Search

Husiraci Environmental health specialists often perform environmental assessments (EAs) when a suspected or confirmed foodborne illness outbreak is linked to a food establishment. Information from EAs helps officials determine the cause of the outbreak and develop strategies to prevent future outbreaks; however, EAs are not always conducted. To determine facilitators and barriers to conducting EAs, we analyzed open-ended responses reported to the National Environmental Assessment Reporting System about these assessments. We found that EAs were conducted most often when illness was identified, a jurisdiction had a policy to investigate illnesses, and there were resources for such a response. EAs were not conducted in instances such as limited resources, insufficient training, uncooperative facility personnel, or if the establishment fell outside of health department jurisdiction. Identifying the facilitators and barriers to conducting EAs can enable health departments to develop strategies that improve their ability to conduct EAs., Introduction Foodborne illness is a significant public health problem in the U.S. (Angelo, Nisler, Hall, Brown, & Gould, 2017; Centers for Disease Control and Prevention [CDC], 2013; Gould et al., [...]

Every year, roughly 1 in 6 Americans (48 million people) get sick, 128,000 are hospitalized, and 3,000 die of foodborne diseases (Centers for Disease Control and Prevention [CDC], 2016). Furthermore, [...]

Allogeneic cell therapies, defined by genetically mismatched transplantation, have the potential to become a cost-effective solution for cell-based cancer immunotherapy. However, this type of therapy is often accompanied by the development of graft-versus-host disease (GvHD), induced by the mismatched major histocompatibility complex (MHC) between healthy donors and recipients, leading to severe complications and death. To address this issue and increase the potential for allogeneic cell therapies in clinical practice, minimizing GvHD is a crucial challenge. Innate T cells, encompassing subsets of T lymphocytes including mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, and gamma delta T (γδ T) cells, offer a promising solution. These cells express MHC-independent T-cell receptors (TCRs), allowing them to avoid MHC recognition and thus GvHD. This review examines the biology of these three innate T-cell populations, evaluates research on their roles in GvHD modulation and allogeneic stem cell transplantation (allo HSCT), and explores the potential futures for these therapies. [ABSTRACT FROM AUTHOR]

This study examined relationships between foodborne outbreak investigation characteristics, such as the epidemiological methods used, and the success of the investigation, as determined by whether the investigation identified an outbreak agent (i.e. pathogen), food item and contributing factor. This study used data from the Centers for Disease Control and Prevention's (CDC) National Outbreak Reporting System and National Environmental Assessment Reporting System to identify outbreak investigation characteristics associated with outbreak investigation success. We identified investigation characteristics that increase the probability of successful outbreak investigations: a rigorous epidemiology investigation method; a thorough environmental assessment, as measured by number of visits to complete the assessment; and the collection of clinical samples. This research highlights the importance of a comprehensive outbreak investigation, which includes epidemiology, environmental health and laboratory personnel working together to solve the outbreak. [ABSTRACT FROM AUTHOR]

Human behaviour is thought to spread through face-to-face social networks, but it is difficult to identify social influence effects in observational studies (9-13), and it is unknown whether online social [...]

This study examined how having had a similar experience to a target person's experience affected three facets of empathy: empathic concern, empathic accuracy, and perceived empathy. Women who had never been mothers, who were pregnant with their first child, or who had just given birth to their first child (20 in each group) served as perceivers, watching videotapes of new-mother targets (N = 20) and providing measures of emotional and cognitive empathy. When perceivers had experienced the same life events as the targets, they expressed greater empathic concern and reported greater understanding of targets. However, experience had a much smaller effect on empathic accuracy, limited to comparisons between new-mother and never-pregnant perceivers and only for accuracy at guessing stereotypic attitudes, not individual thoughts. Perceived empathy, in contrast, appeared to be influenced by targets' knowledge of whether perceivers had experienced similar events.

Invariant natural killer T (iNKT) cells have the capacity to mount potent anti-tumor reactivity and have therefore become a focus in the development of cell-based immunotherapy. iNKT cells attack tumor cells using multiple mechanisms with a high efficacy; however, their clinical application has been limited because of their low numbers in cancer patients and difficulties in infiltrating solid tumors. In this study, we aimed to overcome these critical limitations by using α-GalCer, a synthetic glycolipid ligand specifically activating iNKT cells, to recruit iNKT to solid tumors. By adoptively transferring human iNKT cells into tumor-bearing humanized NSG mice and administering a single dose of tumor-localized α-GalCer, we demonstrated the rapid recruitment of human iNKT cells into solid tumors in as little as one day and a significantly enhanced tumor killing ability. Using firefly luciferase-labeled iNKT cells, we monitored the tissue biodistribution and pharmacokinetics/pharmacodynamics (PK/PD) of human iNKT cells in tumor-bearing NSG mice. Collectively, these preclinical studies demonstrate the promise of an αGC-driven iNKT cell-based immunotherapy to target solid tumors with higher efficacy and precision. [ABSTRACT FROM AUTHOR]

Simple Summary: This study seeks to evaluate innate T cells for antitumor therapies that can target both tumor cells and immunosuppressive tumor-associated macrophages (TAMs). With their innate immune-like nature, mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, and gamma delta T (γδT) cells do not demonstrate the harmful graft-versus-host effects associated with many conventional αβ T cell trials, and could be engineered to target both tumor cells and anti-inflammatory TAMs. The success of these trials could suggest potent new avenues for the field of cell-based cancer immunotherapy. The field of T cell-based and chimeric antigen receptor (CAR)-engineered T (CAR-T) cell-based antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) and tumor-associated immunosuppression, have proven to be substantial roadblocks to widespread adoption and implementation. Recent developments in innate immune cell-based CAR therapy have opened several doors for the expansion of this therapy, especially as it relates to allogeneic cell sources and solid tumor infiltration. This study establishes in vitro killing assays to examine the TAM-targeting efficacy of MAIT, iNKT, and γδT cells. This study also assesses the antitumor ability of CAR-engineered innate T cells, evaluating their potential adoption for clinical therapies. The in vitro trials presented in this study demonstrate the considerable TAM-killing abilities of all three innate T cell types, and confirm the enhanced antitumor abilities of CAR-engineered innate T cells. The tumor- and TAM-targeting capacity of these innate T cells suggest their potential for antitumor therapy that supplements cytotoxicity with remediation of tumor microenvironment (TME)-immunosuppression. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) accumulate in the solid tumor microenvironment (TME) and have been shown to promote tumor growth and dampen antitumor immune responses. TAM-mediated suppression of T-cell antitumor reactivity is considered to be a major obstacle for many immunotherapies, including immune checkpoint blockade and adoptive T/CAR-T-cell therapies. An ex vivo culture system closely mimicking the TME can greatly facilitate the study of cancer immunotherapies. Here, we report the development of a 3D TME-mimicry culture that is comprised of the three major components of a human TME, including human tumor cells, TAMs, and tumor antigen-specific T cells. This TME-mimicry culture can readout the TAM-mediated suppression of T-cell antitumor reactivity, and therefore can be used to study TAM modulation of T-cell-based cancer immunotherapy. As a proof-of-principle, the studies of a PD-1/PD-L1 blockade therapy and a MAO-A blockade therapy were performed and validated. [ABSTRACT FROM AUTHOR]

Objectives: We determined how often emergency physician pediatric musculoskeletal (MSK) radiograph interpretations were discordant to that of a radiologist and led to an adverse event (AE). We also established the variables independently associated with this outcome. Methods: This prospective cohort study was conducted in an urban, tertiary care children's emergency department (ED). We enrolled children who presented to an ED with an extremity injury and received radiographs. ED physicians documented their radiograph interpretation, which was compared to a radiology reference standard. Patients received telephone follow‐up and had institutional medical records reviewed in 3 weeks. An AE occurred if there were clinical sequelae and/or repeat health care visits due to a delay in correct radiograph interpretation. Results: We enrolled 2,302 children (mean [±SD] age = 9.0 [4.4] years; 1,288 (56.0%) male]. Of these, 180 (7.8%; 95% confidence interval = 6.8 to 9.0) ED physician discordant interpretations resulted in an AE. Specifically, there were no negative clinical outcomes; however, relative to cases diagnosed correctly at the index ED, patients whose fracture was not initially identified encountered 77.2% more subsequent ED visits, while those falsely diagnosed with a fracture experienced 41.5% additional orthopedic clinic visits. Odds of an ED discrepant interpretation was significantly higher if a physician's pretest probability of a fracture was ≤ 20% versus> 20% (adjusted odds ratio [aOR] = 1.6), patient's pain score was ≤ 2 versus> 2 (aOR = 1.6), and injury was located in a joint versus other location (aOR = 1.7). Conclusions: Emergency physician discordant pediatric MSK radiograph interpretations that resulted in an AE occurred with regular frequency in a pediatric ED setting. AEs were primarily an increase in subsequent health care visits. Importantly, a low clinical suspicion for a fracture or injury located in the joint were risk factors for ED physician discordant interpretations. [ABSTRACT FROM AUTHOR]

This study aimed to determine the success of university student volunteers in obtaining consent from parents to allow review of their child’s personal health information (PHI) for emergency research screening. This study also aimed to examine the variables associated with successful consent. This was a prospective cross-sectional study conducted at a pediatric emergency department (ED). University students, who functioned as delegates of the health information custodian, approached parents for consent. Of 2,506 parents, 1,852 (73.9%) provided consent to allow review of their child’s PHI for research screening. Variables associated with successful consent were high (≥12 months) versus low (<12 months) volunteer experience (OR = 2.0), research related (vs. unrelated) to the child’s chief complaint (OR = 2.0), child treated regularly by specialists at the study institution (OR = 1.7), and ED presentation mid-week vs. weekend (OR = 1.7) and morning vs. evening presentation (OR = 1.4). When approached by a university student volunteer, about 25% of parents declined to have their child’s PHI reviewed for research screening. This model of obtaining consent may put some emergency research at risk for selection bias. Variables that increase the odds of successful consent can be considered in program design to improve the effectiveness of this model. [ABSTRACT FROM PUBLISHER]

Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease. [ABSTRACT FROM AUTHOR]

The balance between cellular lineages can be controlled by reactive oxygen species (ROS). Cellular differentiation into adipocytes is highly dependent on the production of ROS to initiate the process through activation of multiple interlinked factors that stimulate mitotic clonal expansion and cellular maturation. The signal transducer and activator of transcription family of signaling proteins have accepted roles in adipogenesis and associated lipogenesis. Non-canonical mitochondrial localization of STAT3 and other members of the STAT family however opens up new avenues for investigation of its role in the aforementioned processes. Following recent observations of differences in mitochondrially localized serine 727 phosphorylated STAT3 (mtSTAT3-pS727) in preadipocytes and adipocytes, here, we hypothesize and speculate further on the role of mitochondrial STAT3 in adipogenesis. [ABSTRACT FROM AUTHOR]