Medicine and Health Sciences Commons^™

Distinct Reproductive Phenotypes Segregate With Differences In Body Weight In Adolescent Polycystic Ovary Syndrome., Angie Chen-Patterson, Angelina Bernier, Tania S. Burgert, Vanessa Davis, Tazeena Khan, David Geller, Emily Paprocki, Rachana Shah, Selma F. Witchel, Camila Pereira-Eshraghi, Aviva B. Sopher, Melanie G. Cree, Laura C. Torchen

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis.

METHODS: Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G.

RESULTS: Reproductive phenotypes differed between the groups, with LN-G …

Increasing Patient Awareness And Education Surrounding Prescription Weight Loss Medications, Anirudh A. Hirve

Family Medicine Clerkship Student Projects

Obesity is a growing problem in the United States. While it remains important for clinicians to emphasize health supportive behaviors including dietary modification and exercise when counseling patients, the advent of new weight loss medications has created a need for patient education materials regarding these interventions for a growing number of patients who request them at primary care visits. This project created a smart phrase in the electronic medical record summarizing weight loss medications currently available on the market to transform patient counseling and enable better shared decision making between patients and providers.

Action Apac: Understanding Perceptions, Attitudes And Behaviours In Obesity And Its Management Across South And Southeast Asia, Kwang Wei Tham, Asma Ahmed, Apussanee Boonyavarakul, Mariana Mercado Garcia, Miroslava Guajardo, Zubaidah Nor Hanipah, Tran Quang Nam, Nemencio A. Nicodemus, Faruque Pathan, Jack Garcia Uranga Romano, Sidartawan Soegonda, Edgardo L. Tolentino, Ambika Gopalakrishnan (A G) Unnikrishnan, Brian J. Oldfield

Ateneo School of Medicine and Public Health Publications

To identify perceptions and attitudes among people with obesity (PwO) and healthcare professionals (HCPs) toward obesity and its management in nine Asia-Pacific (APAC) countries, a cross-sectional online survey was conducted among adult PwO with self-reported body mass index of ≥25 kg/m2 (≥27 kg/m2, Singapore), and HCPs involved in direct patient care. In total, 10 429 PwO and 1901 HCPs completed the survey. Most PwO (68%) and HCPs (84%) agreed that obesity is a disease; however, a significant proportion of PwO (63%) and HCPs (41%) believed weight loss was the complete responsibility of PwO and only 43% of PwO discussed weight …

Prevalence Of Liver Cirrhosis And Its Association With Obesity Among Mexican Americans: An Evidence Synthesis, Alexa Perlick, Abaigeal Thompson, Colton Wayne, Angel Rendon, Jose E. Campo Maldonado

Research Colloquium

Introduction: Chronic liver disease is the 6^th and 7^th leading cause of death in Hispanic men and Hispanics, respectively.¹ In contrast to other causes of liver disease, the prevalence of nonalcoholic liver disease has been growing as is diabetes and obesity.²

Objective: There is a paucity of data regarding the prevalence of cirrhosis for Mexican Americans in South Texas. The aim of this evidence synthesis is to investigate the prevalence of cirrhosis in Hispanic populations and its relationship with obesity.

Methods: PubMed was used to perform a thorough literature search on September10, 2020. The terms “liver …

Vitamin D Deficiency Among Children And Adolescents Living In Sunny South Texas, Yoscelina E. Martinez-Lopez, Margarita Faz, Beatriz Tapia, Juan C. Lopez-Alvarenga, Francisco J. Cervantes

Research Symposium

Background: Exposure to sunlight is essential to produce Vitamin D (ViD). Recent studies suggest obesity is associated with low ViD concentration. Living in South Texas with 220 sunny days a year should be enough to maintain adequate ViD levels. We aimed to analyze ViD levels and obesity in children and adolescents.

Methods: We included 1239 pediatric (1.5 to 18.8 years old) participants (primary care clinic from Laredo) with registered CDC percentiles of BMI (pBMI) and serum concentrations of ViD (Atellica™). Data are described as median (p25, p75), Loess correlation between pBMI and ViD, ANCOVA to adjust by age, sex, and …

A Case Of Osteogenesis Imperfecta In A Patient Diagnosed In Adulthood, Khalid Sheikh, M. Lastovica, N. S. Appareddy, R. Wagner, E. Luna

Research Symposium

Background: Osteogenesis imperfecta (OI) is an extremely rare inherited connective tissue disorder, with an incidence of 1 in 20,000 births in the United States. Our aim is to assist other providers in diagnosing and managing patients with OI and concurrent medical morbidities.

Case Presentation: A 21 year old male with a BMI of 34 and a lifetime history of over 10 fractures presented to the Emergency department after a complex seizure at home. The seizure was witnessed by his mother and lasted less than one minute. He had another seizure two weeks prior to presentation. In the ED, the patient …

Progression Of Comorbidities In Youth With Overweight Or Obesity During The Covid-19 Pandemic., Erica Wee, Ashley K. Sherman, Safa Farrukh, Mark A. Clements, Kelsee Halpin, Yun Yan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Childhood obesity rates have continued to increase with the COVID-19 pandemic. However, data are limited on the impact of increasing obesity on associated comorbidities.

METHODS: We evaluated the progression of overweight- or obesity-associated comorbidities by investigating change in laboratory results pre-COVID-19 pandemic and post-COVID-19 pandemic onset in youth with overweight or obesity. We defined progression of comorbidities based on increase in category rather than absolute change in value.

RESULTS: HbA1c progression was seen in 19%, and LDL cholesterol progression was seen in 26%, as defined by categories. HbA1c progression and LDL cholesterol progression were significantly correlated. HbA1c and LDL …

Prevention Of Obesity-Related Morbidity & Mortality In Adults, Rachelle Virgin

Masters Theses/Capstone Projects

Poster presentation on the prevention of obesity related morbidity and mortality in adults.

Influence Of Aerobic Exercise On Appetite-Regulating Hormones, Ghrelin-O-Acyltransferase And Perceived Hunger In Normal Weight And Obese Adults, Michael Bruneau, Richard Wood, Susan Sotir, Samuel Headley, Elizabeth O'Neil, Juan Muñiz, May Cheung, Marissa Pontarelli

Department of Medical Oncology Faculty Papers

Background: Obesity is a major public health issue in the United States (U.S.), affecting an estimated 78 million US adults. Aerobic exercise (AE) is recommended by the American College of Sports Medicine to prevent and treat obesity, yet the effects of AE on circulating hunger hormones including acylated ghrelin and its biological catalyst, ghrelin o-acyltransferase (GOAT) are less known. Objectives: We investigated the effects of AE on circulating concentrations of appetite regulating hormones and GOAT in a pilot sample of adults classified with normal weight (NW) and obese (OB) body weight status. Methods: Using a quasi-experimental design, nine adults with …

How Do Glp-Ira Medications Affect Gut And Brain Hunger Signaling To Allow For Reduction In Weight And Better Glycemic Control In Adults With Obesity And Type 2 Diabetes?, David White

Graduate Research Projects

No abstract provided.

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Sciences Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

Vitamin K-1 Intake And Incident Diabetes In The Danish Diet, Cancer, And Health Study, Pratik Pokharel, Jamie W. Bellinge, Frederik Dalgaard, Kevin Murray, Marc Sim, Bu B. Yeap, Emma Connolly, Lauren C. Blekkenhorst, Catherine P. Bondonno, Joshua R. Lewis, Gunnar Gislason, Anne Tjønneland, Kim Overvad, Jonathan M. Hodgson, Carl Schultz, Nicola P. Bondonno

Research outputs 2022 to 2026

Context: Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors. Objective: To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes. Methods: Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes …

The Impact Of Single Nucleotide Polymorphisms On Cortisol Receptor Activity In Populations With Obesity, Cassidy Michalicka

Honors Theses

Cortisol is a crucial part of the endocrine system; it has the capacity to affect nearly every organ and tissue in the human body. When functioning correctly, cortisol is known to regulate the body’s stress response, control metabolism, suppress inflammation, regulate blood pressure, regulate blood sugar, regulate our body’s circadian rhythm, and much more. When the concentration of cortisol in the blood is elevated for an excessive period, the body responds with symptoms such as hyperglycemia, hypertension, weight gain, and moon face. Commonly this is known as Cushing’s Syndrome (CS), and interestingly, we have seen a phenotypic resemblance when contrasted …

Feasibility And Efficacy Of Bisphosphonate Use For The Prevention Of Bone And Muscle Loss, Laura E. Flores

Theses & Dissertations

Loss of bone and muscle mass often occurs in tandem, increasing the risk of fragility fractures. Whereas many drugs are approved for the treatment of bone loss, there are few treatments available for the concomitant loss of bone and muscle. Identification of a treatment to mitigate pathologic bone and muscle atrophy has the potential to impact countless populations and influence approaches for healthy aging. Bisphosphonates have emerged as a potential treatment for both bone and muscle loss in cellular, murine, and observational human studies. Our findings of modest weight maintenance in postmenopausal women treated with 12-months of risedronate, relative to …

Pediatric Growth Patterns In Youth-Onset Type 2 Diabetes Mellitus: Implications For Physiologically-Based Pharmacokinetic Models., Chelsea M. Hosey, Kelsee Halpin, Valentina Shakhnovich, Chengpeng Bi, Brooke Sweeney, Yun Yan, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

An accurate understanding of the changes in height and weight of children with age is critical to the development of models predicting drug concentrations in children (i.e., physiologically-based pharmacokinetic models). However, curves describing the growth of a typical population of children may not accurately characterize growth of children with various conditions, such as obesity. Therefore, to develop height and weight versus age growth curves for youth who were diagnosed with type 2 diabetes, we extracted data from electronic medical records. Robust nonlinear models were parameterized to the equations describing height and weight versus age as defined by the Centers for …

Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda

Arts & Sciences Electronic Theses and Dissertations

Pancreatic β-cells perform glucose-stimulated insulin secretion, a process required to maintain systemic glucose homeostasis. Obesity promotes glycemic and inflammatory stress, causing β-cell death and dysfunction, resulting in diabetes. Efforts to improve β-cell function in obesity have been hampered by observations that β-cells are highly heterogeneous, varying in morphology, function, and gene expression. There is great need to understand the breadth of β-cell heterogeneity in health and obesity to improve diabetic therapies.High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we show that as they resolve hyperglycemia, obese SM/J …

Therapeutic Efficacy Of Antioxidants In Ameliorating Obesity Phenotype And Associated Comorbidities, Steven Tun, Caleb James Spainhower, Cameron Lee Cottrill, Hari Vishal Lakhani, Sneha S. Pillai, Anum Dilip, Hibba Chaudhry, Joseph I. Shapiro, Komal Sodhi

Pharmacology, Physiology and Toxicology

Obesity has been a worldwide epidemic for decades. Despite the abundant increase in knowledge regarding the etiology and pathogenesis of obesity, the prevalence continues to rise with estimates predicting considerably higher numbers by the year 2030. Obesity is characterized by an abnormal lipid accumulation, however, the physiological consequences of obesity are far more concerning. The development of the obesity phenotype constitutes dramatic alterations in adipocytes, along with several other cellular mechanisms which causes substantial increase in systemic oxidative stress mediated by reactive oxygen species (ROS). These alterations promote a chronic state of inflammation in the body caused by the redox …

The Β3-Adrenergic Receptor Agonist Mirabegron Improves Glucose Homeostasis In Obese Humans, Brian S. Finlin, Hasiyet Memetimin, Beibei Zhu, Amy L. Confides, Hemendra J. Vekaria, Riham H. El Khouli, Zachary R. Johnson, Philip M. Westgate, Jianzhong Chen, Andrew J. Morris, Patrick G. Sullivan, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

BACKGROUND. Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.

METHODS. Before and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and …

Prediction Of Neonatal Birthweight Associated With Maternal Obesity And Diabetes, Laura Gleason, Rebekah Mccurdy, Md, Mph

Phase 1

Introduction: To design a model that will predict neonatal birth weight within obese mothers by diabetic status.

Methods: A secondary data analysis of an RCT (NCT 02909582) was utilized to create a neonatal birth weight prediction model. Women (n=325) with a BMI > 35 kg/m2 from a tertiary academic institution, 2016 – 2019, were included to estimate the risk of large for gestational age (LGA) infants and neonatal birth weight based on maternal prepregnancy BMI and diabetic status. LGA was defined as an infant birth weight > 90th percentile. Analysis included Chi-square, t-test, multivariate logistic and linear regression.

Results: Mean birthweight did …

Adapting The Diabetes Prevention Program For Low And Middle-Income Countries: Protocol For A Cluster Randomised Trial To Evaluate 'Lifestyle Africa'., Delwyn Catley, Thandi Puoane, Lungiswa Tsolekile, Ken Resnicow, Kandace Fleming, Emily A. Hurley, Joshua M. Smyth, Mara Z. Vitolins, Estelle V. Lambert, Naomi Levitt, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Low and middle-income countries like South Africa are experiencing major increases in burden of non-communicable diseases such as diabetes and cardiovascular conditions. However, evidence-based interventions to address behavioural factors related to these diseases are lacking. Our study aims to adapt the CDC's National Diabetes Prevention Program (DPP) within the context of an under-resourced urban community in Cape Town, South Africa.

Methods/analysis: The new intervention (Lifestyle Africa) consists of 17 weekly sessions delivered by trained community health workers (CHWs). In addition to educational and cultural adaptations of DPP content, the programme adds novel components of text messaging and …

Colostrum And Mature Breast Milk Analysis Of Serum Irisin And Sterol Regulatory Element-Binding Proteins-1c In Gestational Diabetes Mellitus, Syeda Sadia Fatima, Erum Khalid, Asma Akbar Ladak, Syed Adnan Ali

Department of Biological & Biomedical Sciences

Background: We aimed to evaluate irisin and SREBP-1c levels in serum, colostrum and mature breast milk in women with and without gestational diabetes (GDM); and to relate them with maternal glucose, lipid profile and weight status of babies.
Methods: GDM positive women (n = 33) and normal glucose tolerant women (NGT) (n = 33) were recruited. Maternal blood samples were collected at 28th week of gestation and later at 6-week post-partum while breast milk samples of the lactating mothers were collected within 72 hours of birth (colostrum) and at 6 weeks post-partum (mature milk). Irisin and SREBP-1c levels were analyzed …

Rising Rural Body-Mass Index Is The Main Driver Of The Global Obesity Epidemic In Adults, Con Burns, Tara Coppinger, Janette Walton, Et Al

Publications

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to …

Relationship Between Binge Eating Disorder And Circadian Chronotype, Leon B. Jons

Theses & Dissertations

Binge eating disorder (BED) is a common condition in the general population and is more common in individuals with obesity. The later timing of food intake has been associated with an increase incidence of obesity. The purpose of this study was to evaluate the relationship between circadian chronotype and BED in a population of individuals with obesity. The sample consists of a retrospective review of 170 subjects presenting to an obesity medicine clinic who had been clinically evaluated for BED and chronotype.

No significant correlation was found between BED and a late chronotype in this population. In a secondary analysis …

Cardio Metabolic Risk Factors For Atrial Fibrillation In Type 2 Diabetes Mellitus: Focus On Hypertension, Metabolic Syndrome And Obesity, Mihnea-Alexandru Gaman, Elena-Codruta Dobrica, Emilia G. Pascu, Matei-Alexandru Cozma, Mirela-Elena Epingeac, Amelia M. Gaman, Anca M. Pantea Stoian, Ovidiu G. Bratu, Camelia C. Diaconu

Journal of Mind and Medical Sciences

Objective. Atrial fibrillation (AF) in type 2 diabetes mellitus (T2DM) has been little explored so far. However, there are several cardio metabolic risk factors for AF in T2DM patients, such as arterial hypertension, obesity or the metabolic syndrome. Our objective was to evaluate cardio metabolic risk factors for AF in T2DM patients. Methods. We studied the medical records of T2DM patients hospitalized in the Internal Medicine department of an emergency referral hospital in Bucharest, Romania. The study was observational, retrospective and carried out between January-June 2018. Results. The study group included 221 T2DM patients (with a mean age of 68.65 …

Examining The Impact Of Race And Rurality On Health Differences Among Overweight Youth Accessing Pediatric Endocrinology Care, Kelsee Halpin, Janelle R. Noel-Macdonnell, Yun Yan

Journal of Health Disparities Research and Practice

Methods: This study examines the impact of race and rurality on health differences, including prevalence of prediabetes and type 2 diabetes (T2D), among overweight children accessing pediatric endocrine specialty care. Cross-sectional analysis of overweight/obese youth 10 to 18 years of age receiving pediatric endocrinology consultation for weight gain, hyperglycemia, and/or T2D from 2013 to 2016 at a Midwest tertiary pediatric center.

Results: The 722 patients were 42% white, 25% black, 22% Hispanic; 88% lived in urban areas and 12% in rural areas. Rurality was determined using zip code approximation of Rural-Urban Commuting Area (RUCA) codes. After adjusting for confounders, black …

Guggulsterone Activates Adipocyte Beiging Through Direct Effects On 3t3-L1 Adipocytes And Indirect Effects Mediated Through Raw264.7 Macrophages., Colette N Miller, Janaiya S Samuels, Yusra Azhar, Ashish Parmar, Rangaiah Shashidharamurthy, Srujana Rayalam

PCOM Scholarly Papers

Background: Plant-derived phytochemicals have been of emerging interest as anti-obesity compounds due to their apparent effects on promoting reduced lipid accumulation in adipocytes. Despite such promising evidence, little is known about the potential mechanisms behind their anti-obesity effects. The aim of this study is to establish potential anti-obesity effects of the phytochemical guggulsterone (GS). Methods: Mature 3T3-L1 adipocytes were treated with GS, derived from the guggul plant native in northern India, to investigate its effects on mitochondrial biogenesis and adipocyte "beiging." Further, to explore the relationship between macrophages and adipocytes, 3T3-L1s were treated with conditioned media from GS-treated RAW264.7 macrophages. …

Pancreatogenic Type 3c Diabetes, Anca Mihaela Pantea Stoian, Giorgiana Ditu, Mircea Diculescu, Mircea Manuc, Andra Iulia Suceveanu, Dana Manuc, Camelia C. Diaconu, Adrian Paul Suceveanu, Cornelia Nitipir, Razvan Hainarosie, Catalina Poiana, Cristian Serafinceanu

Journal of Mind and Medical Sciences

Background. The relationship between chronic pancreatitis and diabetes is well established. This form of diabetes is secondary to exocrine pancreatic disorder and is known as diabetes mellitus type 3c (T3cDM).

Materials and Methods. In this retrospective study we included 261 patients, 59 patients being diagnosed with chronic pancreatitis and secondary diabetes mellitus, and admitted in the Fundeni Clinical Institute, 2nd Department of Gastroenterology or N.C. Paulescu Institute/ Carol Davila University of Medicine and Pharmacy.

Results and Discussions. Patients were 22.2% women and 77.8% men, with an average age of 56.8 years and 53.4 years respectively. 63% came from urban areas. …

Metabolic Syndrome And The Risk Of Breast Cancer And Subtypes By Race, Menopause And Bmi, Daniel T. Dibaba, Dejana Braithwaite, Tomi Akinyemiju

Epidemiology and Environmental Health Faculty Publications

The objective of this study was to investigate the association of metabolic syndrome (MetS) with the risk of invasive breast cancer and molecular subtypes across race, menopause, and body mass index (BMI) groups. We examined the association of metabolic syndrome and its components with risk of invasive breast cancer among 94,555 female participants of the National Institute of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, accounting for ductal carcinoma in situ as a competing risk. Cox proportional hazard regression with the Fine and Gray method was used to generate hazard ratios (HR) and 95% confidence intervals (CI) …

Divergent Relationship Of Circulating Ctrp3 Levels Between Obesity And Gender: A Cross-Sectional Study, Roy Marshall Wagner, Kamesh Sivagnanam, W. Andrew Clark, Jonathan M. Peterson

W. Andrew Clark

C1q TNF Related Protein 3 (CTRP3) is a novel adipose tissue derived secreted factor, or adipokine, which has been linked to a number of beneficial biological effects on metabolism, inflammation, and survival signaling in a variety of tissues. However, very little is known about CTRP3 in regards to human health. The purpose of this project was to examine circulating CTRP3 levels in a clinical population, patients with symptoms requiring heart catheterization in order to identify the presence of obstructive coronary artery disease (CAD). It was hypothesized that serum CTRP3 levels would be decreased in the presence of CAD.

Methods

Body …

Development And Validation Of The Body Knowledge Questionnaire (Phase 2), David A. Hernandez, Cheri Ann Hernandez

Journal of Social, Behavioral, and Health Sciences

This study evaluated the psychometric properties of the Body Knowledge Questionnaire (BKQ), an instrument that measures weight management integration: an individual’s attitudes, preferences, and behaviors associated with weight self-management. The BKQ was revised following a pilot study demonstrating its validity and reliability, and new items were added based on data gathered through four focus groups of obese and normal-weight survey completers. Additional items were derived from the extant literature on weight management and integration. A panel of 30 health professionals who work in the area of weight management, bariatrics, and nutrition science reviewed the revised BKQ for content validity. Two …