles, is negatively correlated with the rate of lumbo-pelvic deformity. Moreover, ectopic fat infiltration with highly expressed adipogenesis promoting genes in the paravertebral muscles may reflect pathology of sarcopenia and may cause age-related lumbo-pelvic deformity., Study Design. A retrospective analysis of a prospective, non-randomized cohort dataset. Objective. To cross-sectionally examine the prevalence of sarcopenia and the association between spine-pelvic deformity and skeletal muscle volume loss and ectopic fat infiltration into lumbar paravertebral muscles (PVMs) in patients who underwent lumbar surgery. Summary of Background Data. Muscle quality deterioration has been considered the main pathology of sarcopenia, reducing muscle strength directly. The qualitative deterioration as well as volume loss in PVM, which contributes significantly to core body extension, might cause aging-related spine deformity. Methods. In total, 184 patients were included. Sarcopenia was diagnosed at baseline, and all patients underwent whole-body X-ray. The amount of fat in lumbar PVM was evaluated with the Goutallier classification in magnetic resonance imaging findings. The expression of adipogenesis- and atrophy-promoting factors in PVM was evaluated with quantitative polymerase chain reaction. Results. In total, 36.1% of adults aged ≥60 years were diagnosed with sarcopenia. The values of skeletal muscle indexes of the limb and trunk were inversely correlated with the sagittal vertical axis, pelvic tilt (PT), and pelvic incidence minus lumbar lordosis (PI-LL) values. The PT and PI-LL were greater, PVM area was smaller, and Goutallier grade was greater in sarcopenic adults than in non-sarcopenic older adults. Additionally, the PVM area correlated with the LL value, and Goutallier's grade correlated with the PT and PI-LL values. Moreover, the amount of ectopic fat in PVMs inversely correlated with skeletal muscle indexes. The expression levels of atrophy gene-1 and muscle ring-finger protein-1 did not differ between the groups and did not correlate with the PVM area. In contrast, the expression of Pparg and Cebpa was upregulated in sarcopenic older adults, where it correlated with Goutallier's grade. Conclusion. The volume loss of skeletal muscle, including lumbar PVM, and ectopic fat infiltration into the PVM, may cause the lumbo-pelvic deformity. Level of Evidence: 3

High-mobility group box 2 (HMGB2) is a chromatin-associated protein that is an important regulator of gene transcription, recombination, and repair processes. The functional importance of HMGB2 has been reported in various organs, including the testis, heart, and cartilage. However, its role in the ovary is largely unknown. In this study, ovary tissues from wild-type (WT) and HMGB2-knock-out (KO) mice were examined by histopathological staining and immunohistochemistry. The ovary size and weight were significantly lower in HMGB2-KO mice than in age-matched WT littermates. Histopathological analysis revealed ovarian atrophy and progressive fibrosis in 10-month-old HMGB2-KO mouse ovaries. Compared to age-matched WT mice, the numbers of oocytes and developing follicles were significantly decreased at 2 months of age and were completely depleted at 10 months of age in HMGB2-KO mice. Immunohistochemistry revealed the expression of HMGB2 in the granulosa cells of developing follicles, oocytes, some corpora lutea, and stromal cells. Importantly, HMGB2-positive cells were co-localized with estrogen receptor beta (ERβ), but not ERα. Estrogen response element-binding activity was demonstrated by southwestern histochemistry, and it was decreased in HMGB2-KO mouse ovaries. Cell proliferation activity was also decreased in HMGB2-KO mouse ovaries in parallel with the decreased folliculogenesis. These results indicated that the depletion of HMGB2 induced ovarian atrophy that was characterized by a decreased ovarian size and weight, progressive fibrosis, as well as decreased oocytes and folliculogenesis. In conclusion, we demonstrated the crucial role of HMGB2 in mouse ovarian folliculogenesis through ERβ expression.

Background Several clinical and basic studies have shown that an association exists between achieving decompression of the spinal cord within a few hours and neurological recovery, even in patients with complete paralysis due to cervical spine dislocation. This study aimed to clarify the impact of helicopter emergency medical services(HEMS)and craniocervical traction using a halo ring on rapid reduction of lower cervical spine dislocation in rural Japan. Methods The success rate of and factors inhibiting closed reduction, time from injury to reduction and functional prognosis of lower cervical spine dislocations treated between July 2012 and January 2020 were retrospectively analysed. Results Fourteen patients were transported by HEMS (group H), seven were by ambulances (group A) and two were by themselves. Although the average travelled distance and injury severity score were significantly higher in group H (64.5 km, 28.0) than in group A (24.7 km, 18.6), there was no significant difference in the average time to admission or the time to start craniocervical traction after admission between group H (159.4 min, 52.2 min) and group A (163.6 min, 53.2 min). The urgent traction could be administered for 20 patients. The success rate of closed reduction was 95%, and neurological deterioration following traction was not observed in any cases. The average traction time and weight for reduction were 30.3 min and 16.3 kg, respectively. Patients’ body size and fracture-dislocation types did not significantly affect the traction time or weight. The rate of reduction within 4 h after injury was higher in group H (79%) than in group A (33%). Herniated discs were found at dislocation levels in five patients by magnetic resonance imaging scans performed after closed reduction, and all cases of inner fixation were treated via the posterior approach an average of 5.7 days after admission. After these treatment, three of nine AIS A patients recovered the ability to walk, and all the three patients underwent successful closed reduction within 4 h after injury. Conclusion HEMS and highly successful closed reduction considerably contributed to the early reduction of cervical spine dislocation and can potentially improve complete paralysis.

BACKGROUND Most people currently use the internet to obtain information about many subjects, including health information. Thus, medical associations need to provide accurate medical information websites. Although medical associations have their own patient education pages, it is not clear if these websites actually show up in search results. OBJECTIVE The aim of this study was to evaluate how well medical associations function as online information providers by searching for information about musculoskeletal-related pain online and determining the ranking of the websites of medical associations. METHODS We conducted a Google search for frequently searched keywords. Keywords were extracted using Google Ads Keyword Planner associated with “pain” relevant to the musculoskeletal system from June 2016 to December 2019. The top 20 search queries were extracted and searched using the Google search engine in Japan and the United States. RESULTS The number of suggested queries for “pain” provided by Google Ads Keyword Planner was 930 in the United States and 2400 in Japan. Among the top 20 musculoskeletal-related pain queries chosen, the probability that the medical associations’ websites would appear in the top 10 results was 30% in the United States and 45% in Japan. In five queries each, the associations’ websites did not appear among the top 100 results. No significant difference was found in the rank of the associations’ website search results (P=.28). CONCLUSIONS To provide accurate medical information to patients, it is essential to undertake effective measures for search engine optimization. For orthopedic associations, it is necessary that their websites should appear among the top search results.

Background Most people currently use the internet to obtain information about many subjects, including health information. Thus, medical associations need to provide accurate medical information websites. Although medical associations have their own patient education pages, it is not clear if these websites actually show up in search results. Objective The aim of this study was to evaluate how well medical associations function as online information providers by searching for information about musculoskeletal-related pain online and determining the ranking of the websites of medical associations. Methods We conducted a Google search for frequently searched keywords. Keywords were extracted using Google Ads Keyword Planner associated with “pain” relevant to the musculoskeletal system from June 2016 to December 2019. The top 20 search queries were extracted and searched using the Google search engine in Japan and the United States. Results The number of suggested queries for “pain” provided by Google Ads Keyword Planner was 930 in the United States and 2400 in Japan. Among the top 20 musculoskeletal-related pain queries chosen, the probability that the medical associations’ websites would appear in the top 10 results was 30% in the United States and 45% in Japan. In five queries each, the associations’ websites did not appear among the top 100 results. No significant difference was found in the rank of the associations’ website search results (P=.28). Conclusions To provide accurate medical information to patients, it is essential to undertake effective measures for search engine optimization. For orthopedic associations, it is necessary that their websites should appear among the top search results.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Although various surgical procedures have been developed for chronic rotator cuff tear repair, the re-tear rate remains high with severe fat infiltration. However, little is known about the molecular regulation of this process. Mesenchymal stem cells (MSCs) in the intra-muscular space are origin of ectopic fat cells in skeletal muscle. We have previously shown that high-mobility group box 2 (HMGB2), which is a nuclear protein commonly associated with mesenchymal differentiation, is involved in the early articular cartilage degeneration. In this study, we addressed the role of HMGB2 in adipogenesis of MSCs and fat infiltration into skeletal muscles. HMGB2 was highly expressed in undifferentiated MSCs and co-localized with platelet-derived growth factor receptor α (PDGFRA) known as an MSC-specific marker, while their expressions were decreased during adipocytic differentiation. Under the deficiency of HMGB2, the expressions of adipogenesis-related molecules were reduced, and adipogenic differentiation is substantially impaired in MSCs. Moreover, HMGB2+ cells were generated in the muscle belly of rat supraspinatus muscles after rotator cuff transection, and some of these cells expressed PDGFRA in intra-muscular spaces. Thus, our findings suggest that the enhance expression of HMGB2 induces the adipogenesis of MSCs and the fat infiltration into skeletal muscles through the cascade of HMGB2-PDGFRA.

Background Although a loss of rotator cuff integrity leads to the superior migration of the humeral head, the parameters that characterize the anterolateral migration of the humeral head have not been established. The purpose of this study was to investigate the correlation between the translation of the humeral head scale (T-scale) and clinical outcomes of rotator cuff repair, as well as the correlation between the T-scale and radiologic parameters. Methods One hundred thirty-five consecutive patients with full-thickness rotator cuff tears underwent primary rotator cuff repair. The T-scale, which indicates the distance from the center of the humeral head to the lateral coracoacromial arch, was measured on axial computed tomography scans, and the acromiohumeral interval (AHI) was measured radiographically. The correlation of the two parameters with the clinical scores of the Japanese Orthopaedic Association and University of California–Los Angeles scores and active forward elevation (FE) were evaluated at the preoperative and postoperative stages, respectively. Results The postoperative T-scale and AHI correlated well with the postoperative FE and clinical scores in the patients with large-massive tears but not in those patients with small-medium tears and preoperative large-massive tears. A significant correlation was observed between the postoperative T-scale and AHI. The T-scale was subject to cuff repair integrity. Conclusions We demonstrated that the postoperative T-scale was well correlated with the clinical results and postoperative AHI after rotator cuff repair for large-massive tears, indicating that poor outcomes are associated with combined superior and anterolateral migration of the humeral head following retears.