Hyporheic Interactions Increase Zinc Exposure and Effects on Hyalella azteca in Sediments under Flow‐Through Conditions

Groundwater–surface water interactions in the hyporheic transition zone can influence contaminant exposure to benthic macroinvertebrates. In streams, hyporheic flows are subject to varying redox conditions, which influence biogeochemical cycling and metal speciation. Despite these relationships, little is known about how these interactions influence the ecological risk of contaminants. The present study investigated the effects of hyporheic flows and zinc (Zn)‐contaminated sediments on the amphipod Hyalella azteca. Hyporheic flows were manipulated in laboratory streams during 10‐d experiments. Zinc toxicity was evaluated in freshly spiked and aged sediments. Hyporheic flows altered sediment and porewater geochemistry, oxidizing the sediments and causing changes to redox‐sensitive endpoints. Amphipod survival was lowest in the Zn sediment exposures with hyporheic flows. In freshly spiked sediments, porewater Zn drove mortality, whereas in aged sediments simultaneously extracted metals (SEM) in excess of acid volatile sulfides (AVS) normalized by the fraction of organic carbon (fOC) [(SEM‐AVS)/fOC] influenced amphipod responses. The results highlight the important role of hyporheic flows in determining Zn bioavailability to benthic organisms, information that can be important in ecological risk assessments. Environ Toxicol Chem 2019;38:2447–2458. © 2019 SETACPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152028/1/etc4554.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152028/2/etc4554_am.pd

Local Persistence of Novel MRSA Lineage after Hospital Ward Outbreak, Cambridge, UK, 2011–2013

To the Editor: Previously, we reported the use of whole-genome sequencing to investigate a putative methicillin-resistant Staphylococcus aureus (MRSA) outbreak in 2011 in the special care baby unit (SCBU) at the Cambridge University Hospitals National Health Service Foundation Trust (CUH) in the United Kingdom (1). The report identified 26 related cases of infection with or asymptomatic carriage of MRSA and showed that transmission occurred within the SCBU, between mothers on a postnatal ward, and in the community; the outbreak apparently resolved at the end of 2011. The outbreak strain, sequence type (ST) 2371, was of a novel multilocus ST related to the dominant hospital-associated lineage in the UK (ST22, EMRSA-15), but unlike most ST22 strains, this strain was Panton-Valentine leucocidin–positive (2). Since then, ST2371 has been identified as a prevalent communityassociated MRSA clone in Southern India, and sporadic isolates have also been detected by whole-genome sequencing of MRSA in Denmark (3–5)The study was supported by grants from the UKCRC Translational Infection Research (TIR) Initiative, and the Medical Research Council (Grant Number G1000803) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to Prof. Peacock); by a Healthcare Infection Society Major Research Grant; and by Wellcome Trust grant number 098051 awarded to the Wellcome Trust Sanger Institute

Myasthenia Gravis in pregnancy: Systematic review and case series

Background: Myasthenia gravis is an autoimmune disease which can impact pregnancy. Methods: Six databases were systematically searched for studies with at least five subjects reporting pregnancy outcomes for women with myasthenia gravis in pregnancy. Assessment of bias was performed for all included studies. Forty-eight cases from our own centre were also included in the analysis. Results: In total, 32 publications met inclusion criteria for systematic review, for a total of 33 unique data sets including 48 cases from our institution. Outcome data was available for 824 pregnancies. Spontaneous vaginal delivery occurred in 56.3% of pregnancies. Overall risk of myasthenia gravis exacerbation was 33.8% with a 6.4% risk of myasthenic crisis in pregnancy and 8.2% postpartum. The incidence risk of transient neonatal myasthenia gravis was 13.0%. Conclusions: The current systematic review provides the best estimates of risk currently available to aid in counselling women with myasthenia gravis in pregnancy

Inter-individual Differences in Tolerance to a Simulated Hemorrhage Challenge During Heat Stress: Cerebrovascular Control

A high degree of inter-individual variability exists in heat stress (HS) -induced reductions in orthostatic tolerance relative to normothermia (NT), which may be associated with HS-mediated reductions in cerebral perfusion, and thus mechanisms of cerebrovascular control during hypotensive challenges. This study tested two hypotheses; 1) the magnitude of increase in cerebral autoregulation (CA) would be negatively correlated with the difference in tolerance to graded lower body negative pressure (LBNP) 30 [assessed with a cumulative stress index (CSI)] during HS relative to NT (CSIdiff), and 2) cerebrovascular sensitivity to HS-induced hypocapnia would be positively correlated with CSIdiff. Subjects (N=13) were exposed to LBNP on two occasions (NT and HS) separated by \u3e72h to assess CSI. On a third day, indices of CA were assessed during NT and HS by spectral and transfer function analyses, and cerebrovascular sensitivity to changes in PaCO2 was determined during NT, HS, and HS+LBNP (-20 mm Hg; HSLBNP). Estimates of CA were improved during HS compared to NT (P0.05). Hyperventilation-induced hypocapnia reduced cerebral vascular conductance (CVCi) during HS and HSLBNP relative to NT (P0.05 for all). In summary, HS augments mechanisms of cerebrovascular control to protect against orthostatic challenges; however, individual differences in these responses do not predict tolerance to a simulated hemorrhage when internal temperature is elevated

Systematic Surveillance Detects Multiple Silent Introductions and Household Transmission of Methicillin-Resistant Staphylococcus aureus USA300 in the East of England.

BACKGROUND: The spread of USA300 methicillin-resistant Staphylococcus aureus (MRSA) across the United States resulted in an epidemic of infections. In Europe, only sporadic cases or small clusters of USA300 infections are described, and its prevalence in England is unknown. We conducted prospective surveillance for USA300 in the east of England. METHODS: We undertook a 12-month prospective observational cohort study of all individuals with MRSA isolated from community and hospital samples submitted to a microbiology laboratory. At least 1 MRSA isolate from each individual underwent whole-genome sequencing. USA300 was identified on the basis of sequence analysis, and phylogenetic comparisons were made between these and USA300 genomes from the United States. RESULTS: Between April 2012 and April 2013, we sequenced 2283 MRSA isolates (detected during carriage screening and in clinical samples) from 1465 individuals. USA300 was isolated from 24 cases (1.6%). Ten cases (42%) had skin and soft tissue infection, and 2 cases had invasive disease. Phylogenetic analyses identified multiple introductions and household transmission of USA300. CONCLUSIONS: Use of a diagnostic laboratory as a sentinel for surveillance has identified repeated introductions of USA300 in eastern England in 2012-2013, with evidence for limited transmission. Our results show how systematic surveillance could provide an early warning of strain emergence and dissemination.This work was supported by grants from the UK Clinical Research Collaboration Translational Infection Research Initiative, and the Medical Research Council (Grant Number G1000803) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to Prof. Peacock); by a Healthcare Infection Society Major Research Grant (to Prof. Peacock), and by Wellcome Trust grant number 098051 awarded to the Wellcome Trust Sanger Institute. MST is a Wellcome Trust Clinical PhD Fellow. MET is a Clinician Scientist Fellow, supported by the Academy of Medical Sciences and the Health Foundation, and by the National Institute for Health Research Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/infdis/jiw16

User Guide for Luminescence Sampling in Archaeological and Geological Context

Luminescence dating provides a direct age estimate of the time of last exposure of quartz or feldspar minerals to light or heat and has been successfully applied to deposits, rock surfaces, and fired materials in a number of archaeological and geological settings. Sampling strategies are diverse and can be customized depending on local circumstances, although all sediment samples need to include a light-safe sample and material for dose-rate determination. The accuracy and precision of luminescence dating results are directly related to the type and quality of the material sampled and sample collection methods in the field. Selection of target material for dating should include considerations of adequacy of resetting of the luminescence signal (optical and thermal bleaching), the ability to characterize the radioactive environment surrounding the sample (dose rate), and the lack of evidence for post-depositional mixing (bioturbation in soils and sediment). Sample strategies for collection of samples from sedimentary settings and fired materials are discussed. This paper should be used as a guide for luminescence sampling and is meant to provide essential background information on how to properly collect samples and on the types of materials suitable for luminescence dating. La datación por luminiscencia proporciona una estimación directa de la edad del último momento en el que el cuarzo o los minerales de feldespato se expusieron a la luz o al calor y que se ha aplicado exitosamente a depósitos, superficies rocosas y materiales expuestos al fuego en distintos contextos arqueológicos y geológicos. Las estrategias de muestreo son diversas y pueden ser individualizadas dependiendo de las circunstancias locales, aunque todas las muestras de sedimentos deben incluir una muestra segura que no haya sido expuesta a la luz y material para calcular la tasa de la dosis. La exactitud y precisión de los resultados de la datación por luminiscencia están directamente relacionadas con el tipo y la calidad de los materiales muestreados y los métodos de recolección de muestras en el campo. La elección del material de estudio para su datación debe incluir las siguientes consideraciones en torno a la idoneidad de poder reposicionar la señal de luminiscencia (blanqueador óptico y térmico), la capacidad de caracterizar el ambiente radiactivo que rodea la muestra (la tasa de la dosis) y el que no exista evidencia de una alteración posdeposicional (bioperturbación en suelos y sedimentos). Se discuten las estrategias de muestreo para la recolección de muestras de contextos sedimentarios y de materiales expuestos al fuego. Este artículo debe utilizarse como una guía para el muestreo por luminiscencia y tiene la intención de proveer información básica de cómo recolectar muestras y sobre los tipos de materiales apropiados para la datación por luminiscencia

Repetitive negative thinking in the perinatal period and its relationship with anxiety and depression

Background: Rumination and worry represent two types of repetitive negative thinking (RNT), and their predictive and maintaining roles are well-established in depression and anxiety, respectively. Furthermore, there is an emerging literature on the link between RNT and psychological wellbeing in the perinatal period. Methods: We conducted a scoping review of studies that have investigated the relationship between RNT and perinatal depression and anxiety. We identified 87 papers eligible for inclusion in the review; they included cross-sectional and longitudinal studies, as well as treatment evaluations (pilot trials and randomised controlled trials). Results: Cross-sectional studies provided evidence of an association between RNT (i.e., rumination and worry) and depression and anxiety, in both pregnancy and postpartum. Longitudinal findings were mixed. Whilst antenatal worry consistently predicted subsequent depression and anxiety (both later in pregnancy and postpartum), rumination did not consistently predict depression. However, there was some evidence that RNT interacted with other processes to predict later psychopathology. Three randomised controlled trials evaluated whether psychological treatments reduce RNT in the perinatal period, only one of which included a clinical sample. Limitations: No experimental investigations were eligible for inclusion in the review. Conclusions: Further studies are needed to further our understanding of the nature and role of RNT in pregnancy and postpartum, and its consequences for maternal mental health. These include (but are not limited to) experimental investigations, studies with large clinical samples, and RCTs evaluating the effectiveness of psychological interventions targeting RNT to prevent and treat perinatal depression and anxiety

Ulocuplumab (BMS-936564 / MDX1338): a fully human anti-CXCR4 antibody induces cell death in chronic lymphocytic leukemia mediated through a reactive oxygen species-dependent pathway.

The CXCR4 receptor (Chemokine C-X-C motif receptor 4) is highly expressed in different hematological malignancies including chronic lymphocytic leukemia (CLL). The CXCR4 ligand (CXCL12) stimulates CXCR4 promoting cell survival and proliferation, and may contribute to the tropism of leukemia cells towards lymphoid tissues. Therefore, strategies targeting CXCR4 may constitute an effective therapeutic approach for CLL. To address that question, we studied the effect of Ulocuplumab (BMS-936564), a fully human IgG4 anti-CXCR4 antibody, using a stroma--CLL cells co-culture model. We found that Ulocuplumab (BMS-936564) inhibited CXCL12 mediated CXCR4 activation-migration of CLL cells at nanomolar concentrations. This effect was comparable to AMD3100 (Plerixafor--Mozobil), a small molecule CXCR4 inhibitor. However, Ulocuplumab (BMS-936564) but not AMD3100 induced apoptosis in CLL at nanomolar concentrations in the presence or absence of stromal cell support. This pro-apoptotic effect was independent of CLL high-risk prognostic markers, was associated with production of reactive oxygen species and did not require caspase activation. Overall, these findings are evidence that Ulocuplumab (BMS-936564) has biological activity in CLL, highlight the relevance of the CXCR4-CXCL12 pathway as a therapeutic target in CLL, and provide biological rationale for ongoing clinical trials in CLL and other hematological malignancies

piRNAs Are Associated with Diverse Transgenerational Effects on Gene and Transposon Expression in a Hybrid Dysgenic Syndrome of D. virilis

Sexual reproduction allows transposable elements (TEs) to proliferate, leading to rapid divergence between populations and species. A significant outcome of divergence in the TE landscape is evident in hybrid dysgenic syndromes, a strong form of genomic incompatibility that can arise when (TE) family abundance differs between two parents. When TEs inherited from the father are absent in the mother's genome, TEs can become activated in the progeny, causing germline damage and sterility. Studies in Drosophila indicate that dysgenesis can occur when TEs inherited paternally are not matched with a pool of corresponding TE silencing PIWI-interacting RNAs (piRNAs) provisioned by the female germline. Using the D. virilis syndrome of hybrid dysgenesis as a model, we characterize the effects that divergence in TE profile between parents has on offspring. Overall, we show that divergence in the TE landscape is associated with persisting differences in germline TE expression when comparing genetically identical females of reciprocal crosses and these differences are transmitted to the next generation. Moreover, chronic and persisting TE expression coincides with increased levels of genic piRNAs associated with reduced gene expression. Combined with these effects, we further demonstrate that gene expression is idiosyncratically influenced by differences in the genic piRNA profile of the parents that arise though polymorphic TE insertions. Overall, these results support a model in which early germline events in dysgenesis establish a chronic, stable state of both TE and gene expression in the germline that is maintained through adulthood and transmitted to the next generation. This work demonstrates that divergence in the TE profile is associated with diverse piRNA-mediated transgenerational effects on gene expression within populations

Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community.

Genome sequencing has provided snapshots of the transmission of methicillin-resistant Staphylococcus aureus (MRSA) during suspected outbreaks in isolated hospital wards. Scale-up to populations is now required to establish the full potential of this technology for surveillance. We prospectively identified all individuals over a 12-month period who had at least one MRSA-positive sample processed by a routine diagnostic microbiology laboratory in the East of England, which received samples from three hospitals and 75 general practitioner (GP) practices. We sequenced at least 1 MRSA isolate from 1465 individuals (2282 MRSA isolates) and recorded epidemiological data. An integrated epidemiological and phylogenetic analysis revealed 173 transmission clusters containing between 2 and 44 cases and involving 598 people (40.8%). Of these, 118 clusters (371 people) involved hospital contacts alone, 27 clusters (72 people) involved community contacts alone, and 28 clusters (157 people) had both types of contact. Community- and hospital-associated MRSA lineages were equally capable of transmission in the community, with instances of spread in households, long-term care facilities, and GP practices. Our study provides a comprehensive picture of MRSA transmission in a sampled population of 1465 people and suggests the need to review existing infection control policy and practice