Corrigendum: miR-31-3p functions as a tumor suppressor by directly targeting GABBR2 in prostate cancer.

[This corrects the article DOI: 10.3389/fonc.2022.945057.].

3D cotton-type anisotropic biomimetic scaffold with low fiber motion electrospun via a sharply inclined array collector for induced osteogenesis.

Electrospinning is an effective method to fabricate fibrous scaffolds that mimic the ECM of bone tissue on a nano- to macro-scale. However, a limitation of electrospun fibrous scaffolds for bone tissue engineering is the structure formed by densely compacted fibers, which significantly impedes cell infiltration and tissue ingrowth. To address this problem, several researchers have developed numerous techniques for fabricating 3D fibrous scaffolds with customized topography and pore size. Despite the success in developing various 3D electrospun scaffolds based on fiber repulsion, the lack of contact points between fibers in those scaffolds has been shown to hinder cell attachment, migration, proliferation, and differentiation due to excessive movement of the fibers. In this article, we introduce a Dianthus caryophyllus-inspired scaffold fabricated using SIAC-PE, a modified collector under specific viscosity conditions of PCL/LA solution. The developed scaffold mimicking the structural similarities of the nature-inspired design presented enhanced cell proliferation, infiltration, and increased expression of bone-related factors by reducing fiber movements, presenting high space interconnection, high porosity, and controlled fiber topography.

Trends in Incidence and Drug Prescriptions for Croup in Children Under 5 Years of Age: A 2002-2019 Population-Based Study.

BACKGROUND: Tracking national croup trends can provide important insights for childhood health management. This study aimed to analyze the incidence and drug prescription trends in Korean children over a two-decade period. METHODS: This population-based study encompassed 479,783 children aged < 5 years from 2002-2019, utilizing the National Health Insurance Service-National Sample Cohort. We identified participants with a primary croup diagnosis who were admitted to or visited the emergency room. Age-specific and age-adjusted incidence rates/10,000 person-years were calculated. We assessed using orthogonal polynomial contrasts and stratified by various factors (sex, age, residential area, economic status, comorbidities, and healthcare facility types). We observed changes in the use of five medications: inhaled steroids, systemic steroids, inhaled epinephrine, antibiotics, and short-acting bronchodilators. Generalized binomial logistic regression was used to analyze factors influencing prescription strategies. RESULTS: In 2002, the croup-related visits were 16.1/10,000 person-years, increasing to 98.3 in 2019 (P for trend < 0.001). This trend persisted, regardless of age, sex, region, and economic status. Children with comorbid atopic dermatitis or asthma maintained consistent croup rates, while those without comorbidities increased. Treatment trends showed decreasing antibiotic (73-47%) and oxygen use (21.3-3.4%), with increasing nebulized epinephrine (9.3-41.5%) and multiple drug prescriptions (67.8-80.3%). Primary care centers exhibited a greater increase in prescription usage and hospitalization duration than did tertiary healthcare institutions. CONCLUSION: Over the past two decades, croup incidence has risen, accompanied by increased epinephrine use and decreased antibiotic prescriptions. Longer hospitalization and higher medication use were mainly observed in primary care facilities.

Cutaneous nerve distribution around first extensor compartment of the wrist: Clinical implications for ultrasound-guided injections.

Purpose: To evaluate the course of the cutaneous nerve regarding the first extensor compartment to determine whether the dorsal or volar approach is safer for local injection into the first extensor compartment guided by ultrasound. Methods: We dissected the radial side of the wrists from 28 cadavers (52 wrists). Four-points along the imaginary line were set: the styloid process and 1 cm, 2 cm, and 3 cm proximal to the styloid process. The numbers of superficial radial nerve (SRN) and lateral antebrachial cutaneous nerve (LACN) branches were counted, and distances from the imaginary line at these points and nerve diameters were recorded. Digital images were superimposed to observe overall distribution of cutaneous nerve. Results: There were means of 3.3 SRN and 0.9 LACN branches observed in each wrist. The mean number of both SRN and LACN branches was 2.3 on the dorsal side and 1.9 on the volar side. The superimposed images indicated that both the dorsal and volar sides comprised abundant cutaneous nerves and that their paths varied markedly between patients. However, we observed that larger nerves with meaningful diameters were more abundant on the dorsal than the volar side. Conclusion: There were similar numbers of cutaneous nerves on both the dorsal and volar sides; however, we observed greater abundance of thicker cutaneous nerves on the dorsal side, and these were closer to the reference line than on the volar side. This anatomical study suggests that the risk imposed to cutaneous nerves would therefore be reduced when injection on the volar side.

Psoas muscle area is associated with prognosis in elderly patients with hip fracture.

INTRODUCTION: Sarcopenia is a key predictor of prognosis in patients with hip fractures. This study utilized computed tomography (CT) scan (1) to determine the association between psoas muscle cross-sectional area (CSA) and mortality, along with other muscles, and (2) to confirm the correlation between muscle CSA and appendicular lean mass (ALM) measured using DXA in elderly patients with hip fracture. MATERIALS AND METHODS: Patients who were aged ≥ 50 years and underwent surgical treatment for hip fracture were eligible for this study. After a series of exclusion criteria, 217 female patients were included. Patient data, including clinical characteristics, such as body mass index (BMI), CSA, and ALM, were retrospectively collected. The Kaplan-Meier survival method and Cox proportional hazards regression analysis were used for the statistical analyses. The correlation between CSA/BMI and ALM was also assessed. RESULTS: Patients in the lowest quartile of psoas muscle CSA/BMI had shorter survival times than those in the other quartiles. When the Cox proportional hazards regression analysis was adjusted for multiple variables, the lowest quartile of the CSA/BMI of the psoas was a risk factor for mortality. The CSA/BMI of the psoas showed the highest correlation coefficient. The CSA/BMI ratio of the other muscles showed a moderately positive correlation with ALM. CONCLUSION: The CSA of the psoas is associated with prognosis in elderly patients with hip fractures and shows a moderately positive correlation with ALM. Hence, the CSA of psoas is useful for predicting survival and muscle mass in elderly patients with hip fractures.

Targeting class A GPCRs for hard tissue regeneration.

G protein-coupled receptors (GPCRs) play important roles in various pathogeneses and physiological regulations. Owing to their functional diversity, GPCRs are considered one of the primary pharmaceutical targets. However, drugs targeting GPCRs have not been developed yet to regenerate hard tissues such as teeth and bones. Mesenchymal stromal cells (MSCs) have high proliferation and multi-lineage differentiation potential, which are essential for hard tissue regeneration. Here, we present a strategy for targeting class A GPCRs for hard tissue regeneration by promoting the differentiation of endogenous MSCs into osteogenic and odontogenic progenitor cells. Through in vitro screening targeted at class A GPCRs, we identified six target receptors (LPAR1, F2R, F2RL1, F2RL2, S1PR1, and ADORA2A) and candidate drugs with potent biomineralization effects. Through a combination of profiling whole transcriptome and accessible chromatin regions, we identified that p53 acts as a key transcriptional activator of genes that modulate the biomineralization process. Moreover, the therapeutic potential of class A GPCR-targeting drugs was demonstrated in tooth pulpotomy and calvarial defect models. The selected drugs revealed potent regenerative effects in both tooth and bone defects, represented by newly formed highly mineralized regions. Consequently, this study provides translational evidence for a new regenerative strategy for damaged hard tissue.

Trabecular structural difference between the superior and inferior regions of the vertebral body: a cadaveric and clinical study.

Background: Osteoporotic vertebral compression fractures commonly involve the superior vertebral body; however, their associated causes have not yet been clearly established. This study aimed to determine the trabecular structural differences between the superior and inferior regions of the vertebral body using cadaveric and clinical studies. Materials and methods: First, five vertebrae were collected from three human cadavers. The trabecular structures of the superior and inferior regions of each vertebral body were analyzed using micro-computed tomography (micro-CT), finite element analysis (FEA), and biomechanical test. Based on the results of the ex vivo study, we conducted a clinical study. Second, spine CT images were retrospectively collected. Bone volume and Hounsfield unit were analyzed for 192 vertebral bodies. Finally, after sample size calculation based on the pilot study, prospectively, 200 participants underwent dual-energy X-ray absorptiometry (DXA) of the lateral spine. The bone mineral densities (BMDs) of the superior and inferior regions of each lumbar vertebral body were measured. The paired t-test and Wilcoxon signed-rank test were used for the statistical analyses, and p-value < 0.05 was considered significant. Results: Cadaver studies revealed differences between the superior and inferior trabecular bone structures. The bone volume ratio, BMD, and various other trabecular parameters advocated for decreased strength of the superior region. Throughout the biomechanical study, the limitations of the compression force were 3.44 and 4.63 N/m2 for the superior and inferior regions, respectively. In the FEA study, the inferior region had a lower average displacement and higher von Mises stress than the superior region. In the clinical spine CT-based bone volume and BMD study, the bone volume was significantly higher in the inferior region than in the superior region. In the lateral spine DXA, the mean BMD of the superior region of vertebral bodies was significantly lower compared with that of the inferior region. Conclusion: The superior trabecular structure of the lumbar vertebral bodies possesses more biomechanical susceptibility compared with the inferior trabecular structure, confirming its dominant role in causing osteoporotic vertebral fractures. Physicians should also focus on the BMD values of the superior region of the vertebral body using lateral spine DXA to evaluate osteoporosis.

The Effect of the COVID-19 Pandemic on Early Adolescent Fractures in the Republic of Korea.

Background and Objectives: Restrictions on daily activities to slow down the propagation of COVID-19 have changed the epidemiological pattern of pediatric fractures in many countries. However, the effect of the pandemic on pediatric fractures has not been fully studied. In this study, we investigated the impact of COVID-19 on early adolescent fractures in Korea. Materials and methods: We conducted a retrospective follow-up on a nationwide cohort of Korean early adolescents born between 2006 and 2009. The prevalence and incidence of pediatric fractures and the frequency of surgical treatment were compared between two different eras. Results: The prevalence and incidence of fractures during the pandemic have both shown a significant decrease: prevalence reduced from 34,626 to 24,789 (p < 0.001), while incidence decreased from 29,804 to 18,898 (p < 0.001). Considering sex, the shift in fracture prevalence was statistically significant (p = 0.020), whereas the incidence was not (p = 0.862). The decline in both fracture prevalence and incidence exhibited significant variation across birth year groups (prevalence, p < 0.001; incidence, p < 0.001), with a more pronounced reduction observed in the older age groups. While the proportion of patients who required surgeries has increased, the mean frequency of surgical treatment per patient remained at a similar level (by prevalence, p = 0.181; by incidence, p = 0.735). The decline in both fracture prevalence and incidence has shown significant variation in relation to fracture sites (prevalence, p < 0.001; incidence, p < 0.001), with a decrease in distal limb fractures and an increase in forearm and axial body fractures. Conclusions: The pediatric fracture pattern in Korea has been notably influenced by the COVID-19 pandemic, warranting further investigation into causal factors. Our findings should help predict epidemiology in the post-pandemic period and thus aid policymaking and patient management.

Comparison of whole trunk muscle mass between healthy and lumbar herniated nucleus pulposus patients using abdominal pelvic computed tomography.

Background: Paraspinal muscle asymmetry is associated with low back pain (LBP) problems. This study aimed to analyze skeletal muscle areas around the lumbar vertebra and compare the ratio of anterior and posterior muscles between patients with lumbar herniated nucleus pulposus (HNP) and healthy individuals using abdominal pelvic computed tomography (APCT). Methods: After propensity score matching, 122 HNP patients and 122 non-HNP individuals were finally used for analyses. In APCT, axial cut images were collected at the level of the third lumbar vertebra lower end plate and only the muscle structure was obtained. After obtaining the muscular portion of their image, we measured the skeletal muscle area (SMA). Second, for analysis relation of sarcopenia and HNP, the status of low skeletal muscle mass was determined using a previously reported criteria based on APCT scans in the Republic of Korea. Results: From the analysis of the anterior-posterior muscles, the ratio of anterior SMA was statistically significantly larger in the HNP group than in the non-HNP group. Regarding the anatomical classification of trunk muscles, a statistically significant left-right imbalance to peripheral muscle in HNP men was observed. Regarding the status of low skeletal muscle mass, no statistical difference in prevalence between the two groups were observed. Moreover, no statistical difference in the prevalence of low skeletal muscle mass obesity was observed. Conclusion: The lumbar flexor muscle was larger in HNP than others, showing trunk muscle imbalance. However, low skeletal muscle mass is not associated with HNP.

miR-4284 Functions as a Tumor Suppressor in Renal Cell Carcinoma Cells by Targeting Glutamate Decarboxylase 1.

MicroRNAs (miRNAs) play a crucial role as oncogenic or tumor suppressors in the pathogenesis and progression of tumors. However, few studies have investigated the exact role of miR-4284 in renal cell carcinoma (RCC). We aimed to investigate the role of miR-4284 as a tumor suppressor in renal cancer cell lines. A498 and Caki-1 were transfected with miR-4284. The Cell Counting Kit-8, colony formation, apoptosis assays, and quantitative reverse transcription-polymerase chain reaction were used to evaluate tumor growth-inhibiting functions. The wound-healing, transwell, and sphere-formation assays were conducted to investigate tumorigenic characteristics. The potential target genes of miR-4284 were predicted and experimentally verified. A xenograft experiment was performed to estimate the tumor-growth-suppressive function of miR-4284. miR-4284 overexpression suppressed proliferation, induced apoptosis, and suppressed tumorigenic features of renal cancer cells. Glutamate decarboxylase 1 (GAD1) was directly targeted by miR-4284. A xenograft mouse model injected with Caki-1 cells transfected with miR-4284 showed significantly decreased tumor growth rate and volume. miR-4284 affected tumor growth, metastasis, and apoptosis of renal cancer cells in vitro and in vivo. These findings highlight the potential of miR-4284 as a target for anticancer miRNA therapeutics in RCC.

Network analysis of osteoporosis provides a global view of associated comorbidities and their temporal relationships.

We performed comorbidity-network analysis to obtain global view of comorbidity related with osteoporosis. We selected 10000-patients with osteoporosis registered in the National-Health-Insurance Service cohort-database. We found 45-significant disease-clusters. Of these, 14-disease-clusters were related to fra, while 10 were related to musculoskeletal diseases. Our findings will serve as basic data for further studies. PURPOSE: Osteoporosis causes devastating fractures; however, its exact etiology remains unknown. Elucidating associated comorbidities and their temporal relationships could provide better insights into its pathogenesis. Comorbidity-network analysis was performed to obtain global view of these associations. METHODS: We randomly selected 10000-patients with osteoporosis registered in the National-Health-Insurance Service cohort-database. These patients were identified using ICD-10 codes M81-M82, which represent osteoporosis without pathological fractures. Control group was created through propensity score matching. The comorbidities in each group were grouped into similar classifications to form "disease cluster"; 126 such clusters were identified. To create a comorbidity network, we selected disease clusters with high associations (i.e., odds ratios and relative risks ranked in the upper 50th percentile). To identify the temporal relationships between these clusters and osteoporosis, trajectories of directions were identified. RESULTS: Finally, we found 45 significant disease clusters. Of these, 14 disease clusters were related to fractures or injuries, while 10 were related to musculoskeletal diseases. Temporal analysis revealed that 15 disease clusters preceded osteoporosis; these included the following three with the strongest associations: "other fracture", "disorders of bone density and structure (M83-M85)", and "sequelae of injuries of neck and trunk (T91)". Thirty disease clusters followed osteoporosis; these included the following three with the strongest associations: "spine fracture," "spondylopathies (M45-M49)", and "pelvic region and thigh fracture,". CONCLUSION: We obtained a global view of the osteoporosis comorbidity network, which is otherwise difficult to achieve through study of individual diseases. Our findings will serve as the basic data for further studies.

Reliability of the TT-TG Index Versus TT-TG Distance on MRI: Morphometric Analyses in Asian Children and Adolescents.

Background: The tibial tuberosity-trochlear groove (TT-TG) distance measured on magnetic resonance imaging (MRI) is commonly used to decide the treatment for patellar instability; however, the patient's joint size is not considered in this measurement. The TT-TG index has been proposed as a knee size-adjusted measurement for tibial tuberosity location. Purpose: To evaluate the reliability of the TT-TG index compared with the TT-TG distance by analyzing variations in measurement according to age and sex in a pediatric Asian population. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A total of 698 knee MRI scans were collected in patients between 4 and 18 years of age who did not have any patellofemoral problems. Patient age, sex, height, and weight were recorded. The scans were divided into 5 groups according to patient age (4-6 years, 46 scans; 7-9 years, 56 scans; 10-12 years, 122 scans; 13-15 years, 185 scans; and 16-18 years, 289 scans); MRI scans were also divided by sex (497 male, 201 female). Three independent observers measured the TT-TG distance and TT-TG index on each scan, and age- and sex-based differences in the measurements were evaluated after adjusting for body mass index (BMI). The reliability of the measurements was calculated with the intraclass correlation coefficient (ICC). Results: Good to excellent inter- and intraobserver agreement was found for TT-TG distance (ICC, 0.74) and TT-TG index (ICC, 0.88). The TT-TG distance was significantly different among the groups and increased with age, while variations in the TT-TG index were minimal between age groups and sexes. This finding was also consistent after compensating for the effect of BMI. Conclusion: The TT-TG distance changed with age, while the TT-TG index was relatively constant. Therefore, the TT-TG index may be more reliable and effective for diagnosing and planning treatment, especially in children and adolescents.

Prediction of Progressive Collapse in Osteoporotic Vertebral Fractures Using Conventional Statistics and Machine Learning.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The objective of this study was to determine prognostic factors for the progression of osteoporotic vertebral fracture (OVF) following conservative treatment. SUMMARY OF BACKGROUND DATA: Few studies have evaluated factors associated with progressive collapse (PC) of OVFs. Furthermore, machine learning has not been applied in this context. MATERIALS AND METHODS: The study involved the PC and non-PC groups based on a compression rate of 15%. Clinical data, fracture site, OVF shape, Cobb angle, and anterior wedge angle of the fractured vertebra were evaluated. The presence of intravertebral cleft and the type of bone marrow signal change were analyzed using magnetic resonance imaging. Multivariate logistic regression analysis was performed to identify prognostic factors. In machine learning methods, decision tree and random forest models were used. RESULTS: There were no significant differences in clinical data between the groups. The proportion of fracture shape ( P <0.001) and bone marrow signal change ( P =0.01) were significantly different between the groups. Moderate wedge shape was frequently observed in the non-PC group (31.7%), whereas the normative shape was most common in the PC group (54.7%). The Cobb angle and anterior wedge angle at diagnosis of OVFs were higher in the non-PC group (13.2±10.9, P =0.001; 14.3±6.6, P <0.001) than in the PC group (10.3±11.8, 10.4±5.5). The bone marrow signal change at the superior aspect of the vertebra was more frequently found in the PC group (42.5%) than in the non-PC group (34.9%). Machine learning revealed that vertebral shape at initial diagnosis was a main predictor of progressive vertebral collapse. CONCLUSION: The initial shape of the vertebra and bone edema pattern on magnetic resonance imaging appear to be useful prognostic factors for progressive collapse in osteoporotic vertebral fractures.

Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study.

Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been widely prescribed to infected patients; however, the safety of them has not been investigated in patients with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to evaluate the association between the previous use of acetaminophen or NSAIDs and the clinical outcomes of SARS-CoV-2 infection. A nationwide population-based cohort study was conducted using the Korean Health Insurance Review and Assessment Database through propensity score matching (PSM). A total of 25,739 patients aged 20 years and older who tested for SARS-CoV-2 were included from 1 January 2015 to 15 May 2020. The primary endpoint was a positive result for a SARS-CoV-2 test, and the secondary endpoint was serious clinical outcomes of SARS-CoV-2 infection, such as conventional oxygen therapy, admission to the intensive care unit, need for invasive ventilation care, or death. Of 1058 patients, after propensity score matching, 176 acetaminophen users and 162 NSAIDs users were diagnosed with coronavirus disease 2019. After PSM, 162 paired data sets were generated, and the clinical outcomes of the acetaminophen group were not significantly different from those of the NSAIDs group. This suggests that acetaminophen and NSAIDs can be used safely to control symptoms in patients suspected of having SARS-CoV-2.

Effect of the Duration of NSAID Use on COVID-19.

Background and Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control pain and fever. However, their effect on COVID-19 infected patients has not been fully studied. In this study, we investigated the effect of the duration of NSAIDs use on COVID-19 infection and clinical outcomes. Materials and Methods: In South Korea, 25,739 eligible patients who received COVID-19 testing between 1 January and 31 July 2020, were included in this retrospective observational cohort analysis. Based on the date of the first COVID-19 test for each patient, NSAID prescription dates were used to separate patients into two groups (short-term group: <2 weeks; long-term group: 8−12 weeks). COVID-19 infectivity and clinical outcomes were analyzed. We used the propensity score-matching (PSM) method. Results: Of the 580 patients who had taken NSAIDs before the date of COVID-19 test, 534 and 46 patients were grouped in the short- and long-term NSAID-use groups, respectively. We did not find a statistically significant increased risk of COVID-19 infection (adjustment for age and sex, p = 0.413; adjustment for age, sex, region of residence, comorbidity, Charlson Comorbidity Index, and current use of medication, p = 0.259) or change in clinical outcomes, including conventional oxygen therapy, admission of intensive care unit, artificial ventilation, or death, between the two groups in which the PSM method was applied. Conclusions: The duration of NSAIDs use did not have a statistically significant effect on COVID-19 infectivity or clinical outcomes. However, further studies looking at clinical presentation and laboratory test results in a large number of people should be performed.

Genome-Wide Association Study Identifies Genetic Variants Associated with Rotator Cuff Tear-A Pilot Study.

A rotator cuff is a muscle and tendon surrounding the shoulder joint, and a rotator cuff tear can be caused by overuse or injury, which leads to great pain in affected individuals. However, rotator cuff tear is a multifactorial process whose underlying mechanism is still unclear. Many previous studies have suggested an important role of genetic predisposition, such as single-nucleotide polymorphisms (SNPs), in explaining the genesis of tendinopathy. This study aimed to identify specific genes or genetic variants associated with rotator cuff tears by performing a genome-wide association study (GWAS) using an independent case of rotator cuff tears. GWAS was performed using data from CHA Bundang Medical Center with 20 cases of rotator cuff tears, and 20 cases of healthy controls genotyped on the Illumina HiSeq 2500. Tests of association were performed using the Burrows−Wheeler Aligner (BWA) software at 284,246 SNPs. Data were filtered based on sequence ontology, minor allele frequency, and Hardy−Weinberg equilibrium values, and SNPs were considered significant if the p-value was <0.05. The tests of association revealed more than 20 significantly associated SNPs. SNPs showing the highest significance occurred in candidate genes, including LAIR2 (rs2287828, OR 9.116, p-value 5.49 × 10−4) on chromosome 19 and CRIPAK (rs9328733, OR 6, p-value 1.11 × 10−3) and REST (rs2228991, OR 8.222, p-value 1.20 × 10−3) on chromosome 4. This study attempted to identify genetic variants influencing rotator cuff tears through a genome-wide association study using a dense set of SNPs. More than 20 SNPs were significantly associated with rotator cuff tears. The major limitation of this study is that it was conducted on a small study group and requires further validation. Nevertheless, the identification of potential genetic variants related to rotator cuff injury would aid in the early detection of individuals at risk for the development of tendinopathy and will provide insight into future gene therapies.

The Association of Low Skeletal Muscle Mass with Complex Distal Radius Fracture.

Objectives: Sarcopenia is a skeletal muscle loss disease with adverse outcomes, including falls, mortality, and cardiovascular disease (CVD) in older patients. Distal radius fractures (DRF), common in older people, are strongly related to falls. We aimed to investigate the correlation between DRF and low skeletal muscle mass, which strongly correlated to sarcopenia. Methods: We performed a retrospective review of data from patients diagnosed with or without DRF in our institute between 2015 and 2020. Finally, after propensity score matching, data from 115 patients with and 115 patients without DRF were used for analyses. Multivariate logistic regression analysis was performed for sex, body mass index (BMI), the presence of low skeletal muscle mass, bone quality measured by dual-energy X-ray absorptiometry (DXA), and comorbidities (diabetes mellitus, CVD). Results: We found that female sex (odds ratio = 3.435, p = 0.015), CVD (odds ratio = 5.431, p < 0.001) and low skeletal muscle mass (odds ratio = 8.062, p = 0.001) were significant predictors for DRF. BMI and osteoporosis were not statistically significantly related to DRF. Conclusions: Women with low skeletal muscle mass and CVD may be more responsible for DRF than osteoporosis.

Substance P Inhibitor Promotes Tendon Healing in a Collagenase-Induced Rat Model of Tendinopathy.

BACKGROUND: The substance P-neurokinin 1 receptor pathway has been proposed as a therapeutic target for tendinopathy. However, there is a lack of evidence regarding its practical applications. PURPOSE: To investigate the therapeutic effects of substance P inhibitor (SPI) on inflamed tenocytes in vitro and in a collagenase-induced rat model of tendinopathy in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: We analyzed the mRNA levels of inflammatory (cyclooxygenase [COX]-2 and interleukin [IL]-6) and tenogenic (Mohawk and scleraxis [SCX]) markers using reverse transcription quantitative polymerase chain reaction to demonstrate the effects of SPI on lipopolysaccharide-treated (inflamed) tenocytes. A collagenase-induced rat model of tendinopathy was created by injecting 20 µL of collagenase into the Achilles tendon. A behavior test using an incapacitance apparatus was performed to detect changes in postural equilibrium. The tendon specimens were obtained, and their gross findings were examined. The tensile strength was measured, and histopathological evaluation was performed (hematoxylin and eosin, alcian blue, and immunohistochemical staining). RESULTS: The mRNA levels of COX-2, IL-6, Mohawk, and SCX differed significantly between inflamed tenocytes and those treated with SPI. SPI improved the weight burden in a rat model of tendinopathy in a behavioral test. The specimens of the SPI group showed a normal tendon-like appearance. In the biomechanical test, the tensile strength of the SPI group was significantly greater than that of the tendinopathy group. In the histopathological evaluation, the degree of collagen matrix breakdown was mild in the SPI group. In alcian blue staining, only small focal depositions of proteoglycans and glycosaminoglycans were observed in the SPI group. The SPI group showed decreased expression of IL-6 and neurokinin 1 receptor. CONCLUSION: This study suggests that SPI has therapeutic effects on tendon healing and restoration in a collagenase-induced rat model of tendinopathy. CLINICAL RELEVANCE: SPI is a promising agent for tendinopathy in humans.

Finite element analyses of lateral condyle fracture fixation in paediatrics regarding configuration of Kirschner-wire.

BACKGROUND: This study aimed to discover the most stable outcome among different Kirschner-wire (K-wire) configurations for fixation of a lateral condyle fracture (Milch type II) in different loads of stress by using finite element analyses (FEA). METHODS: The right humerus of a 6-year-old boy with a lateral condyle fracture (Milch type II), was modelled with a computer aided engineering. Using FEA, peak von Mises stress and stiffness were evaluated first for a single K-wire fixation by varying the angle (0, 5, 10, 15, 20, 25, 30 degrees). Then, based on the single K-wire result, assessment of peak von Mises stress and stiffness were evaluated via FEA for two- or three-wire fixation under various configurations (two convergent, two parallel, three divergent). RESULTS: Single K-wire fixation by 5 and 25 degrees had the lowest peak von Mises stress. The fracture site showed higher stiffness at 0, 5 and 15 degrees. Considering the collected results and clinical situation, 5 degree K-wire was selected for the FEA of multiple K-wire fixation. For multiple K-wire fixation, three divergent (5-20-35 degrees) K-wires showed better stability, both in peak von Mises stress and stiffness, than any two-K-wire configurations. Among two K-wire fixations, two divergent (5-50 degrees) K-wires provided the lowest von Mises stress in varus and valgus while two divergent (5-65 degrees) K-wires showed better results in flexion, extension, internal and external rotation, and both configurations showed similar results in stiffness. CONCLUSIONS: We successfully created a paediatric lateral condyle fracture (Milch type II) model which was used to conduct FEA on different K-wire configurations to achieve stability of the fracture. Our results show that an initial K-wire inserted at 5 degrees, followed by the insertion of a second divergent wire at either 45 or 60 degrees provides the most stability in two K-wire fixations in this type of fracture repair.

Colchicine as a novel drug for the treatment of osteosarcoma through drug repositioning based on an FDA drug library.

Background: Colchicine is a traditional medication that is currently approved to treat gout and familial Mediterranean fever (FMF). However, colchicine has a wide range of anti-inflammatory activities, and several studies have indicated that it may be useful in a variety of other conditions, such as rheumatic disease, cardiac disease, and cancer. Osteosarcoma, the most common type of bone sarcoma, is derived from primitive bone-forming mesenchymal cells. In this study, we investigated whether colchicine could be used to treat osteosarcoma through the regulation of cell cycle signaling. Methods: Two human osteosarcoma cell lines, U2OS and Saos-2, were used. A clonogenic assay was used to determine the antiproliferative effects of colchicine on osteosarcoma cells. Reactive oxygen species (ROS) production and apoptosis were measured by flow cytometry. Migration and invasion assays were performed to investigate the inhibitory effects of colchicine. The signaling pathways related to colchicine treatment were verified by GO biological process (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results: Colchicine was selected as the lead compound based on the results of initial screening and cell viability assays conducted in Saos-2 and U2Os cells. Colchicine reduced the viability of Saos-2 and U2OS cells in a concentration-dependent manner. It also significantly inhibited colony-forming ability and induced ROS production and apoptosis. It also inhibited the migration and invasion of both Saos-2 and U2OS cells. GOBP and KEGG enrichment analyses indicated the involvement of microtubule-based processes and cancer-related pathways. Conclusions: These findings suggest that colchicine has therapeutic potential in osteosarcoma.