Macphersonnyholm5331

Frequently reported reasons to visit an HCP were intense pain (90.4%) and difficulties in performing daily activities (69%). In 44.1% of patients, the HCP suspected ERA at the first visit. Approximately 25% of patients needed more than five visits before detection of ERA. GPs mainly referred patients to rheumatologists (71%). Thematic analysis uncovered that multiple HCPs were often involved in the journey to RA detection and referral. Conclusion Pain is the most commonly reported initial symptom of ERA and the main reason to visit an HCP, usually a GP. These GPs play a pivotal role in early detection and correct referral. Furthermore, the journey of a patient seems complex, often with multiple HCPs being involved. © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.Inkjet printing has been identified as a cost-effective method to fabricate sensors on polymeric substrates. However, substrate materials suitable for printing are limited by the annealing temperature required by conventional inks. In this article, we describe the fabrication of an inkjet-printed thermistor on polyethylene and cellophane substrates that are not thermally compatible with the conventional inkjet printing processes. Fabrication on these substrates is made possible by a novel plasma-based postprint treatment step that limits the substrate temperature to less then 50 °C. The sensors exhibited a temperature sensitivity of 0.25 Ω°C-1 that was independent of substrate material. The utility of the fabrication process was demonstrated by fabricating thermistors for common indoor and outdoor applications.Objective Treatment delays and suboptimal adherence to posttreatment surveillance may adversely affect head and neck cancer (HNC) outcomes. Such challenges can be exacerbated in safety-net settings that struggle with limited resources and serve a disproportionate number of patients vulnerable to gaps in care. This study aims to characterize treatment delays and adherence with posttreatment surveillance in HNC care at an urban tertiary care public hospital in San Francisco. Study Design Retrospective chart review. Setting Urban tertiary care public hospital in San Francisco. Subjects and Methods We identified all cases of HNC diagnosed from 2008 to 2010 through the electronic medical record. We abstracted data, including patient characteristics, disease characteristics, pathology and radiology findings, treatment details, posttreatment follow-up, and clinical outcomes. Results We included 64 patients. Median time from diagnosis to treatment initiation (DTI) was 57 days for all patients, 54 days for patients undergoing surgery only, 49 days for patients undergoing surgery followed by adjuvant radiation ± chemotherapy, 65 days for patients undergoing definitive radiation ± chemotherapy, and 29 days for patients undergoing neoadjuvant chemotherapy followed by radiation or chemoradiation. Overall, 69% of patients completed recommended treatment. Forty-two of 61 (69%) patients demonstrated adherence to posttreatment visits in year 1; this fell to 14 out of 30 patients (47%) by year 5. Conclusion DTI was persistently prolonged in this study compared with prior studies in other public hospital settings. Adherence to posttreatment surveillance was suboptimal and continued to decline as the surveillance period progressed. © The Authors 2020.In this study, two types of prostate cancer cell lines, highly metastatic PC-3 and low metastatic MDA PCa 2b (PCa) were cultured on bone mimetic scaffolds to recapitulate metastasis to bone. A unique in vitro 3D tumor model that uses a sequential culture (SC) of human mesenchymal stem cells followed by seeding with cancer cells after bone formation was initiated to study the phenotype-specific interaction between prostate cancer cells and bone microenvironment. The PCa cells were observed to be less prolific and less metastatic, and to form multicellular tumoroids in the bone microenvironment, whereas PC-3 cells were more prolific and were highly metastatic, and did not form multicellular tumoroids in the bone microenvironment. The metastatic process exhibited by these two prostate cancer cell lines showed a significant and different effect on bone mineralization and extracellular matrix formation. Excessive bone formation in the presence of PC-3 and significant osteolysis in the presence of PCa were observed, which was also indicated by osteocalcin and MMP-9 expression as measured by ELISA and qRT-PCR. The field emission scanning electron microscopy images revealed that the structure of mineralized collagen in the presence of PC-3 is different than the one observed in healthy bone. All experimental results indicated that both osteolytic and osteoblastic bone lesions can be recapitulated in our tumor testbed model and that different cancer phenotypes have a very different influence on bone at metastasis. The 3D in vitro model presented in this study provides an improved, reproducible, and controllable system that is a useful tool to elucidate osteotropism of prostate cancer cells. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.Osteoarthritis and osteoporosis are widely prevalent and have far-reaching public health implications. There is increasing evidence that epigenetics, in particular, histone 3 lysine 79 methyltransferase DOT1L, plays an important role in the cartilage and bone biology. In this study, we evaluated the role of Dot1l in the articular cartilage, growth plate, and trabecular bone utilizing conditional KO mouse models. We generated chondrocyte-specific constitutive and inducible conditional Dot1l KO mouse lines using Col2a1-Cre and Acan-CreER systems. Prenatal deletion of Dot1l in mouse chondrocytes led to perinatal mortality, accelerated ossification, and dysregulation of Col10a1 expression. Postnatal deletion of Dot1l in mouse chondrocytes resulted in trabecular bone loss decreased extracellular matrix production, and disruption of the growth plate. In addition, pharmacological inhibition of DOT1L in a progeria mouse model partially rescued the abnormal osseous phenotype. In conclusion, Dot1l is important in maintaining the growth plate, extracellular matrix production, and trabecular bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.Bone pain is a serious and debilitating symptom of multiple myeloma (MM) that impairs the quality of life of patients. The underlying mechanisms of the pain are unknown and understudied, and there is a need for immunocompetent preclinical models of myeloma-induced bone pain. The aim of this study was to provide the first in-depth behavioral characterization of an immunocompetent mouse model of MM presenting the clinical disease features osteolytic bone disease and bone pain. We hypothesized that a widely used syngeneic model of MM, established by systemic inoculation of green fluorescent protein-tagged myeloma cells (5TGM1-GFP) in immunocompetent C57Bl/KaLwRijHsd (BKAL) mice, would present pain-related behaviors. Disease phenotype was confirmed by splenomegaly, high serum paraprotein, and tumor infiltration in the bone marrow of the hind limbs; however, myeloma-bearing mice did not present pain-related behaviors or substantial bone disease. Thus, we investigated an alternative model in which 5TGM1-GFP cells wnism including osteolysis and bone marrow denervation. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by severely high triglycerides (TGs). It is associated with a marked increase in risk of recurrent, potentially fatal acute pancreatitis (AP), and symptoms including abdominal pain, fatigue, and anxiety that may substantially reduce quality of life (QoL). A 46-year-old woman with FCS and severely high TGs initially presented with necrotizing pancreatitis with pseudocysts, having previously experienced recurrent AP. The patient reported constant abdominal pain and fatigue, which were evident in her demeanor. SU11274 solubility dmso Initial management included maximum doses of omega-3 fatty acids and fibrates, plus an extremely restricted diet (reduced intake calories, fats, simple sugars; no alcohol). Despite adherence to all management strategies, TGs remained at approximately 2800 mg/dL (31.6 mmol/L) and symptoms persisted. The patient was enrolled in COMPASS, a phase 3, placebo-controlled trial to evaluate the effect of an investigational drug, volanesorsen, on fasting TGs in patients with hypertriglyceridemia (fasting TGs ≥ 500 mg/dL [≥5.7 mmol/L]). The woman, a confirmed FCS patient, continued into the open-label extension study, during which fasting TGs decreased to 146 mg/dL (1.7 mmol/L) following 4 months of treatment. The restrictive diet was maintained throughout treatment and no serious adverse events were reported. Along with sustained TG reduction, the patient experienced progressive, perceived improvements in observable QoL measures and a marked reduction in symptom severity and frequency. In a patient with FCS, reduction in TGs following volanesorsen therapy appeared to be associated with marked improvement in clinical symptoms and observed QoL. © Endocrine Society 2019.To elucidate the mechanism of endometrial cancer (EC) development in young hyperprolactinemic women, this study assessed the hormonal receptor expression, proliferation, and signaling induced by prolactin in endometrial glands (EG) and EC. Prolactin receptor (PRLR) and estrogen receptor alpha (ER-α) in EG were evaluated during the menstrual cycle by immunohistochemistry. The following parameters were compared between EM-E6/E7/TERT cells, which originated from proliferative EG and Ishikawa cells. The expression levels of PRLR, pJAK2 (phosphorylated Janus Activating Kinase 2), its downstream pathways (MAPK, PI3K, and STAT), and ER-α were assessed after adding prolactin by Western blotting. U0126 was used as a MAPK inhibitor. The proliferation caused by estradiol was also examined by MTS assay after adding prolactin. PRLR expression in the EG was significantly higher in the proliferative phase than in the secretory phase, and it was correlated with ER-α expression during the menstrual cycle. After adding prolactin, the expression of pJAK2, PRLR and ER-α was significantly increased in both cell lines, MAPK was activated after adding prolactin in both cell lines, and PI3K and STAT were activated only in EM-E6/E7/TERT cells. The increased proliferation induced by estradiol was enhanced after adding prolactin in both cell lines. All changes caused by prolactin were inhibited in Ishikawa cells pretreated with U0126. Long-term effects of serum prolactin on persistent proliferative endometrium in the presence of estradiol may induce abnormal proliferation of EG in hyperprolactinemic women. Prolactin-PRLR signaling via MAPK may play a crucial role in the progression of EC in hyperprolactinemic women. © Endocrine Society 2019.