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Introduction: The present study consists in a bibliographical' review concerning the articles related to the different manifestations and forms of the septum nasal perforation, with a main emphasis in the description of its techniques of surgical correction. As the etiology, that is fundamentally iatrogenic, accordingly surgical trauma. Other causes include exhibition to chemical industrial reagents, cocaine use, intranasal steroidal therapeutic, neoplasia and, infectious conditions. There is a few data concerning the prevalence of septum perforation in the general population. The decision making about surgical correction or medical treatment depend on the anatomic characteristics and of the pathogenesis of the septal perforation.

The American radium dial worker (RDW) cohort of over 3,200 persons is being revisited as part of the Million Person Study (MPS) to include a modern approach to RDW dosimetry. An exceptional source of data and contextualization in this project is an extensive collection of electronic records (requiring 43 gigabytes (GB) of storage) digitized from existing microfilm and microfiche housed at the United States Transuranium and Uranium Registries (USTUR). Although the type, extent, and quality (e.g., legibility) of record(s) varies between individuals, the remarkable occupational, medical and demographic data include in vivo radiation measurements (e.g., radon breath, whole body counts), autopsy results, medical records (including copies of radiographs), interviews over the years, and correspondence. Of particular dosimetric interest are the details of radiation measurements. For example, there are some instances where hand-written and transcribed values are both available, along with notes providing context for why a particular measurement in a time series of measurements was chosen to assign an intake, or if there were concerns about a particular measurement. Born prior to 1935, RDW have nearly all passed away. Thus, the updated dosimetry, especially for the bone, will allow the correlation of lifetime cumulative dose with radiation risk. Here we review typical information available in this collection of historical records, highlighting some interesting finds, and discuss the relevance to current and ongoing work related to updating the dosimetry of the RDW in the Million Person Study, including providing an example of the usefulness of information contained in these records., (Creative Commons Attribution license.)

In 2018, the International Commission on Radiological Protection (ICRP) released Publication 138, which highlights the ethical values foundational to the system of radiological protection. Additional work, both within and beyond the ICRP, has proposed or recommended ethical values associated with applications of the system in different areas, perhaps most notably in medical, veterinary, and environmental radiological protection. There are also existing ethical frameworks not specifically related to radiological protection that are nonetheless relevant to its practice; for example, the Beauchamp and Childress principles of biomedical ethics are of particular significance when it comes to medical uses of radiation and radioactivity. At first glance, it may seem as if there are unique or isolated sets of ethical values that need to be applied depending on the circumstance. Yet while each area of application will indeed have its own unique aspects and associated value judgements, there are consistent and complementary relationships between these ethical values. This paper reviews the work of the ICRP related to ethics, including brief historical context, and highlights the similarities and differences between sets of ethical values with emphasis on medical, veterinary, and environmental applications of radiological protection., (Creative Commons Attribution license.)

Salt marshes are highly productive and valuable coastal ecosystems that act as filters for nutrients and pollutants at the land-sea interface. The salt marshes of the mid-Atlantic United States often exhibit geochemical behavior that varies significantly from other estuaries around the world, but our understanding of metal mobility and bioavailability remains incomplete for these systems. We sampled abiotic (water and sediment) and native biotic (three halophyte and two bivalve species) compartments of a southeastern United States salt marsh to understand the site- and species-specific metal concentrations, fractionation, and bioavailability for 16 metals and metalloids, including two naturally occurring radionuclides. Location on the marsh platform greatly influenced metal concentrations in sediment and metal bioaccumulation in halophytes, with sites above the mean high-water mark (i.e., high marsh zone) having lower concentrations in sediment but plants exhibiting greater biota sediment accumulation factors (BSAFs). Transition metal concentrations in the sediment were an average of 6× higher in the low marsh zone compared to the high marsh zone and heavy metals were on average 2× higher. Tissue- and species-specific preferential accumulation in bivalves provide opportunities for tailored biomonitoring programs. For example, mussel byssal threads accumulated ten of the sixteen studied elements to significantly greater concentrations compared to soft tissues and oysters had remarkably high soft tissue zinc concentrations (~5000 mg/kg) compared to all other species and element combinations studied. Additionally, some of our results have important implications for understanding metal mobility and implementing effective remediation (specifically phytoremediation) strategies, including observations that (1) heavy metals exhibit distinct concentration spatial distributions and metal fractionation patterns which vary from the transition metals and (2) sediment organic matter fraction appears to play an important role in controlling sediment metal concentrations, fractionation, and plant bioavailability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The US Food and Drug Administration supports innovations to facilitate new indications for high-risk human papillomavirus testing. This report describes the retrospective testing of stored specimens and analysis of existing data to efficiently and cost-effectively support a new indication for the Onclarity human papillomavirus assay (Becton, Dickinson and Company, BD Life Sciences - Integrated Diagnostic Solutions, Sparks, MD). The performance of this index test was compared with that of a predicate test, the cobas human papillomavirus assay (Roche Diagnostics, Indianapolis, IN). Both human papillomavirus assays are based on real-time polymerase chain reaction platforms that detect the presence of 14 high-risk human papillomavirus genotypes. The predicate assay reports human papillomavirus types 16 and 18 as individual results and the other 12 human papillomavirus genotypes as 1 pooled result. The index assay reports 9 independent results (human papillomavirus types 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, and 56/59/66). Both the index and predicate assays are approved by the Food and Drug Administration for cervical cancer screening, but at the time that this study was initiated, the index human papillomavirus assay was not approved for use with cervical specimens collected in PreservCyt (Hologic, Inc, San Diego, CA) liquid-based cytology media., Objective: The performance of the index human papillomavirus assay was compared with that of the predicate human papillomavirus assay for the detection of cervical intraepithelial neoplasia grades 2 or greater and 3 or greater (≥CIN2 or ≥CIN3) using PreservCyt liquid-based cytology specimens collected from women aged 21 to 65 years. In addition, the ability of the index test's extended genotyping to stratify ≥CIN2 and ≥CIN3 risks, using these specimens, was evaluated., Study Design: The New Mexico HPV Pap Registry was used to select an age- and cytology-stratified random sample of 19,879 women undergoing opportunistic cervical screening and follow-up in routine clinical practice across New Mexico. A subset (n = 4820) of PreservCyt specimens was selected from 19,879 women for paired testing by the index and predicate human papillomavirus assays within age and cytology strata and included women with or without cervical biopsy follow-up. Point estimate differences and ratios were calculated for cervical disease detection and positivity rates, respectively, with 95% confidence intervals to determine statistical significance. The cumulative risk of ≥CIN2 or ≥CIN3, with up to 5-year follow-up, was estimated for the index assay using Kaplan-Meier methods., Results: The 5-year cumulative ≥CIN3 detection rates were 5.6% for the index assay and 4.6% for the predicate assay (difference, 1.0%; 95% confidence interval, 0.5%-1.5%). The ≥CIN3 positivity rates within <1 year were 95.3% for the index assay and 94.5% for the predicate assay (ratio, 1.01; 95% confidence interval, 0.98-1.06). The ≥CIN3 cumulative positivity rates for the index and predicate assays were also similar at 5 years. Among cases of ≥CIN3, the positive agreement rates between the index and predicate assays for human papillomavirus types 16 and 18 were 100.0% (95% confidence interval, 95.0%-100.0%) and 90.9% (95% confidence interval, 62.3%-98.4%), respectively. Human papillomavirus type 16 carried the highest ≥CIN2 or ≥CIN3 risk, followed by human papillomavirus types 18/31/33/58/52/45 and human papillomavirus types 35/56/59/51/56/59/66., Conclusion: The index and predicate human papillomavirus assays demonstrated equivalent performance, and extended human papillomavirus genotyping, using the index assay, provided effective ≥CIN2 and ≥CIN3 risk stratification, supporting a new indication for use of the index assay with PreservCyt., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A variety of processes, both natural and anthropogenic, can have a negative impact on surface waters, which in turn can be detrimental to human and environmental health. Few studies have considered the ecotoxicological impacts of concurrently occurring contaminants, and that is particularly true for mixtures that include contaminants of emerging concern (CEC). Motivated by this knowledge gap, the present study considers the potential ecotoxicity of environmentally relevant contaminants in the representative aquatic plant Lemna minor (common duckweed), a model organism. More specifically, biological effects associated with exposure of L. minor to a ubiquitous radionuclide (uranium [U]) and a fluorinated organic compound (perfluorooctanoic acid [PFOA], considered a CEC), alone and in combination, were monitored under controlled laboratory conditions. Lemna minor was grown for 5 days in small, aerated containers. Each treatment consisted of four replicates with seven plants each. Treatments were 0, 0.3, and 3 ppb PFOA; 0, 0.5, and 5 ppb U; and combinations of these. Plants were observed daily for frond number and signs of chlorosis and necrosis. Other biological endpoints examined at the conclusion of the experiment were chlorophyll content and antioxidant capacity. In single-exposure experiments, a slight stimulatory effect was observed on frond number at 0.3 ppb PFOA, whereas both concentrations of U had a detrimental effect on frond number. In the dual-exposure experiment, the combinations with 5 ppb U also had a detrimental effect on frond number. Results for chlorophyll content and antioxidant capacity were less meaningful, suggesting that environmentally relevant concentrations of PFOA and U have only subtle effects on L. minor growth and health status. Environ Toxicol Chem 2023;42:2412-2421. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

Life cycle assessment (LCA) is a modelling technique used to determine the cradle-to-grave environmental and human health impacts from the production of a good or the provision of a service. Radiological protection may benefit from employing tools like LCA to obtain a broader perspective and enable comparison with analyses of non-radiological systems. Despite structural similarities to other well-established decision-aiding techniques (DATs), the impact assessment within LCA (i.e. LCIA) is not commonly used in the optimisation of radiological protection process. This paper provides a brief review of LCA, including LCIA, along with more traditional DATs (such as multi-attribute utility analysis) used in the optimisation process for comparison. Basic concrete shielding was considered as a simple, illustrative example; concrete attenuates emissions from a radiation source but is also associated with a financial cost as well as costs with respect to energy, material, and water use. LCA offers quantification of these and other key resources (termed 'impact categories'). Ultimately, we offer that, depending on the circumstance, LCA can be a useful tool in radiological protection decision-making, complementing existing techniques., (Creative Commons Attribution license.)

Characterization of biological and chemical responses to ionizing radiation by various organisms is essential for potential applications in bioremediation, alternative modes of detecting nuclear material, and national security. Escherichia coli DH10β is an optimal system to study the microbial response to low-dose ionizing radiation at the transcriptional level because it is a well-characterized model bacterium and its responses to other environmental stressors, including those to higher radiation doses, have been elucidated in prior studies. In this study, RNA sequencing with downstream transcriptomic analysis (RNA-seq) was employed to characterize the global transcriptional response of stationary-phase E. coli subjected to 239 Pu, 3 H (tritium), and 55 Fe, at an approximate absorbed dose rate of 10 mGy day -1 for 1 day and 15 days. Differential expression analysis identified significant changes in gene expression of E. coli for both short- and long-term exposures. Radionuclide source exposure induced differential expression in E. coli of genes involved in biosynthesis pathways of nuclear envelope components, amino acids, and siderophores, transport systems such as ABC transporters and type II secretion proteins, and initiation of stress response and regulatory systems of temperature stress, the RpoS regulon, and oxidative stress. These findings provide a basic understanding of the relationship between low-dose exposure and biological effect of a model bacterium that is critical for applications in alternative nuclear material detection and bioremediation. IMPORTANCE Escherichia coli strain DH10β, a well-characterized model bacterium, was subjected to short-term (1-day) and long-term (15-day) exposures to three different in situ radiation sources comprised of radionuclides relevant to nuclear activities to induce a measurable and identifiable genetic response. We found E. coli had both common and unique responses to the three exposures studied, suggesting both dose rate- and radionuclide-specific effects. This study is the first to provide insights into the transcriptional response of a microorganism in short- and long-term exposure to continuous low-dose ionizing radiation with multiple in situ radionuclide sources and the first to examine microbial transcriptional response in stationary phase. Moreover, this work provides a basis for the development of biosensors and informing more robust dose-response relationships to support ecological risk assessment.

Radiological contamination of coastal habitats poses potential risk for native fauna, but the bioavailability of aqueous radium (Ra) and other dissolved metals to marine bivalves remains unclear. This study was the first to examine the tissue-specific disposition of aqueous 226 Ra in a coastal mussel, specifically the Atlantic ribbed mussel Geukensia demissa . Most organ groups reached steady-state concentrations within 7 days during experimental exposure, with an average uptake rate constant of 0.0013 mL g -1 d -1 . When moved to Ra-free synthetic seawater, mussels rapidly eliminated aqueous 226 Ra (average elimination rate constant 1.56 d -1 ). The biological half-life for aqueous 226 Ra ranged from 8.9 h for the gills and labial palps to 15.4 h for the muscle. Although previous field studies have demonstrated notable 226 Ra accumulation in the soft tissues of marine mussels and that, for freshwater mussels, tissue-incorporated 226 Ra derives primarily from the aqueous phase, our tissue-specific bioconcentration factors (BCFs) were on the order of (8.3 ± 1.5) × 10 -4 indicating low accumulation potential of aqueous 226 Ra in estuarine mussels. This suggests marine and estuarine mussels obtain 226 Ra from an alternate route, such as particulate-sorbed Ra ingested during filter-feeding or from a contaminated food source.

Abstract: This work investigates the uptake and root-shoot transport of plutonium (Pu) and iron (Fe) in corn ( Zea mays ) to gain insight into the Pu uptake pathway. Plutonium has no known biological function in plants yet may feasibly enter plants through the uptake pathway used by Fe (an essential nutrient), as these two elements have similar chemical properties. A series of experiments was conducted in which two hydroponically grown corn strains (one normal and one deficient in the transporter protein for Fe) were exposed to varying concentrations of complexed Pu and Fe. Results suggest that while Fe did inhibit Pu uptake to a certain extent, Pu was able to use alternative uptake pathways. In a 10 ppb Pu:1 ppb Fe hydroponic solution, all shoots had detectable shoot Pu concentrations compared to only 22% of plants when the Fe concentration was raised to 10 ppb. While root Pu accumulation was reduced for the corn strain deficient in the Fe transporter protein at lower Pu media concentrations, there were no differences at higher Pu concentrations, signifying the existence of substitute transport routes. A comparison of citrate and deferoxamine B (DFOB) ligand influence found that Pu complexed with DFOB remained in the roots of the plant, while movement of Pu into the shoots of the plant was more prevalent with the Pu-citrate complex. This study advances understanding of the behavior and mobility of Pu in the terrestrial environment and specifically the interactions between Pu and an essential nutrient in a common crop species., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Health Physics Society.)

Analysis of gene expression has become an important tool in understanding low-dose effect mechanisms of ionizing radiation at the cellular level. Metal binding to nucleic acids needs to be considered when interpreting these results, as some radioactive metals, particularly actinides, may produce free radicals and cause oxidative stress damage via chemical means at rates much higher than free radical formation related to their radiological properties. Bacteria exposed in situ to low dose rates of plutonium-239 ( 239 Pu) and iron-55 ( 55 Fe) were previously analysed for gene expression. The work herein was motivated by an interest in more precisely identifying the distribution of radionuclides in these bacteria as well as the practical need to ensure appropriate transport and handling of the associated ribonucleic acid (RNA) extractions. RNA extractions were performed on bacteria growth media with and without bacteria cells (i.e. with and without RNA) at several different concentrations of 239 Pu and 55 Fe to inform the level of specificity of the extraction membrane as well as provide insight into internal (uptake) vs external (sorption) accumulation of these radionuclides in bacteria cells. Results of the study suggest that 239 Pu and 55 Fe detected in RNA extraction samples during long term cell studies is the result of binding to RNA prior to the time of extraction, as opposed to flow through or binding after cell lysis, and it highlights the practical importance of nucleic acid sample characterization to radiation protection more generally., (© 2023 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

This study examines the ability of the grass species Andropogon virginicus to alter the subsurface transport and redistribution of a suite of radionuclides ( 99 Tc, 133 Cs (stable analog for 135 Cs and 137 Cs), 237 Np, 238 U) with varying chemical behaviors in a Savannah River Site soil via the use of vegetated and unvegetated soil columns. After an acclimation period, a small volume of solution containing all radionuclides was introduced into the columns via Rhizon© pore water sampling tubes. Plants were grown for an additional 4 weeks before shoots were harvested, and columns were prepared for sampling. Plant presence led to decreased radionuclide release from the columns, mainly due to radionuclide specific combinations of system hydrology differences resulting from plant transpiration as well as plant uptake. For the most mobile radionuclides, 99 Tc followed by 237 Np, plant presence resulted in significantly different soil concentration profiles between vegetated and unvegetated columns, including notable upward migration for 237 Np in columns with plants. Additionally, plant uptake of 99 Tc was the greatest of all the radionuclides, with plant tissues containing an average of 44 % of the 99 Tc, while plant uptake only accounted for <2 % of 237 Np and <0.5 % of 133 Cs and 238 U in the system. Although overall plant uptake of 133 Cs and 238 U were similar, the majority of 133 Cs taken up by plants was associated with 133 Cs already available in the aqueous phase while 238 U uptake was mainly associated with the solid phase, meaning that plant activity resulted in a fraction of the native 238 U being mobilized and thus, made available for plant uptake. Overall, this study quantified the influence of several plant-mediated physical and biogeochemical factors that have significant influence on radionuclide mobility and transport in this complex system which can be further utilized in future system or site-specific environmental transport and risk assessment models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Perfluorooctanoic acid (PFOA), a surfactant, is a member of the perfluoroalkyl acids (PFAAs) family and is a contaminant of emerging concern for human and environmental health. Perfluorooctanoic acid is a persistent organic pollutant, but currently little is known about (a) the potential ecological and toxicological effects of PFOA and (b) how PFOA moves in the environment. This study uses a radiotracer ( 14 C-PFOA) to study the uptake and translocation of PFOA in hydroponically grown brown mustard [Brassica juncea (L.) Czern.], a representative crop species. Plants were exposed in quadruplicate over the course of 7 d (with plants sampled on Days 4 and 7) to PFOA concentrations of 0, 1, 5, 10, and 15 mg L -1 . Uptake was quantified via liquid scintillation counting of samples from the nutrient solution, roots, stems, and leaves. Transfer factors (roots to shoots) ranged from 0.15 to 4.73 kg kg -1 . Bioconcentration factors (solution to plant) ranged from 0.36 to 62.29 L kg -1 . Factors were influenced by plant compartment, day sampled, and treatment level., (© 2022 The Authors. Journal of Environmental Quality published by Wiley Periodicals LLC on behalf of American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Glial cells are non-neuronal elements of the nervous system (NS) and play a central role in its development, maturation, and homeostasis. Glial cell interest has increased, leading to the discovery of novel study fields. The CRISPR/Cas system has been widely employed for NS understanding. Its use to study glial cells gives crucial information about their mechanisms and role in the central nervous system (CNS) and neurodegenerative disorders. Furthermore, the increasingly accelerated discovery of genes associated with the multiple implications of glial cells could be studied and complemented with the novel screening methods of high-content and single-cell screens at the genome-scale as Perturb-Seq, CRISP-seq, and CROPseq. Besides, the emerging methods, GESTALT, and LINNAEUS, employed to generate large-scale cell lineage maps have yielded invaluable information about processes involved in neurogenesis. These advances offer new therapeutic approaches to finding critical unanswered questions about glial cells and their fundamental role in the nervous system. Furthermore, they help to better understanding the significance of glial cells and their role in developmental biology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barragán-Álvarez, Flores-Fernandez, Hernández-Pérez, Ávila-Gónzalez, Díaz, Padilla-Camberos, Dublan-García, Gómez-Oliván and Diaz-Martinez.)

Central to applying the principle of optimisation in the system of radiological protection is the evaluation of what level of radiation exposure should be considered 'as low as reasonably achievable' (ALARA), after taking into account the prevailing circumstances. Determining what is 'reasonable' is an abstract, although somewhat intuitive concept with many potential interpretations depending on both the situation and those involved, whether individuals or organisations. There are common themes in the types of considerations that need to be addressed to determine 'reasonableness' regardless of the exposure situation. However, despite the consistent and agreeable nature of these themes, there remains a gap in how to apply them in real situations. For example, without measurable goalposts (or a clear process for setting such goalposts) for determining what constitutes ALARA, we can find ourselves misinterpreting the optimisation process as keeping exposures 'as low as possible'. We propose herein, by consolidating and building on existing ideas, an easily understandable and actionable 'reasonableness' framework. This simple, yet broadly applicable tool is intended to help radiation protection experts in the systematic, deliberative, and collaborative reflection on all of the factors that make up 'reasonable' before making a decision-whether it be a proposed medical treatment or clean-up of a contaminated site. Each process execution and decision itself will necessarily retain the complexity of the prevailing circumstance. The proposed 'Rs' of Reasonable represent Relationships (stakeholders, empathy, and trust), Rationale (contextual, technical, and ethical), and Resources (technological, financial, and time)., (© 2022 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelination and axonal degeneration in the central nervous system (CNS). Bacterial and fungal infections have been associated with the development of MS; microbial components that are present in several microbes could contribute to MS pathogenesis. Among such components, curdlan is a microbial 1,3-β-glucan that can stimulate dendritic cells, and enhances T helper (Th) 17 responses. We determined whether curdlan administration could affect two animal models for MS: an autoimmune model, experimental autoimmune encephalomyelitis (EAE), and a viral model, Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD). We induced relapsing-remitting EAE by sensitizing SJL/J mice with the myelin proteolipid protein (PLP) 139-151 peptide and found that curdlan treatment prior to PLP sensitization converted the clinical course of EAE into hyperacute EAE, in which the mice developed a progressive motor paralysis and died within 2 weeks. Curdlan-treated EAE mice had massive infiltration of T cells and neutrophils in the CNS with higher levels of Th17 and Th1 responses, compared with the control EAE mice. On the other hand, in TMEV-IDD, we found that curdlan treatment reduced the clinical scores and axonal degeneration without changes in inflammation or viral persistence in the CNS. In summary, although curdlan administration exacerbated the autoimmune MS model by enhancing inflammatory demyelination, it suppressed the viral MS model with reduced axonal degeneration. Therefore, microbial infections may play contrasting roles in MS depending on its etiology: autoimmunity versus viral infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sato, Nakamura, Katsuki, Khadka, Ahmad, Omura, Martinez and Tsunoda.)

Gender balance refers to the equitable treatment and access to opportunities for all genders. In order to achieve true gender balance, a variety of proactive approaches developed collaboratively, with insight from multiple perspectives, need to be implemented. With that purpose, the participation of women in professions related to radiation and radiation protection was prioritised and given high visibility by allocating a 'Women in Radiation' (WiR) Special Session at the 15th International Congress of the International Radiation Protection Association (IRPA), hosted by South Korea on 20 January 2021. In this session, various issues related to gender balance and equity/equality were highlighted by the panellists, and further elaborated in a subsequent discussion with attendees. The main goal of the WiR Special Session was to convene women from different organisations, career and age stages, disciplines and countries, in particular to consider the Asian-Oceanic vision and status of gender equality, along with other topics to support a 'Call for Action', with concrete recommendations subsequently provided to IRPA. The discussion stressed the main needs and challenges faced by women working in various radiation fields, along with raising awareness of possible professional and employment opportunities. This paper identifies some steps necessary to encourage, enhance and support the inclusion of more diversity in nuclear professions with specific emphasis on women. In conclusion, gender balance and equality must be at the heart of any strategic plan for the future of the radiological protection profession; international cooperation between relevant bodies is essential for success and could serve as a catalyst for specific policy statements aimed at achieving a balanced representation of women in radiological protection., (© 2022 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Purpose: This paper reviews the history of the radium dial workers in the United States, summarizes the scientific progress made since the last evaluation in the early 1990s, and discusses current progress in updating the epidemiologic cohort and applying new dosimetric models for radiation risk assessment., Background: The discoveries of radiation and radioactivity led quickly to medical and commercial applications at the turn of the 20th century, including the development of radioluminescent paint, made by combining radium with phosphorescent material and adhesive. Workers involved with the painting of dials and instruments included painters, handlers, ancillary workers, and chemists who fabricated the paint. Dial painters were primarily women and, prior to the mid to late 1920s, would use their lips to give the brush a fine point, resulting in high intakes of radium. The tragic experience of the dial painters had a significant impact on industrial safety standards, including protection measures taken during the Manhattan Project. The dial workers study has formed the basis for radiation protection standards for intakes of radionuclides by workers and the public., Epidemiologic Approach: The mortality experience of 3,276 radium dial painters and handlers employed between 1913 and 1949 is being determined through 2019. The last epidemiologic follow-up was 30 years ago when most of these workers were still alive. Nearly 65% were born before 1920, 37.5% were teenagers when first hired, and nearly 50% were hired before 1930 when the habit of placing brushes in mouths essentially stopped. Comprehensive dose reconstruction techniques are being applied to estimate organ doses for each worker related to the intake of 226 Ra, 228 Ra, and associated photon exposures. Time dependent dose-response analyses will estimate lifetime risks for specific causes of death., Discussion: The study of radium dial workers is part of the Million Person Study of low-dose health effects that is designed to evaluate radiation risks among healthy American workers and veterans. Despite being one of the most important and influential radiation effects studies ever conducted, shifting programmatic responsibilities and declining funding led to the termination of the radium program of studies in the early 1990s. Renewed interest and opportunity have arisen. With scientific progress made in dosimetric methodology and models, the ability to perform a study over the entire life span, and the potential applicability to other scenarios such as medicine, environmental contamination and space exploration, the radium dial workers have once again come to the forefront.

The impact of low doses of ionising radiation on biological and environmental systems have been historically difficult to study. Modern biological tools have provided new methods for studying these mechanisms but applying these tools to a dose-response relationship may require refinement of dosimetric techniques that incorporate a detailed understand of radionuclide accumulation in biological cells, particularly when assessing the impact of low doses of ionising radiation. In this work Pseudomonas putida ( KT2440) grown in liquid culture was exposed to low dose rates (10-20 mGy d -1 ) of 239 Pu and 55 Fe, both alone and in combination, for a period of 20 days, and the accumulation of 239 Pu and 55 Fe in cell pellets was analysed via liquid scintillation counting. The study also considered of cells grown with 239 Pu and stable Fe (primarily 56 Fe). In addition to the analysis of cell pellet and media samples, this work includes analysis of the radiological content of ribonucleic acid extraction samples to examine uptake of radionuclides. Results indicate that 239 Pu inhibited the uptake of 55 Fe, and that the presence of stable and radioactive isotopes of Fe in cultures may promote pathways for Fe accumulation that are used by 239 Pu. The work herein provides foundational insight into future dosimetric models for our work with environmental bacteria., (© 2021 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Introduction: The novel coronavirus pandemic (COVID-19) represents a major public health problem and it is key to find a treatment that reduces mortality. Our objective was to estimate whether treatment with 400 mg/day of Hydroxychloroquine for 10 days reduces in-hospital mortality in subjects with severe respiratory disease due to COVID-19 compared with placebo., Material and Methods: A double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of Hydroxychloroquine for the treatment of severe disease by COVID-19 through an intention-to-treat analysis. Eligible for the study were adults aged more than 18 years with COVID-19 confirmed by RT-PCR and lung injury requiring hospitalization with or without mechanical ventilation. Primary outcome was 30-day mortality. Secondary outcomes: days of mechanical ventilation, days of hospitalization and cumulative incidence of serious adverse events., Results: A total of 214 patients with COVID-19 were recruited, randomized and analyzed. They were hypoxemic with a mean SpO2 of 65% ± 20, tachycardic (pulse rate 108±17 min-1) and tachypneic (32 ±10 min-1); 162 were under mechanical ventilation at randomization. Thirty-day mortality was similar in both groups (38% in Hydroxychloroquine vs. 41% in placebo, hazard ratio [HR] 0.88, 95% Confidence Interval [95%CI] 0.51-1.53). In the surviving participants, no significant difference was found in secondary outcomes., Conclusion: No beneficial effect or significant harm could be demonstrated in our randomized controlled trial including 214 patients, using relatively low doses of Hydroxychloroquine compared with placebo in hospitalized patients with severe COVID-19., Competing Interests: CONACYT (National Council of Science and Technology of Mexico) and SANOFI participated. SANOFI provided the tested drug and identical placebo. Commercial funding does not alter our adherence to PLOS ONE editorial policies.

This data set contains the data used in Twarog et al. (2021) to examine the robustness and utility of response surface models in drug combination analysis. It includes simulated experimental data for the evaluation of traditional index methods, as well as a processed library of interaction metrics evaluated on the Merck OncoPolyPharmacology Screen (O'Neil et al., 2016), the scripts used to implement those metrics on all tested combinations in that screen, and scripts to evaluate the performance of those metrics in comparison with real-world mechanistic classifications. Finally, the data set includes data from several published and unpublished drug combination experiments, and scripts which allow the analyses of those experiments to be replicated and applied to new data., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article. This manuscript adheres to the Ethics in publishing standards (https://www.elsevier.com/about/policies/publishing-ethics#Authors)., (© 2021 The Authors. Published by Elsevier Inc.)

As we progress towards more diverse, equitable, and inclusive communities, workplaces, and organizations in radiation protection (RP), we begin to consider the experiences of our fellow radiation protectionists in parallel with our own. This is to identify, and ideally take down, barriers to pursuing a fulfilling career and positive professional relationships. Recognition and active consideration of differential experiences and needs will help promote both personal and community level success. Over the past few years there have been concerted efforts within the RP community to consider and promote the participation of women. An example outcome of this effort is that we are seeing more women assuming prominent leadership positions in our community. As we celebrate the progress made towards equity, specifically with respect to women, it is important to consider that other factors such as race and gender identity can present their own barriers. Those at the intersection of these or other identities often find themselves in the so-called 'double bind' of more pronounced, or stacking, barriers to success. This paper briefly highlights the need for considering the intersectionality of race and gender in the promotion of equity for all women., (© 2021 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Quantitative evaluation of how drugs combine to elicit a biological response is crucial for drug development. Evaluations of drug combinations are often performed using index-based methods, which are known to be biased and unstable. We examine how these methods can produce misleadingly structured patterns of bias, leading to erroneous judgments of synergy or antagonism. By contrast, response surface models are less prone to these defects and can be applied to a wide range of data that have appeared in recent literature, including the measurement of combination therapeutic windows and the analysis of discrete experimental measures, three-way drug combinations, and atypical response behaviors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Abstract: Ethics and societal values form one of the three pillars supporting and informing the system of radiological protection, complementing the science and building from our individual and collective experience. Although the International Commission on Radiological Protection has recently highlighted the ethical foundations of the system of radiological protection (the System) with Publication 138, with Publication 91 outlining ethical principles of environmental radiation protection, the System has yet to specifically address the ethics associated with animals outside of the natural environment such as livestock, pets, or research animals. Therefore, in conjunction with the Commission's recent efforts in elaborating on the application and implementation of the System in veterinary practice is the consideration of the associated ethical values and principles foundational to the practice, with special attention given to the animal exposed. This paper outlines progress made in the latter area and proposes a practical, consistent approach to the ethics and values of the radiation protection of animals. Complementary to the ethical values of the System specified in Publication 138 are the correlated ethical values of respect for life, animal welfare, sustainable development, solidarity, and autonomy that are particularly relevant in veterinary practice. In addition to the procedural and ethical values of transparency, accountability and inclusiveness, additional procedural values of empathy and stewardship are needed in the implementation of the System in veterinary practice and in its application to non-human biota in general., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Health Physics Society.)

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

As we work towards a holistic approach to radiation protection, we begin to consider and integrate protection beyond humans to include, among other things, non-human biota. Non-human biota not only includes environmental flora and fauna, but also livestock, companion animals, working animals, etc. Although under consideration, there is currently little guidance in terms of protection strategies for types of non-human biota beyond wildlife. For example, in recent years, veterinary procedures that make use of ionising radiation have increased in number and have diversified considerably, which has made radiation protection in veterinary applications of ionising radiation more challenging, both for humans and the animal patients. In fact, the common belief that doses to professionals and members of the public from these applications will be very low to negligible, and doses to the animals will not be acutely harmful nor even affect their lifetime probability of developing cancer, needs to be revisited in the light of higher dose diagnostic and interventional techniques, and certainly in the case of therapeutic applications. This paper provides a brief overview of the initiatives of the International Commission on Radiological Protection concerning radiation protection aspects of veterinary practice, and poses a variety of perspectives for consideration and further discussion.

Inhibition of members of the bromodomain and extraterminal (BET) family of proteins has proven a valid strategy for cancer chemotherapy. All BET identified to date contain two bromodomains (BD; BD1 and BD2) that are necessary for recognition of acetylated lysine residues in the N-terminal regions of histones. Chemical matter that targets BET (BETi) also interact via these domains. Molecular and cellular data indicate that BD1 and BD2 have different biological roles depending upon their cellular context, with BD2 particularly associated with cancer. We have therefore pursued the development of BD2-selective molecules both as chemical probes and as potential leads for drug development. Here we report the structure-based generation of a novel series of tetrahydroquinoline analogs that exhibit >50-fold selectivity for BD2 versus BD1. This selective targeting resulted in engagement with BD-containing proteins in cells, resulting in modulation of MYC proteins and downstream targets. These compounds were potent cytotoxins toward numerous pediatric cancer cell lines and were minimally toxic to nontumorigenic cells. In addition, unlike the pan BETi (+)-JQ1, these BD2-selective inhibitors demonstrated no rebound expression effects. Finally, we report a pharmacokinetic-optimized, metabolically stable derivative that induced growth delay in a neuroblastoma xenograft model with minimal toxicity. We conclude that BD2-selective agents are valid candidates for antitumor drug design for pediatric malignancies driven by the MYC oncogene. SIGNIFICANCE: This study presents bromodomain-selective BET inhibitors that act as antitumor agents and demonstrates that these molecules have in vivo activity towards neuroblastoma, with essentially no toxicity., (©2020 American Association for Cancer Research.)

Context.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16 INK4a immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs)., Objective.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses., Design.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available., Results.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall ( P trend ≤ .001) and within each HPV risk group ( P trend ≤ .001 except for low-risk HPV [ P trend < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group ( P trend < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies ( P < .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL + cytology, or to be diagnosed as CIN3 + by the EP ( P < .001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies ( P < .001)., Conclusions.—: p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.

The radiation safety culture of those working in university open-source radioactive material laboratories was assessed by conducting both surveys and behavioral observations. Baseline results (n = 82, 89% response rate) of assessed safety culture categories indicated safety practices and safety compliance were the most in need of improvement. Specific training based on these results was provided to laboratory members at Princeton University, with creative signage and a safety newsletter posted in and around laboratories for reinforcement, in a targeted effort to improve the radiation safety culture. Signage posted utilized pop cultural memes and other engaging graphics designed to raise awareness of appropriate safety practices and the minimum laboratory attire expected while working in radioactive material laboratories. Postintervention results (n = 38, 43% response rate) indicated improvement in 4 out of the 10 safety culture indicators considered as well as fewer instances of improper safety practices. Collaborative techniques and increased communication between researchers and radiation safety staff appear to have initiated an improvement in the radiation safety culture in open-source radioactive material laboratories at Princeton University.

Competing Interests: None

This paper discusses the development, comparison, and application of three anatomically representative computational phantoms for the grass species Andropogon virginicus, an indigenous grass species in the Southeastern United States. Specifically, the phantoms developed in this work are: (1) a stylized phantom where plant organs (roots or shoots) are represented by simple geometric shapes, (2) a voxel phantom developed from micro-CT imagery of a plant specimen, and (3) a hybrid phantom resulting from the refinement of (2) by use of non-uniform rational basis spline (NURBS) surfaces. For each computational phantom, Monte Carlo dosimetric modeling was utilized to determine whole-organism and organ specific dose coefficients (DC) associated with external and internal exposure to 99 Tc, 137 Cs, 237 Np, and 238 U for A. virginicus. Model DCs were compared to each other and to current values for the ICRP reference wild grass in order to determine if noteworthy differences resulted from the utilization of more anatomically realistic phantom geometry. Modeled internal DCs were comparable with ICRP values. However, modeled external DCs were more variable with respect to ICRP values; this is proposed to be primarily due to differences in organism and source geometry definitions. Overall, the three anatomical phantoms were reasonably consistent. Some noticeable differences in internal DCs were observed between the stylized model and the voxel or hybrid models for external DCs for shoots and for cases of crossfire between plant organs. Additionally, uptake data from previous hydroponic (HP) experiments was applied in conjunction with hybrid model DCs to determine dose rates to the plant from individual radionuclides as an example of practical application. Although the models within are applied to a small-scale, hypothetical scenario as proof-of-principle, the potential, real-world utility of such complex dosimetric models for non-human biota is discussed, and a fit-for purpose approach for application of these models is proposed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Determination of neutron dose can be challenging and requires knowledge of neutron flux as a function of energy. The goal of this project was to characterize the thermal neutron flux of a 37 GBq PuBe alpha-neutron source and model the associated neutron dose using version MCNPX of the Monte-Carlo N-Particle transport codes. The PuBe source was placed in a neutron howitzer, and foil activation (dysprosium foils with and without cadmium covers) was used at various distances to determine thermal neutron flux, which was then used to verify the MCNPX model representing the system. The model was then adapted for dosimetric modeling to enable future neutron dose-response studies.

Previously, we have established two distinct progressive multiple sclerosis (MS) models by induction of experimental autoimmune encephalomyelitis (EAE) with myelin oligodendrocyte glycoprotein (MOG) in two mouse strains. A.SW mice develop ataxia with antibody deposition, but no T cell infiltration, in the central nervous system (CNS), while SJL/J mice develop paralysis with CNS T cell infiltration. In this study, we determined biomarkers contributing to the homogeneity and heterogeneity of two models. Using the CNS and spleen microarray transcriptome and cytokine data, we conducted computational analyses. We identified up-regulation of immune-related genes, including immunoglobulins, in the CNS of both models. Pro-inflammatory cytokines, interferon (IFN)-γ and interleukin (IL)-17, were associated with the disease progression in SJL/J mice, while the expression of both cytokines was detected only at the EAE onset in A.SW mice. Principal component analysis (PCA) of CNS transcriptome data demonstrated that down-regulation of prolactin may reflect disease progression. Pattern matching analysis of spleen transcriptome with CNS PCA identified 333 splenic surrogate markers, including Stfa2l1 , which reflected the changes in the CNS. Among them, we found that two genes ( PER1 / MIR6883 and FKBP5 ) and one gene ( SLC16A1/MCT1 ) were also significantly up-regulated and down-regulated, respectively, in human MS peripheral blood, using data mining.

Human induced pluripotent stem cells (hiPSCs) enable in vitro high-throughput pharmacological screening assays of diseased tissue. Together with recent genome-wide association studies (GWAS), hiPSCs enable the identification of key mutations for the development of effective treatments based on precise drugs. In concert with CRISPR/Cas9 systems, hiPSC technology can reveal therapeutic targets in metabolic disorders. The ex vivo CRISPR correction of autologous patient-derived hiPSCs has led to the development of replacement cell therapies, providing better patient prognoses., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Theiler's murine encephalomyelitis virus (TMEV) induces different diseases in the central nervous system (CNS) and heart, depending on the mouse strains and time course, with cytokines playing key roles for viral clearance and immune-mediated pathology (immunopathology). In SJL/J mice, TMEV infection causes chronic TMEV-induced demyelinating disease (TMEV-IDD) in the spinal cord about 1 month post-inoculation (p.i.). Unlike other immunopathology models, both pro- and anti-inflammatory cytokines can play dual roles in TMEV-IDD. Pro-inflammatory cytokines play beneficial roles in viral clearance while they are also detrimental in immune-mediated demyelination. Anti-inflammatory cytokines suppress not only protective anti-viral immune responses but also detrimental autoreactive immune responses. Conversely, in C3H mice, TMEV infection induces a non-CNS disease, myocarditis, with three distinctive phases: phase I, viral pathology with interferon and chemokine responses; phase II, immunopathology mediated by acquired immune responses; and phase III, cardiac fibrosis. Although the exact mechanism(s) by which a single virus, TMEV, induces these different diseases in different organs is unclear, our bioinformatics approaches, especially principal component analysis (PCA) of transcriptome data, allow us to identify the key factors contributing to organ-specific immunopathology. The PCA demonstrated that in vitro infection of a cardiomyocyte cell line reproduced the transcriptome profile of phase I in TMEV-induced myocarditis; distinct interferon/chemokine-related responses were induced in vitro in TMEV-infected cardiomyocytes, but not in infected neuronal cells. In addition, the PCA of the in vivo CNS transcriptome data showed that decreased lymphatic marker expressions were weakly associated with inflammation in TMEV infection. Here, dysfunction of lymphatic vessels is shown to potentially contribute to immunopathology by delaying the clearance of cytokines and immune cells from the inflammatory site, although this can also confine the virus at these sites, preventing virus spread via lymphatic vessels. On the other hand, in the heart, dysfunction of lymphatics was associated with reduced lymphatic muscle contractility provoked by pro-inflammatory cytokines. Therefore, TMEV infection may induce different patterns of cytokine expressions as well as lymphatic vessel dysfunction by rather different mechanisms between the CNS and heart, which might explain observed patterns of organ-specific immunopathology.

Hydroponic uptake studies were conducted to evaluate the uptake and translocation of Tc, Cs (stable analog for Cs), Np, and U into established and seedling Andropogon virginicus specimens under controlled laboratory conditions. Plant specimens were grown in analyte-spiked Hoagland nutrient solution for 24 h, 3 d, and 5 d. Translocation to shoots was greatest for Tc and Cs, likely due to their analogous nature to plant nutrients, while U (and Np to a lesser extent) predominantly partitioned to root tissue with less extensive translocation to the shoots. Plant age contributed significantly to differences in concentration ratios for all nuclides in shoot tissues (p ≤ 0.024), with higher concentration ratios for seedling specimens. Additionally, duration of exposure was associated with significant differences in concentration ratios of Cs and Tc for seedlings (p = 0.007 and p = 0.030, respectively) while plant part (root or shoot) was associated with significant differences in concentration ratios of established plants (p < 0.001 for both nuclides). Statistically significant increases in radionuclide uptake in seedling specimens relative to established plants under controlled conditions suggests that, in addition to geochemical factors, plant life stage of wild grasses may also be an important factor influencing radionuclide transport in the natural environment.

This paper presents the perspectives of past presidents of the Health Physics Society who also happen to be women. Only 6 out of 63 Society presidents have been women, and of these six, five are still living and briefly reflect on their experiences here, alongside a brief discussion of the first female president of the Society. These perspectives provide historical insight into the evolution and happenings of the Society as well as adding personal touches to the office of the president that hopefully will encourage junior Society members to consider serving.

This study considers whether a relationship exists between response to lithium (Li) exposure and select vegetation indices (VI) determined from reflectance spectra in each of four plant species: Arabidopsis thaliana , Helianthus annuus (sunflower), Brassica napus (rape), and Zea mays (corn). Reflectance spectra were collected every week for three weeks using an ASD FieldSpec Pro spectroradiometer with both a contact probe (CP) and a field of view probe (FOV) for plants treated twice weekly in a laboratory setting with 0 mM (control) or 15 mM of lithium chloride (LiCl) solution. Plants were harvested each week after spectra collection for determination of relevant physical endpoints such as relative water content and chlorophyll content. Mixed effects analyses were conducted on selected endpoints and vegetation indices (VI) to determine the significance of the effects of treatment level and length of treatment as well as to determine which VI would be appropriate predictors of treatment-dependent endpoints. Of the species considered, A. thaliana exhibited the most significant effects and corresponding shifts in reflectance spectra. Depending on the species and endpoint, the most relevant VIs in this study were NDVI, PSND, YI, R 1676 /R 1933 , R 750 /R 550 , and R 950 /R 750 .

While most disease-modifying drugs (DMDs) regulate multiple sclerosis (MS) by suppressing inflammation, they can potentially suppress antiviral immunity, causing progressive multifocal leukoencephalopathy (PML). The DMD glatiramer acetate (GA) has been used for MS patients who are at high risk of PML. We investigated whether GA is safe for use in viral infections by using a model of MS induced by infection with Theiler's murine encephalomyelitis virus (TMEV). Treatment of TMEV-infected mice with GA neither enhanced viral loads nor suppressed antiviral immune responses, while it resulted in an increase in the Foxp3/Il17a ratio and IL-4/IL-10 production. This is the first study to suggest that GA could be safe for MS patients with a proven viral infection.

Aberrant hedgehog (Hh) signaling contributes to the pathogenesis of multiple cancers. Available inhibitors target Smoothened (Smo), which can acquire mutations causing drug resistance. Thus, compounds that inhibit Hh signaling downstream of Smo are urgently needed. We identified dynarrestin, a novel inhibitor of cytoplasmic dyneins 1 and 2. Dynarrestin acts reversibly to inhibit cytoplasmic dynein 1-dependent microtubule binding and motility in vitro without affecting ATP hydrolysis. It rapidly and reversibly inhibits endosome movement in living cells and perturbs mitosis by inducing spindle misorientation and pseudoprometaphase delay. Dynarrestin reversibly inhibits cytoplasmic dynein 2-dependent intraflagellar transport (IFT) of the cargo IFT88 and flux of Smo within cilia without interfering with ciliogenesis and suppresses Hh-dependent proliferation of neuronal precursors and tumor cells. As such, dynarrestin is a valuable tool for probing cytoplasmic dynein-dependent cellular processes and a promising compound for medicinal chemistry programs aimed at development of anti-cancer drugs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Obesity affects millions of people worldwide, constituting a public health problem associated with premature mortality. Agave fructans decrease fat mass, body and liver weight, and generate satiety in rodents. In the present study the effects of agave fructans on weight control, lipid profile, and physical tolerability were evaluated in obese people. Twenty-eight obese volunteers were randomly divided into two groups. In the first group, 96 mg/bw of agave fructans was administered for 12 weeks; in the second group, maltodextrin as a placebo was administered for 12 weeks. All participants consumed a low-calorie diet of 1500 kcal/day. Anthropometric and biochemical measurements were taken at baseline and at the end of the study. The body mass index (BMI) of the agave fructans treated group was reduced significantly from the baseline to the final measurements. Hip and waist circumferences decreased statistically in both groups. A decrease of 10% in total body fat was observed in the agave fructans treated group, resulting in a statistically significant difference in the final versus baseline measurements between the Agave fructans treated group and the placebo treated group. Triglycerides were reduced significantly in the agave fructans treated group. Glucose values did not change in either group. Agave fructans intake was safe and well tolerated throughout the study. The results showed that the ingestion of agave fructans enhanced the decrease in BMI, the decrease in total body fat, and the decrease in triglycerides in obese individuals who consume a low-calorie diet.

Intracerebral Theiler's murine encephalomyelitis virus (TMEV) infection in mice induces inflammatory demyelination in the central nervous system. Although C57BL/6 mice normally resistant to TMEV infection with viral clearance, we have previously demonstrated that RORγt-transgenic (tg) C57BL/6 mice, which have Th17-biased responses due to RORγt overexpression in T cells, became susceptible to TMEV infection with viral persistence. Here, using T-bet-tg C57BL/6 mice and Gata3-tg C57BL/6 mice, we demonstrated that overexpression of T-bet, but not Gata3, in T cells was detrimental in TMEV infection. Unexpectedly, T-bet-tg mice died 2 to 3 weeks after infection due to failure of viral clearance. Here, TMEV infection induced splenic T cell depletion, which was associated with lower anti-viral antibody and T cell responses. In contrast, Gata3-tg mice remained resistant, while Gata3-tg mice had lower IFN-γ and higher IL-4 production with increased anti-viral IgG1 responses. Thus, our data identify how overexpression of T-bet and Gata3 in T cells alters anti-viral immunity and confers susceptibility to TMEV infection.

Neutrophils are short-lived leukocytes that migrate to sites of infection as part of the acute immune response, where they phagocytose, degranulate, and form neutrophil extracellular traps (NETs). During NET formation, the nuclear lobules of neutrophils disappear and the chromatin expands and, accessorized with neutrophilic granule proteins, is expelled. NETs can be pathogenic in, for example, sepsis, cancer, and autoimmune and cardiovascular diseases. Therefore, the identification of inhibitors of NET formation is of great interest. Screening of a focused library of natural-product-inspired compounds by using a previously validated phenotypic NET assay identified a group of tetrahydroisoquinolines as new NET formation inhibitors. This compound class opens up new avenues for the study of cellular death through NET formation (NETosis) at different stages, and might inspire new medicinal chemistry programs aimed at NET-dependent diseases., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Contributions from men to radiation science are well known, particularly the early contributions from such luminaries as William Roentgen, James Chadwick, Niels Bohr, Robert Oppenheimer, and the like. Although not ignored per se, beyond Marie Curie and Lise Meitner, the contributions of female nuclear scientists are not as widely recognized. This paper provides a concise historical summary of contributions to radiation science from the discovery of radiation through the current status of international leadership within the radiation protection community. Beyond lead scientists and academics, this paper also considers support personnel as well as the role women have played in the advancement of radiation epidemiology.