Experiences of Early-Career Educators\u27 Preparedness to Identify and Address Substance Abuse Behaviors and Academic Success in the Classroom: A Phenomenological Study

This transcendental phenomenological study aimed to describe the experiences of preparedness of early-career teachers (i.e., teachers in their first five years in the profession) who have dealt with student addiction behaviors and academic decline in the classroom within several Northeast Pennsylvania public school districts. Mezirow’s transformational learning theory guided this study as it addressed how adults interpret and make meaning through life experiences. The central research question guiding this study was: How do early-career teachers describe their experiences dealing with student addiction behaviors in the classroom while preserving their academic success? Fifteen early-career teachers in the public school system (grades 6-12) provided input through three data collection methods: an open-ended individual interview, journal prompts, and a focus group. Several major themes emerged during data analysis: Teachers\u27 feelings of preparedness and teaching experience, teacher preparedness for classroom necessities, teacher support/resources, and teacher preparedness and collaborative pursuits. These themes confirm that teachers’ experiences with substance abuse students could benefit other unprepared teachers to successfully incorporate specific strategies into the classrooms and confirm the need for additional research in this area of education. Data were analyzed using steps outlined by Moustakas and included; epoché, transcendental-phenomenological reduction, imaginative variation, and essence development

Transmitochondrial embryonic stem cells containing pathogenic mtDNA mutations are compromised in neuronal differentiation

Objectives:  Defects of the mitochondrial genome (mtDNA) cause a series of rare, mainly neurological disorders. In addition, they have been implicated in more common forms of movement disorders, dementia and the ageing process. In order to try to model neuronal dysfunction associated with mitochondrial disease, we have attempted to establish a series of transmitochondrial mouse embryonic stem cells harbouring pathogenic mtDNA mutations. Materials and methods: Transmitochondrial embryonic stem cell cybrids were generated by fusion of cytoplasts carrying a variety of mtDNA mutations, into embryonic stem cells that had been pretreated with rhodamine 6G, to prevent transmission of endogenous mtDNA. Cybrids were differentiated into neurons and assessed for efficiency of differentiation and electrophysiological function. Results:  Neuronal differentiation could occur, as indicated by expression of neuronal markers. Differentiation was impaired in embryonic stem cells carrying mtDNA mutations that caused severe biochemical deficiency. Electrophysiological tests showed evidence of synaptic activity in differentiated neurons carrying non-pathogenic mtDNA mutations or in those that caused a mild defect of respiratory activity. Again, however, neurons carrying mtDNA mutations that resulted in severe biochemical deficiency had marked reduction in post-synaptic events. Conclusions:  Differentiated neurons carrying severely pathogenic mtDNA defects can provide a useful model for understanding how such mutations can cause neuronal dysfunction

Estimating the global burden of Epstein–Barr virus‑related cancers

Background: More than 90% of the adult population globally is chronically infected by the Epstein–Barr virus (EBV). It is well established that EBV is associated with a number of malignancies, and advances in knowledge of EBV-related malignancies are being made every year. Several studies have analysed the global epidemiology and geographic distribution of EBV-related cancers. However, most have only described a single cancer type or subtype in isolation or limited their study to the three or four most common EBV-related cancers. This review will present an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers. Method: We have reviewed the literature on defining features, distribution and outcomes across six cancers with a relatively large EBV-related case burden: Nasopharyngeal carcinoma (NPC), Gastric carcinoma (GC), Hodgkin lymphoma (HL), Burkitt lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL) and Extranodal NK/T-cell lymphoma, Nasal type (ENKTL-NT). We retrieved published region-specific EBV-related case proportions for NPC, GC, HL and BL and performed meta-analyses on pooled region-specific studies of EBV-related case proportions for DLBCL and ENKTL-NT. We match these pooled proportions with their respective regional incidence and mortality numbers retrieved from a publicly available cancer database. Additionally, we also reviewed the literature on several other less common EBV-related cancers to summarize their key characteristics herein. Conclusion: We estimated that EBV-related cases from these six cancers accounted for 239,700–357,900 new cases and 137,900–208,700 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of disease that could benefit from an EBV-specific therapeutic

Estimating usual intakes mainly affects the micronutrient distribution among infants, toddlers and pre-schoolers from the 2012 Mexican National Health and Nutrition Survey

Abstract Objective To compare estimates from one day with usual intake estimates to evaluate how the adjustment for within-person variability affected nutrient intake and adequacy in Mexican children. Design In order to obtain usual nutrient intakes, the National Cancer Institute’s method was used to correct the first 24 h dietary recall collected in the entire sample ( n 2045) with a second 24 h recall collected in a sub-sample ( n 178). We computed estimates of one-day and usual intakes of total energy, fat, Fe, Zn and Na. Setting 2012 Mexican National Health and Nutrition Survey. Subjects A total of 2045 children were included: 0–5·9 months old ( n 182), 6–11·9 months old ( n 228), 12–23·9 months old ( n 537) and 24–47·9 months old ( n 1098). From these, 178 provided an additional dietary recall. Results Although we found small or no differences in energy intake (kJ/d and kcal/d) between one-day v . usual intake means, the prevalence of inadequate and excessive energy intake decreased somewhat when using measures of usual intake relative to one day. Mean fat intake (g/d) was not different between one-day and usual intake among children >6 months old, but the prevalence of inadequate and excessive fat intake was overestimated among toddlers and pre-schoolers when using one-day intake ( P< 0·05). Compared with usual intake, estimates from one day yielded overestimated prevalences of inadequate micronutrient intakes but underestimated prevalences of excessive intakes among children aged >6 months. Conclusions There was overall low variability in energy and fat intakes but higher for micronutrients. Because the usual intake distributions are narrower, the prevalence of inadequate/excessive intakes may be biased when estimating nutrient adequacy if one day of data is used

Model of HIV-1 Disease Progression Based on Virus-Induced Lymph Node Homing and Homing-Induced Apoptosis of CD4+ Lymphocytes

Several proposed theories have described the progression of HIV infection. Even so, no concrete evidence supports any as comprehensive, including, for example, why the CD4+ T-cell counts fall from 1000/mm^3 of blood to roughly 100/mm^3 over an average 10-year period, whereas concomitant viral loads are relatively constant, increasing by several orders of magnitude in late-stage disease. Here, we develop and validate a theoretical model that altered lymphocyte circulation patterns between the lymph system and blood due to HIV-induced enhanced lymph-node homing and subsequent apoptosis of resting CD4+ T cells can explain many aspects of HIV-1 disease progression. These results lead to a recalculation of the CD4+ lymphocyte dynamics during highly active antiretroviral therapy, and also suggest new targets for therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83499/1/Kirschner_et_al.jaids2000.pd

Site-specific recombinatorics : in situ cellular barcoding with the Cre Lox system

Background: Cellular barcoding is a recently developed biotechnology tool that enables the familial identification of progeny of individual cells in vivo. In immunology, it has been used to track the burst-sizes of multiple distinct responding T cells over several adaptive immune responses. In the study of hematopoiesis, it revealed fate heterogeneity amongst phenotypically identical multipotent cells. Most existing approaches rely on ex vivo viral transduction of cells with barcodes followed by adoptive transfer into an animal, which works well for some systems, but precludes barcoding cells in their native environment such as those inside solid tissues. Results: With a view to overcoming this limitation, we propose a new design for a genetic barcoding construct based on the Cre Lox system that induces randomly created stable barcodes in cells in situ by exploiting inherent sequence distance constraints during site-specific recombination. We identify the cassette whose provably maximal code diversity is several orders of magnitude higher than what is attainable with previously considered Cre Lox barcoding approaches, exceeding the number of lymphocytes or hematopoietic progenitor cells in mice. Conclusions: Its high diversity and in situ applicability, make the proposed Cre Lox based tagging system suitable for whole tissue or even whole animal barcoding. Moreover, it can be built using established technology

Dynamics of Naive and Memory CD4+ T Lymphocytes in HIV-1 Disease Progression

Understanding the dynamics of naive and memory CD4+ T cells in the immune response to HIV-1 infection can help elucidate typical disease progression patterns observed in HIV-1 patients. Although infection markers such as CD4+ T-cell count and viral load are monitored in patient blood, the lymphatic tissues (LT) have been shown to be an important viral reservoir. Here, we introduce the first comprehensive theoretical model of disease progression based on T-cell subsets and virus circulating between the two compartments of LT and blood. We use this model to predict several trademarks observed in adult HIV-1 disease progression such as the establishment of a setpoint in the asymptomatic stage. Our model predicts that both host and viral elements play a role in determining different disease progression patterns. Viral factors include viral infectivity and production rates, whereas host factors include elements of specific immunity. We also predict the effect of highly active antiretroviral therapy and treatment cessation on cellular and viral dynamics in both blood and LT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83367/1/seema-jaids-2002.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/83367/4/Errata.Bajaria_et_al.2002.pd

Anomalies in T cell function are associated with individuals at risk of mycobacterium abscessus complex infection

The increasing global incidence and prevalence of non-tuberculous mycobacteria (NTM) infection is of growing concern. New evidence of person-to-person transmission of multidrug-resistant NTM adds to the global concern. The reason why certain individuals are at risk of NTM infections is unknown. Using high definition flow cytometry, we studied the immune profiles of two groups that are at risk of Mycobacterium abscessus complex infection and matched controls. The first group was cystic fibrosis (CF) patients and the second group was elderly individuals. CF individuals with active M. abscessus complex infection or a history of M. abscessus complex infection exhibited a unique surface T cell phenotype with a marked global deficiency in TNFa production during mitogen stimulation. Importantly, immune-based signatures were identified that appeared to predict at baseline the subset of CF individuals who were at risk of M. abscessus complex infection. In contrast, elderly individuals with M. abscessus complex infection exhibited a separate T cell phenotype underlined by the presence of exhaustion markers and dysregulation in type 1 cytokine release during mitogen stimulation. Collectively, these data suggest an association between T cell signatures and individuals at risk of M. abscessus complex infection, however, validation of these immune anomalies as robust biomarkers will require analysis on larger patient cohorts

Mining, visualizing and comparing multidimensional biomolecular data using the Genomics Data Miner (GMine) web-server

Genomics Data Miner (GMine) is a user-friendly online software that allows non-experts to mine, cluster and compare multidimensional biomolecular datasets. Various powerful visualization techniques are provided, generating high quality figures that can be directly incorporated into scientific publications. Robust and comprehensive analyses are provided via a broad range of data-mining techniques, including univariate and multivariate statistical analysis, supervised learning, correlation networks, clustering and multivariable regression. The software has a focus on multivariate techniques, which can attribute variance in the measurements to multiple explanatory variables and confounders. Various normalization methods are provided. Extensive help pages and a tutorial are available via a wiki server. Using GMine we reanalyzed proteome microarray data of host antibody response against Plasmodium falciparum. Our results support the hypothesis that immunity to malaria is a higher-order phenomenon related to a pattern of responses and not attributable to any single antigen. We also analyzed gene expression across resting and activated T cells, identifying many immune-related genes with differential expression. This highlights both the plasticity of T cells and the operation of a hardwired activation program. These application examples demonstrate that GMine facilitates an accurate and in-depth analysis of complex molecular datasets, including genomics, transcriptomics and proteomics data

CD161 expression defines new human γδ T cell subsets

γδ T cells are a highly versatile immune lineage involved in host defense and homeostasis, but questions remain around their heterogeneity, precise function and role during health and disease. We used multi−parametric flow cytometry, dimensionality reduction, unsupervised clustering, and self-organizing maps (SOM) to identify novel γδ T cell naïve/memory subsets chiefly defined by CD161 expression levels, a surface membrane receptor that can be activating or suppressive. We used middle-to-old age individuals given immune blockade is commonly used in this population. Whilst most Vδ1+subset cells exhibited a terminal differentiation phenotype, Vδ1− subset cells showed an early memory phenotype. Dimensionality reduction revealed eight γδ T cell clusters chiefly diverging through CD161 expression with CD4 and CD8 expression limited to specific subpopulations. Comparison of matched healthy elderly individuals to bronchiectasis patients revealed elevated Vδ1+ terminally differentiated effector memory cells in patients potentially linking this population with chronic proinflammatory disease