Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8+ T cell response.

Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) ß-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8+ T cell populations specific for variants of the nonstructural protein epitope NS3133 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3133-DENV2-specific repertoire was largely devoid of such TCRs. Structural analysis of a representative TRBV11-2+ TCR demonstrated that cross-serotype reactivity was governed by unique interplay between the variable antigenic determinant and germline-encoded residues in the second ß-chain complementarity-determining region (CDR2ß). Extensive mutagenesis studies of three distinct TRBV11-2+ TCRs further confirmed that antigen recognition was dependent on key contacts between the serotype-defined peptide and discrete residues in the CDR2ß loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs.

Establishing Normative Values for Performance-Based Tests in Older Thai Adults: A Nationwide Cross-Sectional Study.

OBJECTIVE: To determine normative values and identify contributing factors for physical performance tests in older, Thai, community-dwelling adults. DESIGN: Nationwide cross-sectional study. SETTING: Thai older community-dwelling adults. PARTICIPANTS: Thai older community-dwelling adults aged ≥60 years who had no major health problems (N=1430) between March 2021 and August 2022. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Normative values for the timed Up and Go (TUG) test, gait speed test, and 5-times sit-to-stand (5TSTS) test were determined for sex and age groups. Multivariable quantile regression analysis was employed to evaluate the participants, considering factors that may influence physical performance, such as height, and Charlson comorbidity index (CCI). RESULTS: The study included 1430 eligible participants. Their mean age was 68.4±5.8 years, and 58.5% were women. Men demonstrated superior physical performance in the medians (p50) of the TUG (10.0 s vs 11.0 s), gait speed (0.98 m/s vs 0.91 m/s), and 5TSTS (14.0 s vs 16.1 s) tests compared with women. These differences were consistently observed across age groups. Moreover, age, sex, and height were significantly associated with poor physical performance. CONCLUSION: This study observed variations in the normative values of TUG, gait speed, and 5TSTS tests among different age groups of older, Thai, community-dwelling adults. Additionally, our findings identified age, sex, and height as significant contributing factors to physical performance in this population.

Sarcopenia in Thai community-dwelling older adults: a national, cross-sectional, epidemiological study of prevalence and risk factors.

BACKGROUND: Sarcopenia is an age-related condition characterized by a progressive loss of skeletal muscle mass. It leads to declining physical performance, potentially culminating in a diminished quality of life or death. This study investigated the prevalence of sarcopenia and its associated risk factors among Thai community-dwelling individuals of advanced age. METHODS: Between March 2021 and August 2022, we conducted a nationwide community-based epidemiological survey across all six major regions of Thailand. Participants with sarcopenia were identified according to the 2019 criteria of the Asian Working Group for Sarcopenia (AWGS). The risk factors were examined using multivariable logistic regression. RESULTS: Of the 2456 participants, the overall prevalence of sarcopenia was 18.1%, with nearly two-thirds (66.9%) classified as having severe sarcopenia. Multivariate analysis identified six associated risk factors for sarcopenia. They are a lower body mass index (odds ratio [OR] = 11.7, 95% confidence interval [CI] = 7.8-17.4), suboptimal leg calf circumference (OR = 6.3, 95% CI = 4.3-9.5), male sex (OR = 2.8, 95% CI = 2.2-3.7), a history of chronic obstructive pulmonary disease (OR = 2.3, 95% CI = 2.3-5.0), advanced age (OR = 2.1, 95% CI = 1.3-3.3), and an increasing time in the timed up-and-go test (OR = 1.1, 95% CI = 1.0-1.1). CONCLUSIONS: This is the first large-scale national study to represent the prevalence and risk factors for sarcopenia in Thai community-dwelling individuals of advanced age using the AWGS 2019 criteria. Interventions such as lifestyle modifications and appropriate nutrition should be promoted throughout adulthood to maintain muscle strength and delay the onset of sarcopenia, particularly in males. TRIAL REGISTRATION: The Central Research Ethics Committee of the National Research Council of Thailand authorized the study protocol (approval number COA-CREC023/2021).

Dual-Frequency Bioelectrical Impedance Analysis is Accurate and Reliable to Determine Lean Muscle Mass in The Elderly.

BACKGROUND: Dual-frequency bioelectrical impedance analysis (DF-BIA) devices are more accessible and affordable than dual-energy X-ray absorptiometry (DXA); however, no studies have reported the accuracy of DF-BIA in body composition measurement, especially in the Thai elderly. The aims of this study were to (1) compare the accuracies of lean muscle masses measured by DF-BIA devices and DXA and (2) assess the reliability of the DF-BIA device. METHODS: This cross-sectional study was conducted on participants older than 60 years who visited the Orthopedic Clinic of Siriraj Hospital. Whole-body and appendicular skeletal muscle masses (ASMs) were measured using DF-BIA (Tanita RD-545), with DXA (GE Lunar iDXA) as the standard reference. The test-retest reliability of the DF-BIA and the agreement between the devices were assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Regression analysis was used to develop an equation to estimate ASM values from BIA close to those from DXA. RESULTS: The mean age of 88 participants was 73.8 (SD 8.0) years, with women predominating (84.1%). The agreement of BIA and DXA was very high for whole-body lean mass (ICC = 0.954) and ASM (ICC = 0.954), but the mean difference in muscle mass from DF-BIA was overestimated. The ICCs of test-retest reliability for whole-body muscle mass and ASM were 0.987 and 0.988, respectively. The equation for corrected ASM was formulated from a linear equation (R2 = 0.93). CONCLUSIONS: Although lean muscle mass from DF-BIA was minimally overestimated relative to DXA, this device had high accuracy and reliability for lean muscle mass evaluation in the elderly. DXA and DF-BIA are interchangeable for the assessment of muscle mass.

Exploring the osteoporosis treatment gap after fragility hip fracture at a Tertiary University Medical Center in Thailand.

BACKGROUND: (1) To evaluate the prescription rate of anti-osteoporosis medication, and (2) to identify factors associated with patients not receiving anti-osteoporosis medication or, when prescribed, not persisting with medication 1 year after hip fracture treatment. METHODS: We retrospectively reviewed the medical records of all fragility hip fracture patients admitted to the orthopedic unit of the Faculty of Medicine Siriraj Hospital, Mahidol University, between July 1, 2016, and December 31, 2019. We identified patients who did not receive anti-osteoporosis medication both 6 months and 1 year after fracture treatment. Patients who did not receive the medication 1 year after their treatment were enrolled and interviewed using a no-treatment questionnaire. RESULTS: In total, 530 patients with fragility hip fractures were eligible (mean age, 79.0 years), and most (74.5%) were women. Only 148 patients (31.6%) received anti-osteoporosis medication 1 year after hip fracture. Logistic regression analysis identified predictors for not receiving the medication: male sex (OR 1.8; 95% CI 1.1-3.0), Charlson comorbidity index score ≥ 5 (OR 1.5; 95% CI 1.0-2.3), and secondary school education or below (OR 2.0; 95% CI 1.2-3.3). The main reason for not receiving the medication was that healthcare providers neither discussed nor initiated pharmacological treatment for osteoporosis (48.2%). When the medication was prescribed, non-persistence primarily stemmed from transportation difficulties that resulted in patients missing follow-ups (50.0%). CONCLUSIONS: Improved physician attitudes toward anti-osteoporosis medications might enhance the treatment rate. Developing a follow-up team and facilitating access to medications (eg, courier delivery to patients) would promote therapy compliance. TRIAL REGISTRATIONS: The protocol for the first phase and second phase was approved by the Siriraj Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 180/2021) and for the second phase, patients-informed consent forms used in the cross-sectional component were approved by the Siriraj Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 180/2021). The research was registered with the Thai Clinical Trials Registry (TCTR number: 20210824002). The study was conducted in accordance with the Declaration of Helsinki. Each patient (or a relative/caregiver) provided informed consent in writing or by telephone to participate in this second study phase.

Surgical treatment for fragility hip fractures during the COVID-19 pandemic resulted in lower short-term postoperative functional outcome and a higher complication rate compared to the pre-pandemic period.

The COVID-19 pandemic adversely affected the functional outcomes of fragility hip fracture patients. This study revealed a higher in-hospital complication rate and lower postoperative function at 3 months among patients treated during the pandemic. Therefore, modified in-hospital and post-discharge protocols should be developed for implementation during pandemic crisis periods. INTRODUCTION: This study aims to investigate the in-hospital complication rate and short-term postoperative functional outcomes of fragility hip fracture (FHF) patients compared between during the COVID-19 pandemic and the same 14-month time period 1 year prior to the pandemic. METHODS: Using data from the Siriraj Fracture Liaison Service registry, FHF patients treated during the COVID-19 pandemic (1 March 2020 to 30 April 2021) were time-matched with FHF patients treated during the pre-pandemic period (1 March 2018 to 30 April 2019). We collected the rate of in-hospital postoperative complications and the postoperative functional outcomes at discharge and 3 months as measured by the Barthel Index (BI) and EuroQol visual analog scale (EQ-VAS). Functional outcome measures were compared between the pre-pandemic and pandemic periods. RESULTS: There were 197 and 287 patients in the pre-pandemic and pandemic groups, respectively. At the 3-month postoperative follow-up, the mean postoperative BI score and change in BI score were both significantly lower in the pandemic group indicating poorer postoperative function. Moreover, FHF patients treated during the pandemic had significantly more in-hospital complications (36.6% vs. 22.8%, p = 0.002). There was no significant difference in the 3-month EQ-VAS or change in the EQ-VAS between groups. CONCLUSION: The results of this study revealed a higher in-hospital complication rate and lower postoperative function at 3 months among FHF patients treated during the COVID-19 pandemic compared to the pre-pandemic period. Therefore, modified in-hospital and post-discharge protocols should be developed for implementation during pandemic crisis periods.

Development and internal validation of a machine-learning-developed model for predicting 1-year mortality after fragility hip fracture.

BACKGROUND: Fragility hip fracture increases morbidity and mortality in older adult patients, especially within the first year. Identification of patients at high risk of death facilitates modification of associated perioperative factors that can reduce mortality. Various machine learning algorithms have been developed and are widely used in healthcare research, particularly for mortality prediction. This study aimed to develop and internally validate 7 machine learning models to predict 1-year mortality after fragility hip fracture. METHODS: This retrospective study included patients with fragility hip fractures from a single center (Siriraj Hospital, Bangkok, Thailand) from July 2016 to October 2018. A total of 492 patients were enrolled. They were randomly categorized into a training group (344 cases, 70%) or a testing group (148 cases, 30%). Various machine learning techniques were used: the Gradient Boosting Classifier (GB), Random Forests Classifier (RF), Artificial Neural Network Classifier (ANN), Logistic Regression Classifier (LR), Naive Bayes Classifier (NB), Support Vector Machine Classifier (SVM), and K-Nearest Neighbors Classifier (KNN). All models were internally validated by evaluating their performance and the area under a receiver operating characteristic curve (AUC). RESULTS: For the testing dataset, the accuracies were GB model = 0.93, RF model = 0.95, ANN model = 0.94, LR model = 0.91, NB model = 0.89, SVM model = 0.90, and KNN model = 0.90. All models achieved high AUCs that ranged between 0.81 and 0.99. The RF model also provided a negative predictive value of 0.96, a positive predictive value of 0.93, a specificity of 0.99, and a sensitivity of 0.68. CONCLUSIONS: Our machine learning approach facilitated the successful development of an accurate model to predict 1-year mortality after fragility hip fracture. Several machine learning algorithms (eg, Gradient Boosting and Random Forest) had the potential to provide high predictive performance based on the clinical parameters of each patient. The web application is available at www.hipprediction.com . External validation in a larger group of patients or in different hospital settings is warranted to evaluate the clinical utility of this tool. TRIAL REGISTRATION: Thai Clinical Trials Registry (22 February 2021; reg. no. TCTR20210222003 ).

High-dose versus low-dose ergocalciferol for correcting hypovitaminosis D after fragility hip fracture: a randomized controlled trial.

BACKGROUND: Hypovitaminosis D can be observed in most fragility hip fracture patients. However, measurement of 25-hydroxyvitamin D (25(OH)D) level is costly and may not be available in some centers. Without the baseline serum 25(OH)D level, the appropriate dose of vitamin D supplementation is not known. The aim of this study was to evaluate the effectiveness and safety of vitamin D supplementation in fragility hip fracture patients compared between high- and low-dose vitamin D supplementation. METHODS: A total of 140 patients diagnosed with fragility hip fracture were randomly allocated to either the high-dose (60,000 IU/week) or low-dose (20,000 IU/week) vitamin D2 supplementation group for 12 weeks. The number of patients who achieved optimal vitamin D level (serum 25(OH)D > 30 ng/mL), the proportion of patients who developed hypercalcemia, and the functional outcome were compared between groups. RESULTS: Of the 140 patients who were enrolled, 21 patients were lost to follow-up during the study period. The remaining 119 patients (58 and 61 in the high- and low-dose groups, respectively) were included in the final analysis. The high-dose group had a higher rate of serum 25(OH)D restoration to optimal level than the low-dose group (82.8% vs 52.5%, respectively; p < 0.001). Approximately 3.4 and 1.6% of patients in the high- and low-dose groups, respectively, had mild transient hypercalcemia, but none developed moderate, severe, or symptomatic hypercalcemia. There were no differences in functional outcome scores between groups. CONCLUSIONS: In treatment settings where baseline serum 25(OH)D level can't be evaluated in older adults with fragility hip fracture, we recommend high-dose vitamin D2 of approximately 60,000 IU/week for 12 weeks, with subsequent switch to a maintenance dose. This regimen effectively restored serum vitamin D to an optimal level in 82.8% of patients without causing symptomatic hypercalcemia. TRIAL REGISTRATION: The protocol of this study was retrospectively registered in the Thai Clinical Trials Registry database no. TCTR20180302007 on 20 February 2018.

Video-based learning versus traditional lecture-based learning for osteoporosis education: a randomized controlled trial.

BACKGROUND: Patient education about osteoporosis is an important component of osteoporosis treatment. AIM: To compare the effectiveness of osteoporosis education between video-based learning and traditional lecture-based learning. METHODS: Participants who attended the Outpatient Department of Siriraj Hospital during June 2017 to November 2017 were recruited. Ten-question pre- and post-tests were used to evaluate participant osteoporosis knowledge. After finishing the pre-test, patients were randomized to receive osteoporosis education via either traditional lecture-based or video-based learning for 25 min. After the training, patient questions about the subject matter were answered, and then the post-test was administered. Change in score was compared between groups using non-inferiority test at a non-inferiority margin of - 1. RESULTS: Of 413 participants, 207 and 206 people were allocated to the lecture-based group and the video-based group, respectively. There were no significant differences in baseline characteristics, change in score between pre-test and post-test, or change in score between pre-test and retention test between groups. Non-inferiority test revealed the change in score after video-based learning to be non-inferior to traditional lecture-based learning at a difference of > - 1, α = 0.05 (p < 0.001). DISCUSSION: Video-based osteoporosis education can be used as part of a fracture liaison service to provide essential information about osteoporosis to both patients and caregivers. Video-based education is an efficient and effective tool that will reduce dependency on clinicians to provide lecture-based osteoporosis instruction. CONCLUSIONS: Since video- and lecture-based education were found to be equally effective, a standard package for both education techniques should be developed and implemented for all patients.

Maintenance of human chondrogenic phenotype on a dendrimer-immobilized surface for an application of cell sheet engineering.

BACKGROUND: Dedifferentiation of chondrocytes during cell expansion is one of the barriers in tissue construction for cartilage repair. To understand chondrocyte behavior and improve cell expansion in monolayer culture, this study investigated the effects of morphological changes and cellular aggregation on the maintenance of chondrogenic capacity by observing the expression patterns of chondrogenic (collagen type II and aggrecan) and dedifferentiation (collagen type I) markers. Primary human chondrocytes were cultured on either a polystyrene surface (PS) or a polyamidoamine dendrimer surface with a fifth-generation (G5) dendron structure to create a one-step process of cell expansion and the maintenance of chondrogenic activities prior to the construction of cell sheets. RESULTS: During the first two passages (P0 - P2), the relative mRNA level of collagen type II decreased in all cultures, while that of collagen type I increased. Remarkably, the level of collagen type II was higher and aggrecan was retained in the chondrocytes, forming cell aggregates and showing some round-shaped cells with less production of stress fibers on the G5 surface compared to fibroblast-like chondrocytes with abundant stress fibers on the PS surface. The numbers of P2 chondrocytes on the G5 and PS surfaces were nearly the same and sufficient for construction of chondrocyte sheets using a temperature-responsive plate. Without a supporting material during cell sheet manipulation, chondrocyte sheets spontaneously detached and exhibited a honeycomb-like structure of stress fibers. Unlike the chondrocyte sheets constructed from cells on the PS surface, the chondrocyte sheets from cells on the G5 surface had higher chondrogenic activities, as evidenced by the high expression of chondrogenic markers and the low expression of dedifferentiation markers. CONCLUSIONS: The one-step process of cell expansion and maintenance of chondrogenic activity could be obtained using the G5 surface. Human chondrocyte sheets were successfully constructed with high chondrogenic activity. These findings may lead to an alternative cultivation technique for human chondrocytes that offers high clinical potential in autologous chondrocyte implantation.

The Prevalence of Hypovitaminosis D in Patient with Fragility Hip Fracture at a Single Institution in Thailand.

Background: The proportion of people aged 65 years or older continues to increase in Thailand. Consistent with that trend, the number of fragility fracture patients is increasing. Hypovitaminosis D is one of the important factors associated with fragility fracture. Objective: To evaluate serum 25-hydroxyvitamin D (25(OH)D) level and prevalence of hypovitaminosis D in patients with fragility hip fracture in Thailand. Material and Method: This study retrospectively reviewed 25(OH)D level in fragility hip fracture patients treated at Siriraj Hospital between January 2012 and December 2015. Results: Three hundred seventy nine fragility hip fractures were included in this study. Two hundred sixty eight of those patients had serum 25(OH)D level available within one month after fracture. Mean age of patients was 80.8±8.3 years and 74.6% were women. One hundred twenty four patients (46.3%) had vitamin D deficiency (<20 ng/mL) and 86 patients (32.1%) had vitamin D insufficiency (20 to 30 ng/mL). Parathyroid hormone level was available in 159 of 268 patients, and 31.5% of those had hyperparathyroidism (PTH level >65 pg/mL). Conclusion: Orthopedists who treat fragility hip fracture should always include treatment of vitamin D deficiency in their patient management plan. Future studies should establish treatment guidelines regarding dose and duration of vitamin D supplementation in fragility hip fracture patients.

Facet joint orientation and tropism in lumbar degenerative disc disease and spondylolisthesis.

BACKGROUND: Although degenerative disc disease (DDD) and degenerative spondylolisthesis (DS) are two common causes of back pain in elderly, the association between the lumbarfacet joint angle and tropism in these conditions are still unclear. OBJECTIVE: To evaluate the difference in facet joint angles between normal population and lumbar degenerative disc disease and spondylolisthesis patient. MATERIAL AND METHOD: The angle of lumbar facet joints were retrospectively measured with magnetic resonance imaging (MRI) to determine whether there was a difference between degenerative diseases. MRI of patients with DDD, DS, and control group at facet joint between L3-4, L4-5 and L5-S1 level were measured in axial view (60 subjects in each group). RESULTS: There was no difference infacetjoint angle in DDD (44.1 ± 11.9) and control (45.6 ± 8.9), but differed in DS (40.1 ± 10. 7) and control group (p = 0.010) at L4-5 level. Facet tropism showed difference between degenerative groups and control group at L4-5 level. CONCLUSION: DS group showed difference in facet joints angle and tropism when compared with control population, while DDD showed difference only in facet tropism. In addition, longitudinal studies are needed to understand the clinical significant between facet joint angle and tropism in spinal degenerative diseases.

Prevalence of osteoporosis, sarcopenia, and high falls risk in healthy community-dwelling Thai older adults: a nationwide cross-sectional study.

Thailand has transitioned from an aging society to an aged society, which implies that the prevalence of age-related disorders will increase; however, epidemiological data specific to the prevalence of age-related degenerative musculoskeletal disorders among Thai older adults remain limited. Accordingly, the aim of this study was to investigate the prevalence of age-related musculoskeletal diseases, including osteoporosis, sarcopenia, and high falls risk among healthy community-dwelling Thai older adults. This cross-sectional nationwide study enrolled Thai adults aged ≥60 yr from 2 randomly selected provinces from each of the 6 regions of Thailand via stratified multistage sampling during March 2021 to August 2022. All enrolled participants were evaluated for BMD, skeletal muscle mass, grip strength, and gait speed. Osteoporosis was diagnosed according to the World Health Organization definition, and sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Falls risk was determined using the self-rated Fall Risk Questionnaire. A total of 2991 eligible participants were recruited. The mean age of participants was 69.2 ± 6.5 yr (range: 60-107), and 63.1% were female. The prevalence of osteoporosis, sarcopenia, and high falls risk was 29.7%, 18.1%, and 38.5%, respectively. Approximately one-fifth of subjects (19.1%) had at least 2 of 3 risk factors (ie, osteoporosis, sarcopenia, and high falls risk) for sustaining a fragility fracture, and 3.4% had all 3 risk factors. In conclusion, the results of this study revealed a high and increasing prevalence of osteoporosis, sarcopenia, and high falls risk in healthy community-dwelling Thai older adults. Since these conditions are all major risk factors for fragility fracture, modification of Thailand's national health care policy is urgently needed to address the increasing prevalence of these conditions among healthy community-dwelling older adults living in Thailand.

Bone turnover markers reference database in five Southeast Asian countries.

Osteoporosis is highly prevalent, particularly in developing countries. However, bone turnover marker reference ranges for management of osteoporosis in Asian population are yet to be explored and established. Thus, this study aims to develop a regional bone turnover markers (BTMs) reference database by combining country-specific reference database from five ASEAN countries: Malaysia, the Philippines, Singapore, Thailand, and Vietnam. We established a healthy reference population of 746 healthy premenopausal women aged 20 to 44 years old. Serum Procollagen 1 N-Terminal Propeptide (P1NP), Osteocalcin (OC), and Beta-Crosslaps (CTX) concentrations were measured using an automated immunoassay analyzer system, the cobas® modular analyzer systems (Roche Diagnostic Gmbh). The reference interval was defined as the central 95 % range. The estimated reference interval for CTX was 128 to 811 ng/L, OC was 9.0 to 33.0 µg/L, and for P1NP, the range was 22.8 to 96.5 µg/L. Comparison across countries showed that Singaporeans had the highest levels of median CTX along with Thais and Filipinos, who had significantly higher levels of P1NP and OC. Exploratory analysis on the associations with age showed that BTMs decreased with increasing age at 20 to 29 years old and plateaued after 30 years old. When excluding participants in their 20s, the reference interval estimated were CTX: 117-678 ng/L, P1NP: 21.6-85.8 µg/L and OC: 3.5-27.0 µg/L respectively. To the best of our knowledge, this is the first study to report BTMs reference intervals based on a healthy premenopausal Southeast Asian population which will contribute to the appropriate assessment and monitoring of bone turnover rate in the evaluation and management of osteoporosis in the Southeast Asian region. LAY SUMMARY: Osteoporosis is a common health issue, especially in developing countries. However, there is a lack of information on bone health markers specific to the Southeast Asian population. This study aimed to fill this gap by creating a reference database for bone turnover markers (BTMs) in Southeast Asian countries, including Malaysia, the Philippines, Singapore, Thailand, and Vietnam. The researchers studied 746 healthy women aged 20 to 44 years and measured blood markers related to bone health. The reference interval, representing the normal range, was determined. For example, the normal range for CTX was found to be 128 to 811 ng/L, for Osteocalcin was 9.0 to 33.0 µg/L, and for P1NP, the range was 22.8 to 96.5 µg/L. When excluding participants in their 20s, the reference intervals estimated were CTX: 117-678 ng/L, P1NP: 21.6-85.8 µg/L and OC: 3.5-27.0 µg/L respectively. Comparing the results across countries, Singaporeans, Thais, and Filipinos showed variations in their biochemical bone marker levels. Additionally, the study observed changes in the levels with age, with a decrease in BTMs observed after the age of 30. This groundbreaking study provides the first-ever reference intervals for BTMs in a healthy premenopausal Southeast Asian population. These findings will help in the proper assessment and monitoring of bone health, contributing to the management of osteoporosis in the Southeast Asian region.

Three-year outcomes of a fracture liaison service model at a university-based tertiary care hospital in Thailand.

Fragility hip fracture (FHF) is a serious complication of osteoporosis. A fracture liaison service (FLS) is crucial in preventing FHF. Our retrospective data of 489 patients with FHF and 3-year follow-ups demonstrated that the FLS improved functional outcomes. Our study's mortality rates were lower than in other published series. PURPOSE: This study assessed the 3-year outcomes after fragility hip fracture (FHF) treatment by a multidisciplinary team from the Siriraj Fracture Liaison Service (Si-FLS). The review investigated the administration rates of anti-osteoporosis medication, refracture, and mortality; activities of daily living; mobility; and health-related quality of life. METHODS: A retrospective review was performed of the records of Si-FLS patients given FHF treatment between June 2016 and October 2018. The outcomes were evaluated at 3 time points: before discharge, and 1 and 3 years after treatment. RESULTS: The study enrolled 489 patients (average age, 78). The mortality and refracture rates at 1 year after hip fracture were 13.9% and 1.6%, respectively. At the 3-year follow-up, both rates were higher (20.4% and 5.7%, respectively). The Barthel Index and EuroQoL Visual Analogue Scale had risen to a plateau at the 1-year follow-up and remained stable to the 3-year follow-up. One year after treatment, approximately 60% of the patients could ambulate outdoors, and the proportion remained steady until the 3-year follow-up. There was no difference in the 1- and 3-year follow-up anti-osteoporosis medication administration rates (approximately 40%). CONCLUSIONS: This study confirms the benefits of having a multidisciplinary FLS care team to manage older people with FHF. An FLS improves the care of patients with FHF and the social support of caregivers and relatives. The FLS maintained the functional outcomes of the patients through 3 years of postfracture treatment.

Dissonance in views between healthcare professionals and adults with a spinal cord injury with their understanding and interpretation of exercise intensity for exercise prescription.

Objectives: To evaluate the difference between healthcare professionals (HCPs) and adults with spinal cord injury (SCI) in Asia regarding knowledge and interpretation of 'exercise intensity' for aerobic exercise prescription. Methods and study design: A survey was distributed to practising HCP and adults with SCI. It was completed in participants' local language on topics related to the importance of exercise frequency, intensity, time and type; methods for monitoring and terms related to exercise intensity prescription. χ2 analysis was used to detect differences in HCP or those with SCI. Results: 121 HCP and 107 adults with an SCI ≥1 years (C1-L4) participated. Responses revealed 61% of all HCP ranked 'intensity' being most important whereas only 38% respondents from the SCI group ranked it as high importance (p=0.008). For those with SCI, 'frequency' was most important (61%) which was significantly higher than the 45% selected by HCPs (p=0.030). Of the 228 respondents on average only 34% believed that the terms, 'moderate' and 'vigorous' provided enough information for aerobic exercise intensity prescription. HCP most often used HR methods compared with the SCI group (90% vs 54%; p<0.01). Both groups frequently used the subjective measures of exercise intensity, for example, Ratings of Perceived Exertion (8%3 vs 76% for HCP and SCI), HCP also frequently used speed (81%) and SCI also frequently relied on 'the affect' or feelings while exercising (69%). Conclusions: These differences must be considered when developing clinical-practice exercise guidelines and health referral educational pathways for adults with SCI in Asia.

Summary of the Thai Osteoporosis Foundation (TOPF) Clinical Practice Guideline on the diagnosis and management of osteoporosis 2021.

Objectives: The Thai Osteoporosis Foundation (TOPF) is an academic organization that consists of a multidisciplinary group of healthcare professionals managing osteoporosis. The first clinical practice guideline for diagnosing and managing osteoporosis in Thailand was published by the TOPF in 2010, then updated in 2016 and 2021. This paper presents important updates of the guideline for the diagnosis and management of osteoporosis in Thailand. Methods: A panel of experts in the field of osteoporosis was recruited by the TOPF to review and update the TOPF position statement from 2016. Evidence was searched using the MEDLINE database through PubMed. Primary writers submitted their first drafts, which were reviewed, discussed, and integrated into the final document. Recommendations are based on reviews of the clinical evidence and experts' opinions. The recommendations are classified using the Grading of Recommendations, Assessment, Development, and Evaluation classification system. Results: The updated guideline comprises 90 recommendations divided into 12 main topics. This paper summarizes the recommendations focused on 4 main topics: the diagnosis and evaluation of osteoporosis, fracture risk assessment and indications for bone mineral density measurement, fracture risk categorization, management according to fracture risk, and pharmacological management of osteoporosis. Conclusions: This updated clinical practice guideline is a practical tool to assist healthcare professionals in diagnosing, evaluating, and managing osteoporosis in Thailand.

An in-depth analysis of original antigenic sin in dengue virus infection.

The evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simple in vitro enzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.

Construction and Evaluation of Osteochondral-Like Tissue Using Chondrocyte Sheet and Cancellous Bone.

The manipulation of human chondrocyte sheets in target areas frequently results in their tearing because they are thin and fragile. In this study, human cancellous bones were used as a supporting material to create chondrocyte sheet-cancellous bone tissues, and their properties were evaluated. Using cell sheet technology, human chondrocytes were constructed into triple-layered chondrocyte sheets that displayed chondrogenic properties. After transferring the chondrocyte sheets onto cancellous bones, the top area of the chondrocyte sheet-cancellous bone tissues exhibited a smooth surface topography without cell sheet floating within 7 days of culture. The immunofluorescence staining of collagen type II (COL2A1) and fibronectin (FN1) was also performed and examined. Using the shotgun proteomic analysis, the proteins associated with cell adhesion, extracellular matrix (ECM) organization, cell-substrate junction assembly, and cell adhesion mediated by integrin were observed in the chondrocyte sheets, cancellous bones, and chondrocyte sheet-cancellous bone tissues. Three integrin members, including integrin ß4 (ITGB4), ITGB6, and ITGB8, were found in the chondrocyte sheets. Only ITGB8 was found in the chondrocyte sheets and chondrocyte sheet-cancellous bone tissues. During 48 h, the mean velocity of the individual cell migration was low, which did not affect the structure and chondrogenic properties of the chondrocyte sheets. Staining of the filamentous actin (F-actin) cytoskeleton in the migratory cells also provided a better understanding of the dynamic communication between the cell cytoskeleton and adhesion molecules through ITGB8, which may play a key role in the attachment of the chondrocyte sheets and the synthesis of the cartilage ECM. Therefore, we suggest that cancellous bone could be used as a supporting material to construct chondrocyte sheet-cancellous bone tissues for potential treatment of osteochondral lesions. Impact Statement We proposed a method to construct an osteochondral-like tissue by placing human chondrocyte sheets onto cancellous bone. The stationary chondrocyte sheets and the low mean velocity of the individual cell migration on the cancellous bone with the expression of COL2A1 indicated that the cancellous bone served as an appropriate supporting material. Moreover, the cellular mechanism for the adhesion of the chondrocyte sheets on the cancellous bone based on ITGB8-mediated adhesion through the rearrangement of filamentous actin provided a better understanding to improve the construction of osteochondral-like tissues, and to predict the repair mechanism in osteoarthritis therapy.

Evaluation of osteochondral-like tissues using human freeze-dried cancellous bone and chondrocyte sheets to treat osteochondral defects in rabbits.

Human freeze-dried cancellous bone combined with human chondrocyte sheets have recently been used to construct an osteochondral-like tissue, which resembled a cartilage layer on a subchondral bone layer. Nevertheless, the efficacy of these human tissues in a xenogeneic model has been rarely reported. Therefore, this study aimed to evaluate the potential of human freeze-dried cancellous bones combined with human chondrocyte sheets for the treatment of osteochondral defects in rabbits. The key roles of the extracellular matrix (ECM) and released cytokines in these tissues in osteochondral repair were also assessed. Triple-layered chondrocyte sheets were constructed using a temperature-responsive culture surface. Then, they were placed onto cancellous bone to form chondrocyte sheet-cancellous bone tissues. The immunostaining of collagen type II (COL2) and the proteomic analysis of the human tissues were carried out before the transplantation. In our in vitro study, the triple-layered chondrocyte sheets adhered well on the cancellous bone, and the COL2 expression was apparent throughout the tissue structures. From the proteomic analysis results, it was found that the major function of the secreted proteins found in these tissues was protein binding. The distinct pathways were focal adhesion and the ECM-receptor interaction pathways. Among the highly expressed proteins, laminin-alpha 5 (LAMA5) and fibronectin (FN) not only played roles in the protein binding and ECM-receptor interaction, but also were involved in the cytokine-mediated signaling pathway. At 12 weeks after xenogeneic transplantation, compared to the control group, the defects treated with the chondrocyte sheets showed more hyaline-like cartilage tissue, as indicated by the abundance of safranin-O and COL2 with a partial collagen type I (COL1) expression. At 4, 8, and 12 weeks, compared to the defects treated with the cancellous bone, the staining of safranin-O and COL2 was more apparent in the defects treated with the chondrocyte sheet-cancellous bone tissues. Therefore, the human chondrocyte sheets and chondrocyte sheet-cancellous bone tissues provide a potential treatment for rabbit femoral condyle defect. LAMA5 and FN found in these human xenografts and their culture media might play key roles in the ECM-receptor interaction and might be involved in the cytokine-mediated signaling pathway during tissue repair.