Differential gene expression in response to eCry3.1Ab ingestion in an unselected and eCry3.1Abselected western corn rootworm (Diabrotica virgifera virgifera LeConte) population

Diabrotica virgifera virgifera LeConte, the western corn rootworm (WCR) is one of the most destructive pests in the U.S. Corn Belt. Transgenic maize lines expressing various Cry toxins from Bacillus thuringiensis have been adopted as a management strategy. However, resistance to many Bt toxins has occurred. To investigate the mechanisms of Bt resistance we carried out RNA-seq using Illumina sequencing technology on resistant, eCry3.1Ab-selected and susceptible, unselected, whole WCR neonates which fed on seedling maize with and without eCry3.1Ab for 12 and 24 hours. In a parallel experiment RNA-seq experiments were conducted when only the midgut of neonate WCR was evaluated from the same treatments. After de novo transcriptome assembly we identified differentially expressed genes (DEGs). Results from the assemblies and annotation indicate that WCR neonates from the eCry3.1Ab-selected resistant colony expressed a small number of up and down-regulated genes following Bt intoxication. In contrast, unselected susceptible WCR neonates expressed a large number of up and down-regulated transcripts in response to intoxication. Annotation and pathway analysis of DEGs between susceptible and resistant whole WCR and their midgut tissue revealed genes associated with cell membrane, immune response, detoxification, and potential Bt receptors which are likely related to eCry3.1Ab resistance. This research provides a framework to study the toxicology of Bt toxins and mechanism of resistance in WCR, an economically important coleopteran pest species

Fate and Complex Pathogenic Effects of Dioxins and Polychlorinated Biphenyls in Obese Subjects before and after Drastic Weight Loss

BACKGROUND: In humans, persistent organic pollutants (POPs) are stored primarily in adipose tissue. Their total body burden and their contribution to obesity-associated diseases remain unclear. OBJECTIVES: We characterized POP total body burden and their redistribution in obese individuals before and after drastic weight loss and compared these values with a variety of molecular, biological, and clinical parameters. METHODS: Seventy-one obese subjects were enrolled and underwent bariatric surgery. Blood and adipose tissue samples were obtained at different times from these individuals as well as from 18 lean women. RESULTS: POP content (17 dioxins/furans and 18 polychlorinated biphenyl congeners) in different adipose tissue territories was similar, allowing us to assess total POP body burden from a single biopsy. Total POP body burden was 2 to 3 times higher in obese than in lean individuals. We also found increased expression of some POP target genes in obese adipose tissue. Drastic weight loss led to increased serum POPs and, within 6-12 months, to a significant 15% decrease in total polychlorinated biphenyl body burden. Importantly, serum POP levels were positively correlated with liver toxicity markers and lipid parameters, independently of age and body mass index. CONCLUSIONS: POP content in adipose tissue and serum correlate with biological markers of obesity-related dysfunctions. Drastic weight loss leads to a redistribution of POPs and to a moderate decrease of their total body burden

An Emerging Role for Epigenetic Dysregulation in Arsenic Toxicity and Carcinogenesis

Competing Interests Declaration: The authors declare they have no competing financial interests. Abbreviations: AHCY, S-adenosylhomocysteine hydrolase; APL, acute promyelocytic leukemias; As, inorganic arsenic; AS3MT, arsenic (+3 oxidation state) methyltransferase; ChIP-on-chip, chromatin immunoprecipitation-on-chip; ChIP-seq, chromatin immunoprecipitation-sequencing; DEFB1, defensin, beta 1; DNMTs, DNA methyltransferases; H3K4me3, H3K4 tri-methylation; H3K9me2, H3K9 di-methylation; H3K27me3, H3K27 tri-methylation; HATs, histone acetyltransferases; HDACs, histon

Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma

BACKGROUND: Recent evidence suggests that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that tumorous tissues have higher 5α-reductase (5αR) and lower 3α-hydroxysteroid oxidoreductase (3α-HSO) and 20α-HSO activities. The resulting higher levels of 5α-reduced progesterone metabolites such as 5α-pregnane-3,20-dione (5αP) in tumorous tissue promote cell proliferation and detachment, whereas the 4-pregnene metabolites, 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αDHP), more prominent in normal tissue, have the opposite (anti-cancer-like) effects. The aim of this study was to determine if the differences in enzyme activities between tumorous and nontumorous breast tissues are associated with differences in progesterone metabolizing enzyme gene expression. METHODS: Semi-quantitative RT-PCR was used to compare relative expression (as a ratio of 18S rRNA) of 5αR type 1 (SRD5A1), 5αR type 2 (SRD5A2), 3α-HSO type 2 (AKR1C3), 3α-HSO type 3 (AKR1C2) and 20α-HSO (AKR1C1) mRNAs in paired (tumorous and nontumorous) breast tissues from 11 patients, and unpaired tumor tissues from 17 patients and normal tissues from 10 reduction mammoplasty samples. RESULTS: Expression of 5αR1 and 5αR2 in 11/11 patients was higher (mean of 4.9- and 3.5-fold, respectively; p < 0.001) in the tumor as compared to the paired normal tissues. Conversely, expression of 3α-HSO2, 3α-HSO3 and 20α-HSO was higher (2.8-, 3.9- and 4.4-fold, respectively; p < 0.001) in normal than in tumor sample. The mean tumor:normal expression ratios for 5αR1 and 5αR2 were about 35–85-fold higher than the tumor:normal expression ratios for the HSOs. Similarly, in the unmatched samples, the tumor:normal ratios for 5αR were significantly higher than the ratios for the HSOs. CONCLUSIONS: The study shows changes in progesterone metabolizing enzyme gene expression in human breast carcinoma. Expression of SRD5A1 (5αR1) and SRD5A2 (5αR2) is elevated, and expression of AKR1C1 (20α-HSO), AKR1C2 (3α-HSO3) and AKR1C3 (3α-HSO2) is reduced in tumorous as compared to normal breast tissue. The changes in progesterone metabolizing enzyme expression levels help to explain the increases in mitogen/metastasis inducing 5αP and decreases in mitogen/metastasis inhibiting 3αHP progesterone metabolites found in breast tumor tissues. Understanding what causes these changes in expression could help in designing protocols to prevent or reverse the changes in progesterone metabolism associated with breast cancer

Menstruation: science and society

© 2020 The Authors Women's health concerns are generally underrepresented in basic and translational research, but reproductive health in particular has been hampered by a lack of understanding of basic uterine and menstrual physiology. Menstrual health is an integral part of overall health because between menarche and menopause, most women menstruate. Yet for tens of millions of women around the world, menstruation regularly and often catastrophically disrupts their physical, mental, and social well-being. Enhancing our understanding of the underlying phenomena involved in menstruation, abnormal uterine bleeding, and other menstruation-related disorders will move us closer to the goal of personalized care. Furthermore, a deeper mechanistic understanding of menstruation—a fast, scarless healing process in healthy individuals—will likely yield insights into a myriad of other diseases involving regulation of vascular function locally and systemically. We also recognize that many women now delay pregnancy and that there is an increasing desire for fertility and uterine preservation. In September 2018, the Gynecologic Health and Disease Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development convened a 2-day meeting, “Menstruation: Science and Society” with an aim to “identify gaps and opportunities in menstruation science and to raise awareness of the need for more research in this field.” Experts in fields ranging from the evolutionary role of menstruation to basic endometrial biology (including omic analysis of the endometrium, stem cells and tissue engineering of the endometrium, endometrial microbiome, and abnormal uterine bleeding and fibroids) and translational medicine (imaging and sampling modalities, patient-focused analysis of menstrual disorders including abnormal uterine bleeding, smart technologies or applications and mobile health platforms) to societal challenges in health literacy and dissemination frameworks across different economic and cultural landscapes shared current state-of-the-art and future vision, incorporating the patient voice at the launch of the meeting. Here, we provide an enhanced meeting report with extensive up-to-date (as of submission) context, capturing the spectrum from how the basic processes of menstruation commence in response to progesterone withdrawal, through the role of tissue-resident and circulating stem and progenitor cells in monthly regeneration—and current gaps in knowledge on how dysregulation leads to abnormal uterine bleeding and other menstruation-related disorders such as adenomyosis, endometriosis, and fibroids—to the clinical challenges in diagnostics, treatment, and patient and societal education. We conclude with an overview of how the global agenda concerning menstruation, and specifically menstrual health and hygiene, are gaining momentum, ranging from increasing investment in addressing menstruation-related barriers facing girls in schools in low- to middle-income countries to the more recent “menstrual equity” and “period poverty” movements spreading across high-income countries

How much time do nurses have for patients? a longitudinal study quantifying hospital nurses' patterns of task time distribution and interactions with health professionals

<p>Abstract</p> <p>Background</p> <p>Time nurses spend with patients is associated with improved patient outcomes, reduced errors, and patient and nurse satisfaction. Few studies have measured how nurses distribute their time across tasks. We aimed to quantify how nurses distribute their time across tasks, with patients, in individual tasks, and engagement with other health care providers; and how work patterns changed over a two year period.</p> <p>Methods</p> <p>Prospective observational study of 57 nurses for 191.3 hours (109.8 hours in 2005/2006 and 81.5 in 2008), on two wards in a teaching hospital in Australia. The validated Work Observation Method by Activity Timing (WOMBAT) method was applied. Proportions of time in 10 categories of work, average time per task, time with patients and others, information tools used, and rates of interruptions and multi-tasking were calculated.</p> <p>Results</p> <p>Nurses spent 37.0%[95%CI: 34.5, 39.3] of their time with patients, which did not change in year 3 [35.7%; 95%CI: 33.3, 38.0]. Direct care, indirect care, medication tasks and professional communication together consumed 76.4% of nurses' time in year 1 and 81.0% in year 3. Time on direct and indirect care increased significantly (respectively 20.4% to 24.8%, P < 0.01;13.0% to 16.1%, P < 0.01). Proportion of time on medication tasks (19.0%) did not change. Time in professional communication declined (24.0% to 19.2%, P < 0.05). Nurses completed an average of 72.3 tasks per hour, with a mean task length of 55 seconds. Interruptions arose at an average rate of two per hour, but medication tasks incurred 27% of all interruptions. In 25% of medication tasks nurses multi-tasked. Between years 1 and 3 nurses spent more time alone, from 27.5%[95%CI 24.5, 30.6] to 39.4%[34.9, 43.9]. Time with health professionals other than nurses was low and did not change.</p> <p>Conclusions</p> <p>Nurses spent around 37% of their time with patients which did not change. Work patterns were increasingly fragmented with rapid changes between tasks of short length. Interruptions were modest but their substantial over-representation among medication tasks raises potential safety concerns. There was no evidence of an increase in team-based, multi-disciplinary care. Over time nurses spent significantly less time talking with colleagues and more time alone.</p

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD