Academic literature on the topic 'Falu red paint'

Abstract BACKGROUND: Mature circulating red blood cells, though devoid of a nucleus, have been shown to contain an abundance of miRNAs. Further, it has been shown that sickle cell patient-derived RBCs have a dramatic difference in miRNA content than normal RBCs. Given that a range of miRNAs are involved in the regulation of immunity, including the release of inflammatory mediators, we hypothesize that miRNAs enriched in circulating red blood cells function to prolong the inflammatory state in sickle cell disease. Further, we hypothesize that these miRNAs can be used as biomarkers for use in the clinic to predict crisis and differentiate acute versus chronic pain. Exploring this miRNA enrichment in circulating red blood cells in sickle cell patients will provide practical insight for the inflammation state and will inform characteristics of patients who may need greater care in the clinic. METHODS: Twenty steady state patients were recruited and categorized according to their chronic pain status and crisis frequency per year. Whole blood was drawn during routine visits to the OSU Wexner Medical Center Hematology Clinic. Additionally, whole blood was drawn from five patients either in acute pain crisis (recruited prior to crisis) or within a few days of crisis. Samples were subject to double gradient centrifugation and red cells were resuspended in Trizol and cryopreserved. MiRNAs were isolated from red cell Trizol suspensions using a commercial isolation kit (QIAGEN Cat#217004). Isolated miRNAs were then subject to a NanoString Human miR (v3) expression assay. Differential expression analysis was conducted to compare miRNAs with at least 1.5 fold difference (p = 0.05) between steady state and acute crisis. Target prediction and GO ontology analysis was performed for statistically significant miRNAs using DIANA Tools mirPath v3. Follow-up qPCRs were performed using TaqMan Advanced miRNA cDNA Synthesis Kit (Cat#A28007) and TaqMan Advanced miRNA Assays (Cat#A25576) to validate the decreased expression of miRNAs. Additional qPCRs were performed using TaqMan Gene Expression Assays (Cat#4331182) to investigate mRNA regulatory effects of significant miRNAs in the total red cell population. Western blots were also performed to investigate regulatory effects of these miRNAs at the protein level. RESULTS & CONCLUSION: Comparison of RBC miRNA profiles from patients during acute crisis to those in steady state shows several significantly decreased (>1.5 fold) miRNAs in crisis. Among these miRs we have found previously uncharacterized miRNAs, hsa-miR-2116-5p and hsa-miR-302d-3p. DIANA tools miRNA analysis software predicts these miRNAs to be involved in regulation of cell-to-cell adhesion pathways through gene transcripts such as Protocadherin Beta 6 (PCDHB6) and Neural Cell Adhesion Molecule 2 (NCAM2). Interestingly, inspection of miRNA predicted targets that fall under significant GO terms also predicts several individual miRNAs to regulate inflammatory response and nociceptive signaling gene transcripts like A20 (TNFAIP3) and Cathepsin S (CTSS). Validation of these miRNAs was performed via qPCR for 5 out of the 6 significantly decreased miRNAs. Of the 5 miRNAs tested, hsa-miR-2116-5p, hsa-miR-302d-3p, and hsa-miR-1246 were validated as having decreased expression in acute crisis patients compared to steady state. qPCRs were then performed to probe for miRNA based regulation of top predicted target mRNA transcripts. Both CTSS and TNFAIP3 showed increased expression of mRNA transcripts in acute crisis patient red cells as compared to steady state. Next, western blot analysis was performed on red cell protein lysate. Interestingly, this analysis revealed a pattern in activated CTSS expression that was independent of acute crisis. Steady state patients reporting chronic pain showed increased activated CTSS compared to those without chronic pain. Activated CTSS was not found in red cell lysates from three normal, non-SCD donors. Taken together, these results suggest that red blood cells may play a larger role in inflammation and pain responses in sickle cell disease than previously thought. Further these results suggest activated CTSS as a potential biomarker for differentiating chronic pain in patients. Follow-up studies are underway to further stratify and investigate these findings. Disclosures Desai: University of Pittsburgh: Research Funding; Ironwood: Other: Adjudication Committee; NIH: Research Funding; FDA: Research Funding; Selexy/Novartis: Research Funding; Pfizer: Research Funding.

Abstract Red Blood Cell Adhesion in Adult Patients with Sickle Cell Disease, at Baseline and with Pain, Measured on SCD Biochip Microfluidic Assay Alexandra Boye-Doe1, Erina Quinn1, Charlotte Yuan1, Umut A. Gurkan, PhD1, and Jane A. Little, MD2 1Case Western Reserve University, Cleveland, OH; 2Division of Hematology/Oncology, Case Western Reserve University/ University Hospitals Seidman Cancer Center, Cleveland, OH Background: Despite being monogenic, sickle cell disease (SCD) has a variable phenotype, in which clinical complications and manifestations evolve as patients age. In children, pain generally resolves between crises, whereas adults may experience acute, chronic, or acute-on-chronic pain. We have taken a multifaceted approach to characterize adhesion and inflammation during self-identified pain episodes in adults with SCD in order to better understand pain syndromes in adults and the potential for more specifically targeted therapies. In this pilot study, we assessed changes in red blood cell (RBC) adhesion to the subendothelial protein laminin (LN) during crisis in adults with SCD self-reporting for pain crisis on whom we had baseline adhesion data from a routine clinic visit. Methods: Surplus blood from patients' routine bloodwork was used. Crisis samples were collected from patients at the Acute Care Clinic or Emergency Department at University Hospitals Cleveland Medical Center (UHCMC) when patients presented for management of pain. Baseline samples were collected during routine visits to the Sickle Cell Clinic. This study was approved by the IRB at UHCMC. Within a 24-hour period, RBC adhesion to LN was quantitated by microscopy after passage of unprocessed whole blood through a LN-coated microfluidic adhesion assay, the SCD biochip [1]. Samples were analyzed for hemoglobin (Hb) phenotype by high-performance liquid chromatography (HPLC) in the clinical lab. Correlative clinical data, including, baseline lab values, and medical history, were obtained from the patients' medical records and used to characterize our results. Data from people with multiple samples were used as median values. Results: Blood samples from 19 unselected patients with sickle cell hemoglobin SS (HbSS) were obtained at crisis, and compared with baseline samples obtained from 2014 to 2018 (n = 67 samples). 2 groups were identified: Group 1 with increased adhesion (>25% rise from baseline, n= 10) during crisis, and Group 2 with decreased adhesion (>25% fall from baseline, n=8) or no change (<25% change) (n=1) during crisis (Fig. 1). Time between a patient's initial crisis event and when they presented for pain management varied, possibly affecting observed adhesion. Nonetheless, patients showing an increased adhesion in crisis also showed a decrease in Hb (p = 0.039) between their baseline analyses and the crisis visit. A decrease in Hb may associate with increased adhesion, if the latter contributes to crisis-related hemolysis. However, other markers of hemolysis did not change. By contrast, patients with decreasing RBC adhesion showed a decrease in absolute reticulocyte count (ARC, p = 0.019) at their crisis visit. Statistical analysis of HbS, HbA, and HbF levels n = 64 showed no significant change between baseline or crises. Discussion: A decrease in adhesion during crisis may reflect the presence of sickled RBCs that adhere preferentially to other basement membrane proteins such as fibronectin or thrombospondin. In addition, inflammatory white blood cell adhesion, possibly central to vaso-occlusion, is not evaluated in this study. We are currently examining cytokine and monocyte profiles from people with SCD presenting for management of pain, so that we may better understand inflammatory mediators of pain. Our data are the first to try to understand RBC adhesion in people with SCD who present for management of pain, whether this as an isolated or common event for that person. We found that unselected adults with SCD who presented for management of pain had heterogeneous changes in RBC adhesion, which may reflect differences in underlying mechanism. The pathophysiologic heterogeneity of pain in adults with SCD will be important to understand as anti-adhesion therapies are being developed and adopted clinically. Disclosures Little: Doris Duke Charitable Foundations: Research Funding; NHLBI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; PCORI: Research Funding.

Abstract Nursing Home (NH) nurses care for over 1.6 million older residents each year. Among this vulnerable population, an estimated 50 percent of older residents fall each year. Although licensed nurses caring for NH residents who fall intervene to prevent fall recurrence, we know little about nurse’s perceptions of the most effective interventions for various types of falls they manage. The purpose of this qualitative study is to describe and compare licensed nurse’s perceptions of fall prevention interventions believed to be due to acute underlying causes of a fall versus those believed to be due to chronic underlying conditions. This study is a secondary analysis of existing qualitative data from a multi-site parent study conducted in three NH sites in the northeastern U.S. designed to test nurse’s knowledge of falls prevention and interventions. Forty seven registered or licensed practical nurses, English speaking who were full or part time employees were recruited to participate. Most were female (n=46; 98.7%) with a median age of 49.5 years and ten years’ experience. Using Colazzi’s (1978) method, 47 responses of nurse’s were read from typed transcripts and analyzed independently by 2 judges. Significant statement were extracted to derive meanings and form themes. For falls related to acute causes, nurses most often stated they would collaborate with the physician, propose a blood pressure intervention and promote safety. For falls due to chronic causes, nurses promoted ambulation safety, pain interventions and collaborated with specialists. Since nurses intervened differently, identifying fall type is critical in selecting appropriate interventions.

Introduction: The aging process causes a decrease in physical abilities which can cause fall events. Fall events are influenced by fear of falling. Some risk factors of fear of falling were age, gender, balance while walking, use of a walker, depression and a history of previous falls. This study aim was to identify risk factors related to fear of falling among the elderly in nursing home.Methods: A cross-sectional study was used in this study. Respondents were elderly aged ≥60 years, can communicate well, able to read and write and not being sick which causes balance disorders and pain when walking. Respondents totaled 155 obtained by proportional random sampling. A questionnaire was used to retrieve data such as age, gender, use of a walker, depression, previous fall history and balance walking. Results: The results showed a significant relationship between all of these risk factors with the fear of falling (p <0.05) and the power of significance for each variable was different. The age variable was power significance 0.228, gender C = 0.2, previous fall history C = 0.374, use of a walker C = 0.367, balance walking C = 0.355 and depression rs = 0.196. There are three risk factors most closely associated with fear of falling in terms of balance walking (B = 1.424 Exp(B) = 4,153), use of a walker (B = 1,365 Exp(B) = 3,914) and previous fall history (B = 1.425 Exp(B) = 4.159). These factors had strength of 27%. Conclusion: Balance walking, use of a walker and previous fall history were the strongest risk factors.