Immunotherapy of acute myeloid leukemia (AML) has been challenging because the lack of tumor-specific antigens results in "on-target, off-tumor" toxicity. To unlock the full potential of AML therapies, we used CRISPR-Cas9 to genetically ablate the myeloid protein CD33 from healthy donor hematopoietic stem and progenitor cells (HSPCs), creating tremtelectogene empogeditemcel (trem-cel). Trem-cel is a HSPC transplant product designed to provide a reconstituted hematopoietic compartment that is resistant to anti-CD33 drug cytotoxicity.
View Article and Find Full Text PDFInt J Environ Res Public Health
September 2023
Aquifer storage and recovery (ASR) can augment water supplies and hydrologic flows under varying climatic conditions. However, imposing drinking water regulations on ASR practices, including pre-treatment before injection into the aquifer, remains arguable. Microbial inactivation data-, , poliovirus type 1 and -were used in a human health risk assessment to identify how the storage time of recharged water in the Floridan Aquifer enhances pathogen inactivation, thereby mitigating the human health risks associated with ingestion.
View Article and Find Full Text PDFMind-mindedness is associated with positive developmental outcomes. However, much of the literature uses mostly White, middle to high socioeconomic status (SES) samples despite evidence that the benefits of mind-mindedness may vary based on degree of social risk. Additionally, few studies have examined relations between mind-mindedness and language development.
View Article and Find Full Text PDFBackground: Bottled water (BW) consumption in the United States and globally has increased amidst heightened concern about environmental contaminant exposures and health risks in drinking water supplies, despite a paucity of directly comparable, environmentally-relevant contaminant exposure data for BW. This study provides insight into exposures and cumulative risks to human health from inorganic/organic/microbial contaminants in BW.
Methods: BW from 30 total domestic US (23) and imported (7) sources, including purified tapwater (7) and spring water (23), were analyzed for 3 field parameters, 53 inorganics, 465 organics, 14 microbial metrics, and in vitro estrogen receptor (ER) bioactivity.
Background: Mothers play an important role in providing positive sensory experiences to their infants during NICU hospitalization. However, little is known regarding maternal perceptions about sensory-based interventions in the NICU. Further, understanding maternal perceptions was an important part of the process during development of the Supporting and Enhancing NICU Sensory Experiences (SENSE) program.
View Article and Find Full Text PDFAims: The study of microbial inactivation rates in aquifer systems has most often been determined in aerobic and oxidized systems. This study examined the inactivation (i.e.
View Article and Find Full Text PDFObjectives: This study aimed to (1) estimate the total pool of neonatal therapists (occupational therapists, physical therapists, and speech-language pathologists who work in the neonatal intensive care unit [NICU]) and the average number represented in each U.S. based NICU, and (2) investigate the relationships between the number and type of neonatal therapy team members to NICU/hospital, population, and therapy factors.
View Article and Find Full Text PDFSpinal anesthesia (SA) is a safe and effective anesthetic technique for lower abdominal and lower extremity surgery in neonates and infants and is associated with an apparent state of sedation. We report the use of single-shot SA in a 6-week-old infant for a combined magnetic resonance imaging and open surgical biopsy of a deep soft tissue lower extremity mass. By leveraging the unique qualities of SA (sedation and surgical blockade), we avoided the need for general anesthesia.
View Article and Find Full Text PDFWe recently characterised the () mouse as a model of T-cell pre-leukaemia, featuring thymocytes that can engraft in recipient animals and progress to T-cell acute lymphoblastic leukaemia (T-ALL). However, loss of this engraftment ability by deletion of did not result in any loss of leukemogenesis activity. In the present study, we observe that thymocytes overexpress EPHA3, and we characterise thymocyte behaviour in mice with deletion of , which show a markedly reduced incidence of T-ALL.
View Article and Find Full Text PDFManaged aquifer recharge (MAR) offers a collection of water storage and storage options that have been used by resource managers to mitigate the reduced availability of fresh water. One of these technologies is aquifer storage and recovery (ASR), where surface water is treated then recharged into a storage zone within an existing aquifer for later recovery and discharge into a body of water. During the storage phase of ASR, nutrient concentrations in the recharge water have been shown to decrease due, presumably via the uptake by the native aquifer microbial community.
View Article and Find Full Text PDFIntroduction: Healthcare organisations have had to make adaptations to reduce the impact of the Coronavirus 2019 (COVID-19) pandemic. This has necessitated urgent reconfiguration within inflammatory bowel disease (IBD) services to ensure safety of patients and staff and seamless continuity of care provision.
Aim: To describe the adaptations made by a large inflammatory bowel disease service, caring for over 3,500 IBD patients, in response to the COVID-19 pandemic.
Introduction: Lack of comparative trial data on dosing regimens of infliximab in patients with acute severe ulcerative colitis (ASUC) failing intravenous corticosteroids has resulted in variability of rescue regimes in ASUC with potential impact on clinical outcomes. We aimed to evaluate practice variability and physician perspectives in decision-making with rescue therapy.
Methodology: An internet-based survey of members of the inflammatory bowel disease (IBD) section of the British Society of Gastroenterology was conducted.
The endothelial cell adhesion molecule E-selectin is a key component of the bone marrow hematopoietic stem cell (HSC) vascular niche regulating balance between HSC self-renewal and commitment. We now report in contrast, E-selectin directly triggers signaling pathways that promote malignant cell survival and regeneration. Using acute myeloid leukemia (AML) mouse models, we show AML blasts release inflammatory mediators that upregulate endothelial niche E-selectin expression.
View Article and Find Full Text PDFThis study was undertaken as part of the UK LIMPRINT international study to determine the number of people with chronic edema (CO) and its impact on health services. Overall 7436 with CO were recruited in the main UK study from a range of health settings. Factors relating to subjective control of arm and leg CO were defined in the UK.
View Article and Find Full Text PDFThere is no standardized international model for specialist lymphedema services, which covers the types of lymphedema treated and the treatments provided. The aim of this study was to provide a profile of patients attending specialist lymphedema services in different countries to explore similarities and differences. The LIMPRINT core tool was used in specialist lymphedema services in the United Kingdom, France, Italy, and Turkey.
View Article and Find Full Text PDFA liquid culture enrichment-polymerase chain reaction (E-PCR) assay was investigated as a potential tool to overcome inhibition by chemical component, debris, and background biological impurities in soil that were affecting detection assay performance for soil samples containing subsp. (a surrogate for ). To evaluate this assay, 9 g of matched sets of three different soil types (loamy sand [sand], sandy loam [loam] and clay) was spiked with 0, ~4.
View Article and Find Full Text PDFRemoval of carbon through the precipitation and burial of calcium carbonate in marine sediments constitutes over 70% of the total carbon on Earth and is partitioned between coastal and pelagic zones. The precipitation of authigenic calcium carbonate in seawater, however, has been hotly debated because despite being in a supersaturated state, there is an absence of persistent precipitation. One of the explanations for this paradox is the geochemical conditions in seawater cannot overcome the activation energy barrier for the first step in any precipitation reaction; nucleation.
View Article and Find Full Text PDFFollowing a release of Bacillus anthracis spores into the environment, there is a potential for lasting environmental contamination in soils. There is a need for detection protocols for B. anthracis in environmental matrices.
View Article and Find Full Text PDFJBJS Essent Surg Tech
March 2016
Slipped capital femoral epiphysis (SCFE), a common cause of adolescent hip pain, is a displacement of the femoral head through the proximal femoral physis. The exact etiology of SCFE is unknown, but both biochemical and biomechanical factors, including obesity, femoral retroversion, increased physeal obliquity, puberty, and endocrinopathies, play a role. Patients often present with hip, groin, or knee pain and an antalgic gait.
View Article and Find Full Text PDFJ Appl Microbiol
June 2016
Aims: Inactivation rates of Escherichia coli in groundwater have most often been determined in aerobic and oxidized systems. This study examined E. coli inactivation rates in anaerobic and extremely reduced groundwater systems that have been identified as recharge zones.
View Article and Find Full Text PDFEphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. EphB4 over-production promotes ligand-independent signaling pathways that increase cancer cell viability and stimulate migration and invasion. Several studies have shown that normal ligand-dependent signaling is tumour suppressive and therefore novel therapeutics which block the tumour promoting ligand-independent signaling and/or stimulate tumour suppressive ligand-dependent signaling will find application in the treatment of cancer.
View Article and Find Full Text PDFThe EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4.
View Article and Find Full Text PDFBackground: Ephrin-B2 is the sole physiologically-relevant ligand of the receptor tyrosine kinase EphB4, which is over-expressed in many epithelial cancers, including 66% of prostate cancers, and contributes to cancer cell survival, invasion and migration. Crucially, however, the cancer-promoting EphB4 signalling pathways are independent of interaction with its ligand ephrin-B2, as activation of ligand-dependent signalling causes tumour suppression. Ephrin-B2, however, is often found on the surface of endothelial cells of the tumour vasculature, where it can regulate angiogenesis to support tumour growth.
View Article and Find Full Text PDFWe present tight-binding models of 3D topological superconductors in class DIII that support a variety of winding numbers. We show that gapless Majorana surface states emerge at their boundary in agreement with the bulk-boundary correspondence. At the presence of a Zeeman field, the surface states become gapped and the boundary behaves as a 2D superconductor in class D.
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