The aminopeptidase, endoplasmic reticulum aminopeptidase 1 (ERAP1), trims peptides for loading into major histocompatibility complex class I (MHC class I), and loss of this activity has broad effects on the MHC class I peptidome. Here, we investigated the impact of targeting ERAP1 in immune checkpoint blockade (ICB), as MHC class I interactions mediate both activating and inhibitory functions in antitumor immunity. Loss of ERAP sensitized mouse tumor models to ICB, and this sensitivity depended on CD8 T cells and natural killer (NK) cells.
View Article and Find Full Text PDFDue to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after.
View Article and Find Full Text PDFFoot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzootic areas, underscoring the need to develop new fast-acting therapies for FMD control during outbreaks.
View Article and Find Full Text PDFSublingual allergen immunotherapy (SLIT) is an emerging treatment option for allergic asthma and a potential disease-modifying strategy for asthma prevention. The key cellular events leading to such long-term tolerance remain to be fully elucidated. We administered prophylactic SLIT in a mouse model of house dust mite (HDM)-driven allergic asthma.
View Article and Find Full Text PDFObjective: To evaluate the association of insulin injection adherence, smart insulin pen engagement, and glycemic control using real-world data from 16 countries from adults self-administering basal insulin degludec and bolus insulin with a smart insulin pen (NovoPen 6 or NovoPen Echo Plus) alongside continuous glucose monitoring (CGM).
Research Design And Methods: Data were aggregated over 14-day periods. Treatment adherence was defined according to the number of missed basal and missed bolus insulin doses and smart pen engagement according to the number of days with data uploads.
Objective: Iodine fortification (IF) induces an initial increase followed by a decrease in the incidence of hyperthyroidism in the general population. Within the population of hyperthyroid patients, the sex-, age- and subtype distribution changes after IF. The risk of atrial fibrillation (AF) in hyperthyroid patients may be influenced by these factors.
View Article and Find Full Text PDFPolar lakes harbour a unique biogeochemistry that reflects the implications of climatic fluctuations against a susceptible yet extreme environment. In addition to polar, Store Saltsø (Kangerlussuaq, southwestern Greenland) is an endorheic lake with alkaline and oligotrophic waters that host a distinctive ecology adapted to live in such particular physico-chemical and environmental conditions. By exploring the sedimentary record of Store Saltsø at a molecular and compound-specific isotopic level, we were able to understand its ecology and biogeochemical evolution upon climate change.
View Article and Find Full Text PDFAllergen-specific immunoglobulin E (IgE) antibodies mediate pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. Here, we report a population of type 2-polarized MBCs defined as CD23, IL-4Rα, and CD32 at both the transcriptional and surface protein levels.
View Article and Find Full Text PDFThe popularity of quinoa seeds has increased in the last decade due to their high nutritional value and natural gluten-free composition. Consumption of new proteins may pose a risk of introducing new allergies. In the present study the immunogenicity and sensitising capacity of quinoa proteins were assessed in a dose-response experiment in Brown Norway rats in comparison to proteins from spinach and peanut.
View Article and Find Full Text PDFImmune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable.
View Article and Find Full Text PDFBackground: In intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC), outcome prediction is key to decision-making regarding prognostication, neurorehabilitation, and management of family expectations. Current prediction algorithms are largely based on chronic DoC, whereas multimodal data from acute DoC are scarce. Therefore, the Consciousness in Neurocritical Care Cohort Study Using Electroencephalography and Functional Magnetic Resonance Imaging (i.
View Article and Find Full Text PDFARX788 is an anti-HER2 antibody drug conjugate (ADC) developed using Ambrx proprietary Engineered Precision Biologics technology. The manufacturing process of ARX788 has been optimized during the course of early to late-phase clinical development. A comprehensive evaluation of side-by-side comparability between pre- and post-change process for ARX788 drug substance and drug product from a quality perspective was conducted based on ICH Q5E guidelines consisting of batch release assays, physicochemical and biophysical characterization, biological characterization, and forced degradation studies.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic in parallel with concerns about bias in grading resulted in many medical schools adopting pass/fail clinical grading and relying solely on narrative assessments. However, narratives often contain bias and lack specificity. The purpose of this project was to develop asynchronous faculty development to rapidly educate/re-educate > 2000 clinical faculty spread across geographic sites and clinical disciplines on components of a well-written narrative and methods to minimize bias in the assessment of students.
View Article and Find Full Text PDFBackground: There is an urgent need for easy-to-perform bedside measures to detect residual consciousness in clinically unresponsive patients with acute brain injury. Interestingly, the sympathetic control of pupil size is thought to be lost in states of unconsciousness. We therefore hypothesized that administration of brimonidine (an alpha-2-adrenergic agonist) eye drops into one eye should produce a pharmacologic Horner's syndrome if the clinically unresponsive patient is conscious, but not if the patient is unconscious.
View Article and Find Full Text PDFIntroduction: Allergen-specific immunotherapy (IT) is emerging as a viable option for treatment of peanut allergy. Yet, prophylactic IT remains unexplored despite early introduction of peanut in infancy was shown to prevent allergy. There is a need to understand how allergens interact with the immune system depending on the route of administration, and how different dosages of allergen may protect from sensitisation and a clinical active allergy.
View Article and Find Full Text PDFTo evaluate the impact of early vs late palliative care on (1) length of stay (LOS) in the context of expected LOS measures and (2) total cost of care to the hospital for each patient. A prospective cohort study was performed at a single large academic medical center on patients who received an inpatient palliative care consultation. The two cohorts were early palliative care (within 3 days of admission) and late palliative care (after 3 days of admission).
View Article and Find Full Text PDFSelf-control plays an essential role in children's emotional and behavioral adjustment. A central behavioral indicator of self-control is the ability to delay gratification. Few studies have focused on understanding the heterogeneity of self-control behaviors that underlie children's ability to delay gratification.
View Article and Find Full Text PDFThe immune system can eliminate tumors, but checkpoints enable immune escape. Here, we identify immune evasion mechanisms using genome-scale in vivo CRISPR screens across cancer models treated with immune checkpoint blockade (ICB). We identify immune evasion genes and important immune inhibitory checkpoints conserved across cancers, including the non-classical major histocompatibility complex class I (MHC class I) molecule Qa-1/HLA-E.
View Article and Find Full Text PDFJ Physician Assist Educ
September 2022
Introduction: Many physician assistant (PA) students experience mistreatment in clinical learning environments, and accredited PA programs are required to define, publish, and make readily available policies and procedures for student reports of mistreatment. The purpose of this study is to describe the prevalence, content, and dissemination of program policies to address students' reports of mistreatment involving preceptors during supervised clinical experiences.
Methods: To conduct a national policy analysis, the investigators included 10 new survey items in the 2019 Physician Assistant Education Association annual program survey.
Increasingly, medical school curricula seek to integrate the biomedical and clinical sciences. Inclusion of the basic sciences into the clinical curricula is less robust than including clinical content early in medical school. We describe inclusion of biomedical scientists on patient care rounds to increase the visibility of biomedical sciences, to nurture relationships between clinicians and biomedical scientists, and to identify additional opportunities for integration throughout medical school.
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