The Radiation Control for Health and Safety Act of 1968: History, Accomplishments, and Future

Prior to 1968, control of radiation-emitting electronic devices was left to state and local governments, whose regulations proved both inconsistent and ineffective. This was highlighted by General Electric's 1967 recall of 90,000 television sets believed to emit dangerous levels of radiation. Congress soon proposed a federal radiation control bill. The hearings revealed the general lack of data on the harms of radiation exposure and the vast amount of unnecessary radiation that Americans were exposed to each year. As enacted on October 18, 1968, the Radiation Control for Health and Safety Act authorized the Food and Drug Administration to set federal radiation standards, to monitor compliance, and to conduct research. The FDA's Bureau of Radiological Health actively administered the act. The act has produced safe electronic products, considerable scientific knowledge, and a public well aware of the risks of radiation exposure. But for all of its successes, the act has also had its problems. The act does not require pre-market approval, choosing instead to respond once problems arise. The FDA has also seen significant budget cuts and must prioritize its obligations under all the acts it administers. The FDA has turned to the internet to communicate its message to manufacturers and consumers, but at the same time must counter the rise of the popular media and its ability to excite the public regarding potential radiation hazards. How the FDA allocates its decreasing funds and works with the mass media will determine the future of the act

MicroRNA Alterations and Associated Aberrant DNA Methylation Patterns across Multiple Sample Types in Oral Squamous Cell Carcinoma

Background: MicroRNA (miRNA) expression is broadly altered in cancer, but few studies have investigated miRNA deregulation in oral squamous cell carcinoma (OSCC). Epigenetic mechanisms are involved in the regulation of .30 miRNA genes in a range of tissues, and we aimed to investigate this further in OSCC. Methods: TaqManH qRT-PCR arrays and individual assays were used to profile miRNA expression in a panel of 25 tumors with matched adjacent tissues from patients with OSCC, and 8 control paired oral stroma and epithelium from healthy volunteers. Associated DNA methylation changes of candidate epigenetically deregulated miRNA genes were measured in the same samples using the MassArrayH mass spectrometry platform. MiRNA expression and DNA methylation changes were also investigated in FACS sorted CD44high oral cancer stem cells from primary tumor samples (CSCs), and in oral rinse and saliva from 15 OSCC patients and 7 healthy volunteers. Results: MiRNA expression patterns were consistent in healthy oral epithelium and stroma, but broadly altered in both tumor and adjacent tissue from OSCC patients. MiR-375 is repressed and miR-127 activated in OSCC, and we confirm previous reports of miR-137 hypermethylation in oral cancer. The miR-200 s/miR-205 were epigenetically activated in tumors vs normal tissues, but repressed in the absence of DNA hypermethylation specifically in CD44high oral CSCs. Aberrant miR-375 and miR-200a expression and miR-200c-141 methylation could be detected in and distinguish OSCC patient oral rinse and saliva from healthy volunteers, suggesting a potential clinical application for OSCC specific miRNA signatures in oral fluids. Conclusions: MiRNA expression and DNA methylation changes are a common event in OSCC, and we suggest miR-375, miR- 127, miR-137, the miR-200 family and miR-205 as promising candidates for future investigations. Although overall activated in OSCC, miR-200/miR-205 suppression in oral CSCs indicate that cell specific silencing of these miRNAs may drive tumor expansion and progression

Tropical and subtropical Asia's valued tree species under threat

Tree diversity in Asia's tropical and subtropical forests is central to nature-based solutions. Species vulnerability to multiple threats, which affects the provision of ecosystem services, is poorly understood. We conducted a region-wide, spatially explicit vulnerability assessment (including overexploitation, fire, overgrazing, habitat conversion, and climate change) of 63 socio-economically important tree species selected from national priority lists and validated by an expert network representing 20 countries. Overall, 74% of the most important areas for conservation of these trees fall outside of protected areas, with species severely threatened across 47% of their native ranges. The most imminent threats are overexploitation and habitat conversion, with populations being severely threatened in an average of 24% and 16% of their distribution areas. Optimistically, our results predict relatively limited overall climate change impacts, however, some of the study species are likely to lose more than 15% of their habitat by 2050 because of climate change. We pinpoint specific natural forest areas in Malaysia and Indonesia (Borneo) as hotspots for on-site conservation of forest genetic resources, more than 82% of which do not currently fall within designated protected areas. We also identify degraded lands in Indonesia (Sumatra) as priorities for restoration where planting or assisted natural regeneration will help maintain these species into the future, while croplands in Southern India are highlighted as potentially important agroforestry options. Our study highlights the need for regionally coordinated action for effective conservation and restoration

Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer

Abstract Background Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Chemotherapy efficacy depends on relative dose intensity (RDI), and an RDI < 85% is associated with worse overall survival. The pro-inflammatory (interleukin (IL)-6, C-reactive protein (CRP)) and coagulation factors (D-dimer) serve as biomarkers of aging. The purpose of this study is to determine if these biomarkers are associated with reduced RDI in women with stage I–III BC. Methods This study enrolled women with stage I–III BC. Prior to adjuvant or neoadjuvant chemotherapy, peripheral blood was collected for biomarker measurement. Dose reductions and delays were captured and utilized to calculate the RDI delivered. Univariate and multivariate analyses were performed to describe the association between pre-chemotherapy IL-6, CRP, and D-dimer levels and an RDI < 85%, controlling for relevant tumor and patient factors (age, stage, receptor status, chemotherapy regimen, and pre-chemotherapy physical function and comorbidity). Results A total of 159 patients (mean age 58 years, range 30–81, SD 11.3) with stage I–III BC were enrolled. An RDI < 85% occurred in 22.6% (N = 36) of patients and was associated with higher pre-chemotherapy IL-6 (OR 1.14, 95% CI 1.04–1.25; p = 0.006) and D-dimer (OR 2.32, 95% CI 1.27–4.24; p = 0.006) levels, increased age (p = 0.001), increased number of comorbidities (p = 0.01), and decreased physical function by the Medical Outcomes Survey Activities of Daily Living (ADL) Scale (p = 0.009) in univariate analysis. A multivariate model, including two biomarkers (IL-6 and D-dimer), age, ADL, BC stage, and chemotherapy regimen, demonstrated a significant association between the increased biomarkers and reduced RDI < 85% (OR 2.54; p = 0.04). Conclusions Increased pre-chemotherapy biomarkers of aging (IL-6 and D-dimer) are associated with reduced RDI (<85%). Future studies are underway to validate these findings. Trial registration ClinicalTrials.gov, NCT01030250 . Registered on 3 November 2016

Limited Metabolomic Overlap between Commensal Bacteria and Marine Sponge Holobionts Revealed by Large Scale Culturing and Mass Spectrometry-Based Metabolomics: An Undergraduate Laboratory Pedagogical Effort at Georgia Tech

Sponges are the richest source of bioactive organic small molecules, referred to as natural products, in the marine environment. It is well established that laboratory culturing-resistant symbiotic bacteria residing within the eukaryotic sponge host matrix often synthesize the natural products that are detected in the sponge tissue extracts. However, the contributions of the culturing-amenable commensal bacteria that are also associated with the sponge host to the overall metabolome of the sponge holobiont are not well defined. In this study, we cultured a large library of bacteria from three marine sponges commonly found in the Florida Keys. Metabolomes of isolated bacterial strains and that of the sponge holobiont were compared using mass spectrometry to reveal minimal metabolomic overlap between commensal bacteria and the sponge hosts. We also find that the phylogenetic overlap between cultured commensal bacteria and that of the sponge microbiome is minimal. Despite these observations, the commensal bacteria were found to be a rich resource for novel natural product discovery. Mass spectrometry-based metabolomics provided structural insights into these cryptic natural products. Pedagogic innovation in the form of laboratory curricula development is described which provided undergraduate students with hands-on instruction in microbiology and natural product discovery using metabolomic data mining strategies

Additional file 1: Table S1. of Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer

Biomarkers measurement in neo-adjuvant-treated vs. adjuvant-treated patients. (DOC 39 kb

Additional file 1: Table S1. of Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer

Biomarkers measurement in neo-adjuvant-treated vs. adjuvant-treated patients. (DOC 39 kb