Digital Commons Network^™

Dietary Intake Of Total, Heme And Non-Heme Iron And The Risk Of Colorectal Cancer In A European Prospective Cohort Study, Elom K Aglago, Amanda J Cross, Elio Riboli, Veronika Fedirko, David J Hughes, Agnes Fournier, Paula Jakszyn, Heinz Freisling, Marc J Gunter, Christina C Dahm, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Marie-Christine Boutron-Ruault, Joseph A Rothwell, Gianluca Severi, Verena Katzke, Bernard Srour, Matthias B Schulze, Clemens Wittenbecher, Domenico Palli, Sabina Sieri, Fabrizio Pasanisi, Rosario Tumino, Fulvio Ricceri, Bas Bueno-De-Mesquita, Jeroen W G Derksen, Guri Skeie, Torill Enget Jensen, Marko Lukic, Maria-Jose Sánchez, Pilar Amiano, Sandra Colorado-Yohar, Aurelio Barricarte, Ulrika Ericson, Bethany Van Guelpen, Keren Papier, Anika Knuppel, Corinne Casagrande, Inge Huybrechts, Alicia K Heath, Konstantinos K Tsilidis, Mazda Jenab

Faculty, Staff and Student Publications

BACKGROUND: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.

METHODS: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.

RESULTS: Of 450,105 participants (318,680 women) followed for 14.2 …

Well-Being Content Inclusion In Pharmacy Education Across The United States And Canada, Elizabeth Buckley, Simi Gunaseelan, Benjamin D Aronson, Heidi N Anksorus, Victoria Belousova, Tram B Cat, Kristine M Cline, Stacey D Curtis, Christina E Deremer, David Fuentes, Mckenzie S Grinalds, Seena L Haines, Hannah E Johnson, Karen Kopacek, Jessica M Louie, Nkem P Nonyel, Natasha Petry, Shawn Riser Taylor, Suzanne C Harris, Cheryl A Sadowski, Anandi V Law

Faculty, Staff and Student Publications

Objective. To describe the landscape of well-being content inclusion across schools and colleges of pharmacy in the United States and Canada through identification of content implementation, incorporation, and assessment.

Methods. A cross-sectional survey was distributed to all accredited schools and colleges of pharmacy in the United States (n=143) and Canada (n=10). Survey questions included curricular and cocurricular timing, frequency, assessment strategies, and support for well-being initiatives, using a framework of eight dimensions (pillars) of wellness to categorize content.

Results. Descriptive data analyses were applied to 99 completed surveys (65%), 89 (62%) in the United States and 10 (100%) in Canada. …

Effect Of The Physical Fibrillated Sweet Potato (Ipomoea Batatas) Stem On The Plant-Based Patty Analogues, Suyoon Lee, You Young Lee, Yang Kim, Seung Hwan Ham, Min Gyu Lee, Jungwoo Hahn, Young Jin Choi

Faculty, Staff and Student Publications

In this study, a dietary fiber extracted from sweet potato stems (Ipomoea batatas, PS) was evaluated for its ability to improve the quality of vegetable patty analogues. A patty analogues containing 0–50 wt% dietary fiber were prepared to analyze the utilized dietary fiber's performance. To evaluate the manufactured patty analogues, texture profile analysis, color analysis, emulsion stability, and microstructural analysis were conducted. As the PS increased, the hardness decreased, while the total expressible fluids tended to increase. The color analysis revealed that the a* value, which represents red, declined as the PS content increased, and heterogeneous colors showed …

Clinical Outcomes Of Immune Checkpoint Inhibitor Diabetes Mellitus At A Comprehensive Cancer Center, Rebecca Jeun, Priyanka C Iyer, Conor Best, Victor Lavis, Jeena M Varghese, Sireesha Yedururi, Veronica Brady, Isabella C Glitza Oliva, Ramona Dadu, Denai R Milton, Kristy Brock, Sonali Thosani

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients.

Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020.

Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients.

Conclusion: Development of ICI-DM is associated with long-term insulin dependence …

Use Of High-Flow Cannula In Pediatric Patients With Respiratory Failure: A Prospective Cohort Study In Three High-Altitude Hospitals, Natalia Ante-Ardila, Camilo Novoa Garnica, Paola Mora Umaña, Olga Lucía Baquero Castañeda, Alexandra Jiménez Cháves, Melisa Sofía Naranjo, Juan G Piñeros, Carolina Bonilla, Luz M Mejía, María L Mesa-Rubio, Sonia Restrepo-Gualteros, Pedro Barrera, Sergio Moreno-Lopez, Paola Rueda-Guevara, Andrea Ramírez Varela, Fara Group

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Acute respiratory failure (ARF) is a common cause of morbimortality, and a frequent reason for admission to the pediatric intensive care unit (PICU). It requires a high-flow oxygen device as treatment. Our aim is to determine the frequency and main indications for the use of high-flow nasal cannula (HFNC), and the prevalence of HFNC failure and its main causes, in three hospitals.

METHODS: It is a multicenter prospective cohort study, developed in three hospitals in Bogota. Eligible patients were children older than 1 month and younger than 18 years who presented ARF and required management with an …

Botulinum Toxin A Use In The Gastrointestinal Tract: A Reappraisal After Three Decades, Wasay A Mohajir, Shruti Khurana, Khushboo Singh, Reubyn William Chong, Manoop S Bhutani

Faculty, Staff and Student Publications

The discovery of botulinum toxin A (BTX)'s therapeutic properties has led to studies evaluating its usefulness in multiple medical disorders. Its use in the gastrointestinal (GI) tract has been studied for 30 years. Multiple databases, including PubMed, AccessMedicine, ClinicalKey, Cochrane Library, Embase, and Medline, were used to review research from case series to randomized controlled trials on BTX use in the GI tract. This article reviews the current literature on the efficacy of BTX and the strength of recommendations for or against its use in various disorders, including cricopharyngeal dysphagia, achalasia, nonachalasia motility disorders, gastroparesis, obesity, sphincter of Oddi disorders, …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …

Long-Term Maternal Metabolic And Cardiovascular Phenotypes After A Pregnancy Complicated By Mild Gestational Diabetes Mellitus Or Obesity, Ashley N Battarbee, Lisa Mele, Mark B Landon, Michael W Varner, Brian M Casey, Uma M Reddy, Ronald J Wapner, Dwight J Rouse, John M Thorp, Edward K Chien, George Saade, Beth A Plunkett, Sean C Blackwell

Faculty, Staff and Student Publications

Objective:

To evaluate the association of mild gestational diabetes (GDM) and obesity with metabolic and cardiovascular markers 5-10 years after pregnancy.

Study Design:

This was a secondary analysis of 5-10 year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/HOMA-IR, and cardiovascular markers VEGF, VCAM-1, CD40L, GDF-15, and ST-2. Multivariable linear regression estimated the association of GDM and obesity …

Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation In Preterm Pigs, Line I Christiansen, Bo Holmqvist, Xiaoyu Pan, Kristine Holgersen, Sandy E H Lindholm, Nicole L Henriksen, Douglas G Burrin, David Ley, Thomas Thymann, Per Torp Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was …

Necrotizing Enterocolitis In Premature Infants-A Defect In The Brakes? Evidence From Clinical And Animal Studies., Venkatesh Sampath, Maribel Martinez, Michael Caplan, Mark A. Underwood, Alain Cuna

Manuscripts, Articles, Book Chapters and Other Papers

A key aspect of postnatal intestinal adaptation is the establishment of symbiotic relationships with co-evolved gut microbiota. Necrotizing enterocolitis (NEC) is the most severe disease arising from failure in postnatal gut adaptation in premature infants. Although pathological activation of intestinal Toll-like receptors (TLRs) is believed to underpin NEC pathogenesis, the mechanisms are incompletely understood. We postulate that unregulated aberrant TLR activation in NEC arises from a failure in intestinal-specific mechanisms that tamponade TLR signaling (the brakes). In this review, we discussed the human and animal studies that elucidate the developmental mechanisms inhibiting TLR signaling in the postnatal intestine (establishing the …

Total Daily Energy Expenditure Has Declined Over The Past Three Decades Due To Declining Basal Expenditure, Not Reduced Activity Expenditure, John R Speakman, Jasper M A De Jong, Srishti Sinha, Klaas R Westerterp, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Liam J Anderson, Lenore Arab, Kweku Bedu-Addo, Stephane Blanc, Alberto G Bonomi, Pascal Bovet, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Santu Ghosh, Annelies H Goris, Michael Gurven, Lewis G Halsey, Catherine Hambly, Hinke H Haisma, Daniel Hoffman, Sumei Hu, Annemiek M Joosen, Jennifer L Kaplan, Peter Katzmarzyk, William E Kraus, Robert F Kushner, William R Leonard, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, Erwin P Meijer, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, Susan B Roberts, Michael C Rudolph, Luis B Sardinha, Albertine J Schuit, Analiza M Silva, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Brian M Wood, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Anura Kurpad, Amy H Luke, Herman Pontzer, Matthew S Rodeheffer, Jennifer Rood, Dale A Schoeller, William W Wong

Faculty, Staff and Student Publications

Obesity is caused by prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes, is debated3,4. Here we used the IAEA DLW database on energy expenditure of adults in the USA and Europe (n = 4799) to explore patterns in total (TEE: n=4799), basal (BEE: n = 1432) and physical activity energy expenditure (AEE: n = 1432) over time. In both sexes total energy expenditure (TEE) adjusted for body composition and age declined with time, while adjusted AEE increased over time. In males adjusted BEE decreased significantly, but …

Proteomic Predictors Of Incident Diabetes: Results From The Atherosclerosis Risk In Communities (Aric) Study, Mary R Rooney, Jingsha Chen, Justin B Echouffo-Tcheugui, Keenan A Walker, Pascal Schlosser, Aditya Surapaneni, Olive Tang, Jinyu Chen, Christie M Ballantyne, Eric Boerwinkle, Chiadi E Ndumele, Ryan T Demmer, James S Pankow, Pamela L Lutsey, Lynne E Wagenknecht, Yujian Liang, Xueling Sim, Rob Van Dam, E Shyong Tai, Morgan E Grams, Elizabeth Selvin, Josef Coresh

Faculty, Staff and Students Publications

Objective: The plasma proteome preceding diabetes can improve our understanding of diabetes pathogenesis.

Research design and methods: In 8,923 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 47-70 years, 57% women, 19% Black), we conducted discovery and internal validation for associations of 4,955 plasma proteins with incident diabetes. We externally validated results in the Singapore Multi-Ethnic Cohort (MEC) nested case-control (624 case subjects, 1,214 control subjects). We used Cox regression to discover and validate protein associations and risk-prediction models (elastic net regression with cardiometabolic risk factors and proteins) for incident diabetes. We conducted a pathway analysis and examined causality using …

Refugees Living With Dementia: Assessing The Barriers To Healthcare Access In Crisis-Affected Populations In Lebanon And Switzerland, And The Role Humanitarian Actors Have On Addressing Them, Pedro Gomez

Independent Study Project (ISP) Collection

As life expectancies increase in many places around the world, the prevalence of aging populations has increased. Consequently, increased numbers of people globally, especially in developing countries, have been diagnosed with conditions associated with old age. Dementia, a group of conditions associated with impaired cognitive functions, is among these. Notwithstanding, many developing countries have done poorly with regards to diagnosing and treating dementia, with some cultures not even having a word to describe the condition. (ADI 2022). The lack of a diagnosis and knowledge about dementia for some refugee communities has led to healthcare challenges in their host countries (Corfield …

The Effects Of Stigma Against Hiv And Tuberculosis On Patient Mental Health And Healthcare-Seeking Behavior In Dharamshala, Isabel Powell

Independent Study Project (ISP) Collection

HIV and tuberculosis are highly impactful diseases in India, causing severe morbidity, mortality, and suffering for millions. The stigmatization of these diseases unnecessarily exacerbates suffering for those afflicted and their families, compounding to the existing physical and emotional burden of diagnosis. Individual interviews with healthcare workers were conducted at Delek Hospital and the Tibetan Children’s Village in order to identify the existence and effects of stigma in the Tibetan refugee population in Dharamshala. Respondents reported an extremely high burden of tuberculosis in the community, complicated by the refugee status and unique infrastructural challenges of the population. The burden of HIV …

What Makes A Family: How An Empowerment-Based Health Care Delivery Model Employs Family Planning To Positively Impact Families In Rural Maharashtra: A Study In Jamkhed, Ahmadneger, Sezin Sakmar

Independent Study Project (ISP) Collection

The paper examines how an empowerment-based health care delivery model employs family planning services to positively impact families in rural Maharashtra. Family planning services provide those with the ability to become pregnant the option to control their own reproductive lives, whether they choose in favor of or against having children. Contraceptive use advances people’s human rights to choose whether they want to bear children and how many children they want, and people should have the choice of their preferred contraceptive method. The paper examines this issue within the framework of the Comprehensive Rural Health Project’s Jamkhed Model. Through the Jamkhed …

Optimized Acute Treatment Of Migraine Is Associated With Greater Productivity In People With Migraine: Results From The Chronic Migraine Epidemiology And Outcomes (Cameo) Study., Dawn C Buse, Stephanie J. Nahas, Walter Buzz F Stewart, Cynthia E Armand, Michael L Reed, Kristina M Fanning, Aubrey Manack Adams, Richard B Lipton

Department of Neurology Faculty Papers

OBJECTIVE: This study aimed to ascertain whether level of optimization of acute treatment of migraine is related to work productivity across the spectrum of migraine.

METHODS: Data were from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, an internet-based longitudinal survey. Respondents with migraine who reported full-time employment and use of ≥1 acute prescription medication for migraine were included. We determined relationships among lost productive time (LPT; measured with the Migraine Disability Assessment Scale), acute treatment optimization (Migraine Treatment Optimization Questionnaire- ), and monthly headache days (MHDs).

RESULTS: There was a direct relationship between LPT and MHD category. Greater acute …

Heart Failure-Type Symptom Score Trajectories In Ckd: Findings From The Chronic Renal Insufficiency Cohort (Cric) Study, Carl P Walther, Julia S Benoit, Nisha Bansal, Vijay Nambi, Sankar D Navaneethan, Cric Study Investigators

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF.

PREDICTORS: Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters.

OUTCOME: Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire …

Fit24, A Digital Health Intervention To Reduce Type 2 Diabetes Risk Among Hispanic Youth: Protocol For A Feasibility Pilot Study, Erica G Soltero, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: Poor physical activity (PA) and sleep behaviors in Hispanic adolescents contributes to increased risk for type 2 diabetes. Commonly owned digital devices and services like smartphones and text-messaging are highly used among adolescents and are promising intervention tools for reaching this age group. Personal activity trackers assess activity and sleep, making them ideal tools for addressing these behaviors. We propose to examine the feasibility of a 12-week intervention that uses theoretically grounded text messages and a Fitbit device to improve PA and sleep among Hispanic adolescents with obesity, as compared to a wait-list control group with a Fitbit device …

Quantifying The Number Of Us Men With Erectile Dysfunction Who Are Potential Candidates For Penile Prosthesis Implantation, Sirikan Rojanasarot, Abimbola O Williams, Natalie Edwards, Mohit Khera

Faculty, Staff and Students Publications

INTRODUCTION: Penile prosthesis implantation (PPI) is a treatment option recommended in clinical guidelines for erectile dysfunction (ED). However, a limited number of urologists perform PPI procedures in the United States.

AIM: To quantify the number of insured men with ED in the United States and project the number of potential candidates for PPI in 2022.

METHODS: An Excel-based disease impact model was constructed using a top-down estimation approach. The starting US male population consisted of adult men from 2022 US Census data after exclusion of age-specific mortality rates from the National Vital Statistics Reports. Men with health insurance were included …

Pilot Clinical Trial Of Macimorelin To Assess Safety And Efficacy In Patients With Cancer Cachexia, Megan Herodes, Lindsey J Anderson, Samuel Shober, Ellen A Schur, Solomon A Graf, Nicola Ammer, Ramiro Salas, Marco Marcelli, Jose M Garcia

Faculty, Staff and Students Publications

BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects.

METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined a priori as 1-week change in body weight (≥0.8 kg), plasma insulin-like growth factor (IGF)-1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non-parametrically.

RESULTS: …

Natural History Of Tango2 Deficiency Disorder: Baseline Assessment Of 73 Patients, Christina Y Miyake, Erica J Lay, Claudia Soler-Alfonso, Kevin E Glinton, Kimberly M Houck, Mustafa Tosur, Nancy E Moran, Sara B Stephens, Fernando Scaglia, Taylor S Howard, Jeffrey J Kim, Tam Dam Pham, Santiago O Valdes, Na Li, Chaya N Murali, Lilei Zhang, Maina Kava, Deane Yim, Cheyenne Beach, Gregory Webster, Leonardo Liberman, Christopher M Janson, Prince J Kannankeril, Samantha Baxter, Moriel Singer-Berk, Jordan Wood, Samuel J Mackenzie, Michael Sacher, Lina Ghaloul-Gonzalez, Claudia Pedroza, Shaine A Morris, Saad A Ehsan, Mahshid S Azamian, Seema R Lalani

Faculty, Staff and Students Publications

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD.

METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review.

RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at …

Monogenic Early-Onset Lymphoproliferation And Autoimmunity: Natural History Of Stat3 Gain-Of-Function Syndrome, Jennifer W Leiding, Tiphanie P Vogel, Valentine G J Santarlas, Rahul Mhaskar, Madison R Smith, Alexandre Carisey, Alexander Vargas-Hernández, Manuel Silva-Carmona, Maximilian Heeg, Anne Rensing-Ehl, Bénédicte Neven, Jérôme Hadjadj, Sophie Hambleton, Timothy Ronan Leahy, Kornvalee Meesilpavikai, Charlotte Cunningham-Rundles, Cullen M Dutmer, Svetlana O Sharapova, Mervi Taskinen, Ignatius Chua, Rosie Hague, Christian Klemann, Larysa Kostyuchenko, Tomohiro Morio, Akaluck Thatayatikom, Ahmet Ozen, Anna Scherbina, Cindy S Bauer, Sarah E Flanagan, Eleonora Gambineri, Lisa Giovannini-Chami, Jennifer Heimall, Kathleen E Sullivan, Eric Allenspach, Neil Romberg, Sean G Deane, Benjamin T Prince, Melissa J Rose, John Bohnsack, Talal Mousallem, Rohith Jesudas, Maria Marluce Dos Santos Vilela, Michael O'Sullivan, Jana Pachlopnik Schmid, Štěpánka Průhová, Adam Klocperk, Matthew Rees, Helen Su, Sami Bahna, Safa Baris, Lisa M Bartnikas, Amy Chang Berger, Tracy A Briggs, Shannon Brothers, Vanessa Bundy, Alice Y Chan, Shanmuganathan Chandrakasan, Mette Christiansen, Theresa Cole, Matthew C Cook, Mukesh M Desai, Ute Fischer, David A Fulcher, Silvanna Gallo, Amelie Gauthier, Andrew R Gennery, José Gonçalo Marques, Frédéric Gottrand, Bodo Grimbacher, Eyal Grunebaum, Emma Haapaniemi, Sari Hämäläinen, Kaarina Heiskanen, Tarja Heiskanen-Kosma, Hal M Hoffman, Luis Ignacio Gonzalez-Granado, Anthony L Guerrerio, Leena Kainulainen, Ashish Kumar, Monica G Lawrence, Carina Levin, Timi Martelius, Olaf Neth, Peter Olbrich, Alejandro Palma, Niraj C Patel, Tamara Pozos, Kahn Preece, Saúl Oswaldo Lugo Reyes, Mark A Russell, Yael Schejter, Christine Seroogy, Jan Sinclair, Effie Skevofilax, Daniel Suan, Daniel Suez, Paul Szabolcs, Helena Velasco, Klaus Warnatz, Kelly Walkovich, Austen Worth, Stat3 Gof Working Group Members, Mikko R J Seppänen, Troy R Torgerson, Georgios Sogkas, Stephan Ehl, Stuart G Tangye, Megan A Cooper, Joshua D Milner, Lisa R Forbes Satter

Faculty, Staff and Students Publications

BACKGROUND: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.

OBJECTIVE: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.

METHODS: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3.

RESULTS: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median …

Performa Diagnostik Global Leadership Initiative On Malnutrition (Glim) Dibandingkan Dengan Malnutrition Nutritional Assessment (Mna) Dalam Pengkajian Malnutrisi Pada Pasien Geriatri Di Rawat Inap, Astrine Permata Leoni, Wita Rizki Amelia, Purwita Wijaya Laksmi, Ahmad Syauqy

Jurnal Penyakit Dalam Indonesia

Introduction. As many as 76.6% of patients aged 60 years and above (elderly) are malnourished or at risk of malnutrition based on MNA within the first 48 hours of hospital admission. The prevalence of malnutrition varies widely depending on the population studied, the healthcare setting and the tools used for the assessment. To date, SGA is widely used in the diagnosis of malnutrition for adults and MNA for elderly patients. Recently, experts proposed empirical consensus of GLIM criteria for determining the diagnosis of malnutrition in adults. This study aimed to investigate the diagnostic performance of GLIM criteria as a …

Penilaian Domain Pengkajian Paripurna Pasien Geriatri (P3g) Sebagai Faktor Yang Berpengaruh Terhadap Kejadian Pneumonia Nosokomial Pada Pasien Usia Lanjut Yang Dirawat Di Rumah Sakit Umum Pusat Nasional Dr. Cipto Mangunkusumo, Hildebrand Hanoch Victor, Edy Rizal Wahyudi, C. Martin Rumende, C. H. Soejono, A. G. Rooshoeroe, Hamzah Shatri, Leonard Nainggolan, Cosphiadi Irawan

Jurnal Penyakit Dalam Indonesia

Introduction. Nosocomial pneumonia is a lung infection that occurs after the patient is hospitalized for more than 48 hours, without any signs of pulmonary infection at the time of treatment. When compared with young individuals, elderly individuals are more likely to have community-sourced and nosocomial infections with worse outcomes. Comprehensive Geriatric Assessment (CGA) domains are expected to explain the factors that contribute to nosocomial pneumonia in elderly patients. This study aimed to determine the proportion of elderly treated at Dr. Cipto Mangunkusumo National Central General Hospital who experienced nosocomial pneumonia and whether the CGA domains influence the occurrence of nosocomial …

Modulasi Mikrobiota Untuk Memperbaiki Laju Filtrasi Glomerulus, Toksin Uremik, Dan Penanda Inflamasi Pada Gagal Ginjal Kronik: Telaah Sistematik Dan Meta-Analisis, Burhan Gunawan, Raymond Sebastian Purwata, Syarif Hidayat, Roy Akur Pandapotan, Jennifer Jennifer

Jurnal Penyakit Dalam Indonesia

Introduction. Dysbiosis microbiota is considered as one of the consequences and impacts of high uremic toxins in patients with Chronic Kidney Disease (CKD), which can lead to an increased risk of progression and mortality. The aim of this systematic review and meta-analysis was to perform quantitative effect of microbiota modulation for estimated Glomerular Filtration Rate (eGFR), uremic toxin (total-p cresyl/total pCS), and inflammatory marker (hs-CRP) outcome among CKD patients.

Methods. Article searches were conducted from PubMed, ScienceDirect, and Cochrane Library data sources from 2010-2022. Assessment of article quality follows the rules of PRISMA (Preferred Reporting Items in Systematic …

Antibodies For Β2-Microglobulin And The Heavy Chains Of Hla-E, Hla-F, And Hla-G Reflect The Hla-Variants On Activated Immune Cells And Phases Of Disease Progression In Rheumatoid Arthritis Patients Under Treatment, Mepur H. Ravindranath, Narendranath M. Ravindranath, Carly J. Amato-Menker, Fatiha El Hilali, Senthamil R. Selvan, Edward J Filippone, Luis Eduardo Morales-Buenrostro

Department of Medicine Faculty Papers

Rheumatoid arthritis (RA) is a progressive, inflammatory, autoimmune, symmetrical polyarticular arthritis. It is characterized by synovial infiltration and activation of several types of immune cells, culminating in their apoptosis and antibody generation against "altered" autoantigens. β2-microglobulin (β2m)-associated heavy chains (HCs) of HLA antigens, also known as closed conformers (Face-1), undergo "alteration" during activation of immune cells, resulting in β2m-free structural variants, including monomeric open conformers (Face-2) that are capable of dimerizing as either homodimers (Face-3) or as heterodimers (Face-4). β2m-free HCs uncover the cryptic epitopes that can elicit antibodies (Abs). We report here the levels of IgM and IgG Abs …

Enhanced Ca2+-Channeling Complex Formation At The Er-Mitochondria Interface Underlies The Pathogenesis Of Alcohol-Associated Liver Disease, Themis Thoudam, Dipanjan Chanda, Jung Yi Lee, Min Kyo Jung, Ibotombi Singh Sinam, Byung Gyu Kim, Bo Yoon Park, Woong Hee Kwon, Hyo Jeong Kim, Myeongjin Kim, Chae Won Lim, Hoyul Lee, Yang Hoon Huh, Caroline A. Miller, Romil Saxena, Nicholas J. Skill, Nazmul Huda, Praveen Kusumanchi, Jing Ma, Zhihong Yang, Min Ji Kim, Ji Young Mun, Robert A. Harris, Jae Han Jeon, Suthat Liangpunsakul, In Kyu Lee

School of Medicine Faculty Publications

Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 …

Soybean Gmsaul1, A Bona Fide U-Box E3 Ligase, Negatively Regulates Immunity Likely Through Repressing The Activation Of Gmmpk3, Jun-Mei Li, Mei-Yan Ye, Chaofeng Wang, Xiao-Han Ma, Ni-Ni Wu, Chen-Li Zhong, Yanjun Zhang, Ninghui Cheng, Paul A Nakata, Lirong Zeng, Jian-Zhong Liu

Faculty, Staff and Students Publications

E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, …

Disease Risk Of Reintroducing Primates Confiscated From The Illegal Wildlife Trade, Ana Patricia Mendoza Becerra

Dissertations

Zoonotic infections are easily shared between human and other primates, and thus primate trafficking poses a high risk of introducing zoonotic pathogens into urban environments as well as spreading human-associated diseases into natural environments when infected primates are released. The magnitude of these risks has not been thoroughly studied in the context of primate trafficking and rehabilitation of Neotropical primates. In this dissertation, I address some knowledge gaps in disease risk analysis of reintroducing trafficked primates. In chapter 1, I describe the dynamics, diversity, and composition of live wildlife trafficking in urban markets in Peru. I found these markets are …

Delay In Diagnosis Of Pd-1 Inhibitor Induced Secondary Adrenal Insufficiency, Olubunmi Oladunjoye, Ibiyemi Oke, Ian Garrahy, Adeolu O. Oladunjoye, Kyle Macaulay, Jeremy Ellis

Transformative Medicine

Introduction: Immune checkpoint inhibitors including PD-1 inhibitors, were initially approved for the treatment of metastatic melanoma but are now increasingly being used for different types of solid organ malignancies. Despite the important clinical benefits, they are associated with immune-related adverse events. The most critical endocrinopathy associated with PD -1 inhibitor is adrenal insufficiency (AI), which requires prompt diagnosis and management to avoid fatality.

Case presentation: We present the case of a 78-year-old woman with colon adenocarcinoma treated with Nivolumab (PD-1 inhibitor) after her pulmonary metastases progressed on chemotherapy. She presented to the hospital with progressive generalized weakness, fatigue, headache, lightheadedness, …