Metabolic Restructuring during Energy-Limited States: Insights from Artemia franciscana Embryos and Other Animals

Many life history stages of animals that experience environmental insults enter developmental arrested states that are characterized by reduced cellular proliferation, with or without a concurrent reduction in overall metabolism. In the case of the most profound metabolic arrest reported in invertebrates, i.e., anaerobic quiescence in Artemia franciscana embryos, acidification of the intracellular milieu is a major factor governing catabolic and anabolic downregulation. Release of ion gradients from intracellular compartments is the source for approximately 50% of the proton equivalents needed for the 1.5 unit acidification that is observed. Recovery from the metabolic arrest requires re-sequestration of the protons with a vacuolar-type ATPase (V-ATPase). The remarkable facet of this mechanism is the ability of embryonic cells to survive the dissipation of intracellular ion gradients. Across many diapause-like states, the metabolic reduction and subsequent matching of energy demand is accomplished by shifting energy metabolism from oxidative phosphorylation to aerobic glycolysis. Molecular pathways that are activated to induce these resilient hypometabolic states include stimulation of the AMP-activated protein kinase (AMPK) and insulin signaling via suite of daf (dauer formation) genes for diapause-like states in nematodes and insects. Contributing factors for other metabolically-depressed states involve hypoxia-inducible factor-1 and downregulation of the pyruvate dehydrogenase complex. Metabolic similarities between natural states of stasis and some cancer phenotypes are noteworthy. Reduction of flux through oxidative phosphorylation helps prevent cell death in certain cancer types, similar to the way it increases viability of dauer stages in Caenorhabditis elegans. Mechanisms that underlie natural stasis are being used to pre-condition mammalian cells prior to cell biostabilization and storage

Metabolic Restructuring during Energy-Limited States: Insights from Artemia franciscana Embryos and Other Animals

Many life history stages of animals that experience environmental insults enter developmental arrested states that are characterized by reduced cellular proliferation, with or without a concurrent reduction in overall metabolism. In the case of the most profound metabolic arrest reported in invertebrates, i.e., anaerobic quiescence in Artemia franciscana embryos, acidification of the intracellular milieu is a major factor governing catabolic and anabolic downregulation. Release of ion gradients from intracellular compartments is the source for approximately 50% of the proton equivalents needed for the 1.5 unit acidification that is observed. Recovery from the metabolic arrest requires re-sequestration of the protons with a vacuolar-type ATPase (V-ATPase). The remarkable facet of this mechanism is the ability of embryonic cells to survive the dissipation of intracellular ion gradients. Across many diapause-like states, the metabolic reduction and subsequent matching of energy demand is accomplished by shifting energy metabolism from oxidative phosphorylation to aerobic glycolysis. Molecular pathways that are activated to induce these resilient hypometabolic states include stimulation of the AMP-activated protein kinase (AMPK) and insulin signaling via suite of daf (dauer formation) genes for diapause-like states in nematodes and insects. Contributing factors for other metabolically-depressed states involve hypoxia-inducible factor-1 and downregulation of the pyruvate dehydrogenase complex. Metabolic similarities between natural states of stasis and some cancer phenotypes are noteworthy. Reduction of flux through oxidative phosphorylation helps prevent cell death in certain cancer types, similar to the way it increases viability of dauer stages in Caenorhabditis elegans. Mechanisms that underlie natural stasis are being used to pre-condition mammalian cells prior to cell biostabilization and storage

The association of alcohol consumption with mammographic density in a multiethnic urban population

Background Alcohol consumption is associated with higher breast cancer risk. While studies suggest a modest association between alcohol intake and mammographic density, few studies have examined the association in racial/ethnic minority populations. Methods We assessed dense breast area and total breast area from digitized film mammograms in an urban cohort of African American (42%), African Caribbean (22%), white (22%), and Hispanic Caribbean (9%) women (n = 189, ages 40-61). We examined the association between alcohol intake and mammographic density (percent density and dense area). We used linear regression to examine mean differences in mammographic density across alcohol intake categories. We considered confounding by age, body mass index (BMI), hormone contraceptive use, family history of breast cancer, menopausal status, smoking status, nativity, race/ethnicity, age at first birth, and parity. Results Fifty percent currently consumed alcohol. Women who consumed >7 servings/week of alcohol, but not those consuming ≤7 servings/week, had higher percent density compared to nondrinkers after full adjustments (servings/week >7 β = 8.2, 95% Confidence Interval (CI) 1.8, 14.6; ≤7 β = -0.5, 95% CI -3.7, 2.8). There was a positive association between high alcohol intake and dense area after full adjustments (servings/week >7 β = 5.8, 95% CI -2.7, 14.2; ≤7 β = -0.1, 95% CI -4.4, 4.2). We did not observe race/ethnicity modification of the association between alcohol intake and percent density. In women with a BMI of 7 servings/week of alcohol had a 17% increase in percent density compared to nondrinkers (95% CI 5.4, 29.0) and there was no association in women with a BMI ≥ 25 kg/m2 (BMI ≥ 25-30 kg/m2 > 7 β = 5.1, 95% CI -8.5, 18.7 and BMI > 30 kg/m2 > 7 β = 0.5, 95% CI -6.5, 7.5) after adjusting for age and BMI (continuous). Conclusion In a racially/ethnically diverse cohort, women who consumed >7 servings/week of alcohol, especially those with a BMI < 25 kg/m2, had higher percent density. Keywords: Mammographic breast density; Alcohol consumption; Breast cance

Variability in the practice of fertility preservation for patients with cancer

Fertility is important to women and men with cancer. While options for fertility preservation (FP) are available, knowledge regarding the medical application of FP is lacking. Therefore we examined FP practices for cancer patients among reproductive endocrinologists (REs). A 36 item survey was sent to board-certified REs. 98% of respondents reported counseling women with cancer about FP options. Oocyte and embryo cryopreservation were universally offered by these providers, but variability was noted in reported management of these cases-particularly for women with breast cancer. 86% of the respondents reported using letrozole during controlled ovarian stimulation (COS) in patients with estrogen receptor positive (ER+) breast cancer to minimize patient exposure to estrogen. 49% of respondents who reported using letrozole in COS for patients with ER+ breast cancer reported that they would also use letrozole in COS for women with ER negative breast cancer. Variability was also noted in the management of FP for men with cancer. 83% of participants reported counseling men about sperm banking with 22% recommending against banking for men previously exposed to chemotherapy. Overall, 79% of respondents reported knowledge of American Society for Clinical Oncology FP guidelines-knowledge that was associated with providers offering gonadal tissue cryopreservation (RR 1.82, 95% CI 1.14-2.90). These findings demonstrate that RE management of FP in cancer patients varies. Although some variability may be dictated by local resources, standardization of FP practices and communication with treating oncologists may help ensure consistent recommendations and outcomes for patients seeking FP

Anticipated regret to increase uptake of colorectal cancer screening (ARTICS):a randomised controlled trial

Objective. Screening is key to early detection of colorectal cancer. Our aim was to determine whether a simple anticipated regret (AR) intervention could increase colorectal cancer screening uptake. Methods. We conducted a randomised controlled trial of a simple, questionnaire-based AR intervention, delivered alongside existing pre-notification letters. 60,000 adults aged 50-74 from the Scottish National Screening programme were randomised to: 1) no questionnaire (control), 2) Health Locus of Control questionnaire (HLOC) or 3) HLOC plus anticipated regret questionnaire (AR). Primary outcome was guaiac Faecal Occult Blood Test (FOBT) return. Secondary outcomes included intention to return test kit and perceived disgust (ICK). Results. 59,366 people were analysed as allocated (Intentionto- treat (ITT)); there were no overall differences between treatment groups on FOBT uptake (control: 57.3%, HLOC: 56.9%, AR: 57.4%). 13,645 (34.2%) people returned questionnaires. Analysis of the secondary questionnaire measures showed that AR had an indirect effect on FOBT uptake via intention, whilst ICK had a direct effect on FOBT uptake over and above intention. The effect of AR on FOBT uptake was also moderated by intention strength: for less than strong intenders only, uptake was 4.2% higher in the AR (84.6%) versus the HLOC group (80.4%) (95% CI for difference (2.0, 6.5)). Conclusion. The findings show that psychological concepts including anticipated regret and perceived disgust (ICK) are important factors in determining FOBT uptake. However, there was no simple effect of the AR intervention in the ITT. We conclude that exposure to AR in those with low intentions may be required to increase FOBT uptake. Current controlled trials: www.controlledtrials. com number: ISRCTN74986452

Performance of chemically modified reduced graphene oxide (CMrGO) in electrodynamic dust shield (EDS) applications

Electrodynamic Dust Shield (EDS) technology is a dust mitigation strategy that is commonly studied for applications such as photovoltaics or thermal radiators where soiling of the surfaces can reduce performance. The goal of the current work was to test the performance of a patterned nanocomposite EDS system produced through spray-coating and melt infiltration of chemically modified reduced graphene oxide (CMrGO) traces with thermoplastic high-density polyethylene (HDPE). The EDS performance was tested for a dusting of lunar regolith simulant under high vacuum conditions (~10-6 Torr) using both 2-phase and 3-phase configurations. Uncapped (bare) devices showed efficient dust removal at moderate voltages (1000 V) for both 2-phase and 3-phase designs, but the performance of the devices degraded after several sequential tests due to erosion of the traces caused by electric discharges. Further tests carried out while illuminating the dust surface with a UV excimer lamp showed that the EDS voltage needed to reach the maximum cleanliness was reduced by almost 50% for the 2-phase devices (500 V minimum for rough and 1000 V for smooth), while the 3-phase devices were unaffected by the application of UV. Capping the CMrGO traces with low-density polyethylene (LDPE) eliminated breakdown of the materials and device degradation, but larger voltages (3000 V) coupled with UV illumination were required to remove the grains from the capped devices.Comment: 22 pages, 7 figure