Hartvigsenbyskov2780

Ossification of the posterior longitudinal ligament (OPLL) is a spinal disorder characterized by progressive ectopic bone formation in the PLL of the spine. Dickkopf-1 (Dkk1) is a secreted inhibitor of the Wnt pathway that negatively regulates bone formation during skeletal development. However, whether Dkk1 impacts the pathogenesis of OPLL has not been reported. This study is to investigate the role of Dkk1 in the development of OPLL. Our results show that the serum levels of Dkk1 are decreased in OPLL patients compared with non-OPLL controls. The expression of Dkk1 is also reduced in OPLL ligament cells. Downregulation of Dkk1 in ligament cells is associated with activation of the Wnt/β-catenin signaling, as indicated by stabilized β-catenin and increased T-cell factor-dependent transcriptional activity. Functionally, Dkk1 exerts a growth-inhibitory effect by repressing proliferation but promoting apoptosis of ligament cells. Dkk1 also suppresses bone morphogenetic protein 2-induced entire osteogenic differentiation of ligament cells, and this suppression is mediated via its inhibition of the Wnt pathway. Our results demonstrate for the first time that Dkk1 acts as an important negative regulator in the ossification of the PLL. Targeting the Wnt pathway using Dkk1 may represent a potential therapeutic strategy for the treatment of OPLL.We demonstrate an intermolecular reaction cascade to control the force which triggers crosslinking of a mechanochromic polymer of spirothiopyran (STP). Mechanochromism arises from rapid reversible force-sensitive isomerization of STP to a merocyanine, which reacts rapidly with activated C=C bonds. The concentration of such bonds, and hence the crosslinking rate, is controlled by force-dependent dissociation of a Diels-Alder adduct of anthracene and maleimide. Because the adduct requires ca. 1 nN higher force to dissociate at the same rate as that of STP isomerization, the cascade limits crosslinking to overstressed regions of the material, which are at the highest rate of material damage. Using comb polymers decreased the minimum concentration of mechanophores required to crosslinking by about 100-fold compared to previous examples of load-strengthening materials. The approach described has potential for controlling a broad range of reaction sequences triggered by mechanical load.Esophageal squamous cell carcinoma (ESCA) exhibits high intratumoral molecular heterogeneity posing a challenge to cancer therapy. Immune checkpoint blockade therapy has been approved for this disease, but with modest results. RNA-Seq data from paired tumor and surrounding nonmalignant tissue from 14 patients diagnosed with ESCA without previous treatment and from The Cancer Genome Atlas-ESCA cohort were analyzed. Herein, we investigated ESCA immune landscape including mutation-derived neoantigens and immune cell subpopulations. Tumor-associated antigen expression was determined by in silico analyses and confirmed by immunohistochemistry showing that PRAME, CEACAM4, and MAGEA11 proteins are expressed on tumors. Immune checkpoint molecules gene expression was higher in the tumor compared with surrounding nonmalignant tissue, but its expression varies greatly among patients. TCR repertoire and BCR transcripts analysis evidenced low clonal diversity with one TCR clone predicted to be specific for a MAGEA11-derived peptide. A high number of B-cell clones infiltrating the tumors and the abundance of these cells in tertiary lymphoid structures observed in ESCA tumors support B cells as a potential immune modulator in this tumor.Grouping children of different ages in the same preschool classroom (i.e., mixed age) is widespread, but the evidence supporting this practice is mixed. A factor that may play a role in the relation between classroom age composition and child outcomes is peer skill. read more This study used a sample of 6,338 preschoolers (ages 3-5) to examine the influence of both classroom age composition and peer skill on children's behavioral and language outcomes. Results supported the growing literature indicating preschoolers' skills are higher when peer skill is higher, but differences related to classroom age composition were not found. These findings further support the view that peer skill plays an important role in preschool children's outcomes.Traditional orthopaedic devices do not communicate with physicians or patients post-operatively. After implantation, follow-up of traditional orthopaedic devices is generally limited to episodic monitoring. However, the orthopaedic community may be shifting towards incorporation of smart technology. Smart technology in orthopaedics is a term that encompasses a wide range of potential applications. Smart orthopaedic implants offer the possibility of gathering data and exchanging it with an external reader. They incorporate technology that enables automated sensing, measuring, processing, and reporting of patient or device parameters at or near the implant. While including advanced technology in orthopaedic devices has the potential to benefit patients, physicians, and the scientific community, it may also increase the patient risks associated with the implants. Understanding the benefit-risk profile of new smart orthopaedic devices is critical to ensuring their safety and effectiveness. The 2018 FDA public workshop on orthopaedic sensing, measuring, and advanced reporting technology (SMART) devices was held on April 30, 2018, at the FDA White Oak Campus in Silver Spring, MD with the goal of fostering a collaborative dialogue amongst the orthopaedic community. Workshop attendees discussed four key areas related to smart orthopaedic devices engineering and technology considerations, clinical and patient perspectives, cybersecurity, and regulatory considerations. The workshop presentations and associated discussions highlighted the need for the orthopaedic community to collectively craft a responsible path for incorporating smart technology in musculoskeletal disease care.With recent rapid advances in technology, human-like robots have begun functioning in a variety of ways. As increasing anecdotal evidence suggests, robots may offer many unique opportunities for helping individuals with autism spectrum disorders (ASD). Individuals with ASD often achieve a higher degree of task engagement through the interaction with robots than through interactions with human trainees. The type and form of robots to be used for individuals with ASD have been meticulously considered. Simple robots and animal robots are acceptable because of their simplicity and the ease of interesting and engaging interactions. Android robots have the benefit of the potential of generalization into daily life to some extent. Considering the affinity between robots and users is important to draw out the potential capabilities of robotic intervention to the fullest extent. In the robotic condition, factors such as the appearance, biological motion, clothes, hairstyle, and disposition are important. Many factors of a user, such as age, sex, and IQ, may also affect the affinity of individuals with ASD toward a robot. The potential end-users of this technology may be unaware or unconvinced of the potential roles of robots in ASD interventions. If trainers have extensive experience in using robots, they can identify many potential roles of robots based on their experience. To date, only a few studies have been conducted in the field of robotics for providing assistance to individuals with ASD, and future studies are needed to realize an optimal robot for this purpose.To explore bone shape features that are associated with patellofemoral joint (PFJ) osteoarthritic features. Thirty subjects with PFJ degeneration (six males, 53.2 ± 9.8 years) and 23 controls (12 males, 48.1 ± 10.6 years) were included. Magnetic resonance (MR) assessment was performed to provide bone segmentation, morpholgocial grading, and cartilage relaxation times. In addition, subject self-reported symptoms were reported. Logistic regressions were used to identify the shape features that were associated with the presence and worsening of PFJ morphological lesions over 3 years, and worsening of self-reported symptoms. Statistical parametric mapping was used to evaluate the associations between shape features and cartilage relaxation times at 3 years. Results indicated that subjects with PFJ degeneration exhibited a trochlea with longer lateral condyle and shallower trochlear groove (adjusted odds ratio [OR] = 0.30; 95% confidence interval [CI] 0.10, 0.86; P = .025). Subjects with worsening of PFJ degeneration exhibited a patella with equally distributed facets (adjusted OR = 3.14; 95% CI 1.05, 9.37; P = .040) and lateral bump (adjusted OR = 0.14; 95% CI 0.02, 0.83; P = .030). No shape features were associated with worsening of self-reported symptoms. Elevated T1ρ and T2 times at 3 years were associated with a patella with a lateral hook, equally distributed facets, round and thick as well as a trochlea larger in size (R = 0.38~0.46, P = .015~.025). The study demonstrated the ability of 3D statistical shape modeling to quantify patella and trochlear bone shape features that are associated with the presence and progression of PFJ osteoarthritic features.Adult stem cells, such as bone marrow mesenchymal stem cells (BMSCs), are postdevelopmental cells found in many bone tissues. They are capable of multipotent differentiation and have low immune-rejection characteristics. Hepatocytes may become inflamed and produce a large number of free radicals when affected by drugs, poisoning, or a viral infection. The excessive accumulation of free radicals in the extracellular matrix (ECM) eventually leads to liver fibrosis. This study aims to investigate the restorative effects of mouse bone marrow mesenchymal stem cells (mBMSCs) on thioacetamide (TAA)-induced damage in hepatocytes. An in vitro transwell co-culture system of HepG2 cells were co-cultured with mBMSCs. The effects of damage done to TAA-treated HepG2 cells were reflected in the overall cell survival, the expression of antioxidants (SOD1, GPX1, and CAT), the ECM (COL1A1 and MMP9), antiapoptosis characteristics (BCL2), and inflammation (TNF) genes. The majority of the damage done to HepG2 by TAA was significantly reduced when cells were co-cultured with mBMSCs. The signal transducer and activator of transcription 3 (STAT3) and its phosphorylated STAT3 (p-STAT3), as related to cell growth and survival, were detected in this study. The results show that STAT3 was significantly decreased in the TAA-treated HepG2 cells, but the STAT3 and p-STAT3 of HepG2 cells were significantly activated when the TAA-treated HepG2 co-cultured with mBMSCs. Strong expression of interleukin (Il6) messenger RNA in co-cultured mBMSCs/HepG2 indicated mBMSCs secret the cytokines IL-6, which promotes cell survival through downstream STAT3 activation and aid in the recovery of HepG2 cells damaged by TAA.Two-dimensional transvaginal and transabdominal ultrasound (US) examinations are the suggested methods for examining the uterus. Three-dimensional (3D) US, which is not compulsory by society guidelines, provides additional uterine views, reassuring users of pathologic conditions not evident on customary sagittal and transverse views. The 3D coronal plane is rarely seen by 2-dimensional US transducers, let alone in extremely retroverted or axial uteri. Ultrasound machines nowadays feature 3D US capability. Our experience is that the coronal uterine view is a problem solver, helping diagnostic abilities of pelvic imaging. We advocate its liberal use and its acquisition in every pelvic scan. In this Pictorial Essay we present examples to demonstrate its use.