The volume and monetary value of human milk produced by the world's breastfeeding mothers: Results from a new tool

The Mothers' Milk Tool was developed to make more visible the economic value contributed to society by women's unpaid care work through breastfeeding infants and young children. This manuscript describes the development and display key features of the tool, and reports results for selected countries. For the development, we used five steps: (1) defining the tool by reviewing existing tools and scholarly literature to identify uses, approaches, design features, and required data characteristics for a suitable product; (2) specifying the best open-access data available for measurement and easy updating; (3) analyzing development options; (4) testing predictive models to fill identified breastfeeding data gaps; and (5) validating the tool with prospective users and against previous research. We developed an Excel-based tool that allows working offline, displaying preloaded data, imputing data, and inputting users' data. It calculates annual quantities of milk produced by breastfeeding women for children aged 0–35.9 months, and the quantities lost compared to a defined biologically feasible level. It supports calculations for an individual mother, for countries, and global level. Breastfeeding women globally produce around 35.6 billion liters of milk annually, but 38.2% is currently “lost” due to cultural barriers and structural impediments to breastfeeding. The tool can also attribute a monetary value to the production. In conclusion, the Mothers' Milk Tool shows what is at risk economically if women's important capacity for breastfeeding is not protected, promoted, and supported by effective national policies, programs, and investments. The tool is of value to food and health policymakers, public officials, advocates, researchers, national accountants and statisticians, and individual mother/baby dyads, and will assist consideration of breastfeeding in food balance sheets and economic production statistics. The tool supports the 2015 Call to Action by the Global Breastfeeding Collective by facilitating the tracking of progress on breastfeeding targets

Gastro intestinal digestion of dairy and soy proteins in infant formulas: an in vitro study

An in vitro digestion simulating infant gastrointestinal tract studied the digestion of caseins, whey and soy proteins, commonly used in infant formulations, in the presence of proteases only (without lipolytic enzymes). 60 min of gastric phase and 120 min of intestinal phase coupled with gel electrophoresis, confocal microscopy, mastersizer and pH were employed to monitor the degradation of proteins, microstructure, particle size distribution and pH drop of the digesta through the in vitro digestion process. Obtained results showed around 20% of caseins and almost no components of whey were hydrolysed after 60 min in the simulated stomach. In the simulated duodenal phase, 8% of α-lactalbumin was hydrolysed while caseins and β-lactoglobulin completely digested immediately and 30 min respectively after addition of duodenal digestive proteases. Overall, soy proteins indicated lower level of hydrolysis than dairy proteins during in vitro infant digestion as observed by SDS-PAGE.The soy protein fractions glycinin and β-conglycinin were partially hydrolysed during the gastrointestinal phase. The observed pH drop confirms that caseins are easily digested in the duodenal phase compared to whey and soy protein. Gastric digestion resulted in a decrease of the particle size of protein aggregates, but no fat coalescence was observed during both gastric and duodenal digestions in the given conditions

Prostate Field Cancerization and Exosomes: Association Between CD9, Early Growth Response 1 and Fatty Acid Synthase

Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase (FASN). However, the molecular etiology of prostate field cancerization, including EGR‑1 and FASN upregulation, remains largely unknown. It was thus hypothesized that extracellular vesicles, notably exosomes, released by tumor lesions may induce molecular alterations in the surrounding tissues, resulting in field cancerization, priming the tissue, and ultimately promoting multifocal tumorigenesis, which is often observed in prostate cancer. Towards testing this hypothesis, the current study, to the best of our knowledge, for the first time, presents correlative protein expression data, generated in disease‑free, tumor‑adjacent and cancerous human prostate tissues by quantitative immunofluorescence, between the exosomal marker CD9, and EGR‑1 and FASN. Despite the pilot character of the present study, and the static nature and heterogeneity of human tissues, the data suggest that CD9 expression itself is part of a field effect. In support of this hypothesis, the results suggest a possible contribution of exosomes to the induction of field cancerization in the prostate, particularly for EGR‑1. These findings were corroborated in established cell models of cancerous (LNCaP) and non‑cancerous (RWPE‑1) human prostate epithelial cells. The findings of this study warrant further investigation into the functional interface between exosomes and field cancerization, as a detailed understanding of this characterization may lead to the development of clinical applications related to diagnosis and/or prognosis and targeted intervention to prevent progression from pre‑malignancy to cancer

Innovative financing for a gender-equitable first-food system to mitigate greenhouse gas impacts of commercial milk formula: investing in breastfeeding as a carbon offset

Women’s contributions to food production and food security are often overlooked, thus perpetuating inequitable and unsustainable globalized commercial food systems. Women’s role as producers in the first-food system, breastfeeding, is largely invisible and underfunded, encouraging the production and consumption of environmentally unsustainable commercial milk formula (CMF). This policy brief highlights opportunities for including and funding interventions enabling breastfeeding under carbon offset schemes such as the United Nations Clean Development Mechanism (CDM). A Green Feeding Tool is being developed to account for the national carbon and water footprints of CMF. The tool will help ensure that women’s contributions to a sustainable first-food system are not ignored by the CDM and other mechanisms funding greenhouse gas emissions reductions

The Clinical Utility and Specificity of Parent Report of Executive Function among Children with Prenatal Alcohol Exposure

Prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) result in behavioral issues related to poor executive function (EF). This overlap may hinder clinical identification of alcohol-exposed children. This study examined the relation between parent and neuropsychological measures of EF and whether parent ratings aid in differential diagnosis. Neuropsychological measures of EF, including the Delis-Kaplan Executive Function System (D-KEFS), were administered to four groups of children (8–16 years): alcohol-exposed with ADHD (AE+, n = 80), alcohol-exposed without ADHD (AE−, n = 36), non-exposed with ADHD (ADHD, n = 93), and controls (CON, n = 167). Primary caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF). For parent ratings, multivariate analyses of variance revealed main effects of Exposure and ADHD and an interaction between these factors, with significant differences between all groups on nearly all BRIEF scales. For neuropsychological measures, results indicated main effects of Exposure and ADHD, but no interaction. Discriminant function analysis indicated the BRIEF accurately classifies groups. These findings confirm compounded behavioral, but not neuropsychological, effects in the AE+ group over the other clinical groups. Parent-report was not correlated with neuropsychological performance in the clinical groups and may provide unique information about neurobehavior. Parent-report measures are clinically useful in predicting alcohol exposure regardless of ADHD. Results contribute to a neurobehavioral profile of prenatal alcohol exposure

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin