Digital Commons Network^™

Exploring The Food And Drug Administration’S Review And Approval Of Entresto (Sacubitril/Valsartan), Ashley Eadie, Keith Brunt, Matthew Herder

Articles, Book Chapters, & Popular Press

Federal regulatory agencies such as the United States Food and Drug Administration review pharmacological evidence to ensure the safety and efficacy of new and repurposed pharmaceuticals prior to market approval. The discussions, disagreements and procedural decisions contained within such reviews offer unique insight into a pharmaceutical's strengths, weaknesses and opportunities, yet are often overlooked as a significant source of pharmacological information for research and development. To highlight the value of such resources, we present a case study on Entresto, a first-in-class angiotensin receptor-neprilysin inhibitor for the treatment of heart failure with reduced ejection fraction, and explore the regulatory rationale underlying …

In The Name Of Public Health: Misoprostol And The New Criminalization Of Abortion In Brazil, Mariana Prandini Assis, Joanna Erdman

Articles, Book Chapters, & Popular Press

This article explores the criminal regulation of misoprostol as a controlled drug in Brazil as a new form of abortion criminalization. A qualitative analysis of Brazilian case law shows how the courts use a public health rhetoric of unsafe abortion to criminalize the distribution of misoprostol in the informal sector. Rather than an invention of the local bench, this judicial rhetoric reflects global public health discourse and policy on unsafe abortion and the double life of misoprostol as both an essential medicine and a controlled drug. In contrast to previous studies, the article shows that abortion criminalization is not the …

On The Joint Role Of Non-Hispanic Black Race/Ethnicity And Weight Status In Predicting Postmenopausal Weight Gain, Christopher N Ford, Shine Chang, Alexis C Wood, Joann E Manson, David O Garcia, Helena Laroche, Chloe E Bird, Mara Z Vitolins

Children’s Nutrition Research Center Staff Publications

Objectives: To determine how baseline weight status contributes to differences in postmenopausal weight gain among non-Hispanic Blacks (NHBs) and non-Hispanic Whites (NHWs).

Methods: Data were included from 70,750 NHW and NHB postmenopausal women from the Women's Health Initiative Observational Study (WHI OS). Body Mass Index (BMI) at baseline was used to classify women as having normal weight, overweight, obese class I, obese class II or obese class III. Cox proportional hazards was used to estimate the hazard of a 10% or more increase in weight from baseline.

Results: In both crude and adjusted models, NHBs were more likely to experience …

A Moral And Pragmatic Analysis Of Debt And North–South Economic Inequality, George Atisa

Public Affairs and Security Studies Faculty Publications

The North–South inequality hurts both high- and low-income countries in many respects, both directly and indirectly. At the same time, workers from low-income countries work just as hard as those from high-income countries but are often held in abject poverty by circumstances not of their own making. The question the study tries to find answers for is: why do hard-working individuals in both the North and the South bring home different levels of income, yielding big differences in per capita income globally and what can be done about it? Current pro-poor growth policies that include handouts, loans or relocating industries …

Science Dialogue Mapping Of Knowledge And Knowledge Gaps Related To The Effects Of Dairy Intake On Human Cardiovascular Health And Disease, Andrew W Brown, Kathryn A Kaiser, Andrew Keitt, Kevin Fontaine, Madeline Gibson, Barbara A Gower, James M Shikany, Colby J Vorland, Donald C Beitz, Dennis M Bier, J Thomas Brenna, David R Jacobs, Penny Kris-Etherton, Kevin Maki, Michael Miller, Marie-Pierre St-Onge, Margarita Teran-Garcia, David B Allison

Children’s Nutrition Research Center Staff Publications

Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, “dialogue mapping™,” to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a day-long session among experts in nutrition and CVD. Dialogue mapping captures relations among ideas to explicitly, logically, and visually connect issues/questions, ideas, pro/con arguments, and agreements, even if discussed at different times. Experts discussed two propositions: for CVD risk, consumption of full-fat dairy products, 1) should be …

Assessment Of The Gut Bacterial Microbiome And Metabolome Of Girls And Women With Rett Syndrome, Santosh Thapa, Alamelu Venkatachalam, Nabeel Khan, Mohammed Naqvi, Miriam Balderas, Jessica K Runge, Anthony Haag, Kathleen M Hoch, Daniel G Glaze, Ruth Ann Luna, Kathleen J Motil

Children’s Nutrition Research Center Staff Publications

Background: Gastrointestinal problems affect the health and quality of life of individuals with Rett syndrome (RTT) and pose a medical hardship for their caregivers. We hypothesized that the variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome and metabolome in RTT, predisposing these individuals to gastrointestinal dysfunction.

Objectives: We characterized the gut bacterial microbiome and metabolome in girls and young women with RTT (n = 44) and unaffected controls (n = 21), and examined the relation between the composition of the microbiome and variations in the RTT phenotype.

Methods: Demographics and clinical information, including growth and …

Gut Microbiota Profiles Of Young South Indian Children: Child Sex-Specific Relations With Growth, Nirupama Shivakumar, Ambily Sivadas, Sarita Devi, Farook Jahoor, John Mclaughlin, Craig P Smith, Anura V Kurpad, Arpita Mukhopadhyay

Children’s Nutrition Research Center Staff Publications

Gut microbiota has been implicated as a modifier of childhood growth. Here, 16S rRNA sequencing-based fecal microbiota profiles of 18-24 month old Indian children were evaluated (n = 41), in relation to their anthropometric parameters, intestinal permeability, body composition and total energy expenditure. Pathway analyses were conducted to assess microbial functions related to stunting, underweight and wasting. The fecal microbiota was enriched in Prevotella 9, Bifidobacterium and Escherichia-Shigella. Weight, weight-for-age Z-scores (WAZ) and weight-for-length Z-scores (WLZ), along with age, acted as covariates of microbiota variation specifically in boys (n = 23). Bifidobacterium longum subsp longum abundance was positively associated with …

Associations Between Independent Assessments Of Child Appetite Self-Regulation: A Narrative Review, Maria A Papaioannou, Nilda Micheli, Thomas G Power, Jennifer O Fisher, Sheryl O Hughes

Children’s Nutrition Research Center Staff Publications

A variety of eating behaviors among children have been associated with obesity risk and are thought to broadly reflect child appetite self-regulation (ASR). While ASR is thought to occur on cognitive, emotional, motivational, biological, and behavioral levels, the inter-relatedness of ASR constructs as assessed by different methods/measures is not well-characterized. This narrative review describes the correspondence between different methods/measures of child ASR constructs as assessed by self-report questionnaires and/or observational tasks and their relationship to child standardized body mass index (BMIz). Research involving at least two different methods/measures is presented including observational tasks such as the Eating in the Absence …

Crucial Role Of Mammalian Glutaredoxin 3 In Cardiac Energy Metabolism In Diet-Induced Obese Mice Revealed By Transcriptome Analysis, Ninghui Cheng, Qianxing Mo, Jimmonique Donelson, Lingfei Wang, Ghislain Breton, George G Rodney, Jin Wang, Kendal D Hirschi, Xander H T Wehrens, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

Obesity is often associated with metabolic dysregulation and oxidative stress with the latter serving as a possible unifying link between obesity and cardiovascular complications. Glutaredoxins (Grxs) comprise one of the major antioxidant systems in the heart. Although Grx3 has been shown to act as an endogenous negative regulator of cardiac hypertrophy and heart failure, its metabolic impact on cardiac function in diet-induced obese (DIO) mice remains largely unknown. In the present study, analysis of Grx3 expression indicated that Grx3 protein levels, but not mRNA levels, were significantly increased in the hearts of DIO mice. Cardiac-specific Grx3 deletion (Grx3 CKO) mice …

Hypothalamic Perineuronal Nets Are Regulated By Sex And Dietary Interventions, Nan Zhang, Zili Yan, Hailan Liu, Meng Yu, Yang He, Hesong Liu, Chen Liang, Longlong Tu, Lina Wang, Na Yin, Junying Han, Nikolas Scarcelli, Yongjie Yang, Chunmei Wang, Tianshu Zeng, Lu-Lu Chen, Yong Xu

Children’s Nutrition Research Center Staff Publications

Perineuronal nets (PNNs) are widely present in the hypothalamus, and are thought to provide physical protection and ion buffering for neurons and regulate their synaptic plasticity and intracellular signaling. Recent evidence indicates that PNNs in the mediobasal hypothalamus play an important role in the regulation of glucose homeostasis. However, whether and how hypothalamic PNNs are regulated are not fully understood. In the present study, we examined whether PNNs in various hypothalamic regions in mice can be regulated by sex, gonadal hormones, dietary interventions, or their interactions. We demonstrated that gonadal hormones are required to maintain normal PNNs in the arcuate …

Food/Non-Food Classification Of Real-Life Egocentric Images In Low- And Middle-Income Countries Based On Image Tagging Features, Guangzong Chen, Wenyan Jia, Yifan Zhao, Zhi-Hong Mao, Benny Lo, Alex K Anderson, Gary Frost, Modou L Jobarteh, Megan A Mccrory, Edward Sazonov, Matilda Steiner-Asiedu, Richard S Ansong, Thomas Baranowski, Lora Burke, Mingui Sun

Children’s Nutrition Research Center Staff Publications

Malnutrition, including both undernutrition and obesity, is a significant problem in low- and middle-income countries (LMICs). In order to study malnutrition and develop effective intervention strategies, it is crucial to evaluate nutritional status in LMICs at the individual, household, and community levels. In a multinational research project supported by the Bill & Melinda Gates Foundation, we have been using a wearable technology to conduct objective dietary assessment in sub-Saharan Africa. Our assessment includes multiple diet-related activities in urban and rural families, including food sources (e.g., shopping, harvesting, and gathering), preservation/storage, preparation, cooking, and consumption (e.g., portion size and nutrition analysis). …

Associations Between Lipoprotein Subfractions And Area And Density Of Abdominal Muscle And Intermuscular Adipose Tissue: The Multi-Ethnic Study Of Atherosclerosis, Megan M Marron, Matthew Allison, Alka M Kanaya, Britta Larsen, Alexis C Wood, David Herrington, Philip Greenland, Iva Miljkovic

Children’s Nutrition Research Center Staff Publications

Skeletal muscle quantity and quality decrease with older age, which is partly attributed to ectopic fat infiltration and has negative metabolic consequences. To inform efforts to preserve skeletal muscle with aging, a better understanding of biologic correlates of quantity and quality of muscle and intermuscular adipose tissue (IMAT) is needed. We used targeted lipidomics of lipoprotein subfractions among 947 Multi-Ethnic Study of Atherosclerosis participants to provide a detailed metabolic characterization of area and density of abdominal muscle and IMAT. Serum lipoprotein subfractions were measured at the first visit using 1H-Nuclear Magnetic Resonance spectroscopy. Muscle and IMAT area (cm

A Computational Pipeline To Infer Alternative Poly-Adenylation From 3′ Sequencing Data, Hari Krishna Yalamanchili, Nathan D Elrod, Madeline K Jensen, Ping Ji, Ai Lin, Eric J Wagner, Zhandong Liu

Children’s Nutrition Research Center Staff Publications

An increasing number of investigations have established alternative polyadenylation (APA) as a key mechanism of gene regulation through altering the length of 3' untranslated region (UTR) and generating distinct mRNA termini. Further, appreciation for the significance of APA in disease contexts propelled the development of several 3' sequencing techniques. While these RNA sequencing technologies have advanced APA analysis, the intrinsic limitation of 3' read coverage and lack of appropriate computational tools constrain precise mapping and quantification of polyadenylation sites. Notably, Poly(A)-ClickSeq (PAC-seq) overcomes limiting factors such as poly(A) enrichment and 3' linker ligation steps using click-chemistry. Here we provide an …

Regulators, Pivotal Clinical Trials, And Drug Regulation In The Age Of Covid-19, Joel Lexchin, Janice Graham, Matthew Herder, Tom Jefferson, Trudo Lemmens

Articles, Book Chapters, & Popular Press

Medicine regulators rely on pivotal clinical trials to make decisions about approving a new drug, but little is known about how they judge whether pivotal trials justify the approval of new drugs. We explore this issue by looking at the positions of 3 major regulators: the European Medicines Agency, Food and Drug Administration, and Health Canada. Here we report their views and the implications of those views for the approval process. On various points, the 3 regulators are ambiguous, consistent, and demonstrate flexibility. The range of views may well reflect different regulatory cultures. Although clinical trial information from pivotal trials …

Optimizing The Data Available Via Health Canada's Clinical Information Portal, Alexander C. Egilman, Joseph S. Ross, Matthew Herder

Articles, Book Chapters, & Popular Press

Through its Public Release of Clinical Information initiative, Health Canada has provided public access to a vast repository of data that have been submitted to support market authorization of drugs and medical devices. Health Canada has released data from more than 160 submissions for drugs, biologics, vaccines and medical devices. The regulator is currently in its third year of a 4-year phase-in schedule to release clinical data proactively from submissions for all new active substances, new clinical indications, generic drugs and higher-risk devices that are approved, withdrawn or rejected. Substantial clinical data submitted by the industry sponsor of the application, …

Regulating Wave, Tidal And Ocean Thermal Energy, Meinhard Doelle, Theodore Nsoe Adimazoya

Articles, Book Chapters, & Popular Press

Ocean renewable energy sources hold the potential to contribute to the options of low-carbon energy sources and enhance the efforts by the global community to slow down climate change. In this Chapter, we provide a brief background on the current state of technology and development of wave, tidal and ocean thermal energy and consider their potential as forms of renewable energy as well as the potential negative environmental footprints of ocean renewable energy installation and development. Secondly, we examine the relevant international legal and policy framework governing ocean energy, highlighting in particular, the absence of a global legal instrument that …

Tph2 In The Dorsal Raphe Nuclei Regulates Energy Balance In A Sex-Dependent Manner, Hailan Liu, Chunmei Wang, Meng Yu, Yongjie Yang, Yang He, Hesong Liu, Chen Liang, Longlong Tu, Nan Zhang, Lina Wang, Julia Wang, Feng Liu, Fang Hu, Yong Xu

Children’s Nutrition Research Center Staff Publications

AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female …

Intersections Of Environmental Justice And Sustainable Development: Framing The Issues, Sumudu A. Atapattu, Carmen G. Gonzalez, Sara L. Seck

Articles, Book Chapters, & Popular Press

This chapter proceeds as follows. Section 1.2 describes the evolution of the concept of sustainable development from the 1987 report of the World Commission on Environment and Development (WCED) to the Sustainable Development Goals (SDGs). It discusses contem- porary degrowth and green growth movements, before introducing the relatively novel concept of just sustainabilities, a synthesis of environmental justice and sustainable development. Section 1.3 de!nes environmental justice and discusses its relationship to human rights and the social pillar of sustainable development, reflecting on which dimensions of environmental justice are well reflected in this book and which proved more dif!cult to address. …

N Y State Dent J January 2021

The New York State Dental Journal

The New York State Dental Journal (NYSDJ) is produced by the New York State Dental Association (NYSDA) six times a year, in January, March, April, July, September and November. Each issue features clinical and scientific articles written by researchers and practitioners from around the globe and is subject to review by a panel of specialists convened by the Editor.

Issues include cover and feature articles alongside regular columns with regional news impacting the New York membership including editorial and perspectives columns, legal, association activities, component news, continuing education opportunities, and classifieds.

Politics Of The Obesity Epidemic, Jacob Lyle

CMC Senior Theses

American society has long been obsessed with the issue of obesity. The turn of the 20th century broadly marked the beginning of America's current collective understanding of obesity. Throughout the century, the salience of the issue waxed and waned due to various factors. Around 2000, obesity became a major political issue. Media coverage of the issue exploded, and it became a hot topic for political debate. This paper looks to conduct a complete reckoning of the obesity epidemic that includes contextualizing the economic, cultural, and political factors that have shaped the issue throughout the 20th and 21st centuries.

A Determination Of The Aerosolization Efficiency Of Drugs Of Abuse In A Eutectic Mixture With Nicotine In Electronic Cigarettes, Laerissa Reveil

Master of Science in Forensic Science Directed Research Projects

Electronic cigarettes (e-cigarettes) were originally advertised as an alternative nicotine delivery system to facilitate smoking cessation. However, their popularity for recreational use has increased due to focuses on their trendiness, convenience, and discreteness along with concerns for its use to consume drugs other than nicotine (DOTN). With the adulteration of e-liquids, usually containing nicotine, with other substances, a greater understanding on how DOTN interact with the e-liquid constituents and how they are delivered to the user is necessary. E-liquids were prepared with 50:50 propylene glycol:vegetable glycerin, pure nicotine, pure methadone hydrochloride, and 1:1 methadone hydrochloride:nicotine and aerosolized via an automated …

Characterizing The Presence Of Edta In Blood Samples, Alexandra Wright

Master of Science in Forensic Science Directed Research Projects

Blood is often a type of evidence found at crime scenes. There has been a long history of criminal cases involving blood evidence samples that were allegedly planted at the scene by a third party. Ethylenediaminetetraacetic acid, or EDTA, is an anticoagulant that is not naturally occurring in blood samples; it chelates to ions in blood to prevent clotting. If present in a blood evidence sample, it could be indicative that the blood sample may have been planted at the crime scene to implicate a suspect. EDTA is also reported to modify clothing and exist in detergents, to allow dyes …

Identification And Optimization Of Mirna Biomarkers For Body Mass Index (Bmi) Estimation In Forensic Samples, Jennifer J. Shealy

Master of Science in Forensic Science Directed Research Projects

DNA profiles do not provide as much evidentiary value when either all known samples can be excluded or when there is no known suspect. DNA phenotyping is a technique used for investigative purposes to predict externally visible characteristics (EVCs) based on specific markers found in the genome. Most phenotyping panels are currently restricted to markers stable over a lifetime within an individual and are not able to predict environmental or metabolic impacts on EVCs. It is known that miRNA expression levels change due to environmental and metabolic factors, such as BMI, and research has proven associations between circulating plasma miRNAs …

Comparison Of The Bacterial Community Structure Of Bone Swabs To Ground Bone Recovered From Waterlogged Skeletal Remains From A Lentic Environment For Postmortem Submersion Interval (Pmsi) Estimation, Hannah Johnson

Master of Science in Forensic Science Directed Research Projects

Postmortem submersion interval (PMSI) is an essential factor when recovering bodies from aquatic environments. Although several studies exist on postmortem interval (PMI) estimation of mammalian cadavers in terrestrial systems, the same is not true for the aquatic systems. Cartozzo et al. (11) developed PMSI prediction models using bacterial succession data associated with waterlogged skeletal remains. This study is a continuation of the Cartozzo et al. (11) study, but the aim of this study is to compare the bacterial DNA (16S rDNA) community found on the surface of swabs recovered from waterlogged bones to the bacterial DNA obtained from ground bone …

Evaluation Of Cell Lysis Techniques For Direct Amplification Of Sexual Assault Samples, Sarah Schellhammer

Master of Science in Forensic Science Directed Research Projects

Sexual assault is one of the most common crimes committed today with a delay in sample processing, resulting in the “rape kit backlog”. The traditional method to extract DNA from these samples containing both male and female DNA is a differential extraction; taking hours to process. This study examined a variety of different cell lysis techniques to develop a method which can consistently generate high-quality profiles at a fast rate and with low volumes when compared to the currently used method in our laboratory.

Six lysis methods, in addition to the currently used forensicGEM™ Sperm kit, were performed on …

Detection Of 2,4,6-Trinitrotoluene Using A Colorimetric Gold Nanoparticle Air Cassette Filter, Andrea I. Ferrer Vega

Master of Science in Forensic Science Directed Research Projects

Trinitrotoluene (TNT) is an explosive commonly used during military and terrorist activities. Current methods to identify this compound require sampling, transport and analysis at a forensic lab using analytical instrumentation. However, on-site detection is needed to assist efforts to prevent detonation. Gold nanoparticles have been used as sensors throughout the years due to their versatility and surface enhanced Raman scattering properties in the presence of an analyte and low limits of detection. By taking advantage of the Meisenheimer complex that TNT forms in the presence of amines, it is possible to determine its presence at picogram levels. Subsequently, adhering amine …

Determining Time Since Deposition For Human Saliva Stains Using Non-Genetic Signatures, Brian M. Stephenson

Master of Science in Forensic Science Directed Research Projects

Sexual assault cases are common within the forensic community and are constantly backlogged within laboratories for examination. One biological fluid, saliva, can often be present in context with the sexual assault due to the nature of the crime. The question used to be who’s DNA is present, but now since DNA analysis has become much more advanced, the new question of how long has the stain been there, arises. Four donors were used to create four different time point environments including 3 days, 7 days, 1.5 months (41 days), and 3 months (84 days) which were then collected with cotton …

Qualitative And Quantitative Characterization Of Epithelial Cell Mixtures Using Hormone Antibody Probes And Flow Cytometry, Luke Baldridge

Master of Science in Forensic Science Directed Research Projects

“Touch” DNA is evidence that consists of epidermal cells deposited by handling objects and it is becoming more common in evidence samples processed in crime labs. Because “touch” DNA evidence samples may be low-template DNA and are often mixtures, there is a need to both nondestructively estimate the amount of DNA present prior to DNA purification and to identify and characterize mixtures prior to DNA typing. The purpose of this study was to test the use of FITC-labeled anti-testosterone antibodies as a potential tool to estimate the number of contributors in two-, three-, and four-person mixtures of epidermal skin cells, …

Development Of An Analytical Method And Sample Preparation Technique For The Analysis Of Sulfur-Containing Fentanyl Analogs By Uplcmsms, And The Application To Forensic Science, Amber D. Budmark

Master of Science in Forensic Science Directed Research Projects

In February 2018, the US DEA Agency released a statement of the emergency scheduling (Schedule 1) of all fentanyl analogs not already regulated by the CSA due to an alarming increase in overdose deaths linked to synthetic opioids. Fentanyl analogs are pharmacologically similar to fentanyl, but often more potent. This increased potency can create problems with proper dosing of fentanyl analogs leading to untoward effects including an increase in overdoses and deaths. Since 2018, there has been a 38.4% increase in illicitly manufactured fentanyl overdose deaths leading the CDC to make available the FAS Kit and Emergent Panels containing previously …

Comparison Of Semi-Automated And Manual Differential Separation Methods For Mock Sexual Assault Samples, Stephanie Rink

Master of Science in Forensic Science Directed Research Projects

In the event of a sexual assault, separation of suspect from victim DNA is possible through differential extraction if the evidentiary mixture consists of female epithelial cells and male spermatozoa. The basis of differential extraction is the differing properties of epithelial and sperm cell membranes, specifically the comparative sturdiness of the proteins making up the sperm head containing the male DNA. Effective retrieval and separation of male and female DNA fractions is important in generating high-quality STR profiles that can be utilized in identifying suspects in a sexual assault case. Differential extraction has been conventionally performed using Proteinase K (PK) …