Assessing knowledge gaps and educational needs in urine drug test interpretation among health care professionals.

Objectives: Urine drug testing (UDT) is a critical tool used in medical, forensic, and occupational settings, but interpreting results can be challenging. We performed a study to assess the ability of health care professionals to interpret UDT results accurately.

Methods: In total, 911 clinical and laboratory professionals in the United States and Canada responded to a survey with questions gauging expertise in UDT interpretation.

High-fat diet consumption negatively influences closed-head traumatic brain injury in a pediatric rodent model.

Traumatic brain injury (TBI) is one of the most common causes of emergency room visits in children, and it is a leading cause of death in juveniles in the United States. Similarly, a high proportion of this population consumes diets that are high in saturated fats, and millions of children are overweight or obese. The goal of the present study was to assess the relationship between diet and TBI on cognitive and cerebrovascular outcomes in juvenile rats.

Rational Protein Engineering to Enhance MHC-Independent T-cell Receptors.

Chimeric antigen receptor (CAR)-based therapies have pioneered synthetic cellular immunity but remain limited in their long-term efficacy. Emerging data suggest that dysregulated CAR-driven T-cell activation causes T-cell dysfunction and therapeutic failure. To re-engage the precision of the endogenous T-cell response, we designed MHC-independent T-cell receptors (miTCR) by linking antibody variable domains to T-cell receptor constant chains.

Guidelines for in vivo models of developmental programming of cardiovascular disease risk.

Research using animals depends on the generation of offspring for use in experiments or for the maintenance of animal colonies. Although not considered by all, several different factors preceding and during pregnancy, as well as during lactation, can program various characteristics in the offspring. Here, we present the most common models of developmental programming of cardiovascular outcomes, important considerations for study design, and provide guidelines for producing and reporting rigorous and reproducible cardiovascular studies in offspring exposed to normal conditions or developmental insult.

Guidelines for assessing maternal cardiovascular physiology during pregnancy and postpartum.

Maternal mortality rates are at an all-time high across the world and are set to increase in subsequent years. Cardiovascular disease is the leading cause of death during pregnancy and postpartum, especially in the United States. Therefore, understanding the physiological changes in the cardiovascular system during normal pregnancy is necessary to understand disease-related pathology.

VarLOCK: sequencing-independent, rapid detection of SARS-CoV-2 variants of concern for point-of-care testing, qPCR pipelines and national wastewater surveillance.

The COVID-19 pandemic demonstrated the need for rapid molecular diagnostics. Vaccination programs can provide protection and facilitate the opening of society, but newly emergent and existing viral variants capable of evading the immune system endanger their efficacy. Effective surveillance for Variants of Concern (VOC) is therefore important.

Blood-Brain Barrier Dysfunction in Hypertensive Disorders of Pregnancy.

Purpose Of Review: The incidence of hypertensive disorders of pregnancy (HDP), especially preeclampsia has increased significantly over the last two decades. Patients with these disorders often report cerebral and visual symptoms, which are listed as potential diagnosis criteria for preeclampsia, if accompanied by new-onset hypertension. Recent studies indicate that cerebral complications in HDP patients are associated with a compromised blood-brain barrier (BBB).

Targeting of intracellular oncoproteins with peptide-centric CARs.

The majority of oncogenic drivers are intracellular proteins, constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes. However, most cancers have a modest mutational burden that is insufficient for generating responses using neoantigen-based therapies. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks.

Increased hippocampal cannabinoid 1 receptor expression is associated with protection from severe seizures in pregnant mice with reduced uterine perfusion pressure.

Eclampsia, new-onset seizures in pregnancy, can complicate preeclampsia, a hypertensive pregnancy disorder. The mechanisms contributing to increased risk of seizures in preeclampsia are not fully known. One mechanism could be abnormal endocannabinoid system (ECS) activity and impaired neuromodulation.

Costimulatory domains direct distinct fates of CAR-driven T-cell dysfunction.

T cells engineered to express chimeric antigen receptors (CARs) targeting CD19 have demonstrated impressive activity against relapsed or refractory B-cell cancers yet fail to induce durable remissions for nearly half of all patients treated. Enhancing the efficacy of this therapy requires detailed understanding of the molecular circuitry that restrains CAR-driven antitumor T-cell function. We developed and validated an in vitro model that drives T-cell dysfunction through chronic CAR activation and interrogated how CAR costimulatory domains, central components of CAR structure and function, contribute to T-cell failure.

Preeclampsia history and postpartum risk of cerebrovascular disease and cognitive impairment: Potential mechanisms.

Hypertensive disorders of pregnancy such as preeclampsia, eclampsia, superimposed preeclampsia, and gestational hypertension are major causes of fetal and maternal morbidity and mortality. Women with a history of hypertensive pregnancy disorders have increased risk of stroke and cognitive impairments later in life. Moreover, women with a history of preeclampsia have increased risk of mortality from diseases including stroke, Alzheimer's disease, and cardiovascular disease.

Comparison of cardio-focal and chest reconstruction of technetium-99m pyrophosphate scintigraphy for diagnosis of transthyretin cardiac amyloidosis: a quality assurance study.

Background: SPECT improves diagnostic specificity of Technetium-99m pyrophosphate (PYP) scintigraphy. Diagnostic performance of PYP data, reconstructed as either chest or cardio-focal SPECT is not known.

Methods: In this quality assurance study, blinded evaluation of PYP SPECT/CT data from 102 Caucasian patients (mean age 76 ± 11 years, 67% men) was performed by two readers.

Prognostic value of coronary computed tomography angiography compared to radionuclide myocardial perfusion imaging in patients With coronary stents.

Objectives: The aim of this study is to compare the prognostic value of coronary computed tomography angiography (CCTA) with single-photon emission computed tomography (SPECT) in predicting cardiovascular events in patients with stents.

Design: Retrospective analysis.

Setting: University Hospital, London, Ontario Canada

Participants: Between January 2007 and December 2018, 119 patients post-percutaneous coronary intervention (PCI) who were referred for hybrid imaging with CTA and 2-day rest/stress SPECT were enrolled.

Retinal Venule Coverage by Pericytes Decreases in Multiparous Mice in a Time-Dependent Manner Post-Delivery.

Structural changes in the retinal vasculature have been linked to increased cardiovascular risks and also change as a function of age. Because multiparity has been associated with poorer cardiovascular health scores, we hypothesized that changes in retinal vascular caliber would be observed in multiparous, compared to nulliparous, females and retired breeder males. Age-matched nulliparous ( = 6) and multiparous ( = 11, retired breeder females with 4 ± 1 litters), and male breeder ( = 7) SMA-GFP reporter mice were included for assessment of retinal vascular structure.

Costimulatory domains direct distinct fates of CAR-driven T cell dysfunction.

Unlabelled: Chimeric antigen receptor (CAR) engineered T cells often fail to enact effector functions after infusion into patients. Understanding the biological pathways that lead CAR T cells to failure is of critical importance in the design of more effective therapies. We developed and validated an model that drives T cell dysfunction through chronic CAR activation and interrogated how CAR costimulatory domains contribute to T cell failure.

Increased seizure sensitivity in pregnant mice with genetic knockdown of acid sensing ion channel 2a is associated with impaired hippocampal inflammatory response.

Acid sensing ion channels (ASICs) are mechano- and chemo-receptor channels that are activated by drops in extracellular pH as occurs after neurotransmission. In our previous study, we demonstrated that mice subjected to reduced utero-placental perfusion pressure during pregnancy, to mimic the pregnancy complication of preeclampsia, have reduced hippocampal expression of ASIC2a protein. We also showed that pregnant mice with heterozygous expression of ASIC2a (+/-) had increased sensitivity and severity to pentylenetetrazol-induced seizures; however, the mechanisms by which this occurs remain unclear.

Antigen glycosylation regulates efficacy of CAR T cells targeting CD19.

While chimeric antigen receptor (CAR) T cells targeting CD19 can cure a subset of patients with B cell malignancies, most patients treated will not achieve durable remission. Identification of the mechanisms leading to failure is essential to broadening the efficacy of this promising platform. Several studies have demonstrated that disruption of CD19 genes and transcripts can lead to disease relapse after initial response; however, few other tumor-intrinsic drivers of CAR T cell failure have been reported.

Pancreatic cancer growth promoted by bone marrow mesenchymal stromal cell-derived IL-6 is reversed predominantly by IL-6 blockade.

Pancreatic cancer is a highly lethal cancer characterized by local invasiveness, early metastasis, recurrence and high resistance to current therapies. Extensive stroma or desmoplasia is a key histological feature of the disease, and interactions between cancer and stromal cells are critical for pancreatic cancer development and progression. Mesenchymal stromal cells [MSCs] exhibit preferential tropism to primary and metastatic tumor sites and may either suppress or support tumor growth.

Pial Vessel-Associated Microglia/Macrophages Increase in Female Dahl-SS/Jr Rats Independent of Pregnancy History.

As the resident immune cells of the central nervous system, microglia have a wide range of functions such as surveillance, phagocytosis, and signaling through production of chemokines and cytokines. Recent studies have identified and characterized macrophages residing at the meninges, a series of layers surrounding the brain and spinal cord. While perivascular microglia within the brain parenchyma increase following chronic hypertension, there are no reports of changes at the meninges, and specifically, associated with the pial vasculature.

Complementary role of computed tomography angiography with fixed perfusion defects on SPECT myocardial perfusion imaging.

Purpose: We present this case series exploring the complementary role of coronary computed tomography angiography (CCTA) to SPECT myocardial perfusion imaging (MPI) in the detection of myocardial necrosis.

Methods: A cardiac hybrid imaging database search identified 144 patients with a previous history of ST-segment elevation myocardial infarction treated with coronary revascularization. CCTA and MPI scans were evaluated to determine whether CCTA had an added value to MPI in detecting myocardial necrosis.

Secretory pathway Ca-ATPase SPCA2 regulates mitochondrial respiration and DNA damage response through store-independent calcium entry.

A complex interplay between the extracellular space, cytoplasm and individual organelles modulates Ca signaling to impact all aspects of cell fate and function. In recent years, the molecular machinery linking endoplasmic reticulum stores to plasma membrane Ca entry has been defined. However, the mechanism and pathophysiological relevance of store-independent modes of Ca entry remain poorly understood.