JD-312 - A novel small molecule that facilitates cartilage repair and alleviates osteoarthritis progression.

Background: The chondrogenic differentiation of mesenchymal stem cells (MSCs) to enhance cartilage repair and regeneration is a promising strategy to alleviate osteoarthritis (OA) progression. Method: The potency of JD-312 in inducing chondrogenic differentiation of MSCs was assessed and verified. The efficacy of JD-312-treated MSCs was evaluated using a Sprague-Dawley rat DMM model. Additionally, the capacity of JD-312 to successfully recruit bone marrow-derived mesenchymal stem cells (BMSCs) for the treatment of OA in vitro was confirmed via intra-articular injection. The repair status of the articular cartilage was analyzed in vivo through histological examination. Result: In this study, we identify JD-312 as a novel non-toxic small molecule that can promote chondrogenic differentiation in human umbilical cord-derived MSCs (hUCMSCs) and human bone marrow MSCS (hBMSCs) in vitro. We also show that transient differentiation of MSCs with JD-312 prior to in vivo administration remarkably improves the regeneration of cartilage and promotes Col2a1 and Acan expression in rat models of DMM, in comparison to kartogenin (KGN) pre-treatment or MSCs alone. Furthermore, direct intra-articular injection of JD-312 in murine model of OA showed reduced loss of articular cartilage and improved pain parameters. Lastly, we identified that the effects of JD-312 are at least in part mediated via upregulation of genes associated with the focal adhesion, PI3K-Akt signaling and the ECM-receptor interaction pathways, and specifically cartilage oligomeric matrix protein (COMP) may play a vital role. Conclusion: Our study demonstrated that JD-312 showed encouraging repair effects for OA in vivo. The translational potential of this article: Together, our findings demonstrate that JD-312 is a promising new therapeutic molecule for cartilage regeneration with clinical potential.

GPRC5B protects osteoarthritis by regulation of autophagy signaling.

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

YBX1-interacting small RNAs and RUNX2 can be blocked in primary bone cancer using CADD522.

Primary bone cancer (PBC) comprises several subtypes each underpinned by distinctive genetic drivers. This driver diversity produces novel morphological features and clinical behaviour that serendipitously makes PBC an excellent metastasis model. Here, we report that some transfer RNA-derived small RNAs termed tRNA fragments (tRFs) perform as a constitutive tumour suppressor mechanism by blunting a potential pro-metastatic protein-RNA interaction. This mechanism is reduced in PBC progression with a gradual loss of tRNAGlyTCC cleavage into 5' end tRF-GlyTCC when comparing low-grade, intermediate-grade and high-grade patient tumours. We detected recurrent activation of miR-140 leading to upregulated RUNX2 expression in high-grade patient tumours. Both tRF-GlyTCC and RUNX2 share a sequence motif in their 3' ends that matches the YBX1 recognition site known to stabilise pro-metastatic mRNAs. Investigating some aspects of this interaction network, gain- and loss-of-function experiments using small RNA mimics and antisense LNAs, respectively, showed that ectopic tRF-GlyTCC reduced RUNX2 expression and dispersed 3D micromass architecture in vitro. iCLIP sequencing revealed YBX1 physical binding to the 3' UTR of RUNX2. The interaction between YBX1, tRF-GlyTCC and RUNX2 led to the development of the RUNX2 inhibitor CADD522 as a PBC treatment. CADD522 assessment in vitro revealed significant effects on PBC cell behaviour. In xenograft mouse models, CADD522 as a single agent without surgery significantly reduced tumour volume, increased overall and metastasis-free survival and reduced cancer-induced bone disease. Our results provide insight into PBC molecular abnormalities that have led to the identification of new targets and a new therapeutic.

The strategy and clinical relevance of in vitro models of MAP resistance in osteosarcoma: a systematic review.

Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate, adriamycin (doxorubicin) and platinum (cisplatin). Due to the rarity of OS, the generation of relevant cell models as tools for drug discovery is paramount to tackling this issue. Four literature databases were systematically searched using pre-determined search terms to identify MAP resistant OS cell lines and patients. Drug exposure strategies used to develop cell models of resistance and the impact of these on the differential expression of resistance associated genes, proteins and non-coding RNAs are reported. A comparison to clinical studies in relation to chemotherapy response, relapse and metastasis was then made. The search retrieved 1891 papers of which 52 were relevant. Commonly, cell lines were derived from Caucasian patients with epithelial or fibroblastic subtypes. The strategy for model development varied with most opting for continuous over pulsed chemotherapy exposure. A diverse resistance level was observed between models (2.2-338 fold) with 63% of models exceeding clinically reported resistance levels which may affect the expression of chemoresistance factors. In vitro p-glycoprotein overexpression is a key resistance mechanism; however, from the available literature to date this does not translate to innate resistance in patients. The selection of models with a lower fold resistance may better reflect the clinical situation. A comparison of standardised strategies in models and variants should be performed to determine their impact on resistance markers. Clinical studies are required to determine the impact of resistance markers identified in vitro in poor responders to MAP treatment, specifically with respect to innate and acquired resistance. A shift from seeking disputed and undruggable mechanisms to clinically relevant resistance mechanisms may identify key resistance markers that can be targeted for patient benefit after a 40-year wait.

GPRC5B protects osteoarthritis by regulation of autophagy signaling

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

A Systematic Review of the Expression, Signalling and Function of P2 Receptors in Primary Bone Cancer.

Primary bone cancers are rare malignant diseases with significant morbidity and mortality. The treatment regimen relies on a combination of surgery (often involving amputation), chemotherapy and radiotherapy with outcomes dependent on localization of the tumour, grade, size and response to chemotherapy. Both treatment options and survival statistics have remained constant over the past 40 years and alternative therapies need to be explored. Purinergic signalling involving the interaction of extracellular nucleotides with P2 receptors has been investigated in numerous cancers with activation or inhibition a topic of debate. To assess whether purinergic signalling could be a viable target in primary bone cancer a systematic review for relevant primary literature published in PubMed, MEDLINE and Web of Science was performed. Search terms were formulated around three separate distinct topics; expression of P2 receptors in primary bone cancer models, P2 receptor signalling pathways involved and the functional consequences of P2 receptor signalling. Searching identified 30 primary articles after screening and eligibility assessments. This review highlights the diverse expression, signalling pathways and functional roles associated with different P2 receptors in primary bone cancers and provides a systematic summary of which P2 receptors are exciting targets to treat primary bone cancer and its associated symptoms.

Sepsis and Total Joint Arthroplasty.

The number of annual total joint arthroplasties (TJA) is increasing. Periprosthetic joint infections (PJI) occur when there is infection involving the prosthesis and surrounding tissue, which has the potential to develop into sepsis if left untreated. Sepsis in patients who have undergone TJA is life threatening and requires urgent treatment. If sepsis is due to PJI, the focus should be on early intravenous antibiotics with aspiration as soon as possible to diagnose the infection. Patients who develop sepsis after surgery for PJI are particularly at high risk for mortality and need to be treated in the intensive care unit.

A Study on the Knowledge, Awareness, Perceptions and Behaviour (KAPB) of Students of the University of the West Indies, St. Augustine (UWI-STA) Towards Climate Change and its Impact on Human Health

Climate change (CC) is defined as long-term weather changes in the Earth's climate. CC has been linked to increased global temperatures. This affects human health both directly and indirectly: Directly, via increased risk of cardiovascular, respiratory, and vector-borne diseases. Indirectly, via reduced agricultural crop yields and accessibility to healthcare due to extreme weather events. Studies show that spreading awareness on the health impacts of CC encourages motivation towards mitigation (1). Early awareness of climate change and its health impacts is necessary for future generations to mitigate its effects.

Erratum to "Combined Balloon-, Plug- and Coil-assisted Retrograde Transvenous Obliteration of Multiple Portosystemic Shunts to Treat Recurrent Hepatic Encephalopathy: A Case Report" [J Clin Exp Hepatol 10 (2020) 402-406].

[This corrects the article DOI: 10.1016/j.jceh.2019.12.002.].

Ability of SARC-F to Find Probable Sarcopenia Cases in Older Adults.

BACKGROUND/OBJECTIVE: In 2018 EWGSOP2 has suggested low muscle strength as the primary parameter of sarcopenia. The consensus has recommended SARC-F questionnaire as a screening test to find cases with low muscle strength which has been designated as probable sarcopenia. We aimed to study the ability of SARC-F to find probable sarcopenia cases in older patients. DESIGN: Retrospective, cross-sectional. SETTING: Istanbul University Istanbul Faculty of Medicine. PARTICIPANTS: A total of 456 older adults (71.1% female, mean age: 74.6±6.6 years). MEASUREMENTS: We diagnosed probable sarcopenia by EWGSOP 2 criteria, i.e., presence of low handgrip strength (HGS). SARC-F questionnaire was performed by all participants. We used a receiver operating characteristics curve to obtain SARC-F cut-off values to detect probable sarcopenia and calculated the area under the curve and 95% confidence interval (CI). RESULTS: We included 456 participants (71.1% female; mean age: 74.6 ± 6.6 years). Probable sarcopenia was present in 58 (12.7%). SARC-F cut-off ≥ 2 presented the best balance between sensitivity and specificity (sensitivity: 64.9% vs specificity: 67.9%) to detect probable sarcopenia [the area under the receiver operating characteristics curve (AUC) = 0.710; 95% Cl: 0.660-0.752, p< 0.001]. SARC-F with a cut-off point ≥ 1 had sensitivity 84.2% and specificity 40.5% and SARC-F ≥ 4 had high specificity 88.2% with 40.3% sensitivity. CONCLUSION: SARC-F is a good screening tool for sarcopenia in practice. Our findings suggest SARC-F ≥ 1 cut-off point to be used as the probable sarcopenia screening tool regarding its high sensitivity. Consequently, SARC-F ≥ 4 cut-off is better to be used if one prefers to exclude probable sarcopenia.

Vitamin D status in children with intestinal failure who have achieved enteral autonomy.

BACKGROUND: Vitamin D deficiency is highly prevalent in children with intestinal failure (IF) who receive parenteral nutrition (PN), but data on vitamin D status after achieving enteral autonomy (EA) are limited. We aimed to evaluate the prevalence of vitamin D deficiency in this population while exploring clinical variables that may be associated with its development. METHODS: A retrospective review was performed on 29 children with IF who had achieved EA. Deficiency was defined as a mean serum 25-hydroxyvitamin D <30 ng/ml. DATA RESULTS: Sixty-six percent of children had at least one deficient level during the study period, with 38% being deficient based on the mean vitamin D levels. Eighty-four percent had radiologic evidence of osteopenia. Compared with the sufficient group (n=18), the deficient group (n=11) received higher daily mean vitamin D doses (2246 vs 920 IU; P=.02), had shorter remnant small-bowel length (53.8 vs 82.1 cm; P=.03), and were PN dependent for a longer duration (1.3 vs 0.58 years; P=.01). Univariate analyses revealed longer remnant gut length (odds ratio [OR] = 1.03; P=.04) and shorter duration of PN (OR = 0.26; P=.04) to be significantly associated with sufficient vitamin D status. CONCLUSION: Vitamin D deficiency and osteopenia are highly prevalent in pediatric patients with a history of IF who have achieved EA, despite enteral supplementation with higher than standard doses. Shorter remnant small-bowel length and longer duration of PN were associated with vitamin D deficiency. These findings emphasize the importance of prolonged surveillance and highlight the need for alternate dosing regimens.

Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses.

Systemic cobalt (Co) and chromium (Cr) concentrations may be elevated in patients with metal joint replacement prostheses. Several studies have highlighted the detrimental effects of this exposure on bone cells in vitro, but the underlying mechanisms remain unclear. In this study, we use whole-genome microarrays to comprehensively assess gene expression in primary human osteoblasts, osteoclast precursors and mature resorbing osteoclasts following exposure to clinically relevant circulating versus local periprosthetic tissue concentrations of Co2+ and Cr3+ ions and CoCr nanoparticles. We also describe the gene expression response in osteoblasts on routinely used prosthesis surfaces in the presence of metal exposure. Our results suggest that systemic levels of metal exposure have no effect on osteoblasts, and primarily inhibit osteoclast differentiation and function via altering the focal adhesion and extracellular matrix interaction pathways. In contrast, periprosthetic levels of metal exposure inhibit both osteoblast and osteoclast activity by altering HIF-1α signaling and endocytic/cytoskeletal genes respectively, as well as increasing inflammatory signaling with mechanistic implications for adverse reactions to metal debris. Furthermore, we identify gene clusters and KEGG pathways for which the expression correlates with increasing Co2+:Cr3+ concentrations, and has the potential to serve as early markers of metal toxicity. Finally, our study provides a molecular basis for the improved clinical outcomes for hydroxyapatite-coated prostheses that elicit a pro-survival osteogenic gene signature compared to grit-blasted and plasma-sprayed titanium-coated surfaces in the presence of metal exposure.

Success of Simpler Modified Fried Frailty Scale to Predict Mortality among Nursing Home Residents.

OBJECTIVE: Fried frailty scale is the very first and most commonly used assessment scale for an operational definition of frailty with its demonstrated success as a predictor of mobility limitations and mortality. However, it is impractical for use in routine clinical practice. We aimed to study whether a simpler modified Fried frailty scale could predict mortality among nursing home residents. DESIGN: Retrospective longitudinal follow-up study. SETTING: Nursing home. Baseline evaluation was performed in 2009. Mortality was assessed after 4 year. PARTICIPANTS: Two hundred-twenty-four participants were included. MEASUREMENTS: Residents were assessed for demographic characteristics, falls, dementia, the number of regular medications and chronic diseases, body composition by bioimpedance analysis, basic and instrumental activities of daily living besides frailty status by a modified Fried frailty scale. The residents were assessed for mortality after a median follow-up time of 46 months. The association of frailty with mortality was analyzed by the Kaplan-Meier Log-rank test and multivariate Cox Regression analysis. RESULTS: Mortality occurred in 90 (40.2%) of the residents. In multivariate analysis, frailty was an independent predictor of death (Hazzard ratio= 1.4, 95% confidence interval= 1.03-2.6, p=0.03) when adjusted by age, sex, presence of malnutrition, low muscle mass, number of chronic diseases and regular medications. CONCLUSION: Our results suggest that the simpler modified Fried frailty scale can be used as a screening tool for frailty in everyday practice as a tool to identify risky patients for mortality. Future reports studying its role in predicting other adverse outcomes associated with frailty are needed.

Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis.

OBJECTIVES: To determine how gene expression profiles in osteoarthritis joint tissues relate to patient phenotypes and whether molecular subtypes can be reproducibly captured by a molecular classification algorithm. METHODS: We analysed RNA sequencing data from cartilage and synovium in 113 osteoarthritis patients, applying unsupervised clustering and Multi-Omics Factor Analysis to characterise transcriptional profiles. We tested the association of the molecularly defined patient subgroups with clinical characteristics from electronic health records. RESULTS: We detected two patient subgroups in low-grade cartilage (showing no/minimal degeneration, cartilage normal/softening only), with differences associated with inflammation, extracellular matrix-related and cell adhesion pathways. The high-inflammation subgroup was associated with female sex (OR 4.12, p=0.0024) and prescription of proton pump inhibitors (OR 4.21, p=0.0040). We identified two independent patient subgroupings in osteoarthritis synovium: one related to inflammation and the other to extracellular matrix and cell adhesion processes. A seven-gene classifier including MMP13, APOD, MMP2, MMP1, CYTL1, IL6 and C15orf48 recapitulated the main axis of molecular heterogeneity in low-grade knee osteoarthritis cartilage (correlation ρ=-0.88, p<10-10) and was reproducible in an independent patient cohort (ρ=-0.85, p<10-10). CONCLUSIONS: These data support the reproducible stratification of osteoarthritis patients by molecular subtype and the exploration of new avenues for tailored treatments.

Prevalence and Associates of Fear of Falling among Community-Dwelling Older Adults.

OBJECTIVES: We aimed to study the prevalence of fear of falling (FOF), and its association with physical performance, functionality, frailty, sarcopenia, and a variety of geriatric syndromes including cognitive impairment, depression, quality of life and hearing. DESIGN: Retrospective, cross-sectional study. SETTING: Community-dwelling older adults applied to the geriatric outpatient clinic of a university hospital. PARTICIPANTS: A total of 1021community-dwelling older adults >= 60 years of age applying to the geriatric outpatient clinic of a university hospital. MEASUREMENTS: We screened for falls and FOF by single close-ended questions. We performed screening and assessment of probable sarcopenia by SARC-F test and handgrip strength evaluation according to EWGSOP2. We used timed up and go test (TUG), usual gait speed (UGS) for physical performance, and Katz- activities of daily living (ADL) and Lawton-Brody instrumental activities of daily living (IADL) for functional evaluation. We screened anxiety with the Generalized Anxiety Disorder-7 scale. RESULTS: The prevalence of FOF was 44.6% and falls, 37.7%. Prevalence of FOF in sarcopenia screening positive participants was 30.1%; in probable sarcopenic (35/20 kg) participants, 43.9%; in those with undernutrition, 45.7%; in fallers, 51.1%; in females, 80.4%; and in prefrail/frail was 74.7% Multivariate regression analyses revealed that female sex (OR=4.1, 95%CI= 2.0-8.4, p<0.001), anxiety (OR=2.7, 95%CI= 1.1-6.5, p=0.03) and ADL limitation (OR=2.5, 95%CI= 1.03-6.3, p=0.04) were independent associates of FOF. CONCLUSION: FOF accompanied by fall experience or not is prevalent in community-dwelling older adults. It is associated with anxiety and ADL limitations apart from the female sex.

SARC-F Questionnaire Detects Frailty in Older Adults.

BACKGROUND/OBJECTIVES: The physical phenotype of frailty, described by Fried et al., shows significant overlap with sarcopenia. EWGSOP2 recommends the SARC-F questionnaire to screen for sarcopenia. Considering common features between both conditions, we aimed to investigate whether the SARC-F questionnaire could also be a valid and reliable tool to screen or evaluate frailty. DESIGN: Retrospective, cross-sectional. SETTING: Istanbul University Istanbul Faculty of Medicine. PARTICIPANTS: A total of 447 older adults (70.7% female, mean age: 74.5±6.6 years). MEASUREMENTS: Frailty was assessed by the modified Fried scale. SARC-F questionnaire was performed by all participants. We used a receiver operating characteristics curve to obtain SARC-F cut-off values to detect frailty, and calculated the area under the curve and 95% confidence interval. RESULTS: There were 93 (20.8%) older adults with frailty according to the modified Fried scale. SARC-F cut-off ≥1 had 91.4% sensitivity and 44.9% specificity. SARC-F cut-off ≥2 presented the best balance between sensitivity and specificity (sensitivity: 74.1% vs. specificity: 73.7%) to identify frailty (area under curve: 0.807; 95% confidence interval: 0.76-0.84, p<0.001). SARC-F ≥4 had high specificity of 92.6% with a sensitivity of 46.2%. CONCLUSION: We suggest that SARC-F ≥1 point can be used to screen for frailty with high sensitivity, and SARC-F ≥4 can be used to diagnose frailty with high specificity. SARC-F may be used to evaluate frailty in usual geriatric practice.

A molecular quantitative trait locus map for osteoarthritis.

Osteoarthritis causes pain and functional disability for over 500 million people worldwide. To develop disease-stratifying tools and modifying therapies, we need a better understanding of the molecular basis of the disease in relevant tissue and cell types. Here, we study primary cartilage and synovium from 115 patients with osteoarthritis to construct a deep molecular signature map of the disease. By integrating genetics with transcriptomics and proteomics, we discover molecular trait loci in each tissue type and omics level, identify likely effector genes for osteoarthritis-associated genetic signals and highlight high-value targets for drug development and repurposing. These findings provide insights into disease aetiopathology, and offer translational opportunities in response to the global clinical challenge of osteoarthritis.

Progressive Myoclonic Epilepsy'-like presentation of Cerebrotendinous Xanthomatosis in an Indian Family with A Novel C.646+1G>A Splice Site Mutation.

Cerebrotendinous Xanthomatosis (CTX) is a rare autosomal-recessive inborn disorder of bile acid metabolism due to mutations in the CYP27A1 gene. It presents with a diverse range of neurological and non-neurological symptoms. We present a case of CTX with a progressive myoclonic epilepsy (PME) like phenotype and a family history of CTX. The proband had a generalized epilepsy with prominent myoclonus. He also had intellectual decline, ataxia, bipyramidal dysfunction and peripheral neuropathy. The younger sibling had a milder generalized epilepsy without myoclonus along with behavioral issues, ataxia, neuropathy, and prominent tendon xanthomas. Both the siblings had developmental cataracts. MRI Brain of both had dentate hyperintensities with cerebellar atrophy. The proband's EEG showed severe background slowing with multifocal interictal discharges. Targeted gene of analysis proband revealed a novel homozygous 5' splice site variation in intron 3 of the CYP27A1 gene. We present a novel phenotype and genotype of CTX presenting with a syndrome of myoclonic epilepsy. This is the first PME-like presentation of CTX to the best of our knowledge. CTX may present with a PME-like clinical phenotype and should be considered as a treatable cause within the differential diagnostic evluation of syndromic epilepsies involving an atypical familial myoclonic epilepsy.

Power Versus Sarcopenia: Associations with Functionality and Physical Performance Measures.

BACKGROUND/OBJECTIVE: While assessment of sarcopenia has drawn much attention, assessment of low muscle power has not been studied widely. This is, to a large extend, due to a more difficult assessment of power in practice. We aimed to compare the associations of low power and sarcopenia with functional and performance measures. MATERIAL AND METHODS: We designed a retrospective and cross-sectional study. Community-dwelling outpatient older adults applied to a university hospital between 2012 and 2020 composed the population. We estimated body composition by bioimpedance analysis. Other measures were handgrip strength, timed-up-and-go-test (TUG), usual gait speed (UGS), activities of daily living (ADL) and instrumental activities of daily living (IADL) tests. We assessed muscle power by a practical equation using a 5-repetition sit-to-stand power test. We adjusted the power by body weight and defined low muscle power threshold as the lowest sex-specific tertile. We noted demographic characteristics, number of medications, and diseases. We defined sarcopenia by EWGSOP2 definition. RESULTS: Cut points for low relative muscle power were <2.684 and <1.962 W/kg in males and females, respectively. Low muscle power was related with both measures of disability (impaired ADL and IADL) (OR=2.4, 95% CI= 1.4-4.0, p=0.001; OR=2.4, 95% CI= 1.4-4.1, p=0.001; respectively). Low muscle strength (i.e. probable sarcopenia) was only related with disability in IADL (OR=3.6, 95% CI= 1.6-8.; p=0.002); confirmed sarcopenia was related with neither measures. Low muscle power was not related with impaired TUG (p=1) but with impaired UGS (OR=6.6, 95% CI= 3.6-11.0; p<0.001). Probable sarcopenia was not related with impaired TUG (p=0.08) but with impaired UGS (OR=2.4, 95% CI= 1.1-5.3; p=0.03) and confirmed sarcopenia was related with neither measures (p=1, p=0.3; respectively). CONCLUSION: Low muscle power detected by simple and practically applicable CSST (Chair Sit To-Stand Test) power test was a convenient measure associated with functional and performance measures. It was related to functionality and performance measures more than sarcopenia. Future longitudinal studies are needed to examine whether it predicts future impairment in ADL, IADL, and performance measures.

Strategies for Articular Cartilage Repair and Regeneration.

Articular cartilage is an avascular tissue, with limited ability to repair and self-renew. Defects in articular cartilage can induce debilitating degenerative joint diseases such as osteoarthritis. Currently, clinical treatments have limited ability to repair, for they often result in the formation of mechanically inferior cartilage. In this review, we discuss the factors that affect cartilage homeostasis and function, and describe the emerging regenerative approaches that are informing the future treatment options.