How do our senses help us to understand the world? This question, which preoccupied Enlightenment thinkers, also emerged as a key theme in depictions of animals in eighteenth-century art. This book ...examines the ways in which painters such as Chardin, as well as sculptors, porcelain modelers, and other decorative designers portrayed animals as sensing subjects who physically confirmed the value of material experience. The sensual style known today as the Rococo encouraged the proliferation of animals as exemplars of empirical inquiry, ranging from the popular subject of the monkey artist to the alchemical wonders of the life-sized porcelain animals created for the Saxon court. Examining writings on sensory knowledge by La Mettre, Condillac, Diderot and other philosophers side by side with depictions of the animal in art, Cohen argues that artists promoted the animal as a sensory subject while also validating the material basis of their own professional practice.
Inverse associations between dairy consumption and CVD have been reported in several epidemiological studies. Our objective was to conduct a meta-analysis of prospective cohort studies of dairy ...intake and CVD. A comprehensive literature search was conducted to identify studies that reported risk estimates for total dairy intake, individual dairy products, low/full-fat dairy intake, Ca from dairy sources and CVD, CHD and stroke. Random-effects meta-analyses were used to generate summary relative risk estimates (SRRE) for high v. low intake and stratified intake dose-response analyses. Additional dose-response analyses were performed. Heterogeneity was examined in sub-group and sensitivity analyses. In total, thirty-one unique cohort studies were identified and included in the meta-analysis. Several statistically significant SRRE below 1.0 were observed, namely for total dairy intake and stroke (SRRE=0·91; 95% CI 0·83, 0·99), cheese intake and CHD (SRRE=0·82; 95% CI 0·72, 0·93) and stroke (SRRE=0·87; 95% CI 0·77, 0·99), and Ca from dairy sources and stroke (SRRE=0·69; 95% CI 0·60, 0·81). However, there was little evidence for inverse dose-response relationships between the dairy variables and CHD and stroke after adjusting for within-study covariance. The results of this meta-analysis of prospective cohort studies have shown that dairy consumption may be associated with reduced risks of CVD, although additional data are needed to more comprehensively examine potential dose-response patterns.
Little is known about the efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab for patients with Crohn's disease (CD) or ulcerative colitis (UC). We ...analyzed the outcomes of patients receiving vedolizumab along with calcineurin inhibitors.
We collected data on patients with CD (n = 9) or UC (n = 11) who began treatment with vedolizumab from May 20, 2014, through March 30, 2015, and received calcineurin inhibitors (tacrolimus or cyclosporin) during the first 12 months of vedolizumab therapy. Clinical activity scores and inflammatory markers were measured at baseline and at weeks 14, 30, and 52 of vedolizumab treatment. Clinical remission was defined as a Harvey-Bradshaw index score ≤4 or short clinical colitis activity index score ≤2; steroid-free clinical remission was defined as clinical remission without corticosteroids.
By week 14 of treatment, 44% of the patients with CD and 55% of the patients with UC achieved steroid-free clinical remission; after 52 weeks of treatment, 33% of the patients with CD and 45% of the patients with UC were in steroid-free clinical remission. Seven patients received salvage therapy with a calcineurin inhibitor after primary nonresponse to vedolizumab-1 of the 2 patients with UC and 2 of 5 patients with CD stopped taking the calcineurin inhibitors and achieved steroid-free remission at week 52. In total, 16 patients (59%) received 52 weeks of treatment with vedolizumab. Three serious adverse events were associated with calcineurin inhibitors.
Combination therapy of vedolizumab with either cyclosporin or tacrolimus is effective and safe at inducing and maintaining clinical remission in patients with CD and UC with up to 52 weeks of follow-up evaluation. Larger studies of the ability of calcineurin inhibitors to induce remission in patients on vedolizumab are warranted.
Sickle cell disease (SCD) pain and hospitalizations increase during adolescence and adolescents with SCD may be at-risk for experiencing health-related stigma, which may result in poor health ...outcomes. This study examined relations among health-related stigma, pain interference, social support, quality of life (QOL), and hospital outcomes (ie, loneliness, pain reduction, and length of stay LOS) in adolescents hospitalized with SCD pain.
Twelve- to 18-year-old adolescents (N=92) hospitalized with SCD pain completed measures of stigma, pain interference, social support, QOL, and state loneliness. Reduction of pain intensity during hospitalization and LOS were collected from medical chart review.
Higher stigma was associated with higher pain interference, lower QOL, more loneliness, and less pain reduction in the hospital. Pain interference was positively associated with LOS.
These preliminary findings highlight the importance of assessing and addressing SCD-related stigma and pain interference in adolescents hospitalized for SCD pain as these factors may influence treatment outcomes.
•We studied 872 Houston residents who experienced Hurricane Harvey and COVID-19.•Lower neighborhood median income was linked to greater symptoms of PTSD.•Higher neighborhood income inequality was ...linked to greater symptoms of depression.•Higher neighborhood income inequality was linked to greater symptoms of PTSD.•Adjusting for event-specific stressors and traumas rendered these associations null.
Little is known about how neighborhood economic characteristics relate to risk of depression and Posttraumatic Stress Disorder (PTSD) in the context of multiple disasters. We sampled 88 super neighborhoods in Houston, Texas and surveyed 872 residents who were living in Houston during Hurricane Harvey and COVID-19 and lived in the same residence since Hurricane Harvey, about their demographics and symptoms of depression and PTSD. Using data from the American Community Survey, we estimated neighborhood-level unemployment, median income, and income inequality (i.e., Gini coefficient). We investigated whether these underlying neighborhood socioeconomic factors were associated with the mental health consequences of mass traumatic events. We examined associations between neighborhood-level constructs and individual-level depression and PTSD, using multilevel linear models. Partially adjusted multilevel models showed that lower neighborhood median income was associated with higher symptom scores of PTSD, while greater neighborhood income inequality was associated with higher symptom scores of depression and PTSD. However, fully adjusted models showed that these associations are better accounted for by event-specific stressors and traumas. These findings suggest that in the context of multiple large scale traumatic events, neighborhood socioeconomic context may structure individual-level exposure to stressful and traumatic events.
Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies, and pathological fractures. MS ...is distinguished from OD by the development of vascular anomalies. Both disorders are cancer predisposition syndromes with malignancies developing in ~50% of the individuals with OD or MS. Somatic gain-of-function variants in IDH1 and IDH2 have been described in the enchondromas, vascular anomalies and chondrosarcomas of approximately 80% of the individuals with OD and MS. To date, however, no investigation of germline causative variants for these diseases has been comprehensively performed. To search for germline causative variants, we performed whole exome sequencing or whole genome sequencing of blood or saliva DNA in 94 unrelated probands (68 trios). We found that 7 had rare germline missense variants in HIF1A, 6 had rare germline missense variants in VHL, and 3 had IDH1 variants including 2 with mosaic IDH1-p.Arg132His variant. A burden analysis using 94 probands assigned as cases and 2,054 unrelated individuals presenting no OD- or MS-related features as controls, found that variants in HIF1A, VHL, and IDH1 were all significantly enriched in cases compared to controls. To further investigate the role of HIF-1 pathway in the pathogenesis of OD and MS, we performed RNA sequencing of fibroblasts from 4 probands with OD or MS at normoxia and at hypoxia. When cultured in hypoxic conditions, both proband and control cells showed altered expression of a subset of HIF-1 regulated genes. However, the set of differentially expressed genes in proband fibroblasts included a significantly reduced number of HIF-1 regulated genes compared to controls. Our findings suggest that germline or early post-zygotic variants identified in HIF1A, VHL, and IDH1 in probands with OD and MS underlie the development of the phenotypic abnormalities in a subset of individuals with OD and MS, but extensive functional studies are needed to further confirm it.
Psychiatric disorders that are characterized by impairments in sustained attention, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and major ...depression are also sensitive to exacerbation by stress. Sustained attention relies on cholinergic and non-cholinergic projections from the nucleus basalis of Meynert (NBM) in the basal forebrain to the medial prefrontal cortex (mPFC). We have previously shown that central administration of the stress neuropeptide corticotropin releasing factor (CRF) impairs performance on the sustained attention task (SAT) in adult male and female rats. The present study investigated whether this effect was mediated by CRF's action in the NBM. Rats were administered CRF in the NBM and subsequent SAT performance was measured. A high dose of CRF (100 ng) significantly impaired performance on non-signaled events across sex. Because performance on non-signaled events is believed to depend on non-cholinergic (i.e., GABA and glutamate) signaling, high performance liquid chromatography was used to quantify amino acid levels in the NBM and mPFC. We found females have higher levels of glutamate, glutamine, GABA glycine, and alanine in the NBM than males. Importantly, CRF in the NBM led to a local decrease of taurine and several amino acids involved in glutamate synthesis in males and females, changes which may mediate the CRF-induced SAT performance deficit. Together these studies suggest that CRF regulation of amino acids in the NMB contributes to stress-induced attention deficits.
•CRF in the NBM impaired sustained attention.•CRF in the NBM decreased NBM levels of amino acids involved in glutamate synthesis.•CRF in the NBM decreased NBM taurine levels.•There are baseline sex differences in mPFC and NBM amino acid levels.•These data suggest CRF disrupts attention by suppressing glutamate and taurine.
Abstract
Introduction
Treatment of ulcerative colitis (UC) now includes mucosal healing. Adoption of histologic end points is hindered by a lack of evidence guiding optimal sampling, interpretation, ...and reproducibility of results.
Methods
We analyzed biopsy fragments from colonoscopies in 92 patients with UC. Fragments were scored using 6-point histologic inflammatory activity (HIA) scale. Variability was determined using ordinal representations of HIA scores. The most frequently observed score and percentage of biopsy fragments with that score were determined for each biopsy, each segment, and across all 3 segments for each colonoscopy. Mean percentages and 95% confidence intervals (CIs) were calculated.
Results
We reviewed 1802 biopsy fragments. The mean percentages of intrasegment biopsy fragments with the same HIA score were 85.5% (95% CI, 80.9% to 92.9%), 79.6% (95% CI, 76.0% to 87.3%), and 82.7% (95% CI, 79.1% to 90.0%) for the rectum, left colon, and right colon, respectively. The mean percentage of intersegment biopsy fragments with the same HIA score was 70.2% (95% CI, 65.7% to 82.5%). The mean percentages of intrabiopsy fragments with the same HIA score were 83.3% (95% CI, 77.6% to 93.5%), 83.6% (95% CI, 80.1% to 89.7%), and 90.2% (95% CI, 87.6% to 94.7%) for the rectum, left colon, and right colon, respectively. All 3 analyses revealed increased variation when a greater degree of histologic inflammation was present in the biopsies (mean HIA score ≥2).
Conclusions
We found minimal variability between degree of inflammation among biopsy fragments within and among different colorectal segments in UC, suggesting that even a single biopsy would adequately reflect the inflammation of the entire colorectum. These findings have significant implications for the use of histology as a clinical target and trial end point in UC.
Highlights • Corticotropin releasing factor (CRF) evokes more grooming in female than male rats. • Circulating ovarian hormones moderate the sex difference in CRF-evoked grooming. • CRF-activated ...functional connectivity networks differ based on hormonal status. • Hormonal regulation of stress circuitry may establish sex differences in anxiety
Little is known about the combined impact of the COVID-19 pandemic and other major disasters on mental health. Hurricane Harvey hit the Gulf Coast in 2017, resulting in substantial costs, significant ...levels of displacement, and approximately 100 deaths, and was followed in 2020 by the COVID-19 pandemic. We randomly sampled 1167 Houstonians from 88 designated super-neighborhoods and surveyed them about their demographics, event-specific traumas and stressors, and symptoms of current depression and post-traumatic stress disorder (PTSD). We estimated the prevalence of depression (5.8%) and PTSD (12.6%) more than three years after Hurricane Harvey, and assessed the relative influence of event-specific stressors and traumas on current mental health. Overall, we observed evidence for two key findings that are salient for residents of urban environments in the context of multiple disasters. First, stressors were primary influences on depression, whereas both stressors and traumas influenced PTSD. Second, the influences of stressors and traumas on depression and PTSD symptoms faded with time.
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