Research Society Research Articles

Osteocyte RANKL Drives Bone Resorption in Mouse Ligature-Induced Periodontitis.

Mouse ligature-induced periodontitis (LIP) has been used to study bone loss in periodontitis. However, the role of osteocytes in LIP remains unclear. Furthermore, there is no consensus on the choice of alveolar bone parameters and time points to evaluate LIP. Here, we investigated the dynamics of changes in osteoclastogenesis and bone volume (BV) loss in LIP over 14 days. Time-course analysis revealed that osteoclast induction peaked on days 3 and 5, followed by the peak of BV loss on day 7. Notably, BV was restored by day 14. The bone formation phase after the bone resorption phase was suggested to be responsible for the recovery of bone loss. Electron microscopy identified bacteria in the osteocyte lacunar space beyond the periodontal ligament (PDL) tissue. We investigated how osteocytes affect bone resorption of LIP and found that mice lacking receptor activator of NF-κB ligand (RANKL), predominantly in osteocytes, protected against bone loss in LIP, whereas recombination activating 1 (RAG1)-deficient mice failed to resist it. These results indicate that T/B cells are dispensable for osteoclast induction in LIP and that RANKL from osteocytes and mature osteoblasts regulates bone resorption by LIP. Remarkably, mice lacking the myeloid differentiation primary response gene 88 (MYD88) did not show protection against LIP-induced bone loss. Instead, osteocytic cells expressed nucleotide-binding oligomerization domain containing 1 (NOD1), and primary osteocytes induced significantly higher Rankl than primary osteoblasts when stimulated with a NOD1 agonist. Taken together, LIP induced both bone resorption and bone formation in a stage-dependent manner, suggesting that the selection of time points is critical for quantifying bone loss in mouse LIP. Pathogenetically, the current study suggests that bacterial activation of osteocytes via NOD1 is involved in the mechanism of osteoclastogenesis in LIP. The NOD1-RANKL axis in osteocytes may be a therapeutic target for bone resorption in periodontitis. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

No Effect of NSAID Use on Efficacy of Zoledronate: A Post-Hoc Analysis of a Randomized Trial in Osteopenic Older Women.

Bisphosphonates are widely used for the prevention and treatment of osteoporosis. Non-steroidal anti-inflammatory drugs (NSAIDs) are also widely used among the older population group at high risk of fractures. NSAIDs have been shown to impact on bone turnover, and a recent re-analysis of a clinical trial of clodronate found that NSAID use at baseline abrogated any effect of clodronate on either bone density (BMD) or fracture risk. To determine whether NSAIDs influence the efficacy of other bisphosphonates, we have re-analyzed our 6-year randomized controlled trial of zoledronate in 2000 osteopenic postmenopausal women. NSAID use was reported at baseline in 38% of the cohort and anytime use was reported by 65%. The evolution of the zoledronate effects on BMD were almost identical whether or not women were using NSAIDs at baseline, and were significant in both sub-groups at all BMD sites (P < 0.0001). The significant reduction in the risk of fracture in those allocated to zoledronate (P < 0.0001) showed no interaction with baseline use of NSAIDs (P = 0.33) nor with NSAID use at any time during the study (P = 0.28). The odds of fracture were significantly reduced in both NSAID users and non-users. We conclude that the present analysis provides no support for the suggestion that NSAIDs interfere with the efficacy of potent bisphosphonates in terms of their effects on bone density or fracture.

GSTT1 as a Predictive Marker and Enhancer for Osteogenic Potential of Human Adipose-Derived Stromal/Stem Cells.

Adipose-derived stromal/stem cells (ASCs) have been extensively studied as cell sources for regenerative medicine for bone because of their excellent proliferative capacity and the ability to obtain a large number of cells with minimal donor morbidity. On the other hand, the differentiation potential of ASCs is generally lower than that of bone marrow-derived stromal/stem cells and varies greatly depending on donors. In this study, we mined a marker that can predict the osteogenic potential of ASC clones and also investigated the usefulness of the molecule as the enhancer of osteogenic differentiation of ASCs as well as its mechanism of action. Through RNA-seq gene analysis, we discovered that GSTT1 (Glutathione S-transferase theta-1) was the most distinguished gene marker between highly osteogenic and poorly osteogenic ASC clones. Knockdown of GSTT1 in high osteogenic ASCs by siGSTT1 treatment reduced mineralized matrix formation. On the other hand, GSTT1 overexpression by GSTT1 transfection or GSTT1 recombinant protein treatment enhanced osteogenic differentiation of low osteogenic ASCs. Metabolomic analysis confirmed significant changes of metabolites related to bone differentiation in ASCs transfected with GSTT1. A high total antioxidant capacity, low levels of cellular reactive oxygen species, and increased GSH/GSSG ratios were also detected in GSTT1-transfected ASCs. When the in vivo effect of GSTT1-transfected ASCs on bone regeneration was investigated with segmental long-bone defect model in rats, bone regeneration was significantly better after implantation of GSTT1-transfected ASCs compared with that of control vector-transfected ASCs. In conclusion, GSTT1 can be a useful marker to screen the highly osteogenic ASC clones and also a therapeutic factor to enhance the osteogenic differentiation of poorly osteogenic ASC clones. © 2023 American Society for Bone and Mineral Research (ASBMR).

Vitamin E discussion forum position paper on the revision of the nomenclature of vitamin E.

This position paper opens a discussion forum of this Journal dedicated to a scientific debate on Vitamin E nomenclature. With this article we provide the scientific and medical communities with what we consider relevant information in favor of revising the nomenclature of vitamin E. To our knowledge, only RRR-α-tocopherol has been medically used to protect against a deficiency disease in humans, and therefore, it would be appropriate to restrict the term vitamin to this molecule. The direct demonstration of a vitamin function to other tocochromanols (including other tocopherols, tocotrienols and eventually tocomonoenols), has not yet been scientifically shown. In fact, the medical prescription of a molecule against the deficiency disease only because it has been included in the "Vitamin E family", but not tested as vitamin E, could lead to ineffective therapy and potentially dangerous consequences for patients. The idea of this revision launched during the recent 3rd Satellite Symposium on Vitamin E of the 2022 SFRR-Europe meeting, offers a open platform of discussion for the scientists involved in vitamin E research and scientific societies interested to this subject.

Risk factors of postoperative coronal malalignment following long-segment spinal fusion surgery in which multilevel lateral lumbar interbody fusion was used for degenerative lumbar kyphoscoliosis.

In patients with adult spinal deformity, especially degenerative lumbar kyphoscoliosis (DLKS), preoperative sagittal malalignment and coronal malalignment (CM) often coexist. Lateral lumbar interbody fusion (LLIF) has recently been widely chosen for DLKS treatment due to its minimal invasiveness and excellent sagittal alignment correction. However, postoperative CM may remain or occur due to an oblique takeoff phenomenon following multilevel LLIF, resulting in poor clinical outcomes. The authors investigated the risk factors for postoperative CM after long-segment fusion corrective surgery in which multilevel LLIF was used in patients with DLKS. Fifty-four consecutive patients with DLKS, main Cobb angle ≥ 20°, and lumbar lordosis ≤ 20° who underwent corrective spinal fusion surgery, including extreme lateral interbody fusion at ≥ 3 segments, were included at the authors' institute between April 2014 and October 2019. Patients who underwent suitable 3-column osteotomy, classified as grade 3-6 per the Scoliosis Research Society-Schwab criteria, were excluded. Patients were divided into CM and non-CM groups based on postoperative CM evaluated using standard standing-position radiographs obtained 2 years postoperatively. CM was defined as an absolute C7-CSVL (deviation of C7 plumb line off central sacral vertical line; calculated by defining the convex side of the CSVL as positive numerical values) value of ≥ 3.0 cm. Patient demographics and preoperative sagittal alignment parameters were evaluated. The following variables were measured to assess coronal alignment: main Cobb angle; preoperative C7-CSVL; amount of lateral listhesis; L4, L5, and sacral coronal tilt angles; coronal vertebral deformity angles; and coronal spine rigidity. Regarding risk factors for postoperative CM, patient characteristics, preoperative sagittal parameters, and coronal parameters did not significantly differ between the 2 groups, except for preoperative C7-CSVL (p = 0.016). Multivariate logistic regression analysis revealed that preoperative C7-CSVL (+1 cm; OR 1.23, 95% CI 1.05-1.50; p = 0.007) was a significant predictor of postoperative CM. Receiver operating characteristic curve analysis demonstrated that the cutoff value for preoperative C7-CSVL was +0.3 cm, the sensitivity was 85.7%, the specificity was 60.6%, and the area under the curve was 0.70. In corrective fusion surgery for DLKS in which multilevel LLIF was used, the occurrence of postoperative CM was associated with preoperative C7-CSVL. According to the C7-CSVL, which was evaluated by defining the convex side of the CSVL as positive numerical values and the concave side as negative numerical values, the CM group had a significantly higher value of preoperative C7-CSVL than did the non-CM group. Alternative corrective fusion methods, other than multiple LLIFs, may be considered in DLKS cases with a C7-CSVL of +0.3 cm or greater.

Influence of age and severity of Lenke 5 or 6 idiopathic scoliosis on postoperative quality of life in adult patients

IntroductionThoracolumbar adolescent idiopathic scoliosis can continue to progress beyond skeletal maturity. Ideal timing of surgery remains undefined. Earlier intervention, with shorter instrumentation, incurs early partial loss of lumbar motion. Waiting for progression incurs a greater risk of extensive arthrodesis. The aim of the present study was to assess the quality-of-life impact of age and scoliosis severity at surgery. Material and methodsPatients with Lenke 5 or 6 adolescent idiopathic scoliosis, aged 16–45years, were analyzed based on a prospective clinical registry. Oswestry Disability Index (ODI) and Scoliosis Research Society (SRS)-22 scores were collected preoperatively and at 6months, 1year and 2years. Coronal and sagittal alignments were measured on full-spine radiographs, and curve flexibility was assessed on bending radiographs. A mixed linear model was used to assess the impact of age, Cobb angle and flexibility on quality of life. ResultsThirty-six patients were included. Mean ODI was 20.5% preoperatively and 13.8% at 2years (p=0.017). Mean SRS-22 was 3.2 preoperatively and 3.9 at 2years (p<0.001). Mean Cobb angle was 56.6° preoperatively and 23.2° at 2years (p<0.001), with mean preoperative reducibility of 68.1%. Age and ODI correlated preoperatively (r=0.6; p<0.001) and at 6months (r=0.5; p=0.002), as did age and SRS-22 (r=–0.6; p<0.001 and r=–0.6; p<0.001, respectively). Linear regression found a significant negative correlation between thoracolumbar Cobb angle and change in SRS-22 at 6months. DiscussionIn 16–45 year-olds with Lenke 5 or 6 idiopathic scoliosis, age influenced SRS-22 score. Younger patients had better quality of life both pre- and post-operatively. Curve magnitude influenced postoperative score. The present study suggests that early surgical correction in younger patients, where instrumentation can be shorter, does not impair quality of life. Level of evidenceIV; prospective registry study.

High-intensity interval training in patients with intermittent claudication: Presented at the 2022 Vascular Society of Great Britain and Ireland Annual Scientific Meeting, Brighton, United Kingdom, November 23-25, 2022; presented at the 2023 Surgical Research Society Meeting, Nottingham, United Kingdom, March 22-24, 2023; and presented at the 2023 Vascular Annual Meeting of the Society for Vascular Surgery, National Harbor, MD, June

High-intensity interval training in patients with intermittent claudication: Presented at the 2022 Vascular Society of Great Britain and Ireland Annual Scientific Meeting, Brighton, United Kingdom, November 23-25, 2022; presented at the 2023 Surgical Research Society Meeting, Nottingham, United Kingdom, March 22-24, 2023; and presented at the 2023 Vascular Annual Meeting of the Society for Vascular Surgery, National Harbor, MD, June

한국구비문학회 30년, 무가 연구의 성과와 과제

In celebration of the 30th anniversary of the founding of the Korean Oral Literature Society, this study summarizes the research results in the field of shamanic songs over the past period. Shamanic songs are a part of a whole called shamanism. Therefore, we must understand the shamanic research flow within the overall flow of shamanic research, and within that flow, we can discuss the trends, characteristics, and achievements of research in the oral literature society. From this perspective, this study first organized the flow of shamanic research and how the scope and existence of shamanism, the subject of research, were recognized.&#x0D; Korean shamanic research began in the 1960s. Representative researchers were Seo Dae-seok, Kim Tae-gon, and Choi Gil-seong. Among them, Seo Dae-seok and Kim Tae-gon were scholars of Korean literature. Their research trends were clearly distinguished. While Seo Dae-seok made efforts to establish shamanism as 'literature', Kim Tae-gon conducted 'folk' research to understand shamanism in general. As the Korean Oral Literature Society was founded around Seo Dae-seok, the study of 'shamanic songs' as literature was the most central research trend. On the other hand, Kim Tae-gon's research trend is centered around the Folklore Societies and 'Association for Korean ShamanisticStudies'.&#x0D; 『Oral Literature Studies』, the academic journal of the Korean Society of Oral Literature, has published 726 papers so far, of which about 120 are related to the study of shaman songs. These studies were divided into 1) Research on shamanistic Epics, 2) Comparative research with overseas narratives as oral narratives, 3) Research on shamanic songs other than shamanistic Epics, 4) Shamanic research using shamanic songs, and 5) Other research. They were organized. Consequently, the Oral Literature Society's research results in the field of martial arts over the past 30 years have emphasized the study of martial arts as literature and strengthened its differentiation from folk research. A clear line has been drawn in terms of academic identity. However, as a result, the focus on shamanistic Epics research and text analysis research without a basis for field research are pointed out as limitations. In addition to this, the researcher proposed to expand the research from the perspective of ritual language and expression (performance) beyond shamanic song.

The Association between Sleep and Bone Mineral Density: Cross-Sectional Study Using Health Check-up Data in a Local Hospital in Japan.

This study aimed to investigate the association between daily sleep duration of <7 hours and lower bone mineral density (BMD) using data from annual health check-ups conducted in Japan between 2020 and 2022. Multivariate regression models were used, where BMD was the objective variable and daily sleep duration (<5 hours, 5 to <7 hours, 7 to <9 hours [reference], ≥9 hours) was the exposure variable adjusted for age, body mass index, physical activity, smoking status, and alcohol intake for men and women and further adjusted for menopausal status for women. The association between insomnia and BMD was also investigated. BMD was determined using calcaneal quantitative ultrasound and expressed as a percentage of the young adult mean (%YAM). In total, 896 men and 821 women were included. Median age was 54 years (interquartile range [IQR]: 46 to 64) for men and 55 years (IQR: 46 to 64) for women). Median BMD for men and women was 79%YAM (IQR: 71 to 89) and 75%YAM (IQR: 68 to 84), respectively. Approximately 80% of men and women slept <7 hours daily. Multivariate regression showed no association between sleep duration and BMD in men. However, women who slept 5 to <7 hours daily had significantly higher BMD by 3.9% compared with those who slept 7 to<9 hours (p = 0.004). No association between insomnia and BMD was found. Overall, a daily sleep duration of <7 hours was not independently associated with lower BMD compared to those who slept 7 to <9 hours in men and women. However, as there is evidence of both shorter and longer sleep durations being associated with an increased risk of adverse events, including cardiovascular events, our result needs to be interpreted with caution. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A comparative analysis of Altman's Z-score and T. Jury's cash-based credit risk models with the application to the production company and the data for the years 2016-2022

Research Questions: In the present paper the author answers the following research questions: 1) What are the potential strengths of the credit risk model based on the cash flow principle? 2) What are the weaknesses of the accrual-based credit risk model? 3) What are the benefits of the combined use of both cash-based and accrual-based credit risk modeling methods when analyzing companies? Motivation: nowadays there are no researches comparing the accrual-based credit risk model to a cash-based credit risk model with the application to a production company trading its shares on Stock Exchange. However, for investors, auditors and financial institutions it is important to know if there is a difference between these two models in the interpretation of analysis results, and determination of prebankruptcy stage of the company and credit risk default. Idea: in this paper, the author has focused on the comparative analysis of the cash-based credit risk model and the accrual-based credit risk model. The author applies it to the case of a manufacturing company and compares the effectiveness of determining the probability of default using a cash-based credit risk model and an accrual-based credit risk model. Data: the data analysed is obtained from the annual reports, managerial reports and auditor’s reports of Linas Agro Group for the years 2016-2022. The company information is taken from Nasdaq Baltic where Linas Agro Group has its shares traded. Tools: mixed research methods were used, combining quantitative calculations with analysis based on qualitative information. The author elaborates on the cash-based credit risk model based on the improved Timothy Jury’s template. The accrual-based model chosen for comparison and analysis is Altman’s Z-Score model. Findings: The results of the study have shown that the cash-based model is more effective in determining credit risk and default probability. The cash-based model indicated a high-risk default for the manufacturing company in four years out of seven years, while Altman’s Z-Score showed the company to be in the moderate risk grey zone in five years out of seven, and the two last years the model indicated the company in the green zone. The author suggests to financial institutions, financial managers, and investors using a cash-based credit risk model or combination of it with the accrual-based model. Contribution: the paper contributes to the knowledge about the comparison of cash-based and accrual-based credit risk models and emphasizes their strengths and weaknesses. It helps investors, auditors, business owners, and finance professionals to make a decision about which credit risk model to use for the analysis to determine the pre-bankruptcy state of the company, avoid bad loans and improve investment decision-making. It also encourages the academic society for further research and comparison on the topics of accrual-based and cash-based credit risk models in the strive to develop the ultimate credit risk model capable to analyse the data as precisely as possible.

Need-Based Game Design: Developing a CT Game Based on Educational Needs

According to reports and previous research, present and future society show a high need for citizens with technical skills, such as computer programming. The need for technical competent citizens can however be challenging for higher education institutions to accommodate due to low numbers of students in higher education computer science. But also due to the high drop-out rates and low pass rates in introductory programming courses. With that said, it is important to both recruit new students to computer science and to support those who already study the subject, to meet the demands of the present and the future. An approach that has shown great promise in motivating students while still keeping focus on the learning aspects in education, is game-based learning (GBL). To facilitate support in higher education computer science, more specifically courses in fundamental programming, this study had the aim of identifying important design concepts in the development of a need-based educational game on computational thinking (CT). Skills related to programming have commonly been organized as part of the CT concept. To identify the educational needs, e-mail interviews were conducted with teachers that teach higher education courses on computer programming in Swedish universities. Based in an on-going design science project to create a learning game on computational thinking for higher education, the study discusses and compare the identified needs with design theories, such as affordances, emotional design, and sustainable design. The conclusion is a conceptual design of the educational game with a set of recommendations for a need-based game design in educational context.

Increased Risk of Tooth Loss in Postmenopausal Women With Prevalent Vertebral Fractures: An Observational Study.

The association between prevalent fractures and tooth loss in postmenopausal women remains unclear. Herein, we investigated the association between prevalent vertebral and nonvertebral fractures, the number of teeth present at baseline, and the number of teeth lost during follow-up in postmenopausal Japanese women. This cross-sectional study enrolled 843 participants (mean age 68.3 years). The number of teeth at follow-up was evaluated in 655 women in this longitudinal study. The participants were divided into four groups according to their prevalent fracture status: no fractures, vertebral fractures alone, nonvertebral fractures alone, and both fracture types. After adjusting for covariates, Poisson regression analyses were performed to investigate differences in the number of teeth at baseline and that lost during the follow-up period among the four groups. Participants with prevalent vertebral fractures alone had significantly fewer teeth at baseline than those in participants without fractures or nonvertebral fractures alone (p < 0.001 for both). Furthermore, they lost more teeth during the follow-up period than did those with no fractures (p = 0.021) and tended to lose more teeth than did those with nonvertebral fractures alone or both prevalent fracture types. We observed no significant difference in the number of teeth lost between the participants with nonvertebral fractures alone and those with no fractures. Postmenopausal women with prevalent vertebral fractures may be at a higher risk of tooth loss. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

OA08 Atypical femoral fracture secondary to long term bisphosphonate use; are we doing enough to prevent it?

Abstract Introduction Atypical femoral fractures (AFF) are low energy subtrochanteric or femoral shaft fracture associated with long term use of bisphosphonates (BP). Although the absolute risk of AFF is low and ranges between 3.2-50 cases/100,000 person-years, this risk is said to double with prolonged use (&amp;gt;5 years). ROS and American Society for Bone and Mineral Research (ASBMR) recommends regular review of patient at 5 years for oral BP and 3 years for intravenous BP. We would like to share our experience with two AFF which was seen in our bone clinic over the last one year resulting from prolonged bisphosphonates use. Case description Case 1 A 76-year-old Caucasian lady was reviewed for follow-up appointment in bone clinic for the management of steroid induced osteoporosis. She was on AA for 13 years for primary prophylaxis. It was noted that she was experiencing discomfort in her right thigh for the last 8 months. Her initial femoral X-ray showed incomplete AFF of the right femur and she was referred to orthopaedics who suggested conservative management. 6 months later, she unfortunately had a fall resulting in right femur fracture which required intramedullary nailing. X-ray of the contralateral side shows periosteal thickening and she is waiting for prophylactic nailing. Case 2 79 year old white Caucasian presented to the hospital with a fall. She has been on long term steroids for PMR and was on alendronate for 20 years for primary prophylaxis. X-ray showed complete AFF of proximal right femur shaft which required intramedullary nailing, subsequently developed pain in left hip during physiotherapy and X-ray showed incomplete AFF of mid left femur which needed prophylactic nailing. She was then referred to our clinic for further risk stratification. Both the patients had their bisphosphonates stopped and was advised reduced weight bearing along with calcium and vitamin D supplementation. The table summarises the background history and investigations post presentation with AFF: Discussion Bisphosphonates are one of the mainstays for managing steroid induced osteoporosis and for patients with high risk fragility fractures. Despite the increasing awareness of long term complication, we still see patients with AFF who have missed the opportunity for review in primary and secondary care particularly among patients with primary prophylaxis with satisfactory DEXA scan. ROS and ASBMR recommends review of patients who are on oral bisphosphonates at 5 years and for patients on intravenous bisphosphonates at 3 years for further risk stratification to reduce the incidence of AFFs. It also recommends close monitoring in patients with prodromal pain in the hip, groin or thigh especially in those who have high risk factors such as long term glucocorticoid use, Asian race and femoral bowing. Cessation of bisphosphonates can result in 70% reduction of developing AFF. Hence a break in the treatment for approximately 18-24 months needs to be considered for patients who are at lower levels of risk for fragility fracture such as age &amp;lt;75years, no previous history of fragility fracture, DEXA T score more than −2.5 and low FRAX score. Yet, this is not happening in routine clinical practice both in primary and secondary care and patients fall out of safety netting resulting in AFF. We need robust pathway and safety netting for patients who are on long term treatment. This situation could have also been exacerbated by the COVID pandemic which has increased the waiting lists and cancelled appointments. Resulting in many elderly patients having no follow ups and DEXA assessments for risk stratification. Key learning points Following the COVID pandemic there has been a huge impact on the waiting list, which has further pushed follow-up review for patients on long term bisphosphonates. This has resulted in a missed opportunity to identify patients with low risk to have a break in the BPs treatment. We feel that with appropriate treatment pathways needs to be set at primary care and secondary care level to capture these patients on long bisphosphonates after 3 to 5 years of BP use; especially patients who are at higher AFF risk, including patients on glucocorticoids and patients of Asian ancestry. Steps must be put in place to ensure counselling and education is given to patients about risk of AFF and prodromal symptoms such as thigh or groin pain which are initial symptoms, so that they can seek appropriate review at primary care level. ROS and ASBMR Task Force 2013 need to be implemented locally to capture patients with long term BPs treatment. Also, if patients has AFF fracture, imaging of the other leg has to be considered for further evaluation as more than one fourth of the cases have contralateral lesion.

Anti-Siglec-15 Antibody Prevents Marked Bone Loss after Acute Spinal Cord Injury-Induced Immobilization in Rats.

Rapid and extensive sublesional bone loss after spinal cord injury (SCI) is a difficult medical problem that has been refractory to available interventions except the antiresorptive agent denosumab (DMAB). While DMAB has shown some efficacy in inhibiting bone loss, its concurrent inhibition of bone formation limits its use. Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 is expressed on the cell surface of mature osteoclasts. Anti-Siglec-15 antibody (Ab) has been shown to inhibit osteoclast maturation and bone resorption while maintaining osteoblast activity, which is distinct from current antiresorptive agents that inhibit the activity of both osteoclasts and osteoblasts. The goal of the present study is to test a Siglec-15 Ab (NP159) as a new treatment option to prevent bone loss in an acute SCI model. To this end, 4-month-old male Wistar rats underwent complete spinal cord transection and were treated with either vehicle or NP159 at 20 mg/kg once every 2 weeks for 8 weeks. SCI results in significant decreases in bone mineral density (BMD, -18.7%), trabecular bone volume (-43.1%), trabecular connectivity (-59.7%), and bone stiffness (-76.3%) at the distal femur. Treatment with NP159 almost completely prevents the aforementioned deterioration of bone after SCI. Blood and histomorphometric analyses revealed that NP159 is able to greatly inhibit bone resorption while maintaining bone formation after acute SCI. In ex vivo cultures of bone marrow cells, NP159 reduces osteoclastogenesis while increasing osteoblastogenesis. In summary, treatment with NP159 almost fully prevents sublesional loss of BMD and metaphysis trabecular bone volume and preserves bone strength in a rat model of acute SCI. Because of its unique ability to reduce osteoclastogenesis and bone resorption while promoting osteoblastogenesis to maintain bone formation, Siglec-15 Ab may hold greater promise as a therapeutic agent, compared with the exclusively antiresorptive or anabolic agents that are currently used, in mitigating the striking bone loss that occurs after SCI or other conditions associated with severe immobilization. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Effects of Incretin Therapy on Skeletal Health in Type 2 Diabetes-A Systematic Review.

Diabetes poses a significant risk to bone health, with Type 1 diabetes (T1D) having a more detrimental impact than Type 2 diabetes (T2D). The group of hormones known as incretins, which includes gastric inhibitory peptide (GIP) and glucagon-like peptide 1 (GLP-1), play a role in regulating bowel function and insulin secretion during feeding. GLP-1 receptor agonists (GLP-1 RAs) are emerging as the primary treatment choice in T2D, particularly when atherosclerotic cardiovascular disease is present. Dipeptidyl peptidase 4 inhibitors (DPP-4is), although less potent than GLP-1 RAs, can also be used. Additionally, GLP-1 RAs, either alone or in combination with GIP, may be employed to address overweight and obesity. Since feeding influences bone turnover, a relationship has been established between incretins and bone health. To explore this relationship, we conducted a systematic literature review following the PRISMA guidelines. While some studies on cells and animals have suggested positive effects of incretins on bone cells, turnover, and bone density, human studies have yielded either no or limited and conflicting results regarding their impact on bone mineral density (BMD) and fracture risk. The effect on fracture risk may vary depending on the choice of comparison drug and the duration of follow-up, which was often limited in several studies. Nevertheless, GLP-1 RAs may hold promise for people with T2D who have multiple fracture risk factors and poor metabolic control. Furthermore, a potential new area of interest is the use of GLP-1 RAs in fracture prevention among overweight and obese people. Based on this systematic review, existing evidence remains insufficient to support a positive or a superior effect on bone health to reduce fracture risk in people with T2D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Health literacy interventions in adult speech and language therapy: A scoping review.

Reduced health literacy can negatively impact care seeking, satisfaction with careand overall health outcomes. These issues are particularly common among people living with communication difficulties who are seeking care from speech and language therapists (SLTs). As such, the SLT must be aware of and sensitive to health literacy needs within their clinical practice, proactively adapting materials and resources to the health literacy needs of their patients. Despite this required core competency, little is known about the health literacy interventions used by SLTs when working with adult patients, and as such, there is limited and unclear guidance for the practicing clinician, leading to potentially suboptimal care delivery. To explore the characteristics of health literacy interventions discussed in the literature for use by SLTs with adult patients. PubMed, CINAHL, Web of Scienceand The Cochrane Database of Systematic Reviews were searched. Conference proceedings of the annual scientific meetings of the European Society for Swallowing Disorders and the Dysphagia Research Society were also searched. Grey literature was searched via the Open Grey database and, hand-searches of reference lists from included studies were conducted by both authors. Published and unpublished research investigating health literacy interventions provided by qualified SLTs providing care to adult patients in any setting for any speech and language related concerns. No language, geographic, study designor publication date limitations applied. Eligible participants in these studies were classified as: (1) patientsand (2) professionals. Data werecharted in accordance with guidelines from the Joanna Briggs Institute and the PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) independently by both authors. A total of 1112 potentially eligible studies were identified in the initial search, with 15 studies ultimately included in the synthesis. Study design and quality varied significantly. Most explored basic functional health literacy or narratively described core components of health literacy, which an SLT should understand, without employing an investigative research design. Limited research has been conducted onthe use of health literacy interventions within adult speech and language therapy practices. This finding is significant as SLTs regularly work with people living with communication problems, and therefore, addressing health literacy should be a core tenet of service delivery. There is a need for valid, reliableand rigorous investigations of health literacy interventions within speech and language therapy to ultimately improve future patient access to and benefit from the care provided. Patient public involvement in review studies is an emerging area. Due to resource issues, it was not possible to include this element in this study.

SNIP1 reduces extracellular matrix degradation and inflammation via inhibiting the NF-κB signaling pathway in osteoarthritis

Osteoarthritis (OA), the most common joint disease, is characterized by inflammation and cartilage degradation. Previous studies illustrated that Smad nuclear-interacting protein 1 (SNIP1) is an inhibitor of the TGF-β signal transduction pathway and SNIP1 has been reported as an anti-inflammatory factor. This study aimed to explore the role of SNIP1 in OA progression. In this study, the SNIP1 expression was evaluated in OA human and OA mice tissue and interleukin-1 beta (IL-1β)-induced chondrocytes. The Safranin-O (SO) staining and osteoarthritis research society international (OARSI) scoring system was used to evaluate cartilage injury. The gain- and loss-of-function studies for SNIP1 were performed in chondrocytes. The SNIP1 overexpression adenovirus was injected into mice by intra-articular injection. The SNIP1 expression was decreased in OA patients, OA mice, and IL-1β-stimulated chondrocytes. The cartilage injury of medial meniscus-induced OA (DMM-OA) mice at 8 weeks showed more severe than that at 4 weeks. The expression of SNIP1 was lower at 8 weeks than that at 4 weeks. In IL-1β-stimulated chondrocytes, SNIP1 overexpression reduced the expression of TNF-α and IL-6, alleviated ECM degradation, reduced the phosphorylation levels of p65 and IκBα, and decreased the p65 level in nuclear. Moreover, overexpression of SNIP1 alleviated cartilage injury in DMM-OA mice. In brief, our study suggested that SNIP1 alleviated OA and repressed inflammation by inhibiting the activation of NF-κB. This study might provide a new insight into OA treatment.

Total Calcium Intake Is Associated With Trabecular Bone Density in Adolescent Girls With Type 1 Diabetes.

Type 1 diabetes (T1D) confers an increased risk of fracture and is associated with lower bone mineral density (BMD) and altered microarchitecture compared with controls. Adequate calcium (Ca) intake promotes bone mineralization, thereby increasing BMD. The objective of this analysis was to evaluate the associations of total daily Ca intake with bone outcomes among youth with T1D. This was a cross-sectional analysis of girls ages 10-16 years with (n = 62) and without (n = 60) T1D. We measured Ca intake with a validated food-frequency questionnaire and BMD, microarchitecture, and strength estimates with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Total daily Ca intake did not differ between groups (950 ± 488 in T1D versus 862 ± 461 mg/d in controls, p = 0.306). Serum 25OHD was lower in T1D (26.3 ± 7.6 versus 32.6 ± 9.0 ng/mL, p = <0.001), and parathyroid hormone (PTH) was higher in T1D (38.9 ± 11 versus 33.4 ± 9.7 pg/mL, p = 0.004). Trabecular volumetric BMD and thickness at the tibia were lower in T1D (p = 0.013, p = 0.030). Ca intake correlated with trabecular BMD at the radius and tibia among T1D participants (β = 0.27, p = 0.047, and β = 0.28, p = 0.027, β = 0.28, respectively) but not among controls (pinteraction = 0.009 at the radius, pinteraction = 0.010 at the tibia). Similarly, Ca intake was associated with estimated failure load at the tibia in T1D but not control participants (p = 0.038, β = 0.18; pinteraction = 0.051). We observed the expected negative association of Ca intake with parathyroid hormone in controls (p = 0.022, β = -0.29) but not in T1D participants (pinteraction = 0.022). Average glycemia as measured by hemoglobin A1c did not influence the relationship of Ca and PTH among participants with T1D (pinteraction = 0.138). These data suggest that youth with T1D may be particularly vulnerable to dietary Ca insufficiency. Increasing Ca intake may be an effective strategy to optimize bone health in this population. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Past, Present, and Future of Cervical Disc Arthroplasty: Insights From Presidents of the Cervical Spine Research Society.

Past, Present, and Future of Cervical Disc Arthroplasty: Insights From Presidents of the Cervical Spine Research Society.

Closing the Gender Gap Among Canadian Ophthalmology Societies

ABSTRACT Objective To evaluate gender distribution in Canadian ophthalmology societies’ leadership and to determine associations between gender, academic productivity, and institutional rank. Methods We identified members and assessed their gender composition using publicly available updated webpages. SCOPUS database was used to gather research metrics. Results In this study, data was collected from 12 Canadian ophthalmology societies, which included 277 executive committee members. Of these, 70.5% (196) were male and 29.1% (81) were female (p < .0001). Males were significantly more prevalent in presidential leadership roles (39 males vs. 23 females, p = .02), while females were more represented in other leadership categories (77 females vs. 61 males, p = .03). The Canadian Ophthalmological Society (COS) showed an upward trend in female representation from 19.2% in 2016 to 42.3% in 2021. Research productivity showed a positive correlation with society leadership rank, with a correlation coefficient of 0.732 for the m-index (p < .001) and 0.356 for the h-index (p < .05). Academic rank was also positively correlated with society leadership rank, with a correlation coefficient of 0.536 (p < .001). There was no significant difference in h-index (12.7 ± 1.0 for males vs. 13.8 ± 1.5 for females, p = .85) or number of publications (48.6 ± 5.1 for males vs. 60.0 ± 11.3 for females, p = .83) between male and female executive members, but females had a higher m-index (0.67 ± 0.05) compared to males (0.58 ± 0.03, p < .05). In academic rank, males were more likely to be associate professors (25% vs. 5% for females, p = .0001) or instructors (14.8% vs. 6.3% for females, p = .05), while a higher proportion of females held assistant professor positions (47.5% for females vs. 30.1% for males, p = .006). Conclusion In this study, we found that males were more prevalent in executive positions, particularly in presidential roles among Canadian ophthalmology societies. The gender distribution in leadership reflected the gender composition of practicing ophthalmologists in Canada. There was a positive correlation between research productivity and society rank, as well as academic position and society rank. Male and female executive members had similar h-index and number of publications, but females had a higher m-index. These findings highlight the need for continued efforts to address gender disparities in ophthalmology leadership.