COMPARISON OF SURFACE RADIATION DOSE TO THE GONADS BY RADIOGRAPHIC EXAMINATION OF THE LUMBAR SPINE USING COMPUTED RADIOGRAPHY AND DIRECT DIGITAL RADIOGRAPHY

Objectives: The objectives are aimed to study the comparison of SRD to the gonads by radiographic examination of the lumbar spine using computed radiography (CR) and direct digital radiography (DR) and to evaluate dose differences according to gender.Methods: A total of 120 subjects with an equal number of males and females referred for lumbar spine anteroposterior (AP) and lateral was included in the study. Sixty patients had undergone X-ray in CR X-ray unit and 60 in DR X-ray unit. SRD to gonads from a radiographic examination of the lumbar spine was measured in CR and DR using Mult-O-Meter, and obtained value of SRD was in μGy. Statistical analysis was performed using Statistical Package for the Social Sciences. Data were represented as a median and interquartile range. Mann–Whitney U-test was used for the comparison of SRD to gonads. Two-way analysis of variance (ANOVA) test was used to find out the statistically significant difference in SRD to the gonads according to gender from radiography of lumbar spine taken using CR and direct DR.Results: There was a statistically significant difference in SRD to gonads from radiography of lumbar spine AP and lateral taken using CR and direct DR (p<0.001). There was no statistically significant difference in SRD to the gonads in males and females from radiography of lumbar spine AP (p=0.577) and lateral (p=0.164) taken using CR and direct DR.Conclusion: It was found that SRD to gonads from lumbar spine AP was 54% lower in direct DR and SRD to gonads from lumbar spine lateral was 68% lower in direct DR than CR

BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease

SummaryThe adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing

Atomic collisional data for neutral beam modeling in fusion plasmas

The injection of energetic neutral particles into the plasma of magnetic confinement fusion reactors is a widely-accepted method for heating such plasmas; various types of neutral beam are also used for diagnostic purposes. Accurate atomic data are required to properly model beam penetration into the plasma and to interpret photoemission spectra from both the beam particles themselves (e.g. beam emission spectroscopy) and from plasma impurities with which they interact (e.g. charge exchange recombination spectroscopy). This paper reviews and compares theoretical methods for calculating ionization, excitation and charge exchange cross sections applied to several important processes relevant to neutral hydrogen beams, including H + Be4+ and H + H+. In particular, a new cross section for the proton-impact ionization of H (1s) is recommended which is significantly larger than that previously accepted at fusion-relevant energies. Coefficients for an empirical fit function to this cross section and to that of the first excited states of H are provided and uncertainties estimated. The propagation of uncertainties in this cross section in modeling codes under JET-like conditions has been studied and the newly-recommended values determined to have a significant effect on the predicted beam attenuation. In addition to accurate calculations of collisional atomic data, the use of these data in codes modeling beam penetration and photoemission for fusion-relevant plasma density and temperature profiles is discussed. In particular, the discrepancies in the modeling of impurities are reported. The present paper originates from a Coordinated Research Project (CRP) on the topic of fundamental atomic data for neutral beam modeling that the International Atomic Energy Agency (IAEA) ran from 2017 to 2022; this project brought together ten research groups in the fields of fusion plasma modeling and collisional cross section calculations. Data calculated during the CRP is summarized in an appendix and is available online in the IAEA’s atomic database, CollisionDB

Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies

Health and social impacts of open defecation on women: a systematic review

Background The significance of sanitation to safeguard human health is irrefutable and has important public health dimensions. Access to sanitation has been essential for human dignity, health and well-being. Despite 15 years of conjunctive efforts under the global action plans like Millennium Development Goals (MDGs), 2.3 billion people have no access to improved sanitation facilities (flush latrine or pit latrine) and nearly 892 million of the total world’s population is still practicing open defecation. Methods The study provides a systematic review of the published literature related to implications of open defecation that goes beyond the scope of addressing health outcomes by also investigating social outcomes associated with open defecation. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) was used to frame the review, empirical studies focusing upon open defecation in women aged 13–50 in low and middle income countries were included in the review. Research papers included in the review were assessed for quality using appropriate critical appraisal tools. In total 9 articles were included in the review; 5 of these related to health effects and 4 related to social effects of open defecation. Results The review identified 4 overarching themes; Health Impacts of open defecation, Increased risk of sexual exploitation, Threat to women’s privacy and dignity and Psychosocial stressors linked to open defecation, which clearly present a serious situation of poor sanitation in rural communities of Lower-Middle Income Countries (LMICs). The findings of the review identified that open defecation promotes poor health in women with long-term negative effects on their psychosocial well-being, however it is a poorly researched topic. Conclusion The health and social needs of women and girls remain largely unmet and often side-lined in circumstances where toilets in homes are not available. Further research is critically required to comprehend the generalizability of effects of open defecation on girls and women

Histone Deacetylase Inhibitors Selectively Target Homology Dependent DNA Repair Defective Cells and Elevate Non-Homologous Endjoining Activity

Background: We have previously used the ATAD5-luciferase high-throughput screening assay to identify genotoxic compounds with potential chemotherapeutic capabilities. The successful identification of known genotoxic agents, including the histone deacetylase inhibitor (HDACi) trichostatin A (TSA), confirmed the specificity of the screen since TSA has been widely studied for its ability to cause apoptosis in cancer cells. Because many cancers have acquired mutations in DNA damage checkpoints or repair pathways, we hypothesized that these cancers may be susceptible to treatments that target compensatory pathways. Here, we used a panel of isogenic chicken DT40 B lymphocyte mutant and human cell lines to investigate the ability of TSA to define selective pathways that promote HDACi toxicity. Results: HDACi induced a DNA damage response and reduced viability in all repair deficient DT40 mutants although ATM-nulls were least affected. The most dramatic sensitivity was observed in mutants lacking the homology dependent repair (HDR) factor BLM or the non-homologous end-joining (NHEJ) and HDR factors, KU/RAD54, suggesting an involvement of either HDR or NHEJ in HDACi-induced cell death. To extend these findings, we measured the frequencies of HDR and NHEJ after HDACi treatment and monitored viability in human cell lines comparably deficient in HDR or NHEJ. Although no difference in HDR frequency was observed between HDACi treated and untreated cells, HDR-defective human cell lines were clearly more sensitive than wild type. Unexpectedly, cells treated with HDACis showed a significantly elevated NHEJ frequency. Conclusions: HDACi targeting drugs induced significant increases in NHEJ activity in human cell lines but did not alter HDR frequency. Moreover, HDR is required for cellular resistance to HDACi therapy; therefore, NHEJ does not appear to be a critical axis for HDACi resistance. Rather, HDACi compounds induced DNA damage, most likely double strand breaks (DSBs), and HDR proficiency is correlated with cell survivalclose4