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) β-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 β-chain complementarity-determining region (CDR2β). 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 CDR2β loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs

PREVALENCE OF OSTEOPOROSIS AND HYPOVITAMINOSIS D AT SIRIRAJ METABOLIC BONE DISEASE CLINIC

<div><p>ABSTRACT Objective: To identify the prevalence of osteoporosis and hypovitaminosis D among patients at the Siriraj Metabolic Bone Disease (MBD) Clinic, and to compare initial vitamin D levels in patients with and without a history of fragility fractures. Methods: Medical records of patients who attended our MBD clinic between 2012 and 2015 were retrospectively reviewed. Patient baseline demographic, clinical, bone mineral density (BMD), and laboratory data were collected and analyzed. Osteoporosis was diagnosed when patients had a BMD T-score <-2.5 or presented with fragility fractures. Results: There were 761 patients included in this study. Of these, 627 patients (82.4%) were diagnosed with osteoporosis and 508 patients (66.8%) had fragility fractures. Baseline serum 25-hydroxyvitamin D (25(OH)D) levels were available in 685 patients. Of these, 391 patients (57.1%) were diagnosed with hypovitaminosis D. When evaluated only in patients with fragility fractures, the average initial 25(OH)D level was 28.2±11.6 ng/mL, and the prevalence of hypovitaminosis D was 57.6%. Conclusion: A high prevalence of osteoporosis and hypovitaminosis D was found among patients at our clinic; two-thirds of patients had a history of fragility fractures, and no difference in initial 25(OH)D levels was seen between patients with and without fragility fractures. Level of Evidence III, Retrospective Study .</p></div

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

Abstract 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)

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

Abstract 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

Additional file 1: of Maintenance of human chondrogenic phenotype on a dendrimer-immobilized surface for an application of cell sheet engineering

Schematic illustrations showing the possible signals involved in the one-step process of expansion and differentiation for human chondrocytes on either the G5 or PS surface for chondrocyte sheet construction. (TIFF 20776 kb

Dissonance in views between health care 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 health care professionals (HCP) 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. Chi-square analysis was used to detect differences in HCP or those with SCI. Results: 121 HCP and 107 adults with a 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 to the SCI group (90 vs. 54%; P Conclusions: These differences must be considered when developing clinical-practice exercise guidelines and health referral educational pathways for adults with SCI in Asia.</p

Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group.

SummaryThe IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures.IntroductionThe burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture.MethodsThe approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation’s Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized.Results and ConclusionThe report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program

Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope.

Cytotoxic T lymphocytes (CTLs) are critical for the control of human immunodeficiency virus, but containment of virus replication can be undermined by mutations in CTL epitopes that lead to virus escape. We analyzed the evolution in vivo of an immunodominant, HLA-A2-restricted CTL epitope and found two principal, diametrically opposed evolutionary pathways that exclusively affect T cell-receptor contact residues. One pathway was characterized by acquisition of CTL escape mutations and the other by selection for wild-type amino acids. The pattern of CTL responses to epitope variants shaped which variant(s) prevailed in the virus population. The pathways notably influenced the amount of plasma virus, as patients with efficient CTL selection had lower plasma viral loads than did patients without efficient selection. Thus, viral escape from CTL responses does not necessarily correlate with disease progression