Digital Commons Network^™

Randomization, Design And Analysis For Interdependency In Aging Research: No Person Or Mouse Is An Island, Daniella E Chusyd, Steven N Austad, Stephanie L Dickinson, Keisuke Ejima, Gary L Gadbury, Lilian Golzarri-Arroyo, Richard J Holden, Yasaman Jamshidi-Naeini, Doug Landsittel, Tapan Mehta, J Michael Oakes, Arthur H Owora, Greg Pavela, Javier Rojo, Michael W Sandel, Daniel L Smith, Colby J Vorland, Pengcheng Xun, Roger Zoh, David B Allison

Children’s Nutrition Research Center Staff Publications

Investigators traditionally use randomized designs and corresponding analysis procedures to make causal inferences about the effects of interventions, assuming independence between an individual's outcome and treatment assignment and the outcomes of other individuals in the study. Often, such independence may not hold. We provide examples of interdependency in model organism studies and human trials and group effects in aging research and then discuss methodologic issues and solutions. We group methodologic issues as they pertain to (1) single-stage individually randomized trials; (2) cluster-randomized controlled trials; (3) pseudo-cluster-randomized trials; (4) individually randomized group treatment; and (5) two-stage randomized designs. Although we present …

Secondhand Smoke Exposure Is Independently Associated With Stroke Among Non-Smoking Adults In West Africa., Akinkunmi Paul Okekunle, Osahon Jeffery Asowata, Adekunle G. Fakunle, Onoja Matthew Akpa, Fred S. Sarfo, Albert Akpalu, Kolawole Wahab, Reginald Obiako, Morenikeji Komolafe, Philip Adebayo

Internal Medicine, East Africa

Background: Stroke is a leading cause of disability and mortality worldwide, but little is known about the contribution of secondhand smoke exposure (SHSE) to stroke epidemiology among indigenous Africans.

Objective: To evaluate the association of SHSE with stroke among indigenous Africans. Methods We analyzed the relationship of SHSE with stroke among 2990 case-control pairs of adults who had never smoked (identified in the SIREN study) using conditional logistic regression at a two-sided P < 0.05.

Results: Multivariable-adjusted odds ratio and 95% confidence interval; 1.25 (1.04, 1.50; P = 0.02) revealed SHSE was positively associated with stroke independent of stroke subtypes.

Conclusion: …

Human Loss-Of-Function Variants In The Serotonin 2c Receptor Associated With Obesity And Maladaptive Behavior, Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes De Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R Cox, Julia M Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Zili Yan, Kristine M Conde, Camille Potts, Jonathan C Bean, Mengjie Wang, Sean M Hartig, Lan Liao, Jianming Xu, Inês Barroso, Jacek Mokrosinski, Yong Xu, I Sadaf Farooqi

Children’s Nutrition Research Center Staff Publications

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed …

Clinical And Demographic Factors Contributing To Asparaginase-Associated Toxicities In Children With Acute Lymphoblastic Leukemia, Priyadarshani Dharia, Michael D Swartz, M Brooke Bernhardt, Han Chen, M Monica Gramatges, Philip J Lupo, Austin L Brown, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

A total of 548 patients (age range: 1-22 years, 60.4% Hispanic, 55.8% male) diagnosed with acute lymphoblastic leukemia were reviewed for pegaspargase-associated hypersensitivity (14.8%), hyperbilirubinemia (9.7%), venous thromboembolism (VTE, 9.7%), and pancreatitis (5.3%). Odds ratios (OR) and 95% confidence intervals (CI) evaluated associations between clinical factors and each toxicity, cumulative number of toxicities, and toxicity clusters identified using k-mode analysis. Most (68.9%) did not experience any toxicity, 24.6% experienced one toxicity, and 6.3% two or more. Age >10 years was associated with hyperbilirubinemia (OR = 3.83; 95% CI: 1.64-8.95), pancreatitis (OR = 3.72; 95% CI: 1.29-10.68), VTE (OR = 4.65; …

A Cluster-Randomized Controlled Trial Of Automated Internet Weight-Loss Programs In Primary Care: Role Of Automated Provider Feedback, Deborah F Tate, Jennifer L Kraschnewski, Caitlin Martinez, Molly Diamond, Susan Veldheer, Kevin O Hwang, Erik B Lehman, Chengwu Yang, Christopher N Sciamanna

Faculty, Staff and Student Publications

OBJECTIVE: Despite the high prevalence of obesity and associated health risks in the United States adult population, few primary care providers (PCPs) have time and training to provide weight-management counseling to their patients. This study aims to compare the effect of referral to a comprehensive automated digital weight-loss program, with or without provider email feedback, with usual care on weight loss in patients with overweight or obesity.

METHODS: A total of 550 adults (mean [SD], 51.4 [11.2] years, BMI = 35.1 [5.5] kg/m

RESULTS: Weight changes (mean [SE]) at 12 months were -0.92 (0.46), -3.68 (0.46), and -3.58 (0.48) kg …

A Phase Ii Randomized Double Blinded Trial Evaluating The Efficacy Of Curcumin With Pre-Operative Chemoradiation For Rectal Cancer, Jillian R Gunther, Awalpreet S Chadha, Sushovan Guha, Gottumukkala S Raju, Dipen M Maru, Mark F Munsell, Yan Jiang, Peiying Yang, Edd Felix, Marilyn Clemons, Geena George Mathew, Pankaj K Singh, John M Skibber, Miguel A Rodriguez-Bigas, George J Chang, Cathy Eng, Marc E Delclos, Christopher H Crane, Prajnan Das, Sunil Krishnan

Faculty, Staff and Student Publications

Background

In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.

Methods

From 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. …

Liver Injury After Sars‐Cov‐2 Vaccination: Features Of Immune-Mediated Hepatitis, Role Of Corticosteroid Therapy And Outcome, Cumali Efe, Anand V Kulkarni, Benedetta Terziroli Beretta-Piccoli, Bianca Magro, Albert Stättermayer, Mustafa Cengiz, Daniel Clayton-Chubb, Craig Lammert, Christine Bernsmeier, Özlem Gül, Fatima Higuera-De La Tijera, Margarita Anders, Ellina Lytvyak, Mete Akın, Tugrul Purnak, Rodrigo Liberal, Mirta Peralta, Berat Ebik, Serkan Duman, Nurhan Demir, Yasemin Balaban, Álvaro Urzua, Fernando Contreras, Maria Grazia Venturelli, Yılmaz Bilgiç, Adriana Medina, Marcos Girala, Fulya Günşar, Maria-Carlota Londoño, Theodoros Androutsakos, Ayelen Kisch, Alper Yurci, Fatih Güzelbulut, Yasir Furkan Çağın, Enver Avcı, Murat Akyıldız, Emine Kübra Dindar-Demiray, Murat Harputluoğlu, Rahul Kumar, Sanjaya K Satapathy, Manuel Mendizabal, Marcelo Silva, Stefano Fagiuoli, Stuart K Roberts, Neşe Karadağ Soylu, Ramazan Idilman, Eric M Yoshida, Aldo J Montano-Loza, George N Dalekos, Ezequiel Ridruejo, Thomas D Schiano, Staffan Wahlin

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series.

APPROACH AND RESULTS: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) …

A New Chapter In An Evolving Pandemic: Successful Pediatric Liver Transplantation With Sars-Cov-2+ Donors, Matthew Benjamin Goss, Daniel Hao Bin Leung, Stephanie Marie Pouch, Flor M Munoz, Elizabeth Andrea Moulton, Tyler Malcolm Mccann Lambing, Sarah Koohmaraie, Nicolas Fernando Moreno, Christine A O'Mahony, John A Goss, Nhu Thao Nguyen Galván

Faculty, Staff and Students Publications

BACKGROUND: Amid a viral pandemic with poorly understood transmissibility and pathogenicity in the pediatric patient, we report the first pediatric liver transplants utilizing allografts from SARS-CoV-2+ donors.

METHODS: We describe the outcomes of two pediatric liver transplant recipients who received organs from SARS-CoV-2 nucleic acid test-positive (NAT+) donors. Data were obtained through the respective electronic medical record system and UNet DonorNet platform.

RESULTS: The first donor was a 3-year-old boy succumbing to head trauma. One of four nasopharyngeal (NP) swabs and 1 of 3 bronchoalveolar lavage (BAL) NAT tests demonstrated SARS-CoV-2 infection before organ procurement. The second donor was a …

Progress In Gastroparesis - A Narrative Review Of The Work Of The Gastroparesis Clinical Research Consortium, Pankaj J Pasricha, Madhusudan Grover, Katherine P Yates, Thomas L Abell, Kenneth L Koch, Richard W Mccallum, Irene Sarosiek, Cheryl E Bernard, Braden Kuo, Robert Bulat, Robert J Shulman, Bruno P Chumpitazi, James Tonascia, Laura A Miriel, Laura A Wilson, Mark L Van Natta, Emily Mitchell, Frank Hamilton, Gianrico Farrugia, Henry P Parkman, Niddk/Nih Gpcrc Consortium

Faculty, Staff and Students Publications

The Gastroparesis Clinical Research Consortium is a multicenter coalition created and funded by the National Institutes of Diabetes and Digestive and Kidney Disorders, with a mission to advance understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis. In this review, we summarize the results of the published Gastroparesis Clinical Research Consortium studies as a ready and convenient resource for gastroenterologists and others to provide a clear understanding of the consortium's experience and perspective on gastroparesis and related disorders.

Children And Caregiver Proxy Quality Of Life From Peanut Oral Immunotherapy Trialschildren And Caregiver Proxy Quality Of Life From Peanut Oral Immunotherapy Trials, Audrey Dunn Galvin, Andrea Vereda, Pablo Rodríguez Del Río, Antonella Muraro, Carla Jones, Robert Ryan, David Norval, Jennifer Jobrack, Aikaterini Anagnostou, Julie Wang

Faculty, Staff and Students Publications

BACKGROUND: Health-related quality of life (HRQoL) is significantly and substantially reduced in individuals with peanut allergy due to many factors associated with unanticipated or potentially fatal reactions. Further insight on the impact of peanut oral immunotherapy in managing peanut allergy on HRQoL is needed. The aim of this analysis was to assess effects of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH), a biologic drug for peanut oral immunotherapy, on HRQoL from three phase 3 and two follow-on trials of PTAH.

METHODS: HRQoL assessments from participants aged 4-17 in the PALISADE (ARC003), ARC004 (PALISADE follow-on), ARTEMIS (ARC010), RAMSES (ARC007), and ARC011 (RAMSES …

Development Of Myelinating Glia: An Overview, Carlo D Cristobal, Hyun Kyoung Lee

Duncan NRI Faculty and Staff Publications

Myelin is essential to nervous system function, playing roles in saltatory conduction and trophic support. Oligodendrocytes (OLs) and Schwann cells (SCs) form myelin in the central and peripheral nervous systems respectively and follow different developmental paths. OLs are neural stem-cell derived and follow an intrinsic developmental program resulting in a largely irreversible differentiation state. During embryonic development, OL precursor cells (OPCs) are produced in distinct waves originating from different locations in the central nervous system, with a subset developing into myelinating OLs. OPCs remain evenly distributed throughout life, providing a population of responsive, multifunctional cells with the capacity to remyelinate …

Risk Factors And Prognostic Significance Of Anemia In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Amanda Grimes, Gladstone Airewele, Shaun Bulsara, Taylor Olmsted Kim, Heather Haq, Erin Peckham-Gregory, Sebastian R Wanless, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Jenny Despotovic, Michael Scheurer

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH).

DESIGN: Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014.

METHODS: Incident cases of anemia were identified from electronic records and matched with CLWH without anemia. We calculated the incidence density of anemia and used conditional logistic regression to evaluate its association with risk factors, stratified by severity and type of anemia. We used a Cox proportional hazards model to evaluate the impact of anemia on survival.

RESULTS: Two thousand, one hundred and thirty-seven children were …

Cic Missense Variants Contribute To Susceptibility For Spina Bifida, Xiao Han, Xuanye Cao, Vanessa Aguiar-Pulido, Wei Yang, Menuka Karki, Paula Andrea Pimienta Ramirez, Robert M Cabrera, Ying Linda Lin, Bogdan J Wlodarczyk, Gary M Shaw, M Elizabeth Ross, Cuilian Zhang, Richard H Finnell, Yunping Lei

Faculty, Staff and Students Publications

Neural tube defects (NTDs) are congenital malformations resulting from abnormal embryonic development of the brain, spine, or spinal column. The genetic etiology of human NTDs remains poorly understood despite intensive investigation. CIC, homolog of the Capicua transcription repressor, has been reported to interact with ataxin-1 (ATXN1) and participate in the pathogenesis of spinocerebellar ataxia type 1. Our previous study demonstrated that CIC loss of function (LoF) variants contributed to the cerebral folate deficiency syndrome by downregulating folate receptor 1 (FOLR1) expression. Given the importance of folate transport in neural tube formation, we hypothesized that CIC variants could contribute to increased …

Early Phase Trial Of Intracystic Injection Of Large Surface Area Microparticle Paclitaxel For Treatment Of Mucinous Pancreatic Cysts, Mohamed Othman, Kalpesh Patel, Somashekar G Krishna, Antonio Mendoza-Ladd, Shelagh Verco, Wasif Abidi, James Verco, Alison Wendt, Gere Dizerega

Faculty, Staff and Students Publications

Background and study aims  Mucinous pancreatic cystic lesions (PCLs) have the potential for malignant transformation, for which the only accepted curative modality is surgery. A novel intracystic therapy with large surface area microparticle paclitaxel (LSAM-PTX) may treat PCLs without local or systemic toxicities. Safety and preliminary efficacy of LSAM-PTX for the treatment of PCLs administered by endoscopic ultrasound-guided fine-needle injection (EUS-FNI) was evaluated.

Patients and methods  Ten subjects with confirmed PCLs (size > 1.5 cm) received intracystic LSAM-PTX via EUS-FNI at volumes equal to those aspirated from the cyst in sequential cohorts at 6, 10, and 15 mg/mL in a standard …

Dawn-To-Dusk Dry Fasting Induces Anti-Atherosclerotic, Anti-Inflammatory, And Anti-Tumorigenic Proteome In Peripheral Blood Mononuclear Cells In Subjects With Metabolic Syndrome, Ayse L Mindikoglu, Jihwan Park, Antone R Opekun, Mustafa M Abdulsada, Zoe R Wilhelm, Prasun K Jalal, Sridevi Devaraj, Sung Yun Jung

Faculty, Staff and Students Publications

BACKGROUND: Metabolic syndrome characterized by abdominal obesity, high blood pressure, elevated fasting glucose and triglyceride levels and low high-density lipoprotein cholesterol level is associated with pro-inflammatory state, increased risk for atherosclerosis, and multiple cancers. Our previous results on subjects with metabolic syndrome showed that 4-week dawn-to-dusk (sunset) dry fasting resulted in significant changes in the serum proteome and improvement in several metabolic risk factors. Peripheral blood mononuclear cells (PBMC) proteomics is a powerful tool that can provide mechanistic insights into how dawn-to-dusk dry fasting affects protein expression in metabolic pathways at cellular level. In this study, we determined whether dawn-to-dusk …

Activated B Cells Suppress T-Cell Function Through Metabolic Competition, Nobuhiko Imahashi, Rafet Basar, Yuefan Huang, Fang Wang, Natalia Baran, Pinaki Prosad Banerjee, Junjun Lu, Ana Karen Nunez Cortes, Nadima Uprety, Emily Ensley, Luis Muniz-Feliciano, Tamara J Laskowski, Judy S Moyes, May Daher, Mayela Mendt, Lucila N Kerbauy, Mayra Shanley, Li Li, Francesca Lorraine Wei Inng Lim, Hila Shaim, Ye Li, Marina Konopleva, Michael Green, Jennifer Wargo, Elizabeth J Shpall, Ken Chen, Katayoun Rezvani

Faculty, Staff and Student Publications

BACKGROUND: B cells play a pivotal role in regulating the immune response. The induction of B cell-mediated immunosuppressive function requires B cell activating signals. However, the mechanisms by which activated B cells mediate T-cell suppression are not fully understood.

METHODS: We investigated the potential contribution of metabolic activity of activated B cells to T-cell suppression by performing in vitro experiments and by analyzing clinical samples using mass cytometry and single-cell RNA sequencing.

RESULTS: Here we show that following activation, B cells acquire an immunoregulatory phenotype and promote T-cell suppression by metabolic competition. Activated B cells induced hypoxia in T cells …

A Phase Ii Randomized Double Blinded Trial Evaluating The Efficacy Of Curcumin With Pre-Operative Chemoradiation For Rectal Cancer, Jillian R Gunther, Awalpreet S Chadha, Sushovan Guha, Gottumukkala S Raju, Dipen M Maru, Mark F Munsell, Yan Jiang, Peiying Yang, Edd Felix, Marilyn Clemons, Geena George Mathew, Pankaj K Singh, John M Skibber, Miguel A Rodriguez-Bigas, George J Chang, Cathy Eng, Marc E Delclos, Christopher H Crane, Prajnan Das, Sunil Krishnan

Faculty, Staff and Student Publications

Background: In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.

Methods: From 2008-2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood …

Clinically Significant Metachronous Colorectal Pathology Detected Among Young-Onset Colorectal Cancer Survivors: Implications For Post-Resection Surveillance Guidelines, Oliver Peacock, Eduardo Vilar, Montserrat Guraieb-Trueba, Selvi Thirumurthi, George J Chang, Y Nancy You

Faculty, Staff and Student Publications

No abstract provided.

Targeted Ablation Of Fn14 Receptor Improves Exercise Capacity And Inhibits Neurogenic Muscle Atrophy, Meiricris Tomaz Da Silva, Aniket S Joshi, Tatiana E Koike, Anirban Roy, Kavya Mathukumalli, Danesh H Sopariwala, Vihang A Narkar, Ashok Kumar

Faculty, Staff and Student Publications

Skeletal muscle atrophy is a prevalent complication in multiple chronic diseases and disuse conditions. Fibroblast growth factor-inducible 14 (Fn14) is a member of the TNF receptor superfamily and a bona fide receptor of the TWEAK cytokine. Accumulating evidence suggests that Fn14 levels are increased in catabolic conditions as well as during exercise. However, the role of Fn14 in the regulation of skeletal muscle mass and function remains poorly understood. In this study, through the generation of novel skeletal muscle-specific Fn14-knockout mice, we have investigated the muscle role of Fn14 in the regulation of exercise capacity and denervation-induced muscle atrophy. Our …

Soy Isoflavones Decrease Fibroglandular Breast Tissue Measured By Magnetic Resonance Imaging In Premenopausal Women: A 2-Year Randomized Double-Blind Placebo Controlled Clinical Trial, Lee-Jane W Lu, Nai-Wei Chen, Donald G Brunder, Fatima Nayeem, Manubai Nagamani, Thomas K Nishino, Karl E Anderson, Tuenchit Khamapirad

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Populations consuming soy have reduced risk for breast cancer, but the mechanisms are unclear. We tested the hypothesis that soy isoflavones, which have ovarian hormone-like effects, can reduce fibroglandular breast tissue (FGBT, 'breast density'), a strong risk marker for breast cancer.

METHODS: Premenopausal women (age 30-42 years) were randomized to consume isoflavones (136.6 mg as aglycone equivalents, n = 99) or placebo (n = 98) for 5 days per week up to 2 years, and changes in breast composition measured by magnetic resonance imaging at baseline and yearly intervals were compared after square root transformation using linear …

Allergic Sensitization Pattern In The Korean Dermatologic Patients, Yujin Han, Yu Ri Woo, Hei Sung Kim, Jeong Deuk Lee, Sookhee Choi, Jeesuk Yu, Sang Hyun Cho

Faculty, Staff and Student Publications

BACKGROUND: Avoiding causative allergens is important for controlling the clinical course of allergic diseases. Allergen sensitization is influenced by many factors including the environment and lifestyle. The socioeconomic development, climate, and lifestyle changes have increased the prevalence of allergic diseases worldwide. However, there is little information about changes in the trend of the common allergens over time.

OBJECTIVE: This study was aimed at identifying the trends of the common allergens in Korea over a 10-year period based on the results of the multiple allergosorbent test chemiluminescent assay (MAST-CLA).

METHODS: We retrospectively reviewed the medical records of 5,760 patients aged ≥18 …

Assessment Of Disease Severity And Quality Of Life In Patients With Atopic Dermatitis From South Korea, Sang Wook Son, Ji Hyun Lee, Jiyoung Ahn, Sung Eun Chang, Eung Ho Choi, Tae Young Han, Yong Hyun Jang, Hye One Kim, Moon-Bum Kim, You Chan Kim, Hyun Chang Ko, Joo Yeon Ko, Sang Eun Lee, Yang Won Lee, Bark-Lynn Lew, Chan Ho Na, Chang Ook Park, Chun Wook Park, Kui Young Park, Kun Park, Young Lip Park, Joo Young Roh, Young-Joon Seo, Min Kyung Shin, Sujin Lee, Sang Hyun Cho

Faculty, Staff and Student Publications

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited.

OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea.

METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. …

Chronic Kidney Disease In Public Renal Practices In Queensland, Australia, 2011–2018, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Vishal Diwan, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative

Faculty, Staff and Student Publications

AIM: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland.

METHODS: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years.

RESULTS: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons …

Immunity To Poliovirus In Afghanistan: A Household Sampling Method For Serological Assessment Based On Geographical Information Systems, Amalia Mendes, Ari Whiteman, Benjamin Nygren, Brian Kaplan, Imtiaz Hussain, Sajid Bashir Soofi, Maureen Martinez, Noha H. Farag

Department of Paediatrics and Child Health

Afghanistan continues to experience challenges affecting polio eradication. Mass polio vaccination campaigns, which aim to protect children under the age of 5, are a key eradication strategy. To date, the polio program in Afghanistan has only employed facility-based seroprevalence surveys, which can be subject to sampling bias. We describe the feasibility in implementing a cross-sectional household poliovirus seroprevalence survey based on geographical information systems (GIS) in three districts. Digital maps with randomly selected predetermined starting points were provided to teams, with a total target of 1,632 households. Teams were instructed to navigate to predetermined starting points and enrol the closest …

A Systematic Review And Meta-Analysis: Assessment Of Hospital Walking Programs Among Older Patients, Christine Loyd, Yue Zhang, Tara Weisberg, James Boyett, Elizabeth R. Huckaby, Jeri Grundhoefer, Steve Otero, Lisa Roberts, Samantha Giordano-Mooga, Carmen Capo-Lugo, Catherine H. Smith, Richard E. Kennedy, Barbara J. King, Cynthia J. Brown

School of Medicine Faculty Publications

Aim: The aim of this study is to assess effect of hospital walking programs on outcomes for older inpatients and to characterize hospital walking dose reported across studies. Design: A systematic review and meta-analysis examining impact of hospital walking and/or reported walking dose among medical-surgical inpatients. For inclusion, studies were observational or experimental, published in English, enrolled inpatients aged ≥ 65 yrs hospitalized for medical or surgical reasons. Methods: Searches of PubMed, CINAHL, Embase, Scopus, NICHSR, OneSearch, ClinicalTrials.gov, and PsycINFO were completed in December 2020. Two reviewers screened sources, extracted data, and performed quality bias appraisal. Results: Hospital walking dose …

Metabolic Targeting Of Nrf2 Potentiates The Efficacy Of The Trap1 Inhibitor G-Tpp Through Reduction Of Ros Detoxification In Colorectal Cancer, Hong-Yuan Tsai, Mary P Bronner, Jordon K March, John F Valentine, Noah F Shroyer, Lisa A Lai, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer. Inhibition of TRAP1 by G-TPP disrupted redox homeostasis and induced cell death. However, colon cancers show a wide range of responses to G-TPP treatment through the induction of variable ER stress responses and ROS accumulation. Interestingly, a strong inverse correlation was observed between …

Comprehensive Review Of Cardiovascular Disease Risk In Nonalcoholic Fatty Liver Disease, Kevan Josloff, Jacob Beiriger, Adnan Khan, Richard J. Gawel, Richard S. Kirby, Aaron Kendrick, Abhinav K. Rao, Roy Wang, Michelle Schafer, Margaret Pearce, Kashyap Chauhan, Yash B. Shah, Gregary D. Marhefka, Dina Halegoua-De Marzio

Department of Medicine Faculty Papers

Nonalcoholic Fatty Liver Disease (NAFLD) is a growing global phenomenon, and its damaging effects in terms of cardiovascular disease (CVD) risk are becoming more apparent. NAFLD is estimated to affect around one quarter of the world population and is often comorbid with other metabolic disorders including diabetes mellitus, hypertension, coronary artery disease, and metabolic syndrome. In this review, we examine the current evidence describing the many ways that NAFLD itself increases CVD risk. We also discuss the emerging and complex biochemical relationship between NAFLD and its common comorbid conditions, and how they coalesce to increase CVD risk. With NAFLD's rising …

Clinical And Molecular Insights Into Gastrointestinal Dysfunction In Myotonic Dystrophy Types 1 & 2, Janel A M Peterson, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and …

Variation In Human Water Turnover Associated With Environmental And Lifestyle Factors, Yosuke Yamada, Xueying Zhang, Mary E T Henderson, Hiroyuki Sagayama, Herman Pontzer, Daiki Watanabe, Tsukasa Yoshida, Misaka Kimura, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Lewis G Halsey, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, William E Kraus, Wantanee Kriengsinyos, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack A Yanovski, Alexia J Murphy-Alford, Cornelia U Loechl, Amy H Luke, Jennifer Rood, Klaas R Westerterp, William W Wong, Motohiko Miyachi, Dale A Schoeller, John R Speakman

Children’s Nutrition Research Center Staff Publications

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lack access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5,604 people from the ages of 8 days to 96 years from 26 countries using isotope tracking (2H) methods. Age, body size, and composition were significantly associated with WT as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People in countries with low human development index (HDI) …

Genomic Profiling For Clinical Decision Making In Myeloid Neoplasms And Acute Leukemia, Eric J Duncavage, Adam Bagg, Robert P Hasserjian, Courtney D Dinardo, Lucy A Godley, Ilaria Iacobucci, Siddhartha Jaiswal, Luca Malcovati, Alessandro M Vannucchi, Keyur P Patel, Daniel A Arber, Maria E Arcila, Rafael Bejar, Nancy Berliner, Michael J Borowitz, Susan Branford, Anna L Brown, Catherine A Cargo, Hartmut Döhner, Brunangelo Falini, Guillermo Garcia-Manero, Torsten Haferlach, Eva Hellström-Lindberg, Annette S Kim, Jeffery M Klco, Rami Komrokji, Mignon Lee-Cheun Loh, Sanam Loghavi, Charles G Mullighan, Seishi Ogawa, Attilio Orazi, Elli Papaemmanuil, Andreas Reiter, David M Ross, Michael Savona, Akiko Shimamura, Radek C Skoda, Francesc Solé, Richard M Stone, Ayalew Tefferi, Matthew J Walter, David Wu, Benjamin L Ebert, Mario Cazzola

Faculty, Staff and Student Publications

Myeloid neoplasms and acute leukemias derive from the clonal expansion of hematopoietic cells driven by somatic gene mutations. Although assessment of morphology plays a crucial role in the diagnostic evaluation of patients with these malignancies, genomic characterization has become increasingly important for accurate diagnosis, risk assessment, and therapeutic decision making. Conventional cytogenetics, a comprehensive and unbiased method for assessing chromosomal abnormalities, has been the mainstay of genomic testing over the past several decades and remains relevant today. However, more recent advances in sequencing technology have increased our ability to detect somatic mutations through the use of targeted gene panels, whole-exome …