Maternal infection and white matter toxicity

Studies examining maternal infection as a risk factor for neurological disorders in the offspring have suggested that altered maternal immune status during pregnancy can be considered as an adverse event in prenatal development. Infection occurring in the mother during the gestational period has been implicated in multiple neurological effects. The current manuscript will consider the issue of immune/inflammatory conditions during prenatal development where adverse outcomes have been linked to maternal systemic infection. The discussions will focus primary on white matter and oligodendrocytes as they have been identified as target processes. This white matter damage occurs in very early preterm infants and in various other human diseases currently being examined for a linkage to maternal or early developmental immune status. The intent is to draw attention to the impact of altered immune status during pregnancy on the offspring for the consideration of such contributing factors to the general assessment of developmental neurotoxicology

The Stars Do Their Rounds

This book was completed for Jan Baker\u27s artists\u27 book class.https://digitalcommons.risd.edu/specialcollections_bookmark_nature/1010/thumbnail.jp

A Personal Tale of Tea

This book was completed for Jan Baker\u27s artists\u27 book class.https://digitalcommons.risd.edu/specialcollections_bookmark_food/1009/thumbnail.jp

Thrombospondin-1 Is a Major Activator of TGF-β1 In Vivo

AbstractThe activity of TGF-β1 is regulated primarily extracellularly where the secreted latent form must be modified to expose the active molecule. Here we show that thrombospondin-1 is responsible for a significant proportion of the activation of TGF-β1 in vivo. Histological abnormalities in young TGF-β1 null and thrombospondin-1 null mice were strikingly similar in nine organ systems. Lung and pancreas pathologies similar to those observed in TGF-β1 null animals could be induced in wild-type pups by systemic treatment with a peptide that blocked the activation of TGF-β1 by thrombospondin-1. Although these organs produced little active TGF-β1 in thrombospondin null mice, when pups were treated with a peptide derived from thrombospondin-1 that could activate TGF-β1, active cytokine was detected in situ, and the lung and pancreatic abnormalities reverted toward wild type

Prediction of clinical outcome in glioblastoma using a biologically relevant nine-microRNA signature

Background Glioblastoma is the most aggressive primary brain tumor, and is associated with a very poor prognosis. In this study we investigated the potential of microRNA expression profiles to predict survival in this challenging disease. Methods MicroRNA and mRNA expression data from glioblastoma (n = 475) and grade II and III glioma (n = 178) were accessed from The Cancer Genome Atlas. LASSO regression models were used to identify a prognostic microRNA signature. Functionally relevant targets of microRNAs were determined using microRNA target prediction, experimental validation and correlation of microRNA and mRNA expression data. Results A 9-microRNA prognostic signature was identified which stratified patients into risk groups strongly associated with survival (p = 2.26e−09), significant in all glioblastoma subtypes except the non-G-CIMP proneural group. The statistical significance of the microRNA signature was higher than MGMT methylation in temozolomide treated tumors. The 9-microRNA risk score was validated in an independent dataset (p = 4.50e−02) and also stratified patients into high- and low-risk groups in lower grade glioma (p = 5.20e−03). The majority of the 9 microRNAs have been previously linked to glioblastoma biology or treatment response. Integration of the expression patterns of predicted microRNA targets revealed a number of relevant microRNA/target pairs, which were validated in cell lines. Conclusions We have identified a novel, biologically relevant microRNA signature that stratifies high- and low-risk patients in glioblastoma. MicroRNA/mRNA interactions identified within the signature point to novel regulatory networks. This is the first study to formulate a survival risk score for glioblastoma which consists of microRNAs associated with glioblastoma biology and/or treatment response, indicating a functionally relevant signatur

Distress in working on dementia wards - a threat to compassionate care: a grounded theory study

Objectives - Nurses and health care workers are under increasing scrutiny from the general public and other professionals over their capacity for compassion. For example, in the UK, recruitment of nurses includes assessment of compassion through ?Values Based Recruitment?. However, compassionate care can be hindered when working in very challenging and pressurised environments. The study aimed to explore the experiences of managing work pressures in front-line NHS staff caring for older adults with dementia. One aspect of the analysis was to explore the factors that facilitate or hinder self-compassion and mindfulness, since these ways of responding to extreme pressure are likely to facilitate compassion towards others. Method- Ten front-line staff (a mixture of nurses and Health Care Assistants) from three inpatient dementia wards took part in qualitative interviews which were then analysed using constructivist grounded theory methods. Results - A theoretical framework was generated which highlighted the role of structural and interpersonal types of work pressure on individual responses and ways of managing pressure. A range of helpful and unhelpful strategies were employed and although many participants appreciated the importance of taking time to process and reflect on difficult emotions and experiences during work, there were significant structural and personal barriers to practicing mindfulness and self-compassion more fully. A sense of professionalism along with various organisational factors meant that much processing of difficult emotions had to take place largely out of work hours. Conclusions - Recruiting staff with high levels of compassion and training compassion to existing staff are not likely to significantly improve compassionate care alone in the context of extremely challenging work environments. Rather, organisational changes need to be made to model and reward self-compassion; staff training should focus on self-compassion and mindfulness, without which compassion to others is hindered. Strong professional values which may instil in care staff a belief in not displaying emotions at work should be considered carefully by professional bodies in order to provide guidance from pre-qualification onwards about how to balance professional conduct with appropriate expression of emotion in response to extreme situations

Australian spiny mountain crayfish and their temnocephalan ectosymbionts: an ancient association on the edge of coextinction?

Australian spiny mountain crayfish (Euastacus, Parastacidae) and their ecotosymbiotic temnocephalan flatworms (Temnocephalida, Platyhelminthes) may have co-occurred and interacted through deep time, during a period of major environmental change. Therefore, reconstructing the history of their association is of evolutionary, ecological, and conservation significance. Here, time-calibrated Bayesian phylogenies of Euastacus species and their temnocephalans (Temnohaswellia and Temnosewellia) indicate near-synchronous diversifications from the Cretaceous. Statistically significant cophylogeny correlations between associated clades suggest linked evolutionary histories. However, there is a stronger signal of codivergence and greater host specificity in Temnosewellia, which co-occurs with Euastacus across its range. Phylogeography and analyses of evolutionary distinctiveness (ED) suggest that regional differences in the impact of climate warming and drying had major effects both on crayfish and associated temnocephalans. In particular, Euastacus and Temnosewellia show strong latitudinal gradients in ED and, conversely, in geographical range size, with the most distinctive, northern lineages facing the greatest risk of extinction. Therefore, environmental change has, in some cases, strengthened ecological and evolutionary associations, leaving host-specific temnocephalans vulnerable to coextinction with endangered hosts. Consequently, the extinction of all Euastacus species currently endangered (75%) predicts coextinction of approximately 60% of the studied temnocephalans, with greatest loss of the most evolutionarily distinctive lineages

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

A validated microRNA profile with predictive potential in glioblastoma patients treated with bevacizumab

Purpose: We investigated whether microRNA expression data from glioblastoma could be used to produce a profile that defines a bevacizumab responsive group of patients. Patients and Methods: TCGA microRNA expression data from tumors resected at first diagnosis of glioblastoma in patients treated with bevacizumab at any time during the course of their disease were randomly separated into training (n=50) and test (n=37) groups for model generation. MicroRNA-seq data for 51 patients whose treatment included bevacizumab in the BELOB trial were used as an independent validation cohort. Results: Using penalized regression we identified 8 microRNAs as potential predictors of overall survival in the training set. We dichotomized the response score based on the most prognostic minimum of a density plot of the response scores (log-rank HR=0.16, p=1.2e-5) and validated the profile in the test cohort (one-sided log-rank HR=0.34, p=0.026). Analysis of the profile using all samples in the TCGA glioblastoma dataset, regardless of treatment received, (n=473) showed that the prediction of patient benefit was not significant (HR=0.84, p=0.083) suggesting the profile is specific to bevacizumab. Further independent validation of our microRNA profile in RNA-seq data from patients treated with bevacizumab (alone or in combination with CCNU) at glioblastoma recurrence in the BELOB trial confirmed that our microRNA profile predicted patient benefit from bevacizumab (HR=0.59, p=0.043). Conclusion: We have identified and validated an 8-microRNA profile that predicts overall survival in patients with glioblastoma treated with bevacizumab. This may be useful for identifying patients who are likely to benefit from this agent

Figuring Rhetoric: From Antistrophe to Apostrophe through Catastrophe

This essay explores rhetoric tropologically through various strophes: antistrophe, catastrophe, and apostrophe. Our purpose is to delineate problems and possibilities that these tropes pose for rhetoric in an effort to create new rhetorics. We seek to display the antistrophic and catastrophic figurations of rhetoric and then use visual lenses of photography and cinema to disrupt the figurations. Following the disruption, we seek to heighten sensibilities to other figurations, in particular an apostrophic figuration. We cast apostrophe as a figure for change because it marks a deeply felt turn toward difference and otherness. Turned as such, rhetoric becomes erotic