How High? Trends in Cannabis Use Prior to First Admission to Inpatient Psychiatry in Ontario, Canada, between 2007 and 2017

Objectives: To examine the trends in cannabis use within 30 days of first admission to inpatient psychiatry in Ontario, Canada, between 2007 and 2017, and the characteristics of persons reporting cannabis use. Methods: A retrospective cross-sectional analysis was conducted for first-time admissions to nonforensic inpatient psychiatric beds in Ontario, Canada, between January 1, 2007, and December 31, 2017, using data from the Ontario Mental Health Reporting System (N = 81,809). Results: Across all years, 20.1% of patients reported cannabis use within 30 days of first admission. Use increased from 16.7% in 2007 to 25.9% in 2017, and the proportion with cannabis use disorders increased from 3.8% to 6.0%. In 2017, 47.9% of patients aged 18 to 24 and 39.2% aged 25 to 34 used cannabis, representing absolute increases of 8.3% and 10.7%, respectively. Increases in cannabis use were found across almost all diagnostic groups, with the largest increases among patients with personality disorders (15% increase), schizophrenia or other psychotic disorders (14% increase), and substance use disorders (14% increase). A number of demographic and clinical factors were significantly associated with cannabis use, including interactions between schizophrenia and gender (area under the curve = 0.88). Conclusions: As medical cannabis policies in Canada have evolved, cannabis use reported prior to first admission to inpatient psychiatry has increased. The findings of this study establish a baseline for evaluating the impact of changes in cannabis-related policies in Ontario on cannabis use prior to admission to inpatient psychiatry

HMGA1 Induces Intestinal Polyposis in Transgenic Mice and Drives Tumor Progression and Stem Cell Properties in Colon Cancer Cells

Although metastatic colon cancer is a leading cause of cancer death worldwide, the molecular mechanisms that enable colon cancer cells to metastasize remain unclear. Emerging evidence suggests that metastatic cells develop by usurping transcriptional networks from embryonic stem (ES) cells to facilitate an epithelial-mesenchymal transition (EMT), invasion, and metastatic progression. Previous studies identified HMGA1 as a key transcription factor enriched in ES cells, colon cancer, and other aggressive tumors, although its role in these settings is poorly understood.To determine how HMGA1 functions in metastatic colon cancer, we manipulated HMGA1 expression in transgenic mice and colon cancer cells. We discovered that HMGA1 drives proliferative changes, aberrant crypt formation, and intestinal polyposis in transgenic mice. In colon cancer cell lines from poorly differentiated, metastatic tumors, knock-down of HMGA1 blocks anchorage-independent cell growth, migration, invasion, xenograft tumorigenesis and three-dimensional colonosphere formation. Inhibiting HMGA1 expression blocks tumorigenesis at limiting dilutions, consistent with depletion of tumor-initiator cells in the knock-down cells. Knock-down of HMGA1 also inhibits metastatic progression to the liver in vivo. In metastatic colon cancer cells, HMGA1 induces expression of Twist1, a gene involved in embryogenesis, EMT, and tumor progression, while HMGA1 represses E-cadherin, a gene that is down-regulated during EMT and metastatic progression. In addition, HMGA1 is among the most enriched genes in colon cancer compared to normal mucosa.Our findings demonstrate for the first time that HMGA1 drives proliferative changes and polyp formation in the intestines of transgenic mice and induces metastatic progression and stem-like properties in colon cancer cells. These findings indicate that HMGA1 is a key regulator, both in metastatic progression and in the maintenance of a stem-like state. Our results also suggest that HMGA1 or downstream pathways could be rational therapeutic targets in metastatic, poorly differentiated colon cancer

HMGA1 drives stem cell, inflammatory pathway, and cell cycle progression genes during lymphoid tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Although the <it>high mobility group A1 </it>(<it>HMGA1</it>) gene is widely overexpressed in diverse cancers and portends a poor prognosis in some tumors, the molecular mechanisms that mediate its role in transformation have remained elusive. <it>HMGA1 </it>functions as a potent oncogene in cultured cells and induces aggressive lymphoid tumors in transgenic mice. Because HMGA1 chromatin remodeling proteins regulate transcription, <it>HMGA1 </it>is thought to drive malignant transformation by modulating expression of specific genes. Genome-wide studies to define HMGA1 transcriptional networks during tumorigenesis, however, are lacking. To define the HMGA1 transcriptome, we analyzed gene expression profiles in lymphoid cells from <it>HMGA1a </it>transgenic mice at different stages in tumorigenesis.</p> <p>Results</p> <p>RNA from lymphoid samples at 2 months (before tumors develop) and 12 months (after tumors are well-established) was screened for differential expression of > 20,000 unique genes by microarray analysis (Affymetrix) using a parametric and nonparametric approach. Differential expression was confirmed by quantitative RT-PCR in a subset of genes. Differentially expressed genes were analyzed for cellular pathways and functions using Ingenuity Pathway Analysis. Early in tumorigenesis, HMGA1 induced inflammatory pathways with NFkappaB identified as a major node. In established tumors, HMGA1 induced pathways involved in cell cycle progression, cell-mediated immune response, and cancer. At both stages in tumorigenesis, HMGA1 induced pathways involved in cellular development, hematopoiesis, and hematologic development. Gene set enrichment analysis showed that stem cell and immature T cell genes are enriched in the established tumors. To determine if these results are relevant to human tumors, we knocked-down HMGA1 in human T-cell leukemia cells and identified a subset of genes dysregulated in both the transgenic and human lymphoid tumors.</p> <p>Conclusions</p> <p>We found that <it>HMGA1 </it>induces inflammatory pathways early in lymphoid tumorigenesis and pathways involved in stem cells, cell cycle progression, and cancer in established tumors. <it>HMGA1 </it>also dyregulates genes and pathways involved in stem cells, cellular development and hematopoiesis at both early and late stages of tumorigenesis. These results provide insight into <it>HMGA1 </it>function during tumor development and point to cellular pathways that could serve as therapeutic targets in lymphoid and other human cancers with aberrant <it>HMGA1 </it>expression.</p

HMGA1 Reprograms Somatic Cells into Pluripotent Stem Cells by Inducing Stem Cell Transcriptional Networks

PMC3499526BACKGROUND: Although recent studies have identified genes expressed in human embryonic stem cells (hESCs) that induce pluripotency, the molecular underpinnings of normal stem cell function remain poorly understood. The high mobility group A1 (HMGA1) gene is highly expressed in hESCs and poorly differentiated, stem-like cancers; however, its role in these settings has been unclear. METHODS/PRINCIPAL FINDINGS: We show that HMGA1 is highly expressed in fully reprogrammed iPSCs and hESCs, with intermediate levels in ECCs and low levels in fibroblasts. When hESCs are induced to differentiate, HMGA1 decreases and parallels that of other pluripotency factors. Conversely, forced expression of HMGA1 blocks differentiation of hESCs. We also discovered that HMGA1 enhances cellular reprogramming of somatic cells to iPSCs together with the Yamanaka factors (OCT4, SOX2, KLF4, cMYC - OSKM). HMGA1 increases the number and size of iPSC colonies compared to OSKM controls. Surprisingly, there was normal differentiation in vitro and benign teratoma formation in vivo of the HMGA1-derived iPSCs. During the reprogramming process, HMGA1 induces the expression of pluripotency genes, including SOX2, LIN28, and cMYC, while knockdown of HMGA1 in hESCs results in the repression of these genes. Chromatin immunoprecipitation shows that HMGA1 binds to the promoters of these pluripotency genes in vivo. In addition, interfering with HMGA1 function using a short hairpin RNA or a dominant-negative construct blocks cellular reprogramming to a pluripotent state. CONCLUSIONS: Our findings demonstrate for the first time that HMGA1 enhances cellular reprogramming from a somatic cell to a fully pluripotent stem cell. These findings identify a novel role for HMGA1 as a key regulator of the stem cell state by inducing transcriptional networks that drive pluripotency. Although further studies are needed, these HMGA1 pathways could be exploited in regenerative medicine or as novel therapeutic targets for poorly differentiated, stem-like cancers.JH Libraries Open Access Fun

Understanding your forage test results

Balanced nutrition is important for efficient livestock production. Daily nutrient requirements vary depending on the phase of production. Knowing the nutrient composition of feeds and matching feeds to animal requirements at a given stage of production will ensure that nutritional needs are met. Forage analysis is a management tool that provides information needed for proper livestock nutrition.Published April 2002. A more recent revision exists. Facts and recommendations in this publication may no longer be valid. Please look for up-to-date information in the OSU Extension Catalog: http://extension.oregonstate.edu/catalo

The Standardized Field Sobriety Tests (SFST) and measures of cognitive functioning

Objective The Standardized Field Sobriety Tests (SFST) are utilised widely to assess fitness to drive when law enforcement suspects a driver's ability to drive is impaired, whether by drugs or alcohol. The SFST ostensibly achieve this through assessment of the level of drivers' cognitive and psychomotor impairment, although no studies have explicitly assessed the relatedness of cognitive ability and performance on the SFST. The current study aimed to assess the relationship between the three components of the SFST with a well validated computerised cognitive battery. Method A sub-set of 61 placebo condition participants comprised the sample, with 33 females and 28 males (mean age 25.45 years). Correlations between the individual SFST subscales 'Horizontal Gaze Nystagmus' (HGN), the 'One Leg Stand' (OLS) and the 'Walk and Turn' test (WAT) and Cognitive Drug Research (CDR) sub-scales of 'Quality of Working Memory', 'Power of Attention' and 'Continuity of Attention' were analysed using point-biserial correlation. Results Sixty participants were included for analyses. A weak-moderate positive (five subscales) and a moderate-strong negative (two subscales) association was noted between seven of the nine individual CDR subscales and the SFST subscale of the WAT test (all p &lt; 0.05). Individually, a moderate positive association was noted between the sub-scale 'Nystagmus lack of smooth pursuit' and 'digit vigilance reaction time' and 'choice reaction time; reaction time' (both p &lt; 0.05) and 'Nystagmus head move and/or jerk' and 'simple reaction time' (p &lt; 0.001). When assessed as a partially composite factor, a comparable association was also noted between the composite score of the SFST subscale 'Nystagmus head move and/or jerk' and both (a) simple and (b) digit vigilance reaction time (both p &lt; 0.05). No association was noted between any of the individual cognitive variables and the SFST subscale 'OLS', or between composite cognitive scores 'Quality of Working Memory', 'Power of Attention' and 'Continuity of Attention' and total SFST scores. Discussion Variation in some aspects of cognitive performance was found to be moderately and positively correlated with some individual aspects of the SFST; particularly among tasks which assess reaction time. Impairment of these cognitive processes can also contribute to the completion of complex tasks such as driving or the SFST. Complex behavioural tasks such as driving are often severely impaired due to intoxication, and thus in a practical sense, the SFST can still be considered a useful screening tool to identify drug or alcohol impaired drivers

Initial Drop File

Drop File for raw coded questionnaires and survey