Environmental Exposures during Puberty: Window of Breast Cancer Risk and Epigenetic Damage.

During puberty, a woman's breasts are vulnerable to environmental damage ("window of vulnerability"). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures

HETDEX Public Source Catalog 1: 220K Sources Including Over 50K Lyman Alpha Emitters from an Untargeted Wide-area Spectroscopic Survey

We present the first publicly released catalog of sources obtained from the Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). HETDEX is an integral field spectroscopic survey designed to measure the Hubble expansion parameter and angular diameter distance at 1.88<z<3.52 by using the spatial distribution of more than a million Ly-alpha-emitting galaxies over a total target area of 540 deg^2. The catalog comes from contiguous fiber spectra coverage of 25 deg^2 of sky from January 2017 through June 2020, where object detection is performed through two complementary detection methods: one designed to search for line emission and the other a search for continuum emission. The HETDEX public release catalog is dominated by emission-line galaxies and includes 51,863 Ly{\alpha}-emitting galaxy (LAE) identifications and 123,891 OII-emitting galaxies at z<0.5. Also included in the catalog are 37,916 stars, 5274 low-redshift (z<0.5) galaxies without emission lines, and 4976 active galactic nuclei. The catalog provides sky coordinates, redshifts, line identifications, classification information, line fluxes, OII and Ly-alpha line luminosities where applicable, and spectra for all identified sources processed by the HETDEX detection pipeline. Extensive testing demonstrates that HETDEX redshifts agree to within deltaz < 0.02, 96.1% of the time to those in external spectroscopic catalogs. We measure the photometric counterpart fraction in deep ancillary Hyper Suprime-Cam imaging and find that only 55.5% of the LAE sample has an r-band continuum counterpart down to a limiting magnitude of r~26.2 mag (AB) indicating that an LAE search of similar sensitivity with photometric pre-selection would miss nearly half of the HETDEX LAE catalog sample. Data access and details about the catalog can be found online at http://hetdex.org/.Comment: 38 pages, 20 figures. Data access and details about the catalog can be found online at http://hetdex.org/. A copy of the catalogs presented in this work (Version 3.2) is available to download at Zenodo doi:10.5281/zenodo.744850

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Emergency Management Performance Grant (EMPG) funding allocations and relevance for US disaster policy

The Emergency Management Performance Grant (EMPG) program has long been a cornerstone of state and local emergency management preparedness efforts. Through the EMPG program, the Federal Emergency Management Agency (FEMA) administers grants to state and local emergency management agencies to accomplish a wide range of tasks such as the development of response and recovery plans, the creation of emergency operation centers, and the hiring of staff, among other activities required to be effective. EMPG provides the predominant federal funding for this mission, and many agencies depend on these funds for their operations. Despite the importance of EMPG, there is a dearth of empirical research about the program. This study explores this gap by evaluating how EMPG funds were distributed across United States counties from 2014 to 2020. Using FEMA and US Census data, we conducted a county-level analysis using robust regression statistical analysis to determine factors affecting funding awards. Findings indicate that high population, high diversity, a strong economy, and high risk (measured using both the National Risk Index score and the number of federal disaster declarations per county) increased the likelihood that a county would receive EMPG funds, with high-risk urban counties rather than rural counties receiving more funding

Accuracy of MR imaging-estimated proton density fat fraction for classification of dichotomized histologic steatosis grades in nonalcoholic fatty liver disease.

PurposeTo evaluate the diagnostic performance of previously proposed high-specificity magnetic resonance (MR) imaging-estimated proton density fat fraction (PDFF) thresholds for diagnosis of steatosis grade 1 or higher (PDFF threshold of 6.4%), grade 2 or higher (PDFF threshold of 17.4%), and grade 3 (PDFF threshold of 22.1%) by using histologic findings as a reference in an independent cohort of adults known to have or suspected of having nonalcoholic fatty liver disease (NAFLD).Materials and methodsThis prospective, cross-sectional, institutional review board-approved, HIPAA-compliant single-center study was conducted in an independent cohort of 89 adults known to have or suspected of having NAFLD who underwent contemporaneous liver biopsy. MR imaging PDFF was estimated at 3 T by using magnitude-based low-flip-angle multiecho gradient-recalled-echo imaging with T2* correction and multipeak modeling. Steatosis was graded histologically (grades 0, 1, 2, and 3, according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system). Sensitivity, specificity, and binomial confidence intervals were calculated for the proposed MR imaging PDFF thresholds.ResultsThe proposed MR imaging PDFF threshold of 6.4% to diagnose grade 1 or higher steatosis had 86% sensitivity (71 of 83 patients; 95% confidence interval [CI]: 76, 92) and 83% specificity (five of six patients; 95% CI: 36, 100). The threshold of 17.4% to diagnose grade 2 or higher steatosis had 64% sensitivity (28 of 44 patients; 95% CI: 48, 78) and 96% specificity (43 of 45 patients; 95% CI: 85, 100). The threshold of 22.1% to diagnose grade 3 steatosis had 71% sensitivity (10 of 14 patients; 95% CI: 42, 92) and 92% specificity (69 of 75 patients; 95% CI: 83, 97).ConclusionIn an independent cohort of adults known to have or suspected of having NAFLD, the previously proposed MR imaging PDFF thresholds provided moderate to high sensitivity and high specificity for diagnosis of grade 1 or higher, grade 2 or higher, and grade 3 steatosis. Prospective multicenter studies are now needed to further validate these high-specificity thresholds

Triglyceride Saturation in Patients at Risk of NASH and NAFLD: A Cross-Sectional Study

Chemical shift magnetic resonance imaging (MRI) is commonly used to estimate the amount of fat in tissues, namely the proton density fat fraction (PDFF). In addition to PDFF, the type of fat can be inferred and characterized in terms of the number of double bonds (NDB), number of methylene-interrupted double bonds (NMIDB) and the chain length (CL) of the fatty acid chains. The saturation index is potentially a marker for metabolic disorders. This study assesses the feasibility of estimating these parameters independently or in a constrained manner. Correlations with spectroscopy were measured in 109 subjects’ subcutaneous and visceral fat depots (p = 2 × 10−28), and with the NAFLD Activity Score (NAS) from histological evaluation of biopsies. The findings indicate that imaging estimates are comparable to spectroscopy (p = 0.0002), but there is no significant association of NDB with NAS (p = 0.1)

Environmental Exposures during Puberty: Window of Breast Cancer Risk and Epigenetic Damage

During puberty, a woman&rsquo;s breasts are vulnerable to environmental damage (&ldquo;window of vulnerability&rdquo;). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures