Food Insecurity Is Under-reported in Surveys That Ask About the Past Year.

INTRODUCTION: Food insecurity affects one in ten Americans in a typical year; recent U.S. Department of Agriculture data show that this food insecurity rate was stable from 2019 to 2021. However, data from Los Angeles County and other U.S. regions show that food insecurity spiked during the early months of the COVID-19 pandemic. One reason for this discrepancy may be that food insecurity measures assess experiences over different time frames. This study investigated the discrepancies in food insecurity rates by comparing past-week and past-year food insecurity measures and explored the role of recall bias. METHODS: Data were obtained from a representative survey panel of Los Angeles adults (N=1,135). Participants were surveyed about past-week food insecurity eleven times throughout 2021 and once about past-year food insecurity in December 2021. Data were analyzed in 2022. RESULTS: Of the participants who reported past-week food insecurity at any time in 2021, only two thirds also reported past-year food insecurity in December 2021, suggesting that one third of participants under-reported past-year food insecurity. Logistic regression models indicated that three characteristics were significantly associated with under-reporting of past-year food insecurity: having reported past-week food insecurity at fewer survey waves, not reporting recent past-week food insecurity, and having a relatively high household income. CONCLUSIONS: These results suggest substantial under-reporting of past-year food insecurity, related to recall bias and social factors. Measuring food insecurity at multiple points throughout the year may help to improve the accuracy of reporting and public health surveillance of this issue.

Multiplexed NIR-II Probes for Lymph Node-Invaded Cancer Detection and Imaging-Guided Surgery.

Tumor-lymph node (LN) metastasis is the dominant prognostic factor for tumor staging and therapeutic decision-making. However, concurrently visualizing metastasis and performing imaging-guided lymph node surgery is challenging. Here, a multiplexed-near-infrared-II (NIR-II) in vivo imaging system using nonoverlapping NIR-II probes with markedly suppressed photon scattering and zero-autofluorescence is reported, which enables visualization of the metastatic tumor and the tumor metastatic proximal LNs resection. A bright and tumor-seeking donor-acceptor-donor (D-A-D) dye, IR-FD, is screened for primary/metastatic tumor imaging in the NIR-IIa (1100-1300 nm) window. This optimized D-A-D dye exhibits greatly improved quantum yield of organic D-A-D fluorophores in aqueous solutions (≈6.0%) and good in vivo performance. Ultrabright PbS/CdS core/shell quantum dots (QDs) with dense polymer coating are used to visualize cancer-invaded sentinel LNs in the NIR-IIb (>1500 nm) window. Compared to clinically used indocyanine green, the QDs show superior brightness and photostability (no obvious bleaching even after continuous laser irradiation for 5 h); thus, only a picomolar dose is required for sentinel LNs detection. This combination of dual-NIR-II image-guided surgery can be performed under bright light, adding to its convenience and appeal in clinical use.

Albumin-chaperoned cyanine dye yields superbright NIR-II fluorophore with enhanced pharmacokinetics.

NIR-II fluorescence imaging greatly reduces scattering coefficients for nearly all tissue types at long wavelengths, benefiting deep tissue imaging. However, most of the NIR-II fluorophores suffer from low quantum yields and/or short circulation time that limit the quality of NIR-II imaging. Here, we engineered a supramolecular assembly of protein complex with lodged cyanine dyes to produce a brilliant NIR-II fluorophore, providing a NIR-II quantum yield of 21.2% with prolonged circulation time. Computational modeling revealed the mechanism for fluorescence enhancement and identified key parameters governing albumin complex for NIR-II fluorophores. Our complex afforded high-resolution microvessel imaging, with a 3-hour imaging window compared to 2 min for free dye alone. Furthermore, the complexation strategy was applied to an antibody-derived assembly, offering high-contrast tumor imaging without affecting the targeting ability of the antibody. This study provides a facile strategy for producing high-performance NIR-II fluorophores by chaperoning cyanine dyes with functional proteins.

Rational design of a super-contrast NIR-II fluorophore affords high-performance NIR-II molecular imaging guided microsurgery.

In vivo molecular imaging in the "transparent" near-infrared II (NIR-II) window has demonstrated impressive benefits in reaching millimeter penetration depths with high specificity and imaging quality. Previous NIR-II molecular imaging generally relied on high hepatic uptake fluorophores with an unclear mechanism and antibody-derived conjugates, suffering from inevitable nonspecific retention in the main organs/skin with a relatively low signal-to-background ratio. It is still challenging to synthesize a NIR-II fluorophore with both high quantum yield and minimal liver-retention feature. Herein, we identified the structural design and excretion mechanism of novel NIR-II fluorophores for NIR-II molecular imaging with an extremely clean background. With the optimized renally excreted fluorophore-peptide conjugates, superior NIR-II targeting imaging was accompanied by the improved signal-to-background ratio during tumor detection with reducing off-target tissue exposure. An unprecedented NIR-II imaging-guided microsurgery was achieved using such an imaging platform, which provides us with a great preclinical example to accelerate the potential clinical translation of NIR-II imaging.

Three-dimensional texture analysis of optical coherence tomography images of ovarian tissue.

Ovarian cancer has the lowest survival rate among all gynecologic cancers due to predominantly late diagnosis. Optical coherence tomography (OCT) has been applied successfully to experimentally image the ovaries in vivo; however, a robust method for analysis is still required to provide quantitative diagnostic information. Recently, texture analysis has proved to be a useful tool for tissue characterization; unfortunately, existing work in the scope of OCT ovarian imaging is limited to only analyzing 2D sub-regions of the image data, discarding information encoded in the full image area, as well as in the depth dimension. Here we address these challenges by testing three implementations of texture analysis for the ability to classify tissue type. First, we test the traditional case of extracted 2D regions of interest; then we extend this to include the entire image area by segmenting the organ from the background. Finally, we conduct a full volumetric analysis of the image volume using 3D segmented data. For each case, we compute features based on the Grey-Level Co-occurence Matrix and also by introducing a new approach that evaluates the frequency distribution in the image by computing the energy density. We test these methods on a mouse model of ovarian cancer to differentiate between age, genotype, and treatment. The results show that the 3D application of texture analysis is most effective for differentiating tissue types, yielding an average classification accuracy of 78.6%. This is followed by the analysis in 2D with the segmented image volume, yielding an average accuracy of 71.5%. Both of these improve on the traditional approach of extracting square regions of interest, which yield an average classification accuracy of 67.7%. Thus, applying texture analysis in 3D with a fully segmented image volume is the most robust approach to quantitatively characterizing ovarian tissue.

Near-Infrared-II (NIR-II) Bioimaging via Off-Peak NIR-I Fluorescence Emission.

Significantly reduced photon scattering and minimal tissue autofluorescence levels in the second biological transparency window (NIR-II; 1000-1700 nm) facilitate higher resolution in vivo biological imaging compared to tradition NIR fluorophores (~700-900 nm). However, the existing palette of NIR-II fluorescent agents including semiconducting inorganic nanomaterials and recently introduced small-molecule organic dyes face significant technical and regulatory hurdles prior to clinical translation. Fortunately, recent spectroscopic characterization of NIR-I dyes (e.g., indocyanine green (ICG), IRDye800CW and IR-12N3) revealed long non-negligible emission tails reaching past 1500 nm. Repurposing the most widely used NIR dye in medicine, in addition to those in the midst of clinical trials creates an accelerated pathway for NIR-II clinical translation. This review focuses on the significant advantage of imaging past 1000 nm with NIR-I fluorophores from both a basic and clinical viewpoint. We further discuss optimizing NIR-I dyes around their NIR-II/shortwave infrared (SWIR) emission, NIR-II emission tail characteristics and prospects of NIR-II imaging with clinically available and commercially available dyes.

Role of miRNAs in development and disease: Lessons learnt from small organisms.

MicroRNAs (miRNAs) constitute a class of small (18-22 nucleotides) non-coding RNAs that regulate gene expression at the post-transcriptional level. Caenorhabditis elegans, Drosophila melanogaster, and many other small organisms have been instrumental in deciphering the biological functions of miRNAs. While some miRNAs from small organisms are highly conserved across the taxa, others are organism specific. The miRNAs are known to play a crucial role during development and in various cellular functions such as cell survival, cell proliferation, and differentiation. The miRNAs associated with fragile X syndrome, Parkinson's disease, Alzheimer's disease, diabetes, cancer, malaria, infectious diseases and several other human diseases have been identified from small organisms. These organisms have been used as platforms in deciphering the functions of miRNAs in the pathogenesis of human diseases and to study miRNA biogenesis. Small organisms have also been used in the development of miRNA-based diagnostic, prognostic and therapeutic strategies. The molecular techniques such as genome sequencing, northern blot analysis, and quantitative RT-PCR, have been used in deciphering the functions of miRNAs in small organisms. How miRNAs from small organisms especially those from Drosophila and C. elegans regulate development and disease pathogenesis is the focus of this review. The outstanding questions raised by our current understanding are discussed.

Intermittent Dosing with Sulindac Provides Effective Colorectal Cancer Chemoprevention in the Azoxymethane-Treated Mouse Model.

Sulindac is an NSAID that can provide effective chemoprevention for colorectal cancer. In this study, alternative dosing regimens of sulindac were evaluated for their chemoprevention effectiveness in the azoxymethane-treated A/J mouse model of colorectal cancer. High-resolution endoscopic optical coherence tomography was utilized to time-serially measure tumor number and tumor burden in the distal colon as the biological endpoints. Four treatment groups were studied: (i) daily for 20 weeks (sulindac-daily); (ii) for 2 weeks, then no sulindac for 2 weeks, cycle repeated 5 times (sulindac-2); (iii) for 10 weeks ("on"), then no sulindac for 10 weeks ("off"; sulindac-10); and (iv) no sulindac (sulindac-none). Sulindac-2 and sulindac-daily had statistically significantly lower final tumor counts and slopes (change in number of tumors per week) when compared with sulindac-none (P < 0.0001). All of the treatment groups had statistically significantly lower final tumor burdens and slopes when compared with sulindac-none (P < 0.001). There was a prolonged latency period in the sulindac-10 group, with no significant difference between the "off" portion of this treatment and sulindac-none. These results suggest that, although daily doses of sulindac provide the most optimal effects, intermittent doses of sulindac in a 50% duty cycle with an overall 4-week period (sulindac-2 model) can provide highly effective chemoprevention of colorectal cancer in this model. After cessation of sulindac treatment (sulindac-10 "off"), there is no evidence of either a persistent chemopreventive effect or a rebound effect. Cancer Prev Res; 10(8); 459-66. ©2017 AACR.

Dme-miR-314-3p modulation in Cr(VI) exposed Drosophila affects DNA damage repair by targeting mus309.

microRNAs (miRNAs) as one of the major epigenetic modulators negatively regulate mRNAs at post transcriptional level. It was therefore hypothesized that modulation of miRNAs by hexavalent Chromium [Cr(VI)], a priority environmental chemical, can affect DNA damage. In a genetically tractable model, Drosophila melanogaster, role of maximally up-regulated miRNA, dme-miR-314-3p, on DNA damage was examined by exposing the third instar larvae to 5.0-20.0 µg/ml Cr(VI) for 24 and 48 h. mus309, a Drosophila homologue of human Bloom's syndrome and predicted as one of the potential targets of this miRNA, was confirmed as its target by 5'RLM-RACE assay. A significant down-regulation of mus309 was observed in dme-miR-314-3p overexpression strain (myo-gal4>UAS-miR-314-3p) as compared with that in parental strains (myo-gal4 and UAS-miR-314-3p) and in w(1118). A significant increase in DNA damage including double strand breaks generation was observed in exposed myo-gal4>UAS-miR-314 and mus309 mutants as compared with that in parental strain and in unexposed control. A significant down-regulation of cell cycle regulation genes (CycA, CycB and cdc2) was observed in these exposed genotypes. Collectively, the study demonstrates that dme-miR-314-3p can mediate the downregulation of repair deficient gene mus309 leading to increased DNA damage and cell cycle arrest in exposed organism which may affect Cr(VI) mediated carcinogenesis.

MiRNA profiling provides insights on adverse effects of Cr(VI) in the midgut tissues of Drosophila melanogaster.

Cr(VI), a well-known environmental chemical, is reported to cause various adverse effects on exposed organisms including genomic instability and carcinogenesis. Despite available information on the underlying mechanism of Cr(VI) induced toxicity, studies regarding toxicity modulation by epigenetic mechanisms are limited. It was therefore, hypothesized that the global miRNA profiling in Cr(VI) exposed Drosophila, a genetically tractable model organism, will provide information about mis-regulated miRNAs along with their targeted genes and relevant processes. Third instar larvae of Drosophila melanogaster (Oregon R(+)) were exposed to 5.0-20.0 µg/ml of Cr(VI) for 24 and 48 h. Following miRNA profile analysis on an Agilent platform, 28 of the 36 differentially expressed miRNAs were found to be significantly mis-regulated targeting major biological processes viz., DNA damage repair, oxidation-reduction processes, development and differentiation. Down-regulation of mus309 and mus312 under DNA repair, acon to oxidation-reduction and pyd to stress activated MAPK cascade respectively belonging to these gene ontology classes concurrent with up-regulation of dme-miR-314-3p, dme-miR-79-3p and dme-miR-12-5p confirm their functional involvement against Cr(VI) exposure. These findings assume significance since majority of the target genes in Drosophila have functional homologues in humans. The study further recommends Drosophila as a model to explore the role of miRNAs in xenobiotic induced toxicity.

Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster.

Dichloroacetic acid (DCA), a water disinfection by-product, has attained emphasis due to its prospect for clinical use against different diseases including cancer along with negative impact on organisms. However, these reports are based on the toxicological as well clinical data using comparatively higher concentrations of DCA without much of environmental relevance. Here, we evaluate cellular as well as organismal effects of DCA at environmentally and mild clinically relevant concentrations (0.02-20.0 µg/ml) using an established model organism, Drosophila melanogaster. Flies were fed on food mixed with test concentrations of DCA for 12-48 h to examine the induction of reactive oxygen species (ROS) generation, oxidative stress (OS), heat shock genes (hsps) and cell death along with organismal responses. We also examined locomotor performance, ROS generation, glutathione (GSH) depletion, expression of GSH-synthesizing genes (gclc and gclm), and hsps at different days (0, 10, 20, 30, 40, 50) of the age in flies after prolonged DCA exposure. We observed mild OS and induction of antioxidant defense system in 20.0 µg/ml DCA-exposed organism after 24 h. After prolonged exposure to DCA, exposed organism exhibited improved survival, elevated expression of hsp27, gclc, and gclm concomitant with lower ROS generation and GSH depletion and improved locomotor performance. Conversely, hsp27 knockdown flies exhibited reversal of the above end points. The study provides evidence for the attenuation of cellular and functional decline in aged Drosophila after prolonged DCA exposure and the effect of hsp27 modulation which further incites studies towards the therapeutic application of DCA.

Cellular internalization and stress response of ingested amorphous silica nanoparticles in the midgut of Drosophila melanogaster.

BACKGROUND: Amorphous silica nanoparticles (aSNPs) are used for various applications including food industry. However, limited in vivo studies are available on absorption/internalization of ingested aSNPs in the midgut cells of an organism. The study aims to examine cellular uptake of aSNPs (<30nm) in the midgut of Drosophila melanogaster (Oregon R(+)) owing to similarities between the midgut tissue of this organism and human and subsequently cellular stress response generated by these nanoparticles. METHODS: Third instar larvae of D. melanogaster were exposed orally to 1-100µg/mL of aSNPs for 12-36h and oxidative stress (OS), heat shock genes (hsgs), membrane destabilization (Acridine orange/Ethidium Bromide staining), cellular internalization (TEM) and apoptosis endpoints. RESULTS: A significant increase was observed in OS endpoints in the midgut cells of exposed Drosophila in a concentration- and time-dependent manner. Significantly increased expression of hsp70 and hsp22 along with caspases activation, membrane destabilization and mitochondrial membrane potential loss was also observed. TEM analysis showed aSNPs-uptake in the midgut cells of exposed Drosophila via endocytic vesicles and by direct membrane penetration. CONCLUSION: aSNPs after their internalization in the midgut cells of exposed Drosophila larvae show membrane destabilization along with increased cellular stress and cell death. GENERAL SIGNIFICANCE: Ingested aSNPs show adverse effects on the cells of GI tract of the exposed organism thus their industrial use as a food-additive may raise concern to human health.