The use and prescription of pangolin in traditional Vietnamese medicine

It is now acknowledged that demand stemming from traditional medicine stimulates a continued market for illegal wildlife trade globally. Increasing demand for pangolin fuels widespread unsustainable extraction and an illicit international trade that is threatening pangolin populations worldwide. Vietnam is an important transit country in this trafficking network and a significant consumer country, particularly due to their longstanding tradition of consuming wildlife products as traditional medicine. We conducted 51 semi-structured, questionnaire-based interviews with traditional Vietnamese medicine practitioners in Hanoi, Vietnam to explore the factors influencing their prescription of pangolin. The results show that traditional Vietnamese medicine practitioners are important drivers of pangolin use and that prescription continues despite prohibitive legislation. The main influencing factors were money, illegality (as a deterrent) and supply. Wealthier patients were more likely to use pangolin as medicine and patients generally trusted a doctor’s prescription. Awareness of regulations related to pangolin use in traditional medicine was low and pangolin use continued without fear of the law. Lactation, abscesses and circulation were the most prescribed uses for pangolin scales. All respondents believed that pangolin can be substituted, however, a belief remained that substitutes are inferior to pangolin. This study provides a unique perspective of pangolin use in one of the main pangolin consumption countries in the world. The results suggest that the law is not being implemented effectively and that increased enforcement efforts are necessary. Furthermore, these insights serve to inform future demand-reduction campaigns whereby the most common uses and substitutes for pangolin scales may be targeted

A Toxicogenomic Comparison of Primary and Photochemically Altered Air Pollutant Mixtures

Background: Air pollution contributes significantly to global increases in mortality, particularly within urban environments. Limited knowledge exists on the mechanisms underlying health effects resulting from exposure to pollutant mixtures similar to those occurring in ambient air. In order to clarify the mechanisms underlying exposure effects, toxicogenomic analyses are used to evaluate genomewide transcript responses and map these responses to molecular networks

Regional-Specific Effects of Ovarian Hormone Loss on Synaptic Plasticity in Adult Human APOE Targeted Replacement Mice

The human apolipoprotein ε4 allele (APOE4) has been implicated as one of the strongest genetic risk factors associated with Alzheimer’s disease (AD) and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR) mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX) mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD

Polycyclic Aromatic Hydrocarbons in Maternal and Umbilical Cord Blood from Pregnant Hispanic Women Living in Brownsville, Texas

Venous blood was drawn from 35 pregnant Hispanic women living in Brownsville, Texas, and matched cord blood was collected at birth. Gas chromatography/mass spectrometry was used to measure concentrations of 55 individual PAHs or groups of PAHs. Results indicate that these women and their fetuses were regularly exposed to multiple PAHs at comparatively low concentrations, with levels in cord blood generally exceeding levels in paired maternal blood. While the possibility of related adverse effects on the fetus is uncertain, these exposures in combination with socioeconomically-disadvantaged and environmentally-challenging living conditions raise legitimate public health concerns

Epigenetic Changes Induced by Air Toxics: Formaldehyde Exposure Alters miRNA Expression Profiles in Human Lung Cells

Bac k g r o u n d: Exposure to formaldehyde, a known air toxic, is associated with cancer and lung disease. Despite the adverse health effects of formaldehyde, the mechanisms underlying formaldehydeinduced disease remain largely unknown. Research has uncovered microRNAs (miRNAs) as key posttranscriptional regulators of gene expression that may influence cellular disease state. Although studies have compared different miRNA expression patterns between diseased and healthy tissue, this is the first study to examine perturbations in global miRNA levels resulting from formaldehyde exposure. Objectives: We investigated whether cellular miRNA expression profiles are modified by formaldehyde exposure to test the hypothesis that formaldehyde exposure disrupts miRNA expression levels within lung cells, representing a novel epigenetic mechanism through which formaldehyde may induce disease. Me t h o d s: Human lung epithelial cells were grown at air–liquid interface and exposed to gaseous formaldehyde at 1 ppm for 4 hr. Small RNAs and protein were collected and analyzed for miRNA expression using microarray analysis and for interleukin (IL-8) protein levels by enzyme-linked immunosorbent assay (ELISA). Res u l t s: Gaseous formaldehyde exposure altered the miRNA expression profiles in human lun

In Vitro Exposure to Isoprene-Derived Secondary Organic Aerosol by Direct Deposition and its Effects on COX-2 and IL-8 Gene Expression

Atmospheric oxidation of isoprene, the most abundant non-methane hydrocarbon emitted into Earth's atmosphere primarily from terrestrial vegetation, is now recognized as a major contributor to the global secondary organic aerosol (SOA) burden. Anthropogenic pollutants significantly enhance isoprene SOA formation through acid-catalyzed heterogeneous chemistry of epoxide products. Since isoprene SOA formation as a source of fine aerosol is a relatively recent discovery, research is lacking on evaluating its potential adverse effects on human health. The objective of this study was to examine the effect of isoprene-derived SOA on inflammation-associated gene expression in human lung cells using a direct deposition exposure method. We assessed altered expression of inflammation-related genes in human bronchial epithelial cells (BEAS-2B) exposed to isoprene-derived SOA generated in an outdoor chamber facility. Measurements of gene expression of known inflammatory biomarkers interleukin 8 (IL-8) and cyclooxygenase 2 (COX-2) in exposed cells, together with complementary chemical measurements, showed that a dose of 0.067 µg cm−2 of SOA from isoprene photooxidation leads to statistically significant increases in IL-8 and COX-2 mRNA levels. Resuspension exposures using aerosol filter extracts corroborated these findings, supporting the conclusion that isoprene-derived SOA constituents induce the observed changes in mRNA levels. The present study is an attempt to examine the early biological responses of isoprene SOA exposure in human lung cells

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Development and initial validation of the Influences on Patient Safety Behaviours Questionnaire

YesBackground: Understanding the factors that make it more or less likely that healthcare practitioners (HCPs) will perform certain patient safety behaviors is important in developing effective intervention strategies. A questionnaire to identify determinants of HCP patient safety behaviors does not currently exist. This study reports the development and initial validation of the Influences on Patient Safety Behaviors Questionnaire (IPSBQ) based on the Theoretical Domains Framework. Methods: Two hundred and thirty-three HCPs from three acute National Health Service Hospital Trusts in the United Kingdom completed the 34-item measure focusing on one specific patient safety behavior (using pH as the first line method for checking the position of a nasogastric tube). Confirmatory factor analysis (CFA) was undertaken to generate the model of best fit. Results: The final questionnaire consisted of 11 factors and 23 items, and CFA produced a reasonable fit: χ2 (175) = 345.7, p < 0.001; CMIN/DF = 1.98; GFI = 0.90 and RMSEA = 0.06, as well as adequate levels of discriminant validity, and internal consistency (r = 0.21 to 0.64). Conclusions: A reliable and valid theoretically underpinned measure of determinants of HCP patient safety behavior has been developed. The criterion validity of the measure is still unknown and further work is necessary to confirm the reliability and validity of this measure for other patient safety behaviors

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts