Collagen type II solution extracted from supercritical carbon dioxide decellularized porcine cartilage: regenerative efficacy on post-traumatic osteoarthritis model.

Osteoarthritis (OA) of the knee is a common degenerative articular disorder and is one of the main causes of pain and functional disability. Cartilage damage is frequently linked to elevated osteoarthritis incidence. Supercritical carbon dioxide (scCO2) decellularized cartilage graft produced from the porcine cartilage is an ideal candidate for cartilage tissue engineering. In the present study, we derived collagen type II (Col II) solution from the scCO2 decellularized porcine cartilage graft (dPCG) and compared its efficacy with hyaluronic acid (HA) in the surgical medial meniscectomy (MNX) induced post-traumatic osteoarthritis (PTOA) model. Dose-dependent attenuation of the OA (12.3 ± 0.8) progression was observed in the intra-articular administration of Col II solution (7.3 ± 1.2) which significantly decreased the MNX-induced OA symptoms similar to HA. The pain of the OA group (37.4 ± 2.7) was attenuated dose-dependently by Col II solution (45.9 ± 4.1) similar to HA (43.1 ± 3.5) as evaluated by a capacitance meter. Micro-CT depicted a dose-dependent attenuation of articular cartilage damage by the Col II solution similar to HA treatment. A significant (p < 0.001) dose-dependent elevation in the bone volume was also observed in Col II solution-treated OA animals. The protective competence of Col II solution on articular cartilage damage is due to its significant (p < 0.001) increase in the expression of type II collagen, aggrecan and SOX-9 similar to HA. To conclude, intra-articular administration of type II collagen solution and HA reestablished the injured cartilage and decreased osteoarthritis progression in the experimental PTOA model.

The Pediatric Autism Research Cohort (PARC) Study: protocol for a patient-oriented prospective study examining trajectories of functioning in children with autism.

INTRODUCTION: The developmentally variable nature of autism poses challenges in providing timely services tailored to a child's needs. Despite a recent focus on longitudinal research, priority-setting initiatives with stakeholders highlighted the importance of studying a child's day-to-day functioning and social determinants of health to inform clinical care. To address this, we are conducting a pragmatic multi-site, patient-oriented longitudinal investigation: the Pediatric Autism Research Cohort (PARC) Study. In young children (<7 years of age) newly diagnosed with autism, we will: (1) examine variability in trajectories of adaptive functioning from the point of diagnosis into transition to school; and (2) identify factors associated with trajectories of adaptive functioning. METHODS AND ANALYSIS: We aim to recruit 1300 children under 7 years of age with a recent (within 12 months) diagnosis of autism from seven sites: six in Canada; one in Israel. Participants will be followed prospectively from diagnosis to age 8 years, with assessments at 6-month intervals. Parents/caregivers will complete questionnaires administered via a customized online research portal. Following each assessment timepoint, families will receive a research summary report describing their child's progress on adaptive functioning and related domains. Analysis of the longitudinal data will map trajectories and examine child, family and service characteristics associated with chronogeneity (interindividual and intraindividual heterogeneity over time) and possible trajectory turning points around sensitive periods like the transition to school. ETHICS AND DISSEMINATION: Ethics approvals have been received by all sites. All parents/respondents will provide informed consent when enrolling in the study. Using an integrated knowledge translation approach, where stakeholders are directly engaged in the research process, the PARC Study will identify factors associated with trajectories of functioning in children with autism. Resulting evidence will be shared with government policy makers to inform provincial and national programs. Findings will be disseminated at conferences and published in peer-reviewed journals.

Functional difficulties in children and youth with autism spectrum disorder: analysis of the 2019 Canadian Health Survey on Children and Youth. / Difficultés fonctionnelles chez les enfants et les jeunes atteints d'un trouble du spectre de l'autisme : une analyse de l'Enquête canadienne sur la santé des enfants et des jeunes de 2019.

INTRODUCTION: This study examined the prevalence of functional difficulties and associated factors in Canadian children/youth aged 5 to 17 years diagnosed with autism spectrum disorder (ASD). METHODS: We analyzed data from the 2019 Canadian Health Survey on Children and Youth (CHSCY), a nationally representative survey of Canadian children/youth that used the Washington Group Short Set on Functioning (WG-SS) to evaluate functioning in six daily tasks. For each functional domain, binary outcomes were derived (no/some difficulty, a lot of difficulty/no ability). We used logistic regression to identify associations between demographic characteristics, educational experiences, and perceived mental and general health and the most common functional difficulties, namely those related to remembering/concentrating, communication and self-care. All estimates were weighted to be representative of the target population. The bootstrap method was used to calculate variance estimates. RESULTS: Analysis of the records of 660 children/youth with ASD revealed that the most common functional difficulties were remembering/concentrating (22%; 95% CI: 18-27), communicating (19%; 95% CI: 15-23) and self-care (13%; 95% CI: 10-17). Lower perceived mental health was associated with increased functional difficulties with remembering/concentrating. ASD diagnosis at a lower age and lower perceived general health were associated with increased functional difficulty with communication. Parental expectations for postsecondary education were associated with decreased functional difficulty for self-care. CONCLUSION: One or more functional difficulties from the WG-SS was present in 39% of Canadian children/youth aged 5 to 17 years with ASD. Functional difficulties with remembering/concentrating, communication and self-care were most common.

Trajectory research in children with an autism diagnosis: A scoping review.

LAY ABSTRACT: The types of outcomes studied in children on the autism spectrum include clinical characteristics, such as social functioning, communication, language, or autism symptoms. Research that measures these outcomes at multiple timepoints is useful to improve our understanding of what to expect as children develop. In trajectory studies, researchers assess outcomes at three or more timepoints. This method has advantages over two-timepoint studies because it allows researchers to describe changes in the speed of development, such as accelerations, plateaus, or slowdowns. We identified and reviewed 103 published trajectory studies in children (to age 18 years) with an autism diagnosis. Importantly, we did not include studies of treatments or their effects, nor did we summarize the results of studies. Instead, this review summarizes the characteristics of the available published research, including the methods used, the many different outcomes that have been studied over time and the ages over which they have been studied. This summary may be of interest to autistic people and caregivers (parents) who want to know about the existence of research that provides answers about what to expect during an autistic child's development. We have recommended that future trajectory research efforts try to make up for the lack of studies from low- and middle-income countries; that more attention is given to the following outcomes that are meaningful to caregivers and autistic people; and to try to fill in the age gaps where more outcome-specific data are needed.

High-protein diet with immediate post-exercise protein drink: Impact on appetite in middle-aged obesity.

Successful management of obesity can be challenging if individuals constantly experience cravings. The present study investigated the effects of a high-protein diet, including a high-protein drink consumed immediately after high-intensity interval training (HIIT), on appetite and weight loss in obese middle-aged individuals. A total of 52 obese middle-aged individuals (58.2 ± 4.11 years old) were randomly assigned to one of three groups: the exercise group (E, n=19), exercise and high-protein diet group (ED, n=21), and a control group (n=12). The E and ED groups engaged in cycling HIIT (comprising 90 % of peak heart rate (HRpeak) for 3 min, followed by 70 % of HRpeak for 3 min, for a total of 5 cycles) three times a week for 3 months. The ED group consumed a high-protein drink immediately after HIIT and had a daily protein intake of 1.6g/kg. Body composition and eating behavior were assessed before and after the intervention. Additionally, appetite levels were measured before and after each exercise session, before dinner, and before bedtime during three phases of the intervention: the first phase (weeks 3-4), the second phase (weeks 5-8), and the third phase (weeks 9-12). Results showed that only the ED group experienced a decrease in body mass index (from 27.4 ± 4.28 to 26.8 ± 4.09 kg/m2, p=0.04). Appetite significantly increased after exercise in both E and ED groups (p values for the three phases ranged from 0.04 to 0.001 for the E group and from 0.042 to 0.003 for the ED group). The desire to eat significantly increased after exercise in the E group (phase 1: p = 0.026; phase 2: p = 0.011; phase 3: p = 0.003), but not in the ED group. Furthermore, the frequency of late-night snacking decreased in the ED group (the score changed from 2.4 ± 0.86 to 2.7 ± 0.80, p = 0.034). Notably, the E group tended to have a higher pre-dinner appetite score than the ED group in the third phase (p = 0.063). In summary, a high daily protein intake, combined with the consumption of high-protein drinks after exercise, resulted in reduced post-exercise appetite and a decrease in the frequency of late-night snacking.

Successful lung transplantation for artificial stone-associated accelerated silicosis: a case report.

This report focuses on the occupational health risks associated with the use of artificial stones containing high levels of crystalline silica in the production of kitchen countertops. It presents the case of a 43-yr-old man who developed severe silicosis due to his occupation involving cutting and polishing quartz stone raw materials. A retrospective analysis of the patient's medical records and occupational history was conducted. The diagnosis of severe silicosis, moderate restrictive lung disease, and bilateral pneumothorax was based on clinical manifestations, pulmonary function test, radiological findings, and histological reports. The patient underwent lung transplantation, and his pulmonary function improved post-surgery. The study highlights the significant health risks associated with procedures involving artificial stones and emphasizes the importance of awareness and protective measures for employees and workers. Clinicians should be cautious when diagnosing respiratory symptoms in patients with a history of occupational exposure to artificial stones containing high levels of crystalline silica.

RNA-binding protein-regulated fibronectin is essential for EGFR-activated metastasis of head and neck squamous cell carcinoma.

There is a higher expression level of epidermal growth factor receptor (EGFR) in up to 90% of advanced head and neck squamous cell carcinoma (HNSCC) tissue than in normal surrounding tissues. However, the role of RNA-binding proteins (RBPs) in EGFR-associated metastasis of HNSCC remains unclear. In this study, we reveal that RBPs, specifically nucleolin (NCL) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), correlated with the mesenchymal phenotype of HNSCC. The depletion of RBPs significantly attenuated EGF-induced HNSCC metastasis. Intriguingly, the EGF-induced EMT markers, such as fibronectin, were regulated by RBPs through the ERK and NF-κB pathway, followed by the enhancement of mRNA stability of fibronectin through the 5' untranslated region (5'-UTR) of the gene. The upregulation of fibronectin triggered the integrin signaling activation to enhance tumor cells' attachment to endothelial cells and increase endothelial permeability. In addition, the concurrence of EGFR and RBPs or EGFR and fibronectin was associated with overall survival and disease-free survival of HNSCC. The in vivo study showed that depletion of NCL, hnRNPA2B1, and fibronectin significantly inhibited EGF-promoted extravasation of tumor cells into lung tissues. The depletion of fibronectin or treatment with integrin inhibitors dramatically attenuated EGF-induced HNSCC metastatic nodules in the lung. Our data suggest that the RBPs/fibronectin axis is essential for EGF-induced tumor-endothelial cell interactions to enhance HNSCC cell metastasis.

Classification of Color Fundus Photographs Using Fusion Extracted Features and Customized CNN Models.

This study focuses on overcoming challenges in classifying eye diseases using color fundus photographs by leveraging deep learning techniques, aiming to enhance early detection and diagnosis accuracy. We utilized a dataset of 6392 color fundus photographs across eight disease categories, which was later augmented to 17,766 images. Five well-known convolutional neural networks (CNNs)-efficientnetb0, mobilenetv2, shufflenet, resnet50, and resnet101-and a custom-built CNN were integrated and trained on this dataset. Image sizes were standardized, and model performance was evaluated via accuracy, Kappa coefficient, and precision metrics. Shufflenet and efficientnetb0demonstrated strong performances, while our custom 17-layer CNN outperformed all with an accuracy of 0.930 and a Kappa coefficient of 0.920. Furthermore, we found that the fusion of image features with classical machine learning classifiers increased the performance, with Logistic Regression showcasing the best results. Our study highlights the potential of AI and deep learning models in accurately classifying eye diseases and demonstrates the efficacy of custom-built models and the fusion of deep learning and classical methods. Future work should focus on validating these methods across larger datasets and assessing their real-world applicability.

Variable patterns of daily activity participation across settings in autistic youth: A latent profile transition analysis.

LAY ABSTRACT: What people do or engage in in their daily lives, or daily life participation, is often linked to their state of being happy and healthy, as well as potential for living independently. To date, little research has been conducted on daily activity participation by autistic youth at home, at school or in the community. Learning more about individual differences in participation levels and what might influence them can help to create custom supports for autistic youth and their families. In this study, 158 caregivers of autistic youth were asked how often their children took part in 25 common activities at two assessments, about one year apart. The analysis showed three profiles for each of the home and school settings and two profiles for the community setting. These profiles reflected distinct patterns in how often autistic youth took part in various daily activities, particularly in doing homework, school club activities and community gatherings. Most autistic youth were in profiles marked by often taking part at home but less often at school and in the community, and about three-fourths of them tended to stay in the same profile over time. Autistic youth with limited participation profiles were more likely to have lower scores on measures of cognitive ability and daily life skills and more challenging behaviour, and faced more barriers in their environment. These findings show how important it is to think about each autistic person's strengths and weaknesses, and changing needs, to better support their daily life participation.

Early developmental profiles of sensory features and links to school-age adaptive and maladaptive outcomes: A birth cohort investigation.

Sensory-based subtypes among autistic children have been well documented, but little is known about longitudinal sensory subtypes beyond autistic populations. This prospective study aimed to identify subtypes based on trajectories of parent-reported sensory features measured at 6-19 months, 3-4, and 6-7 years of age among a community-based birth cohort (N = 1,517), and to examine their associations with school-age clinical and adaptive/maladaptive outcomes on a subset sample (N = 389). Latent class growth analysis revealed five trajectory subtypes varying in intensity and change rates across three sensory domains. In contrast to an Adaptive-All Improving subtype (35%) with very low sensory features and overall better school-age outcomes, an Elevated-All Worsening subtype (3%), comprised of more boys and children of parents with less education, was associated with most elevated autistic traits and poorest adaptive/maladaptive outcomes. Three other subtypes (62% in total) were generally characterized by stable or improving patterns of sensory features at mild to moderate levels, and challenges in certain outcome domains. Our findings indicate that characterizing children based on early sensory trajectories may contribute to earlier detection of subgroups of children with sensory challenges who are more likely to experience developmental challenges by school age, followed by early targeted interventions for improved long-term outcomes.

Probing the Stoichiometry Dependence of Enzyme-Catalyzed Junction Zone Network Formation in Aiyu Pectin Gel via a Reaction Kinetics Model.

We investigate the enzymatic self-catalyzed gelation process in aiyu gel, a natural ion crosslinked polysaccharide gel. The gelation process depends on the concentration ratio (Rmax) of the crosslinking calcium ions and all galacturonic acid binding sites. The physical gel network formation relies on the assembly of calcium-polysaccharide crosslink bonds. The crosslinks are initially transient and through break-up/rebinding gradually re-organizing into long, stable junction zones. Our previous study formulated a reaction kinetics model to describe enzymatic activation, crosslinker binding, and crosslink microstructural reorganization, in order to model the complex growth of elasticity. In this study, we extend the theory for the time-dependent profile of complex moduli and examine the interplay of enzyme conversion, crosslink formation, and crosslink re-organization. The adjusted model captures how the gelation and structural rearrangement characteristic times vary with the polymer and calcium concentrations. Furthermore, we find that calcium ions act as both crosslinkers and dopants in the excess calcium ion scenario and the binding dynamics is determined by Rmax. This study provides perspectives on the dynamic binding behaviors of aiyu pectin gel system and the theoretical approach can be generalized to enzyme-catalyzed ionic gel systems.

Sensory Reactivity of Infants at Elevated Likelihood of Autism and Associations with Caregiver Responsiveness.

Infants at elevated likelihood of developing autism display differences in sensory reactivity, especially hyporeactivity, as early as 7 months of age, potentially contributing to a developmental cascade of autism symptoms. Caregiver responsiveness, which has been linked to positive social communication outcomes, has not been adequately examined with regard to infant sensory reactivity. This study examined the multiplicative impact of infant sensory hypo- and hyperreactivity on caregiver responsiveness to sensory reactivity and regulation cues in 43 infants at elevated likelihood of autism. Sensory hyperreactivity was found to moderate the association between sensory hyporeactivity and caregiver responsiveness, such that caregivers of infants with moderately high sensory hypo- and hyperreactivity demonstrated higher responsiveness.

Sensory Features of Young Children From a Large Community Sample: Latent Factor Structures of the Sensory Experiences Questionnaire (Version 2.1, Short Form).

IMPORTANCE: Although three sensory factors (hyperresponsiveness [HYPO]; hyporesponsiveness [HYPER]; and sensory interests, repetitions, and seeking behaviors [SIRS]) have been demonstrated among a wide age range of clinical populations, they have not been well validated in the general population, especially with a large community sample of young children. OBJECTIVE: To validate the factor structure of the Sensory Experiences Questionnaire (Version 2.1, Short Form; SEQv2.1) in a community sample and to confirm the factor structure's existence in this sample. DESIGN: Caregivers completed the SEQv2.1, a parent-reported questionnaire designed to capture children's everyday sensory experiences. The latent factors of the SEQv2.1 were examined using confirmatory factor analysis. SETTING: North Carolina. PARTICIPANTS: Caregivers of 2,195 children age 3 yr were initially recruited through state birth records and were eligible to participate if the child did not have a history of serious medical problems and English was the family's primary language. OUTCOMES AND MEASURES: SEQv2.1. RESULTS: The SEQv2.1 showed validity in the community sample. Similar to previous research with clinical populations, the three broad patterns of sensory responsiveness were also confirmed in this large community sample of young children, but associations among the factors differed. CONCLUSIONS AND RELEVANCE: Validation of the three-sensory-factor structure in the general population suggests that these constructs are similar to those found with samples of participants with autism spectrum disorder and developmental disabilities. This finding underscores the importance of understanding the normative development of sensory features across a wider age range to better delineate qualitative differences underlying sensory features between clinical and general populations. What This Article Adds: Occupational therapists seeking to assess children's sensory features can use the SEQv2.1 not only with clinical samples but also with children in the general population.

Risk of NSAID-associated anastomosis leakage after colorectal surgery: a large-scale retrospective study using propensity score matching.

PURPOSE: NSAIDs are commonly used as opioid-sparing analgesics in colorectal surgery. Many efforts are made to elucidate the risk of NSAID-associated anastomotic leakage after colorectal surgery. However, these results still remain controversial. In this study, we applied large-scale retrospective analysis using propensity score matching to fully clarify the association between risk of anastomotic leakage and use of NSAID after colorectal surgery. METHODS: All colorectal cancer patients receiving operation during February 2008 to August 2018 in our multi-institution medical organization research database were enrolled. It is worthy to mention that only patients requiring re-operation within 21 days after colorectal surgery due to anastomotic leakage were counted as anastomosis leakage. Furthermore, a propensity score TriMatch analysis was performed to prevent from interference of confounding factors. RESULTS: A total of 10,584 patients were included in this study and divided into three groups, no NSAIDs group, non-selective NSAIDs group, and selective COX-2 inhibitors group, respectively. Before tri-matching analysis, significant differences in anastomotic leakage rate were observed. After propensity score matching analysis, the ratio of anastomotic leakage requiring re-operation occurred in 2.0%, 3.6%, and 2.0% in no NSAIDs, non-selective NSAIDs, and selective COX-2 inhibitors group, respectively. No significant difference was observed in these three groups. CONCLUSION: These results suggest that NSAIDs are not associated with incidence of anastomosis leakage following colorectal surgery. To our knowledge, it is the first study demonstrating that NSAIDs is not associated with incidence of anastomosis leakage following colorectal surgery using propensity score matching at a larger-scale retrospective study.

Rethinking Autism Intervention Science: A Dynamic Perspective.

Recent advances in longitudinal methodologies for observational studies have contributed to a better understanding of Autism as a neurodevelopmental condition characterized by within-person and between-person variability over time across behavioral domains. However, this finer-grained approach to the study of developmental variability has yet to be applied to Autism intervention science. The widely adopted experimental designs in the field-randomized control trials and quasi-experimental designs-hold value for inferring treatment effects; at the same time, they are limited in elucidating what works for whom, why, and when, given the idiosyncrasies of neurodevelopmental disorders where predictors and outcomes are often dynamic in nature. This perspective paper aims to serve as a primer for Autism intervention scientists to rethink the way we approach predictors of treatment response and treatment-related change using a dynamic lens. We discuss several empirical gaps, and potential methodological challenges and opportunities pertaining to: (1) capturing finer-grained treatment effects in specific behavioral domains as indexed by micro-level within-person changes during and beyond intervention; and (2) examining and modeling dynamic prediction of treatment response. Addressing these issues can contribute to enhanced study designs and methodologies that generate evidence to inform the development of more personalized interventions and stepped care approaches for individuals on the heterogeneous spectrum of Autism with changing needs across development.

Adjunct Non-Elastic Hip Taping Improves Gait Stability in Cane-Assisted Individuals with Chronic Stroke: A Randomized Controlled Trial.

Cane-assisted individuals with chronic stroke may perform with an abnormal gait pattern. One of the important factors of gait training for cane-assisted individuals is inducing improvement in lower limb muscle activity of the paretic side. Non-elastic taping on the hip may be used as an adjunct therapy for improving gait. The objective of this study was to investigate effects of non-elastic hip taping combined with exercise on gait in cane-assisted individuals with chronic stroke. This study is a single-blinded, randomized controlled trial. A total of 21 cane-assisted ambulators with chronic stroke were enrolled. Participants in both groups received a therapeutic exercise program, with the experimental and control groups having adjunct non-elastic taping and sham taping on the hip, respectively. The gait, Berg Balance Scale, 6-min walk test, and Fall Efficacy Scale-International were measured at pre-intervention, post-intervention, and 1-month follow-up. The experimental group resulted in significantly better performance in double-support time compared with the control group. Furthermore, the experimental group showed a significant improvement in double-support time and spatial symmetry at post-intervention and 1-month follow-up compared with pre-intervention. This study demonstrated that non-elastic hip taping combined with exercise could improve gait stability in cane-assisted ambulators. Non-elastic hip taping would be a useful adjunct to rehabilitation strategies for individuals with chronic stroke.

Early measurement of autism risk constructs in the general population: A new factor structure of the First Years Inventory (FYIv3.1) for ages 6-16 months.

Early detection of autism risk in the community is critical to increasing families' access to early intervention, yet few measures have been developed and tested for the general population of infants <16 months to tap a broader range of autism risk constructs. This study aimed to (a) examine the factor structure of the First Years Inventory, version 3.1 (FYIv3.1), with a sample of 6454 infants 6-16 months, and (b) determine the ability of the resulting factors to discriminate clinical outcome groups at 3 years of age. The FYIv3.1 is a parent-report tool designed to detect early behavioral risk signs that may be associated with a later diagnosis of ASD and related neurodevelopmental conditions. Factor analytic models were used to determine the number of constructs and inter-factor correlations. Findings supported a seven-factor structure: communication, imitation and play (CIP); social attention and affective engagement (SAE); sensory hyperresponsiveness (HYPER); sensory hyporesponsiveness (HYPO); self-regulation in daily routines (SREG); sensory interests, repetitions, and seeking behaviors (SIRS); motor coordination and milestones (MCM). Mean comparisons on these factors demonstrated significant discrimination of the three outcome groups at age 3 years including those classified as having an ASD diagnosis and/or high autism symptoms, those classified as having other developmental disorders/conditions/concerns, and those classified with no known conditions/concerns. These findings support the validity and multidimensionality of early ASD risk constructs, as well as the potential use of the FYIv3.1 for phenotypic subtyping in the general population, and early detection in a broader age range of 6-16 months in future clinical studies. LAY SUMMARY: The FYIv3.1 is a 69-item parent-report questionnaire about infant behaviors that may indicate an elevated likelihood for later neurodevelopmental conditions such as autism. Analyses of responses from 6454 parents of infants 6-16 months indicated that items could be grouped reliably into seven categories. Compared to children with or without other developmental conditions, children in the outcome group with autism spectrum disorder and/or high autism symptoms at age three showed more behavioral risk signs in social-communication, sensory, and motor domains during infancy.

Developmental trajectories of sensory patterns from infancy to school age in a community sample and associations with autistic traits.

This prospective study examined the latent growth trajectories of sensory patterns among a North Carolina birth cohort (N = 1517; 49% boys, 87% White) across infancy (6-19 months), preschool (3-4 years), and school years (6-7 years). Change rates of sensory hyper- and hyporesponsiveness better differentiated children with an autism diagnosis or elevated autistic traits from those with other developmental conditions, including non-autistic children with sensory differences. More sensory hyper- and hyporesponsiveness at infancy followed by steeper increases differentially predicted more autistic traits at school age. Further, children of parents with higher education tended to show stable or improving trajectories. These findings highlight the importance of tracking sensory patterns from infancy for facilitating early identification of associated challenges and tailored support for families.

Targeted activation of androgen receptor signaling in the periosteum improves bone fracture repair.

Low testosterone level is an independent predictor of osteoporotic fracture in elderly men as well as increased fracture risk in men undergoing androgen deprivation. Androgens and androgen receptor (AR) actions are essential for bone development and homeostasis but their linkage to fracture repair remains unclear. Here we found that AR is highly expressed in the periosteum cells and is co-localized with a mesenchymal progenitor cell marker, paired-related homeobox protein 1 (Prrx1), during bone fracture repair. Mice lacking the AR gene in the periosteum expressing Prrx1-cre (AR-/Y;Prrx1::Cre) but not in the chondrocytes (AR-/Y;Col-2::Cre) exhibits reduced callus size and new bone volume. Gene expression data analysis revealed that the expression of several collagens, integrins and cell adhesion molecules were downregulated in periosteum-derived progenitor cells (PDCs) from AR-/Y;Prrx1::Cre mice. Mechanistically, androgens-AR signaling activates the AR/ARA55/FAK complex and induces the collagen-integrin α2ß1 gene expression that is required for promoting the AR-mediated PDCs migration. Using mouse cortical-defect and femoral graft transplantation models, we proved that elimination of AR in periosteum of host mice impairs fracture healing, regardless of AR existence of transplanted donor graft. While testosterone implanted scaffolds failed to complete callus bridging across the fracture gap in AR-/Y;Prrx1::Cre mice, cell-based transplantation using DPCs re-expressing AR could lead to rescue bone repair. In conclusion, targeting androgen/AR axis in the periosteum may provide a novel therapy approach to improve fracture healing.

Physical Properties and Polymorphism of Acrylic Acid-Grafted Poly(1,4-butylene adipate-co-terephthalate)/Organically Modified Layered Double Hydroxide Nanocomposites.

Novel and biodegradable acrylic acid-grafted poly(1,4-butylene adipate-co-terephthalate)/organically modified layered double hydroxide (g-PBAT/m-LDH) nanocomposites were synthesized through the polycondensation and transesterification process, with the covalent linkages between the polymer and the inorganic materials. X-ray diffraction and transmission electron microscopy were used to characterize the structure and morphology of the g-PBAT/m-LDH nanocomposites. The experimental results show that the m-LDH was exfoliated and widely distributed in the g-PBAT matrix. The addition of m-LDH into the g-PBAT extensively improved the storage modulus at -90 °C, when compared to that of the pure g-PBAT matrix. The effects of the minor comonomer of the butylene terephthalate (BT) unit and the addition of m-LDH on the crystallization behavior, and the polymorphic crystals of the g-PBAT at numerous crystallization temperatures, were examined, using a differential scanning calorimeter (DSC). The data indicate that the minor comonomer of the BT unit into g-PBAT can significantly change the starting formation temperatures of the α-form and ꞵ-form crystals, while a change in the starting formation temperatures of the α-form and ꞵ-form crystals using the addition of m-LDH into g-PBAT is not evident.