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"Carter, Jason"
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How to train a train
Loco for locomotives? Get your ticket ready--here's everything you need to know about finding, keeping, and training your very own pet train.
Book
Sex differences in self-report anxiety and sleep quality during COVID-19 stay-at-home orders
Background
COVID-19 and home isolation has impacted quality of life, but the perceived impact on anxiety and sleep remains equivocal. The purpose of this study was to assess the impact of COVID-19 and stay-at-home orders on self-report anxiety and sleep quality, with a focus on sex differences. We hypothesized that the COVID-19 pandemic would be associated with increased anxiety and decreased sleep quality, with stronger associations in women.
Methods
One hundred three participants (61 female, 38 ± 1 years) reported perceived changes in anxiety and sleep quality due to stay-at-home orders during the COVID-19 pandemic and were administered the Spielberger State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI). Chi-square and
T
test analyses were utilized to assess sex differences in reported anxiety and sleep. Analysis of covariance was used to compare the associations between reported impact of COVID-19 and anxiety/sleep parameters.
Results
Women (80.3%) reported higher prevalence of increased general anxiety due to COVID-19 when compared to men (50%;
p
= 0.001) and elevated STAI state anxiety compared to men (43 ± 1 vs. 38 ± 1 a.u.,
p
= 0.007). Despite these differences in anxiety, the perceived impact of COVID-19 on PSQI was not different between sexes. However, when stratified by perceived changes in anxiety due to COVID-19, participants with higher anxiety responses to COVID-19 had higher ISI compared to those with no perceived changes in anxiety (9 ± 1 vs. 5 ± 1 a.u.,
p
= 0.003). Additionally, participants who reported reduced sleep quality due to COVID-19 reported higher state anxiety (45 ± 1 a.u.) compared to those that perceived no change (36 ± 2 a.u.,
p
= 0.002) or increased (36 ± 2 a.u.,
p
< 0.001) sleep quality.
Conclusion
COVID-19 and state-ordered home isolation was associated with higher anxiety and reduced sleep quality, with a stronger association in women with respect to anxiety.
Journal Article
Great, now we've got barbarians!
\"Why do grown-ups make such a fuss about tidiness and cleanliness, anyway? What's the worst that could happen? A couple of ants pass through? A lone little mouse pays a midnight call? No big deal, right? Right? Author Jason Carter Eaton and illustrator Mark Fearing are here to caution you that being a slob might in fact be a big deal--a really big deal\"--Dust jacket flap.
Book
Assessment of sympathetic neural activity in chronic insomnia: evidence for elevated cardiovascular risk
Abstract
Study Objectives
Chronic insomnia affects up to 15 per cent of adults. Recent cross-sectional and prospective epidemiological studies report an association between insomnia and hypertension, including incident hypertension, yet mechanisms underlying the association remain unknown. We hypothesized that participants with chronic insomnia would have elevated sympathetic neural outflow, blunted baroreflex sensitivity, and augmented sympathetic neural and cardiovascular reactivity to stress when compared with good-sleeper controls.
Methods
Twelve participants with chronic insomnia (11 women, 1 man) and 12 controls (8 women, 4 men) underwent one night of laboratory polysomnography, two weeks of at-home wrist actigraphy, and one night of controlled laboratory sleep prior to a comprehensive morning autonomic function test. The autonomic function test consisted of simultaneous recordings of muscle sympathetic nerve activity (MSNA; microneurography), beat-to-beat blood pressure (finger plethysmography), and heart rate (electrocardiogram) during a 10 min supine baseline and a 2 min cold pressor test.
Results
Baseline blood pressure, heart rate, and MSNA were not different between groups, but sympathetic baroreflex sensitivity was significantly blunted in participants with insomnia (−2.1 ± 1.0 vs. −4.3 ± 1.3 bursts/100 heartbeats/mm Hg; p < 0.001). During the cold pressor test, systolic arterial pressure reactivity (Δ21 ± 11 vs. Δ14 ± 8 mm Hg; time × group = 0.04) and total MSNA reactivity (Δ127%, 54%–208% vs. Δ52%, 30%–81%; time × group = 0.02) were augmented in chronic insomnia.
Conclusions
Participants with chronic insomnia demonstrated impaired sympathetic baroreflex function and augmented neural cardiovascular responsiveness to stress, when compared with controls. These findings support growing evidence of cardiovascular risk and physiological hyperarousal in chronic insomnia.
Clinical Trial Registration
NCT02048878. https://clinicaltrials.gov/ct2/show/NCT02048878
Journal Article
How to track a truck
\"A whimsical guide to training a \"pet truck\" instructs young enthusiasts on how to identify the most compatible truck for one's personality and how to use orange cone lures to secure a loyal vehicle.\"-- Provided by publisher.
Book
Emerging interleukin targets in the tumour microenvironment: implications for the treatment of gastrointestinal tumours
The effectiveness of antitumour immunity is dependent on intricate cytokine networks. Interleukins (ILs) are important mediators of complex interactions within the tumour microenvironment, including regulation of tumour-infiltrating lymphocyte proliferation, differentiation, migration and activation. Our evolving and increasingly nuanced understanding of the cell type-specific and heterogeneous effects of IL signalling has presented unique opportunities to fine-tune elaborate IL networks and engineer new targeted immunotherapeutics. In this review, we provide a primer for clinicians on the challenges and potential of IL-based treatment. We specifically detail the roles of IL-2, IL-10, IL-12 and IL-15 in shaping the tumour-immune landscape of gastrointestinal malignancies, paying particular attention to promising preclinical findings, early-stage clinical research and innovative therapeutic approaches that may properly place ILs to the forefront of immunotherapy regimens.
Journal Article
The catawampus cat
The Catawampus Cat walked into town one day at a slant, and since then everyone in town is seeing their world with fresh eyes.
Book
Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases
ObjectiveProgrammed cell death protein 1 (PD-1) checkpoint inhibition and adoptive cellular therapy have had limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We sought to evaluate the effect of interleukin 10 (IL-10) blockade on endogenous T cell and chimeric antigen receptor T (CAR-T) cell antitumour function in CRLM slice cultures.DesignWe created organotypic slice cultures from human CRLM (n=38 patients’ tumours) and tested the antitumour effects of a neutralising antibody against IL-10 (αIL-10) both alone as treatment and in combination with exogenously administered carcinoembryonic antigen (CEA)-specific CAR-T cells. We evaluated slice cultures with single and multiplex immunohistochemistry, in situ hybridisation, single-cell RNA sequencing, reverse-phase protein arrays and time-lapse fluorescent microscopy.ResultsαIL-10 generated a 1.8-fold increase in T cell-mediated carcinoma cell death in human CRLM slice cultures. αIL-10 significantly increased proportions of CD8+ T cells without exhaustion transcription changes, and increased human leukocyte antigen - DR isotype (HLA-DR) expression of macrophages. The antitumour effects of αIL-10 were reversed by major histocompatibility complex class I or II (MHC-I or MHC-II) blockade, confirming the essential role of antigen presenting cells. Interrupting IL-10 signalling also rescued murine CAR-T cell proliferation and cytotoxicity from myeloid cell-mediated immunosuppression. In human CRLM slices, αIL-10 increased CEA-specific CAR-T cell activation and CAR-T cell-mediated cytotoxicity, with nearly 70% carcinoma cell apoptosis across multiple human tumours. Pretreatment with an IL-10 receptor blocking antibody also potentiated CAR-T function.ConclusionNeutralising the effects of IL-10 in human CRLM has therapeutic potential as a stand-alone treatment and to augment the function of adoptively transferred CAR-T cells.
Journal Article
Transcriptomic diversity in human medullary thymic epithelial cells
The induction of central T cell tolerance in the thymus depends on the presentation of peripheral self-epitopes by medullary thymic epithelial cells (mTECs). This promiscuous gene expression (pGE) drives mTEC transcriptomic diversity, with non-canonical transcript initiation, alternative splicing, and expression of endogenous retroelements (EREs) representing important but incompletely understood contributors. Here we map the expression of genome-wide transcripts in immature and mature human mTECs using high-throughput 5’ cap and RNA sequencing. Both mTEC populations show high splicing entropy, potentially driven by the expression of peripheral splicing factors. During mTEC maturation, rates of global transcript mis-initiation increase and EREs enriched in long terminal repeat retrotransposons are up-regulated, the latter often found in proximity to differentially expressed genes. As a resource, we provide an interactive public interface for exploring mTEC transcriptomic diversity. Our findings therefore help construct a map of transcriptomic diversity in the healthy human thymus and may ultimately facilitate the identification of those epitopes which contribute to autoimmunity and immune recognition of tumor antigens.
The thymus generates all T cells, including those that underly autoimmune diseases. Here, using deep sequencing, the authors profile human medullary thymic epithelial cells and establish a web portal to query their transcriptome, which may serve as a tool to help identify the drivers of autoimmunity.
Journal Article