Development of a bioavailability‐based risk assessment approach for nickel in freshwater sediments

To assess nickel (Ni) toxicity and behavior in freshwater sediments, a large‐scale laboratory and field sediment testing program was conducted. The program used an integrative testing strategy to generate scientifically based threshold values for Ni in sediments and to develop integrated equilibrium partitioning‐based bioavailability models for assessing risks of Ni to benthic ecosystems. The sediment testing program was a multi‐institutional collaboration that involved extensive laboratory testing, field validation of laboratory findings, characterization of Ni behavior in natural and laboratory conditions, and examination of solid phase Ni speciation in sediments. The laboratory testing initiative was conducted in 3 phases to satisfy the following objectives: 1) evaluate various methods for spiking sediments with Ni to optimize the relevance of sediment Ni exposures; 2) generate reliable ecotoxicity data by conducting standardized chronic ecotoxicity tests using 9 benthic species in sediments with low and high Ni binding capacity; and, 3) examine sediment bioavailability relationships by conducting chronic ecotoxicity testing in sediments that showed broad ranges of acid volatile sulfides, organic C, and Fe. A subset of 6 Ni‐spiked sediments was deployed in the field to examine benthic colonization and community effects. The sediment testing program yielded a broad, high quality data set that was used to develop a Species Sensitivity Distribution for benthic organisms in various sediment types, a reasonable worst case predicted no‐effect concentration for Ni in sediment (PNECsediment), and predictive models for bioavailability and toxicity of Ni in freshwater sediments. A bioavailability‐based approach was developed using the ecotoxicity data and bioavailability models generated through the research program. The tiered approach can be used to fulfill the outstanding obligations under the European Union (EU) Existing Substances Risk Assessment, EU Registration, Evaluation, Authorisation, and Regulation of Chemicals (REACH), and other global regulatory initiatives. Integr Environ Assess Manag 2016;12:735–746. © 2015 SETACKey PointsA comprehensive, representative sediment toxicity database is available to support risk assessment of Ni in freshwater sediments.Sediment Ni ecotoxicity data were gathered from studies that used spiking approaches that resulted in Ni‐enriched sediments resembling naturally contaminated sediments, thus increasing their relevance.Bioavailability of Ni in sediments, which is controlled by acid volatile sulfides (AVS), varies among different species, with actively bioturbating species showing a lower slope in the relationship between decreasing toxicity with increasing AVS.A bioavailability‐based, tiered approach is presented, where the first tier involves comparison of ambient total Ni concentrations with a RWC threshold value of 136 mg Ni/kg. Site‐specific AVS can be used to calculate a site‐specific threshold if ambient Ni is greater than 136 mg Ni/kg.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134197/1/ieam1720.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134197/2/ieam1720_am.pd

Understanding the direct and indirect mechanisms of xylanase action on starch digestion in broilers

The objective of the current study was to investigate the mechanisms of xylanase action in a maize-soya diet and its effect on starch digestion. A total of 60 broilers were divided into 6 treatment groups; a control group without xylanase, and five other groups supplemented with xylanase (Econase XT 25; 100 g/t) from 1, 2, 3, 4 or 5 weeks before slaughter. At the end of the experiment, digesta was collected from the gizzard, upper and lower small intestine, and both caeca. Digesta pH ranged from pH 2.2-4.4, 5.9-6.6, 6.7-7.8 and 5.7-7.3 in the gizzard, upper small intestine, lower small intestine, and both caeca, respectively, with no effect of xylanase (P > 0.05). Scanning Electron Microscope (SEM) images along with total starch measurements showed the progression of starch digestion through the tract. The SEM did not show any greater disruption to cell wall material with xylanase supplementation. This suggests that xylanase was not working directly on the cell wall and provides evidence for the hypothesis that xylanase works through an indirect mechanism. Peptide YY (PYY) concentration in the blood was higher during the first few weeks of supplementation, with longer periods of supplementation nulling this effect, implying that xylanase may be acting through a prebiotic mechanism. The RT-q PCR results revealed a numerical increase in glucose transporter (GLUT2 and SGLT1) expression at 2 and 3 weeks of xylanase supplementation, respectively, which might suggest a greater absorption capacity of birds. From these results, a potential mechanism of xylanase action in maize-based diets has been proposed

Evaluation of Online Consumer Health Information for Idiopathic Scoliosis Identified by a Google Search

Introduction. This study sought to assess the quality of online consumerhealth information about idiopathic scoliosis. Previous studiesshowed that quality of online health information varies and oftenlacks adherence to expert recommendations and guidelines. Nevertheless,72% of internet users seek health information online. A 2005analysis of online scoliosis information found that the informationwas limited and of poor quality. Methods. Two reviewers vetted the top 10 websites resulting from aGoogleTM search for “scoliosis.” Content was organized into categoriesand rated by three physician evaluators using a 1 - 5 scale basedon quality, accuracy, completeness of information, readability, andwillingness to recommend. Additional information, such as numberof ads and Flesch-Kinkaid reading level, also was collected. Results. The average overall physician score was 47.6 (75 possible).All websites included content that was mostly accurate but varied incompleteness. Physicians unanimously recommended Mayo Clinic,MedicineNet, and Kids Health; none recommended the GoogleTMKnowledge Graph. The Scoliosis Research Society website reachedthe highest overall physician score. Readability ranged from 7th gradeto college level; only that of Kids Health was below 10th grade level. Conclusions. Most essential information provided by the websiteswas accurate and generally well rated by physicians. Website rankingby physicians was inconsistent with the ranking order by GoogleTM,indicating that health seekers reviewing the top GoogleTM-rankedwebsites may not be viewing the websites rated highest by physicians.Physicians should consider patient literacy in website recommendations,as many have an above average literacy level.Kans J Med 2018;11(4):95-101

Phase equilibrium experiments and thermodynamic simulations to constrain the pre-eruptive conditions of the 2021 Tajogaite eruption (Cumbre Vieja volcano, La Palma, Canary Islands)

Phase relations of a tephritic lava erupted at La Palma, Canary Islands, the 2nd of October 2021, during the eruption of Cumbre Vieja volcano were determined experimentally in the temperature/water content space, T (◦C)/H2O (wt%). The crystallisation experiments were carried out at a fixed pressure of 275 MPa for tempera- tures varying from 1000 to 1200 ◦C and with H2O added contents ranging from 0 to 5 wt%. Results from the synthetic products are compared with those obtained from thermodynamic simulations and with the natural phases to constrain the pre-eruptive conditions of the tephritic magma stored in the shallow reservoir. The major phases (clinopyroxene + olivine + oxides) occurring in the natural products were reproduced. The experimental results combined with thermodynamic modelling allow us to constrain the pre-eruptive temperature to ~1100 ◦ C considering H2O to 3 wt% and to restrict the crystallisation of plagioclase at low pressures (< 20 MPa). The results indicate that, under the presence of a pure H2O fluid, amphibole is stable at pressures higher than 300 MPa and temperatures ~1000 ◦C. Our results on pre-eruptive conditions of the 2021 Tajogaite eruption provide important constraints on mechanisms of storage and transport in primitive alkaline magmas

Selection of Multidrug-Resistant Bacteria in Medicated Animal Feeds

Exposure to antimicrobial resistant (AMR) bacteria is a major public health issue which may, in part, have roots in food production practices that are conducive to the selection of AMR bacteria ultimately impacting the human microbiome through food consumption. Of particular concern is the prophylactic use of antibiotics in animal husbandry, such as the medication of feeds with sulfonamides and other antibiotics not considered clinically relevant, but which may nonetheless co-select for multi-drug resistant (MDR) bacteria harboring resistance to medically important antibiotics. Using a MDR Klebsiella pneumoniae strain exhibiting resistance to sulfonamides and beta-lactams (including carbapenem) as a model, we examined the ability of non-medicated and commercially medicated (sulfonamide) animal feeds to select for the model strain when inoculated at low levels by measuring its recovery along with key AMR markers, sul1(sulfonamide) and blaKPC-3 (meropenem), under different incubation conditions. When non-medicated feeds were supplemented with defined amounts of sulfadiazine the model strain was significantly enriched after incubation in Mueller Hinton Broth at 37°C overnight, or in same at room temperature for a week, with consistent detection of both the sul1 and blaKPC-3 markers as determined by polymerase chain reaction (PCR) techniques to screen colony isolates recovered on plating media. Significant recoveries of the inoculated strain and the sul1 and blaKPC-3 markers were observed with one of three commercially medicated (sulfamethazine) feeds tested under various incubation conditions. These results demonstrate that under certain conditions the prophylactic use of so-called non-priority antibiotics in feeds can potentially lead to co-selection of environmental AMR bacteria with resistance to medically important antibiotics, which may have far-reaching implications for human health

A periosteum-derived cell line to study the role of BMP/TGFβ signaling in periosteal cell behavior and function

The periosteum is a thin tissue surrounding each skeletal element that contains stem and progenitor cells involved in bone development, postnatal appositional bone growth, load-induced bone formation, and fracture repair. BMP and TGFβ signaling are important for periosteal activity and periosteal cell behavior, but thorough examination of the influence of these pathways on specific cell populations resident in the periosteum is lacking due to limitations associated with primary periosteal cell isolations and in vitro experiments. Here we describe the generation of a novel periosteum-derived clonal cell (PDC) line from postnatal day 14 mice and use it to examine periosteal cell behavior in vitro. PDCs exhibit key characteristics of periosteal cells observed during skeletal development, maintenance, and bone repair. Specifically, PDCs express established periosteal markers, can be expanded in culture, demonstrate the ability to differentiate into chondrocytes, osteoblasts, and adipocytes, and exhibit an osteogenic response to physical stimulation. PDCs also engage in BMP and/or TGFβ signaling when treated with the activating ligands BMP2 and TGFβ-1, and in response to mechanical stimulation via fluid shear. We believe that this PDC line will be useful for large-scale, long-term experiments that were not feasible when using primary periosteal cells. Anticipated future uses include advancing our understanding of the signaling interactions that occur during appositional bone growth and fracture repair and developing drug screening platforms to discover novel growth and fracture healing factors

Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen

Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID50], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nn-ITN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc)(4) spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. IMPORTANCE The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nn-ITN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope.Peer reviewe

Support needs and barriers to accessing support:Baseline results of a mixed-methods national survey of people bereaved during the COVID-19 pandemic

BACKGROUND: The COVID-19 pandemic is a mass bereavement event which has profoundly disrupted grief experiences. Understanding support needs and access to support among people bereaved at this time is crucial to ensuring appropriate bereavement support infrastructure. AIM: To investigate grief experiences, support needs and use of formal and informal bereavement support among people bereaved during the pandemic. DESIGN: Baseline results from a longitudinal survey. Support needs and experiences of accessing support are reported using descriptive statistics and thematic analysis of free-text data. SETTING/PARTICIPANTS: 711 adults bereaved in the UK between March and December 2020, recruited via media, social media, national associations and community/charitable organisations. RESULTS: High-level needs for emotional support were identified. Most participants had not sought support from bereavement services (59%, n = 422) or their General-Practitioner (60%, n = 428). Of participants who had sought such support, over half experienced difficulties accessing bereavement services (56%, n = 149)/General-Practitioner support (52%, n = 135). About 51% reported high/severe vulnerability in grief; among these, 74% were not accessing bereavement or mental-health services. Barriers included limited availability, lack of appropriate support, discomfort asking for help and not knowing how to access services. About 39% (n = 279) experienced difficulties getting support from family/friends, including relational challenges, little face-to-face contact and disrupted collective mourning. The perceived uniqueness of pandemic bereavement and wider societal strains exacerbated their isolation. CONCLUSIONS: People bereaved during the pandemic have high levels of support needs alongside difficulties accessing support. We recommend increased provision and tailoring of bereavement services, improved information on support options and social/educational initiatives to bolster informal support and ameliorate isolation