Maternal cannabis use is associated with suppression of immune gene networks in placenta and increased anxiety phenotypes in offspring

While cannabis is among the most used recreational drugs during pregnancy, the impact of maternal cannabis use (mCB) on fetal and child development remains unclear. Here, we assessed the effects of mCB on psychosocial and physiological measures in young children along with the potential relevance of the in utero environment reflected in the placental transcriptome. Children (∼3 to 6 y) were assessed for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children (BASC-2) survey, and heart rate variability (HRV) at rest and during auditory startle. For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing. Hair hormone analysis revealed increased cortisol levels in mCB children. In addition, mCB was associated with greater anxiety, aggression, and hyperactivity. Children with mCB also showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone. In the placenta, there was reduced expression of many genes involved in immune system function including type I interferon, neutrophil, and cytokine-signaling pathways. Finally, several of these mCB-linked immune genes organized into coexpression networks that correlated with child anxiety and hyperactivity. Overall, our findings reveal a relationship between mCB and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood.

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Teaching to the Student: Charter School Effectiveness in Spite of Perverse Incentives

Education Finance and Policy ◽

10.1162/edfp_a_00175 ◽

2016 ◽

Vol 11 (1) ◽

pp. 1-42 ◽

Cited By ~ 3

Author(s):

Sarah R. Cohodes

Keyword(s):

Charter Schools ◽

Charter School ◽

School Effectiveness ◽

Standardized Test ◽

School Attendance ◽

Item Type ◽

Test Preparation ◽

Assessment System ◽

Type I ◽

The Impact

Recent work has shown that Boston charter schools raise standardized test scores more than their traditional school counterparts. Critics of charter schools argue that charter schools create those achievement gains by focusing exclusively on test preparation, at the expense of deeper learning. In this paper, I test that critique by estimating the impact of charter school attendance on subscales of the Massachusetts Comprehensive Assessment System and examining them for evidence of score inflation. If charter schools are teaching to the test to a greater extent than their counterparts, one would expect to see higher scores on commonly tested standards, higher-stakes subjects, and frequently tested topics. Despite incentives to reallocate effort away from less frequently tested content to highly tested content, and to coach to item type, I find no evidence of this type of test preparation. Boston charter middle schools perform consistently across all standardized test subscales.

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Differential and longitudinal immune gene patterns associated with reprogrammed microenvironment and viral mimicry in response to neoadjuvant radiotherapy in rectal cancer

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001717 ◽

2021 ◽

Vol 9 (3) ◽

pp. e001717

Author(s):

Anna Wilkins ◽

Elisa Fontana ◽

Gift Nyamundanda ◽

Chanthirika Ragulan ◽

Yatish Patil ◽

...

Keyword(s):

Gene Expression ◽

Rectal Cancer ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Poor Responders ◽

Type I ◽

Immune Gene ◽

Neoadjuvant Radiotherapy ◽

The Impact ◽

Crt Response

BackgroundRectal cancers show a highly varied response to neoadjuvant radiotherapy/chemoradiation (RT/CRT) and the impact of the tumor immune microenvironment on this response is poorly understood. Current clinical tumor regression grading systems attempt to measure radiotherapy response but are subject to interobserver variation. An unbiased and unique histopathological quantification method (change in tumor cell density (ΔTCD)) may improve classification of RT/CRT response. Furthermore, immune gene expression profiling (GEP) may identify differences in expression levels of genes relevant to different radiotherapy responses: (1) at baseline between poor and good responders, and (2) longitudinally from preradiotherapy to postradiotherapy samples. Overall, this may inform novel therapeutic RT/CRT combination strategies in rectal cancer.MethodsWe generated GEPs for 53 patients from biopsies taken prior to preoperative radiotherapy. TCD was used to assess rectal tumor response to neoadjuvant RT/CRT and ΔTCD was subjected to k-means clustering to classify patients into different response categories. Differential gene expression analysis was performed using statistical analysis of microarrays, pathway enrichment analysis and immune cell type analysis using single sample gene set enrichment analysis. Immunohistochemistry was performed to validate specific results. The results were validated using 220 pretreatment samples from publicly available datasets at metalevel of pathway and survival analyses.ResultsΔTCD scores ranged from 12.4% to −47.7% and stratified patients into three response categories. At baseline, 40 genes were significantly upregulated in poor (n=12) versus good responders (n=21), including myeloid and stromal cell genes. Of several pathways showing significant enrichment at baseline in poor responders, epithelial to mesenchymal transition, coagulation, complement activation and apical junction pathways were validated in external cohorts. Unlike poor responders, good responders showed longitudinal (preradiotherapy vs postradiotherapy samples) upregulation of 198 immune genes, reflecting an increased T-cell-inflamed GEP, type-I interferon and macrophage populations. Longitudinal pathway analysis suggested viral-like pathogen responses occurred in post-treatment resected samples compared with pretreatment biopsies in good responders.ConclusionThis study suggests potentially druggable immune targets in poor responders at baseline and indicates that tumors with a good RT/CRT response reprogrammed from immune “cold” towards an immunologically “hot” phenotype on treatment with radiotherapy.

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The impact of cannabis legalization in Uruguay on adolescent cannabis use

International Journal of Drug Policy ◽

10.1016/j.drugpo.2020.102748 ◽

2020 ◽

Vol 80 ◽

pp. 102748

Author(s):

Hannah Laqueur ◽

Ariadne Rivera-Aguirre ◽

Aaron Shev ◽

Alvaro Castillo-Carniglia ◽

Kara E. Rudolph ◽

...

Keyword(s):

Cannabis Use ◽

The Impact

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Modulation of Chicken Intestinal Immune Gene Expression by Small Cationic Peptides as Feed Additives during the First Week Posthatch

Clinical and Vaccine Immunology ◽

10.1128/cvi.00322-13 ◽

2013 ◽

Vol 20 (9) ◽

pp. 1440-1448 ◽

Cited By ~ 17

Author(s):

Michael H. Kogut ◽

Kenneth J. Genovese ◽

Haiqi He ◽

Christina L. Swaggerty ◽

Yiwei Jiang

Keyword(s):

Gene Expression ◽

Proinflammatory Cytokines ◽

Proinflammatory Cytokine ◽

Feed Additives ◽

Feed Additive ◽

Cationic Peptides ◽

Type I ◽

Immune Gene ◽

Content Type ◽

Functional Efficiency

ABSTRACTWe have been investigating modulation strategies tailored around the selective stimulation of the host's immune system as an alternative to direct targeting of microbial pathogens by antibiotics. One such approach is the use of a group of small cationic peptides (BT) produced by a Gram-positive soil bacterium,Brevibacillus texasporus. These peptides have immune modulatory properties that enhance both leukocyte functional efficiency and leukocyte proinflammatory cytokine and chemokine mRNA transcription activitiesin vitro. In addition, when provided as a feed additive for just 4 days posthatch, BT peptides significantly induce a concentration-dependent protection against cecal and extraintestinal colonization bySalmonella entericaserovar Enteritidis. In the present studies, we assessed the effects of feeding BT peptides on transcriptional changes on proinflammatory cytokines, inflammatory chemokines, and Toll-like receptors (TLR) in the ceca of broiler chickens with and withoutS. Enteritidis infection. After feeding a BT peptide-supplemented diet for the first 4 days posthatch, chickens were then challenged withS. Enteritidis, and intestinal gene expression was measured at 1 or 7 days postinfection (p.i.) (5 or 11 days of age). Intestinal expression of innate immune mRNA transcripts was analyzed by quantitative real-time PCR (qRT-PCR). Analysis of relative mRNA expression showed that a BT peptide-supplemented diet did not directly induce the transcription of proinflammatory cytokine, inflammatory chemokine, type I/II interferon (IFN), or TLR mRNA in chicken cecum. However, feeding the BT peptide-supplemented diet primed cecal tissue for increased (P≤ 0.05) transcription of TLR4, TLR15, and TLR21 upon infection withS. Enteritidis on days 1 and 7 p.i. Likewise, feeding the BT peptides primed the cecal tissue for increased transcription of proinflammatory cytokines (interleukin 1β [IL-1β], IL-6, IL-18, type I and II IFNs) and inflammatory chemokine (CxCLi2) in response toS. Enteritidis infection 1 and 7 days p.i. compared to the chickens fed the basal diet. These small cationic peptides may prove useful as alternatives to antibiotics as local immune modulators in neonatal poultry by providing prophylactic protection againstSalmonellainfections.

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Improvement in psychological wellbeing among adolescents with a substance use disorder attending an outpatient treatment programme

Irish Journal of Psychological Medicine ◽

10.1017/ipm.2021.6 ◽

2021 ◽

pp. 1-8

Author(s):

N.M. Gamage ◽

C. Darker ◽

B.P. Smyth

Keyword(s):

Substance Use ◽

Psychological Symptoms ◽

Significant Proportion ◽

Cannabis Use ◽

Psychological Wellbeing ◽

Substance Use Treatment ◽

Disruptive Behaviour ◽

Treatment Programme ◽

The Impact

Objectives: Adolescents with substance use disorders (SUDs) exhibit high rates of comorbid psychological problems. This study aimed to examine the impact of an outpatient substance use treatment programme upon the psychological wellbeing of adolescents. Methods: A prospective study was carried out examining psychological symptoms in a group of adolescents attending the Youth Drug and Alcohol (YoDA) Addiction Service in Dublin. Participants were treated with evidenced based psychological models such as cognitive behavioural therapy, motivational interviewing and systemic family therapy. The Becks Youth Inventory was utilised to assess psychological symptoms at treatment entry and repeated three months later at follow up. Results: Among 36 adolescents who were included in this study, poly-substance misuse was the norm. Almost three-quarter had a cannabis use disorder (CUD). There were significant reductions in mean subscale scores of depression (56.0 to 50.8, p = 0.003), anger (55.2 to 49.5, p < 0.001) and disruptive behaviour (61.6 to 56.5, p = 0.002) at follow up. Although there wasn’t a statistically significant reduction in mean scores for anxiety, we observed a significant proportion of participants (p = 0.008) improving and moving out of a moderate to severe symptom range when examined by category. This was also the case for self-concept (p = 0.04). Furthermore this study revealed a positive correlation between the reduction in days of cannabis use and reduction in depressive scores (Pearson correlation 0.49, p = 0.01) among those with a CUD. Conclusion: The findings indicate that substance use treatment for adolescents is associated with important psychological and behavioural improvements.

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SEM-PLS Approach to Green Building

Encyclopedia ◽

10.3390/encyclopedia1020039 ◽

2021 ◽

Vol 1 (2) ◽

pp. 472-481

Author(s):

Nasim Aghili ◽

Mehdi Amirkhani

Keyword(s):

Structural Equation ◽

Green Building ◽

Well Being ◽

The United States ◽

Assessment Method ◽

Assessment System ◽

Renewable Materials ◽

Sustainable Building ◽

Building Operation ◽

The Impact

Green buildings refer to buildings that decrease adverse environmental effects and maintain natural resources. They can diminish energy consumption, greenhouse gas emissions, the usage of non-renewable materials, water consumption, and waste generation while improving occupants’ health and well-being. As such, several rating tools and benchmarks have been developed worldwide to assess green building performance (GBP), including the Building Research Establishment Environmental Assessment Method (BREEAM) in the United Kingdom, German Sustainable Building Council (DGNB), Leadership in Energy and Environmental Design (LEED) in the United States and Canada, Comprehensive Assessment System for Built Environment Efficiency (CASBEE) in Japan, Green Star in Australia, Green Mark in Singapore, and Green Building Index in Malaysia. Energy management (EM) during building operation could also improve GBP. One of the best approaches to evaluating the impact of EM on GBP is by using structural equation modelling (SEM). SEM is a commanding statistical method to model testing. One of the most used SEM variance-based approaches is partial least squares (PLS), which can be implemented in the SmartPLS application. PLS-SEM uses path coefficients to determine the strength and significance of the hypothesised relationships between the latent constructs.

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The Impact of COVID-19 on the Adaptive Functioning, Behavioral Problems, and Repetitive Behaviors of Italian Children with Autism Spectrum Disorder: An Observational Study

Children ◽

10.3390/children8020096 ◽

2021 ◽

Vol 8 (2) ◽

pp. 96

Author(s):

Martina Siracusano ◽

Eugenia Segatori ◽

Assia Riccioni ◽

Leonardo Emberti Gialloreti ◽

Paolo Curatolo ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Behavioral Problems ◽

Adaptive Functioning ◽

Children With Autism ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Assessment System ◽

Spectrum Disorder ◽

Adaptive Skills ◽

The Impact

Children with autism spectrum disorder (ASD) and their families have represented a fragile population on which the extreme circumstances of the COVID-19 outbreak may have doubly impaired. Interruption of therapeutical interventions delivered in-person and routine disruption constituted some of the main challenges they had to face. This study investigated the impact of the COVID-19 lockdown on adaptive functioning, behavioral problems, and repetitive behaviors of children with ASD. In a sample of 85 Italian ASD children (mean age 7 years old; 68 males, 17 females), through a comparison with a baseline evaluation performed during the months preceding COVID-19, we evaluated whether after the compulsory home confinement any improvement or worsening was reported by parents of ASD individuals using standardized instruments (Adaptive Behavior Assessment System (Second Edition), Achenbach Child Behavior Checklist, Repetitive Behavior Scale-Revised). No significant worsening in the adaptive functioning, problematic, and repetitive behaviors emerged after the compulsory home confinement. Within the schooler children, clinical stability was found in reference to both adaptive skills and behavioral aspects, whereas within preschoolers, a significant improvement in adaptive skills emerged and was related to the subsistence of web-delivered intervention, parental work continuance, and online support during the lockdown.

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STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy

Virology Journal ◽

10.1186/s12985-021-01548-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Lorena Leticia Peixoto de Lima ◽

Allysson Quintino Tenório de Oliveira ◽

Tuane Carolina Ferreira Moura ◽

Ednelza da Silva Graça Amoras ◽

Sandra Souza Lima ◽

...

Keyword(s):

Gene Expression ◽

Viral Load ◽

T Cell ◽

Antiretroviral Therapy ◽

Cell Count ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Α Level ◽

The Impact ◽

Hiv 1

Abstract Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. Conclusions ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING–cGAS pathway.

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Compulsive Buying in Adolescents. The Impact of Gender and Alcohol and Cannabis Use

Sustainability ◽

10.3390/su13073982 ◽

2021 ◽

Vol 13 (7) ◽

pp. 3982

Author(s):

Gloria Pérez de Albéniz-Garrote ◽

Maria Begoña Medina-Gómez ◽

Cristina Buedo-Guirado

Keyword(s):

Compulsive Buying ◽

Cannabis Use ◽

Descriptive Statistics ◽

Cluster Sampling ◽

Toxic Substances ◽

Higher Alcohol ◽

Random Cluster ◽

Prevention Programmes ◽

The Impact ◽

Buying In

The purpose of this study to analyse whether compulsive buying in teenagers is related to gender and alcohol and cannabis use in a sample of 573 students aged 14–17 from secondary education schools in Burgos (Spain) (M = 15.65; SD = 1.04). Random cluster sampling was performed to select the sample. The Compulsive Buying Questionnaire was used together with two extra promts: ‘Indicate how much alcohol you consume’ and ‘Indicate how much cannabis you take’. Descriptive statistics were used in data analysis, while MANOVA was used to study gender differences in alcohol and cannabis use, compulsive buying and their interaction. The results show higher scores for female compulsive buyers than for men, higher scores for alcohol and cannabis users’ compulsive buying than for non-users, respectively, and higher scores for female users than for male users. A certain interaction was also observed between alcohol and cannabis use. A higher alcohol consumption entailed a higher score in compulsive buying, with cannabis users who did not consume alcohol obtaining the highest scores. Thus, prevention programmes should consider teenagers’ gender and the risk of taking toxic substances.

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The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽

10.3390/cells10051046 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1046

Author(s):

Jorge Martinez ◽

Patricio C. Smith

Keyword(s):

Extracellular Matrix ◽

Type I Collagen ◽

Cell Metabolism ◽

Breast Tumors ◽

Extracellular Matrix Remodeling ◽

Type I ◽

Matrix Remodeling ◽

Desmoplastic Reaction ◽

The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

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