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Articles 3421 - 3450 of 9033

Full-Text Articles in Medical Specialties

Beyond Varices: Complications Of Cirrhotic Portal Hypertension In Pediatrics, Anna M Banc-Husu, Henry Shiau, Peace Dike, Benjamin L Shneider Feb 2023

Beyond Varices: Complications Of Cirrhotic Portal Hypertension In Pediatrics, Anna M Banc-Husu, Henry Shiau, Peace Dike, Benjamin L Shneider

Faculty, Staff and Students Publications

Complications of cirrhotic portal hypertension (PHTN) in children are broad and include clinical manifestations ranging from variceal hemorrhage, hepatic encephalopathy (HE), ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) to less common conditions such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy. The approaches to the diagnosis and management of these complications have become standard of practice in adults with cirrhosis with many guidance statements available. However, there is limited literature on the diagnosis and management of these complications of PHTN in children with much of the current guidance available focused on variceal hemorrhage. The aim of this review …


Current Challenges And Future Direction In Surveillance For Hepatocellular Carcinoma In Patients With Nonalcoholic Fatty Liver Disease, George Cholankeril, Hashem B El-Serag Feb 2023

Current Challenges And Future Direction In Surveillance For Hepatocellular Carcinoma In Patients With Nonalcoholic Fatty Liver Disease, George Cholankeril, Hashem B El-Serag

Faculty, Staff and Students Publications

The burden for hepatocellular carcinoma (HCC) attributed to nonalcoholic fatty liver disease (NAFLD) continues to grow in parallel with rising global trends in obesity. The risk of HCC is elevated among patients with NAFLD-related cirrhosis to a level that justifies surveillance based on cost-effectiveness argument. The quality of current evidence for HCC surveillance in all patients with chronic liver disease is poor, and even lower in those with NAFLD. For a lack of more precise risk-stratification tools, current approaches to defining a target population in noncirrhotic NAFLD are limited to noninvasive tests for liver fibrosis, as a proxy for liver-related …


Genetic Variants In Arhgef6 Cause Congenital Anomalies Of The Kidneys And Urinary Tract In Humans, Mice, And Frogs, Verena Klämbt, Florian Buerger, Chunyan Wang, Thomas Naert, Karin Richter, Theresa Nauth, Anna-Carina Weiss, Tobias Sieckmann, Ethan Lai, Dervla M Connaughton, Steve Seltzsam, Nina Mann, Amar J Majmundar, Chen-Han W Wu, Ana C Onuchic-Whitford, Shirlee Shril, Sophia Schneider, Luca Schierbaum, Rufeng Dai, Mir Reza Bekheirnia, Marieke Joosten, Omer Shlomovitz, Asaf Vivante, Ehud Banne, Shrikant Mane, Richard P Lifton, Karin M Kirschner, Andreas Kispert, Georg Rosenberger, Klaus-Dieter Fischer, Soeren S Lienkamp, Mirjam M P Zegers, Friedhelm Hildebrandt Feb 2023

Genetic Variants In Arhgef6 Cause Congenital Anomalies Of The Kidneys And Urinary Tract In Humans, Mice, And Frogs, Verena Klämbt, Florian Buerger, Chunyan Wang, Thomas Naert, Karin Richter, Theresa Nauth, Anna-Carina Weiss, Tobias Sieckmann, Ethan Lai, Dervla M Connaughton, Steve Seltzsam, Nina Mann, Amar J Majmundar, Chen-Han W Wu, Ana C Onuchic-Whitford, Shirlee Shril, Sophia Schneider, Luca Schierbaum, Rufeng Dai, Mir Reza Bekheirnia, Marieke Joosten, Omer Shlomovitz, Asaf Vivante, Ehud Banne, Shrikant Mane, Richard P Lifton, Karin M Kirschner, Andreas Kispert, Georg Rosenberger, Klaus-Dieter Fischer, Soeren S Lienkamp, Mirjam M P Zegers, Friedhelm Hildebrandt

Faculty, Staff and Students Publications

Background: About 40 disease genes have been described to date for isolated CAKUT, the most common cause of childhood CKD. However, these genes account for only 20% of cases. ARHGEF6, a guanine nucleotide exchange factor that is implicated in biologic processes such as cell migration and focal adhesion, acts downstream of integrin-linked kinase (ILK) and parvin proteins. A genetic variant of ILK that causes murine renal agenesis abrogates the interaction of ILK with a murine focal adhesion protein encoded by Parva , leading to CAKUT in mice with this variant.

Methods: To identify novel genes that, when mutated, result in …


Lumasiran For Advanced Primary Hyperoxaluria Type 1: Phase 3 Illuminate-C Trial, Mini Michael, Jaap W Groothoff, Hadas Shasha-Lavsky, John C Lieske, Yaacov Frishberg, Eva Simkova, Anne-Laure Sellier-Leclerc, Arnaud Devresse, Fitsum Guebre-Egziabher, Sevcan A Bakkaloglu, Chebl Mourani, Rola Saqan, Richard Singer, Richard Willey, Bahru Habtemariam, John M Gansner, Ishir Bhan, Tracy Mcgregor, Daniella Magen Feb 2023

Lumasiran For Advanced Primary Hyperoxaluria Type 1: Phase 3 Illuminate-C Trial, Mini Michael, Jaap W Groothoff, Hadas Shasha-Lavsky, John C Lieske, Yaacov Frishberg, Eva Simkova, Anne-Laure Sellier-Leclerc, Arnaud Devresse, Fitsum Guebre-Egziabher, Sevcan A Bakkaloglu, Chebl Mourani, Rola Saqan, Richard Singer, Richard Willey, Bahru Habtemariam, John M Gansner, Ishir Bhan, Tracy Mcgregor, Daniella Magen

Faculty, Staff and Students Publications

Rationale & objective: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease.

Study design: Phase 3, open-label, single-arm trial.

Setting & participants: Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (if age ≥12 months) or increased serum creatinine level (if age < 12 months), and POx ≥20 μmol/L at screening, including patients with or without systemic oxalosis.

Intervention: Lumasiran administered subcutaneously; 3 monthly doses followed by monthly or quarterly weight-based dosing.

Outcome: Primary end point: percent change in POx …


Genotype-Phenotype Relationships Of Truncating Mutations, Pe297g And Pd482g In Bile Salt Export Pump Deficiency, Antonia Felzen, Daan B E Van Wessel, Emmanuel Gonzales, Richard J Thompson, Irena Jankowska, Benjamin L Shneider, Etienne Sokal, Tassos Grammatikopoulos, Agustina Kadaristiana, Emmanuel Jacquemin, Anne Spraul, Patryk Lipiński, Piotr Czubkowski, Nathalie Rock, Mohammad Shagrani, Dieter Broering, Emanuele Nicastro, Deirdre Kelly, Gabriella Nebbia, Henrik Arnell, Björn Fischler, Jan B F Hulscher, Daniele Serranti, Cigdem Arikan, Esra Polat, Dominique Debray, Florence Lacaille, Cristina Goncalves, Loreto Hierro, Gema Muñoz Bartolo, Yael Mozer-Glassberg, Amer Azaz, Jernej Brecelj, Antal Dezsőfi, Pier Luigi Calvo, Enke Grabhorn, Steffen Hartleif, Wendy J Van Der Woerd, Binita M Kamath, Jian-She Wang, Liting Li, Özlem Durmaz, Nanda Kerkar, Marianne Hørby Jørgensen, Ryan Fischer, Carolina Jimenez-Rivera, Seema Alam, Mara Cananzi, Noemie Laverdure, Cristina Targa Ferreira, Felipe Ordoñez Guerrero, Heng Wang, Valerie Sency, Kyung Mo Kim, Huey-Ling Chen, Elisa De Carvalho, Alexandre Fabre, Jesus Quintero Bernabeu, Aglaia Zellos, Estella M Alonso, Ronald J Sokol, Frederick J Suchy, Kathleen M Loomes, Patrick J Mckiernan, Philip Rosenthal, Yumirle Turmelle, Simon Horslen, Kathleen Schwarz, Jorge A Bezerra, Kasper Wang, Bettina E Hansen, Henkjan J Verkade, Natural Course And Prognosis Of Pfic And Effect Of Biliary Diversion (Napped) Consortium Feb 2023

Genotype-Phenotype Relationships Of Truncating Mutations, Pe297g And Pd482g In Bile Salt Export Pump Deficiency, Antonia Felzen, Daan B E Van Wessel, Emmanuel Gonzales, Richard J Thompson, Irena Jankowska, Benjamin L Shneider, Etienne Sokal, Tassos Grammatikopoulos, Agustina Kadaristiana, Emmanuel Jacquemin, Anne Spraul, Patryk Lipiński, Piotr Czubkowski, Nathalie Rock, Mohammad Shagrani, Dieter Broering, Emanuele Nicastro, Deirdre Kelly, Gabriella Nebbia, Henrik Arnell, Björn Fischler, Jan B F Hulscher, Daniele Serranti, Cigdem Arikan, Esra Polat, Dominique Debray, Florence Lacaille, Cristina Goncalves, Loreto Hierro, Gema Muñoz Bartolo, Yael Mozer-Glassberg, Amer Azaz, Jernej Brecelj, Antal Dezsőfi, Pier Luigi Calvo, Enke Grabhorn, Steffen Hartleif, Wendy J Van Der Woerd, Binita M Kamath, Jian-She Wang, Liting Li, Özlem Durmaz, Nanda Kerkar, Marianne Hørby Jørgensen, Ryan Fischer, Carolina Jimenez-Rivera, Seema Alam, Mara Cananzi, Noemie Laverdure, Cristina Targa Ferreira, Felipe Ordoñez Guerrero, Heng Wang, Valerie Sency, Kyung Mo Kim, Huey-Ling Chen, Elisa De Carvalho, Alexandre Fabre, Jesus Quintero Bernabeu, Aglaia Zellos, Estella M Alonso, Ronald J Sokol, Frederick J Suchy, Kathleen M Loomes, Patrick J Mckiernan, Philip Rosenthal, Yumirle Turmelle, Simon Horslen, Kathleen Schwarz, Jorge A Bezerra, Kasper Wang, Bettina E Hansen, Henkjan J Verkade, Natural Course And Prognosis Of Pfic And Effect Of Biliary Diversion (Napped) Consortium

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship.

METHODS: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n …


A Single-Center Study Of Long-Term Effectiveness Of Vedolizumab In Anti-Tnf Refractory Pediatric Inflammatory Bowel Disease, Halee Patel, Lina Karam, Richard Kellermayer Feb 2023

A Single-Center Study Of Long-Term Effectiveness Of Vedolizumab In Anti-Tnf Refractory Pediatric Inflammatory Bowel Disease, Halee Patel, Lina Karam, Richard Kellermayer

Faculty, Staff and Students Publications

OBJECTIVES: Vedolizumab is an anti-α4β7 integrin antibody that has been used successfully in the treatment of adult-onset inflammatory bowel diseases (IBDs: Crohn disease [CD] and ulcerative colitis [UC]). Its off-label use in the pediatric IBD (PIBD) population is increasing, but knowledge on durability beyond 6 months of treatment is limited.

METHODS: A real-life, single-center, retrospective study of PIBD patients treated with vedolizumab was performed. Data on demographics, prior and concomitant treatments, and disease activity were obtained at 14 weeks, 26 weeks, 1 year, and 2 years of therapy. Primary outcome was corticosteroid- and other biologic-free remission (based on pediatric ulcerative …


Effect Of Liquid And Solid Test Meals On Symptoms And Gastric Myoelectrical Activity In Patients With Gastroparesis And Functional Dyspepsia, Kenneth L Koch, Mark Van Natta, Henry P Parkman, Madhusudan Grover, Thomas L Abell, Richard W Mccallum, Hossam A Shaltout, Irene Sarosiek, Gianrico Farrugia, Robert J Shulman, James Tonascia, Laura Miriel, Frank Hamilton, Pankaj J Pasricha, Gastroparesis Clinical Research Consortium Feb 2023

Effect Of Liquid And Solid Test Meals On Symptoms And Gastric Myoelectrical Activity In Patients With Gastroparesis And Functional Dyspepsia, Kenneth L Koch, Mark Van Natta, Henry P Parkman, Madhusudan Grover, Thomas L Abell, Richard W Mccallum, Hossam A Shaltout, Irene Sarosiek, Gianrico Farrugia, Robert J Shulman, James Tonascia, Laura Miriel, Frank Hamilton, Pankaj J Pasricha, Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

BACKGROUND: Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain.

AIMS: To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD.

METHODS: Patients enrolled in the Gastroparesis Clinical Research Consortium Registry were studied. Clinical characteristics were measured with standard questionnaires. GP was determined by 4-h solid-phase gastric scintigraphy. GMA was measured using electrogastrography before and after ingestion of a water load or nutrient bar on separate days. Symptoms were measured on visual analog scales. GMA responses to the water load …


Comparison Of Percentile Tables And Algorithm-Based Calculators For Classification Of Blood Pressures In Children And Adolescents With Obesity: A Secondary Analysis Of A Clinical Trial, William J Pitts, Tami L Cave, Alana Cavadino, Roman J Shypailo, Sarah E Maessen, Paul L Hofman, William Wong, Yvonne C Anderson Feb 2023

Comparison Of Percentile Tables And Algorithm-Based Calculators For Classification Of Blood Pressures In Children And Adolescents With Obesity: A Secondary Analysis Of A Clinical Trial, William J Pitts, Tami L Cave, Alana Cavadino, Roman J Shypailo, Sarah E Maessen, Paul L Hofman, William Wong, Yvonne C Anderson

Faculty, Staff and Students Publications

AIM: Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines.

METHODS: This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index >99th percentile or >91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification …


Sars-Cov-2 Seroprevalence In Children Worldwide: A Systematic Review And Meta-Analysis, Reza Naeimi, Mahdi Sepidarkish, Abolfazl Mollalo, Hamid Parsa, Sanaz Mahjour, Fatemeh Safarpour, Mustafa Almukhtar, Amal Mechaal, Hiam Chemaitelly, Behnam Sartip, Elika Marhoommirzabak, Ali Ardekani, Peter J Hotez, Robin B Gasser, Ali Rostami Feb 2023

Sars-Cov-2 Seroprevalence In Children Worldwide: A Systematic Review And Meta-Analysis, Reza Naeimi, Mahdi Sepidarkish, Abolfazl Mollalo, Hamid Parsa, Sanaz Mahjour, Fatemeh Safarpour, Mustafa Almukhtar, Amal Mechaal, Hiam Chemaitelly, Behnam Sartip, Elika Marhoommirzabak, Ali Ardekani, Peter J Hotez, Robin B Gasser, Ali Rostami

Faculty, Staff and Students Publications

BACKGROUND: The higher hospitalisation rates of those aged 0-19 years (referred to herein as 'children') observed since the emergence of the immune-evasive SARS-CoV-2 Omicron variant and subvariants, along with the persisting vaccination disparities highlighted a need for in-depth knowledge of SARS-CoV-2 sero-epidemiology in children. Here, we conducted this systematic review to assess SARS-CoV-2 seroprevalence and determinants in children worldwide.

METHODS: In this systematic review and meta-analysis study, we searched international and preprinted scientific databases from December 1, 2019 to July 10, 2022. Pooled seroprevalences were estimated according to World Health Organization (WHO) regions (at 95% confidence intervals, CIs) using random-effects …


Telemedicine Use Among Physiatrists During The Early Phase Of The Covid-19 Pandemic And Potential For Future Use, Sameer Siddiqui, Ellen Farr, Nathaniel Dusto, Liqi Chen, Masha Kocherginsky, Felicia Skelton, Monica Verduzco-Gutierrez, Sujin Lee Feb 2023

Telemedicine Use Among Physiatrists During The Early Phase Of The Covid-19 Pandemic And Potential For Future Use, Sameer Siddiqui, Ellen Farr, Nathaniel Dusto, Liqi Chen, Masha Kocherginsky, Felicia Skelton, Monica Verduzco-Gutierrez, Sujin Lee

Faculty, Staff and Students Publications

No abstract provided.


The Behavioral Assessment Screening Tool For Mobile Health (Bastmhealth): Development And Compliance In Two Weeks Of Daily Reporting In Chronic Traumatic Brain Injury, Shannon B Juengst, Brittany Wright, Angelle M Sander, Samuel Preminger, Andrew Nabasny, Lauren Terhorst Feb 2023

The Behavioral Assessment Screening Tool For Mobile Health (Bastmhealth): Development And Compliance In Two Weeks Of Daily Reporting In Chronic Traumatic Brain Injury, Shannon B Juengst, Brittany Wright, Angelle M Sander, Samuel Preminger, Andrew Nabasny, Lauren Terhorst

Faculty, Staff and Students Publications

Objectives:

To develop and evaluate the feasibility of a short form of the Behavioral Assessment Screening Tool (BASTmHealth) for high frequency in situ self-reported assessment of neurobehavioral symptoms using mobile health technology for community-dwelling adults with traumatic brain injury (TBI).

Design:

Prospective, repeated measures study of mHealth assessment of self-reported neurobehavioral symptoms in adults with and without a lifetime history of TBI over a two-week period.

Setting:

Community

Participants:

Community-dwelling adults with (n=52) and without (n=12) a lifetime TBI history consented to the study.

Interventions:

Not applicable

Main Outcome Measures:

BASTmHealth subscales (2-items each): Negative Affect, Fatigue, …


Risk Stratification By Percent Liver Herniation In Congenital Diaphragmatic Hernia, Oluyinka O Olutoye, Steven C Mehl, Anoosha Moturu, Rowland W Pettit, Ryan D Coleman, Adam M Vogel, Timothy C Lee, Sundeep G Keswani, Alice King Feb 2023

Risk Stratification By Percent Liver Herniation In Congenital Diaphragmatic Hernia, Oluyinka O Olutoye, Steven C Mehl, Anoosha Moturu, Rowland W Pettit, Ryan D Coleman, Adam M Vogel, Timothy C Lee, Sundeep G Keswani, Alice King

Faculty, Staff and Students Publications

INTRODUCTION: Congenital diaphragmatic hernia is associated with pulmonary hypoplasia, pulmonary hypertension, and significant neonatal morbidity. Although intrathoracic liver herniation (LH) >20% is associated with adverse outcomes, the relationship between LH

METHODS: A single-center retrospective cohort study was performed from 2011 to 2020 of 80 fetuses with left-sided congenital diaphragmatic hernia that were delivered and repaired at our institution. Perinatal, perioperative, and postoperative data were collected. We evaluated the association of %LH with outcomes as a stratified ordinal variable (0%-10% LH, 10%-19% LH, and >20% LH) and as a continuous variable. Data were analyzed by analysis of variance with Bonferroni post …


The Potential Of Brain Stimulation Techniques For Substance Use Disorder Treatment, Antonio F Corno, Taylor S Koerner, Jorge D Salazar Jan 2023

The Potential Of Brain Stimulation Techniques For Substance Use Disorder Treatment, Antonio F Corno, Taylor S Koerner, Jorge D Salazar

Faculty, Staff and Student Publications

No abstract provided.


Mutations In The Transcriptional Regulator Mecp2 Severely Impact Key Cellular And Molecular Signatures Of Human Astrocytes During Maturation, Jialin Sun, Sivan Osenberg, Austin Irwin, Li-Hua Ma, Nigel Lee, Yangfei Xiang, Feng Li, Ying-Wooi Wan, In-Hyun Park, Mirjana Maletic-Savatic, Nurit Ballas Jan 2023

Mutations In The Transcriptional Regulator Mecp2 Severely Impact Key Cellular And Molecular Signatures Of Human Astrocytes During Maturation, Jialin Sun, Sivan Osenberg, Austin Irwin, Li-Hua Ma, Nigel Lee, Yangfei Xiang, Feng Li, Ying-Wooi Wan, In-Hyun Park, Mirjana Maletic-Savatic, Nurit Ballas

Faculty, Staff and Students Publications

Mutations in the MECP2 gene underlie a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT). We ask whether MECP2 mutations interfere with human astrocyte developmental maturation, thereby affecting their ability to support neurons. Using human-based models, we show that RTT-causing MECP2 mutations greatly impact the key role of astrocytes in regulating overall brain bioenergetics and that these metabolic aberrations are likely mediated by dysfunctional mitochondria. During post-natal maturation, astrocytes rely on neurons to induce their complex stellate morphology and transcriptional changes. While MECP2 mutations cause cell-intrinsic aberrations in the astrocyte transcriptional landscape, surprisingly, they do not affect the neuron-induced …


Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar Jan 2023

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …


A Data-Driven Approach To Construct A Molecular Map Of Trypanosoma Cruzi To Identify Drugs And Vaccine Targets, Swarsat Kaushik Nath, Preeti Pankajakshan, Trapti Sharma, Priya Kumari, Sweety Shinde, Nikita Garg, Kartavya Mathur, Nevidita Arambam, Divyank Harjani, Manpriya Raj, Garwit Kwatra, Sayantan Venkatesh, Alakto Choudhoury, Saima Bano, Prashansa Tayal, Mahek Sharan, Ruchika Arora, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Kamal Rawal Jan 2023

A Data-Driven Approach To Construct A Molecular Map Of Trypanosoma Cruzi To Identify Drugs And Vaccine Targets, Swarsat Kaushik Nath, Preeti Pankajakshan, Trapti Sharma, Priya Kumari, Sweety Shinde, Nikita Garg, Kartavya Mathur, Nevidita Arambam, Divyank Harjani, Manpriya Raj, Garwit Kwatra, Sayantan Venkatesh, Alakto Choudhoury, Saima Bano, Prashansa Tayal, Mahek Sharan, Ruchika Arora, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Kamal Rawal

Faculty, Staff and Students Publications

Chagas disease (CD) is endemic in large parts of Central and South America, as well as in Texas and the southern regions of the United States. Successful parasites, such as the causative agent of CD, Trypanosoma cruzi have adapted to specific hosts during their phylogenesis. In this work, we have assembled an interactive network of the complex relations that occur between molecules within T. cruzi. An expert curation strategy was combined with a text-mining approach to screen 10,234 full-length research articles and over 200,000 abstracts relevant to T. cruzi. We obtained a scale-free network consisting of 1055 nodes …


Protocol For Validation Of The Global Scales For Early Development (Gsed) For Children Under 3 Years Of Age In Seven Countries, Vanessa Cavallera, Gillian Lancaster, Melissa Gladstone, Maureen M. Black, Gareth Mccray, Ambreen Nizar, Salahuddin Ahmed, Muhammad Imran Nisar, Farzana Begum, Fyezah Jehan Jan 2023

Protocol For Validation Of The Global Scales For Early Development (Gsed) For Children Under 3 Years Of Age In Seven Countries, Vanessa Cavallera, Gillian Lancaster, Melissa Gladstone, Maureen M. Black, Gareth Mccray, Ambreen Nizar, Salahuddin Ahmed, Muhammad Imran Nisar, Farzana Begum, Fyezah Jehan

Department of Paediatrics and Child Health

Introduction: Children's early development is affected by caregiving experiences, with lifelong health and well-being implications. Governments and civil societies need population-based measures to monitor children's early development and ensure that children receive the care needed to thrive. To this end, the WHO developed the Global Scales for Early Development (GSED) to measure children's early development up to 3 years of age. The GSED includes three measures for population and programmatic level measurement: (1) short form (SF) (caregiver report), (2) long form (LF) (direct administration) and (3) psychosocial form (PF) (caregiver report). The primary aim of this protocol is to validate …


Going Back In Time: Increasing Penicillin Susceptibility Among Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Jesus G Vallejo, Mary Boyle, Kristina G Hulten, Sheldon L Kaplan, Stephanie A Fritz Jan 2023

Going Back In Time: Increasing Penicillin Susceptibility Among Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Jesus G Vallejo, Mary Boyle, Kristina G Hulten, Sheldon L Kaplan, Stephanie A Fritz

Faculty, Staff and Students Publications

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children’s and St. Louis Children’s Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ …


Digital Health Interventions To Improve Adolescent Hpv Vaccination: A Systematic Review, Jihye Choi, Irene Tamí-Maury, Paula Cuccaro, Sooyoun Kim, Christine Markham Jan 2023

Digital Health Interventions To Improve Adolescent Hpv Vaccination: A Systematic Review, Jihye Choi, Irene Tamí-Maury, Paula Cuccaro, Sooyoun Kim, Christine Markham

Faculty, Staff and Student Publications

Digital technologies are being increasingly utilized in healthcare to provide pertinent and timely information for primary prevention, such as vaccination. This study aimed to conduct a systematic review to describe and assess current digital health interventions to promote HPV vaccination among adolescents and parents of adolescents, and to recommend directions for future interventions of this kind. Using appropriate medical subject headings and keywords, we searched multiple databases to identify relevant studies published in English between 1 January 2017 and 31 July 2022. We screened and selected eligible studies for inclusion in the final analysis. We reviewed a total of 24 …


Brain Nuclear Receptors And Cardiovascular Function, Mengjie Wang, Yongjie Yang, Yong Xu Jan 2023

Brain Nuclear Receptors And Cardiovascular Function, Mengjie Wang, Yongjie Yang, Yong Xu

Faculty, Staff and Students Publications

Brain-heart interaction has raised up increasing attentions. Nuclear receptors (NRs) are abundantly expressed in the brain, and emerging evidence indicates that a number of these brain NRs regulate multiple aspects of cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis, etc. In this review, we will elaborate recent findings that have established the physiological relevance of brain NRs in the context of cardiovascular function. In addition, we will discuss the currently available evidence regarding the distinct neuronal populations that respond to brain NRs in the cardiovascular control. These findings suggest connections between cardiac control and brain dynamics through NR signaling, which …


A Training Curriculum For An Mhealth Supported Peer Counseling Program To Promote Exclusive Breastfeeding In Rural India, Roopa M. Bellad, Niranjana S. Mahantshetti, Umesh S. Charantimath, Tony Ma, Yukiko Washio, Vanessa L. Short, Katie Chang, Parth Lalakia, Frances J. Jaeger, Patricia J. Kelly, Geetanjali Mungarwadi, Chandrashekar C. Karadiguddi, Shivaprasad S. Goudar, Richard J. Derman Jan 2023

A Training Curriculum For An Mhealth Supported Peer Counseling Program To Promote Exclusive Breastfeeding In Rural India, Roopa M. Bellad, Niranjana S. Mahantshetti, Umesh S. Charantimath, Tony Ma, Yukiko Washio, Vanessa L. Short, Katie Chang, Parth Lalakia, Frances J. Jaeger, Patricia J. Kelly, Geetanjali Mungarwadi, Chandrashekar C. Karadiguddi, Shivaprasad S. Goudar, Richard J. Derman

Department of Pediatrics Faculty Papers

BACKGROUND: Despite strong evidence about the benefits of exclusive breastfeeding, that is the baby receiving only breast milk, no other foods or liquids, rates have remained relatively unchanged over the past two decades in low- and middle-income countries. One strategy for increasing exclusive breastfeeding is through community-based programs that use peer counselors for education and support. The use of mobile health applications is also gaining increasing applicability in these countries. Minimal information is available about training peer counselors in the use of mobile technologies to support exclusive breastfeeding. The present article describes our curriculum in the state of Karnataka, India …


Parental Contextual Factors And Decision-Making Related To Periviable Birth: An Integrative Review, Amy L. Wright, Elizabeth Mens, Gausiha Rathitharan Jan 2023

Parental Contextual Factors And Decision-Making Related To Periviable Birth: An Integrative Review, Amy L. Wright, Elizabeth Mens, Gausiha Rathitharan

The Qualitative Report

Parents facing a periviable birth, or birth before 25 weeks of gestation, commonly engage in antenatal consultation with healthcare providers to determine a plan of care. Parents’ pre-existing contextual factors, beliefs, and values influence their decisions regarding birth and the care of their infant. This study aims to understand the role of parental contextual factors and best-practices to their integration during antenatal consultation The Whittemore and Knafl (2005) approach to conducting an integrative review along with thematic analysis was employed to determine and present the findings. Results describe three themes related to how contextual factors influence parental decision-making: personal values …


The Safety Of Appropriate Use Of Over-The-Counter Proton Pump Inhibitors: An Evidence-Based Review And Delphi Consensus, Wilfredo De Jesús-Rojas, Jesús Meléndez-Montañez, José Muñiz-Hernández, André Marra-Nazario, Francisco Alvarado-Huerta, Arnaldo Santos-López, Marcos J Ramos-Benitez, Ricardo A Mosquera Jan 2023

The Safety Of Appropriate Use Of Over-The-Counter Proton Pump Inhibitors: An Evidence-Based Review And Delphi Consensus, Wilfredo De Jesús-Rojas, Jesús Meléndez-Montañez, José Muñiz-Hernández, André Marra-Nazario, Francisco Alvarado-Huerta, Arnaldo Santos-López, Marcos J Ramos-Benitez, Ricardo A Mosquera

Faculty, Staff and Student Publications

The radial spoke head protein 4 homolog A (RSPH4A) gene is one of more than 50 genes that cause Primary ciliary dyskinesia (PCD), a rare genetic ciliopathy. Genetic mutations in the RSPH4A gene alter an important protein structure involved in ciliary pathogenesis. Radial spoke proteins, such as RSPH4A, have been conserved across multiple species. In humans, ciliary function deficiency caused by RSPH4A pathogenic variants results in a clinical phenotype characterized by recurrent oto-sino-pulmonary infections. More than 30 pathogenic RSPH4A genetic variants have been associated with PCD. In Puerto Rican Hispanics, a founder mutation (RSPH4A (c.921+3_921+6delAAGT (intronic)) has …


Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu Jan 2023

Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were …


Comparison Of Parental In-Person Visitation And Webcam Usage Patterns At A Single-Center Neonatal Intensive Care Unit, Shrea Goswami, Emily Mudd, John Chuo, Anirudha Das Jan 2023

Comparison Of Parental In-Person Visitation And Webcam Usage Patterns At A Single-Center Neonatal Intensive Care Unit, Shrea Goswami, Emily Mudd, John Chuo, Anirudha Das

Journal of Patient-Centered Research and Reviews

Purpose: Barriers to parents visiting the neonatal intensive care unit (NICU) in person for infant bonding include socioeconomic status, distance from NICU, and having children at home. Use of NICU bedside webcam can increase access to parent-infant interaction. This study aimed to describe the pattern of webcam logins by parents, relationship of logins to in-person visitation, and maternal factors affecting usage.

Methods: In this retrospective cohort study, data pertaining to parental webcam logins and in-person visitation, maternal screening for depression, anxiety, and stress, and family sociodemographics were collected from medical records. Relationships between chart variables and webcam or …


Shifting Perspectives: A Qualitative Study To Understand Family Expectations At The Time Of Their Child’S Admission, Rosamarie Maiorella, Avital Fischer, Sumeet L. Banker Jan 2023

Shifting Perspectives: A Qualitative Study To Understand Family Expectations At The Time Of Their Child’S Admission, Rosamarie Maiorella, Avital Fischer, Sumeet L. Banker

Journal of Patient-Centered Research and Reviews

Purpose: Patient-centered approaches to health care acknowledge the important role that families have in patients’ lives. Shared expectations between families and providers have the potential to improve patient and family experience, hospital care, and outcomes. We aimed to understand families’ expectations for their child’s admission from the vantage point of the start of a hospital stay.

Methods: This qualitative research studied families of hospitalized children at a large pediatric tertiary care center. Family members were approached if their child was admitted to the general pediatrics team, was under 18 years of age, had a length of stay less than 5 …


Modernization, Collectivism, And Gender Equality Predict Love Experiences In 45 Countries, Piotr Sorokowski, Marta Kowal, Robert J Sternberg, Toivo Aavik, Grace Akello, Mohammad Madallh Alhabahba, Charlotte Alm, Naumana Amjad, Afifa Anjum, Kelly Asao, Chiemezie S Atama, Derya Atamtürk Duyar, Richard Ayebare, Daniel Conroy-Beam, Mons Bendixen, Aicha Bensafia, Boris Bizumic, Mahmoud Boussena, David M Buss, Marina Butovskaya, Seda Can, Antonin Carrier, Hakan Cetinkaya, Ilona Croy, Rosa María Cueto, Marcin Czub, Daria Dronova, Seda Dural, Izzet Duyar, Berna Ertugrul, Agustín Espinosa, Ignacio Estevan, Carla Sofia Esteves, Tomasz Frackowiak, Jorge Contreras Garduño, Karina Ugalde González, Farida Guemaz, Mária Halamová, Iskra Herak, Marina Horvat, Ivana Hromatko, Chin-Ming Hui, Jas Laile Jaafar, Feng Jiang, Konstantinos Kafetsios, Tina Kavčič, Leif Edward Ottesen Kennair, Nicolas Kervyn, Truong Thi Khanh Ha, Imran Ahmed Khilji, Nils C Köbis, Aleksandra Kostic, Hoang Moc Lan, András Láng, Georgina R Lennard, Ernesto León, Torun Lindholm, Trinh Thi Linh, Giulia Lopez, Nguyen Van Luot, Alvaro Mailhos, Zoi Manesi, Rocio Martinez, Sarah L Mckerchar, Norbert Meskó, Marija Pejičić, Girishwar Misra, Conal Monaghan, Emanuel C Mora, Alba Moya-Garófano, Bojan Musil, Jean Carlos Natividade, George Nizharadze, Elisabeth Oberzaucher, Anna Oleszkiewicz, Mohd Sofian Omar-Fauzee, Ike E Onyishi, Baris Özener, Ariela Francesca Pagani, Vilmante Pakalniskiene, Miriam Parise, Farid Pazhoohi, Annette Pisanski, Katarzyna Pisanski, Edna Ponciano, Camelia Popa, Pavol Prokop, Muhammad Rizwan, Mario Sainz, Svjetlana Salkičević, Ruta Sargautyte, Ivan Sarmány-Schuller, Susanne Schmehl, Anam Shahid, Shivantika Sharad, Razi Sultan Siddiqui, Franco Simonetti, Meri Tadinac, Christin-Melanie Vauclair, Luis Diego Vega, Kathryn V Walter, Dwi Ajeng Widarini, Gyesook Yoo, Marta Zaťková, Maja Zupančič, Agnieszka Sorokowska Jan 2023

Modernization, Collectivism, And Gender Equality Predict Love Experiences In 45 Countries, Piotr Sorokowski, Marta Kowal, Robert J Sternberg, Toivo Aavik, Grace Akello, Mohammad Madallh Alhabahba, Charlotte Alm, Naumana Amjad, Afifa Anjum, Kelly Asao, Chiemezie S Atama, Derya Atamtürk Duyar, Richard Ayebare, Daniel Conroy-Beam, Mons Bendixen, Aicha Bensafia, Boris Bizumic, Mahmoud Boussena, David M Buss, Marina Butovskaya, Seda Can, Antonin Carrier, Hakan Cetinkaya, Ilona Croy, Rosa María Cueto, Marcin Czub, Daria Dronova, Seda Dural, Izzet Duyar, Berna Ertugrul, Agustín Espinosa, Ignacio Estevan, Carla Sofia Esteves, Tomasz Frackowiak, Jorge Contreras Garduño, Karina Ugalde González, Farida Guemaz, Mária Halamová, Iskra Herak, Marina Horvat, Ivana Hromatko, Chin-Ming Hui, Jas Laile Jaafar, Feng Jiang, Konstantinos Kafetsios, Tina Kavčič, Leif Edward Ottesen Kennair, Nicolas Kervyn, Truong Thi Khanh Ha, Imran Ahmed Khilji, Nils C Köbis, Aleksandra Kostic, Hoang Moc Lan, András Láng, Georgina R Lennard, Ernesto León, Torun Lindholm, Trinh Thi Linh, Giulia Lopez, Nguyen Van Luot, Alvaro Mailhos, Zoi Manesi, Rocio Martinez, Sarah L Mckerchar, Norbert Meskó, Marija Pejičić, Girishwar Misra, Conal Monaghan, Emanuel C Mora, Alba Moya-Garófano, Bojan Musil, Jean Carlos Natividade, George Nizharadze, Elisabeth Oberzaucher, Anna Oleszkiewicz, Mohd Sofian Omar-Fauzee, Ike E Onyishi, Baris Özener, Ariela Francesca Pagani, Vilmante Pakalniskiene, Miriam Parise, Farid Pazhoohi, Annette Pisanski, Katarzyna Pisanski, Edna Ponciano, Camelia Popa, Pavol Prokop, Muhammad Rizwan, Mario Sainz, Svjetlana Salkičević, Ruta Sargautyte, Ivan Sarmány-Schuller, Susanne Schmehl, Anam Shahid, Shivantika Sharad, Razi Sultan Siddiqui, Franco Simonetti, Meri Tadinac, Christin-Melanie Vauclair, Luis Diego Vega, Kathryn V Walter, Dwi Ajeng Widarini, Gyesook Yoo, Marta Zaťková, Maja Zupančič, Agnieszka Sorokowska

Faculty, Staff and Student Publications

Recent cross-cultural and neuro-hormonal investigations have suggested that love is a near universal phenomenon that has a biological background. Therefore, the remaining important question is not whether love exists worldwide but which cultural, social, or environmental factors influence experiences and expressions of love. In the present study, we explored whether countries' modernization indexes are related to love experiences measured by three subscales (passion, intimacy, commitment) of the Triangular Love Scale. Analyzing data from 9474 individuals from 45 countries, we tested for relationships with country-level predictors, namely, modernization proxies (i.e., Human Development Index, World Modernization Index, Gender Inequality Index), collectivism, and …


Oxygenation Index In The First Three Weeks Of Life Is A Predictor Of Bronchopulmonary Dysplasia Grade In Very Preterm Infants., Fu-Sheng Chou, Rebekah M. Leigh, Srinandini S. Rao, Arvind Narang, Hung-Wen Yeh Jan 2023

Oxygenation Index In The First Three Weeks Of Life Is A Predictor Of Bronchopulmonary Dysplasia Grade In Very Preterm Infants., Fu-Sheng Chou, Rebekah M. Leigh, Srinandini S. Rao, Arvind Narang, Hung-Wen Yeh

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The new bronchopulmonary dysplasia (BPD) grading system was developed based on its correlation with long-term respiratory and neurodevelopmental outcomes and may provide better personalized prognostication. Identifying early-life predictors for accurate BPD grade prediction may allow interventions to be tailored to individual needs. This study aimed to assess whether oxygenation index (OI) dynamics in the first three weeks of life are a predictor of BPD grade.

METHODS: A single-center retrospective study was performed. Generalized additive mixed modeling was used to model OI trajectories for each BPD grade subgroup. A multinomial regression model was then developed to quantify the association between …


Yoga And Mindfulness For Social-Emotional Development And Resilience In 3–5 Year-Old Children: Non-Randomized, Controlled Intervention, Alessandra N. Bazzano, Yaoyao Sun, Yuanhao Zu, Julia M. Fleckman, Emma A. Blackson, Tejal Patel, Angie Shorty-Belisle, Keith H. Liederman, Cody Roi Jan 2023

Yoga And Mindfulness For Social-Emotional Development And Resilience In 3–5 Year-Old Children: Non-Randomized, Controlled Intervention, Alessandra N. Bazzano, Yaoyao Sun, Yuanhao Zu, Julia M. Fleckman, Emma A. Blackson, Tejal Patel, Angie Shorty-Belisle, Keith H. Liederman, Cody Roi

School of Medicine Faculty Publications

Background: Early childhood is the key life course period for development of social-emotional skills, providing the foundation for school readiness and resilience in later life. Age-appropriate yoga and mindfulness programs may contribute to the development of critical skills in children. Young children from minoritized communities that face structural racism and health disparities may benefit from programs that support social-emotional development and contribute to future academic success. Systematic reviews of yoga interventions for young children have indicated the potential for effectiveness in supporting social-emotional development, executive function, and physical activity. However, studies of yoga and mindfulness with non-White children are sparse …


Oxphos Defects Cause Hypermetabolism And Reduce Lifespan In Cells And In Patients With Mitochondrial Diseases, Gabriel Sturm, Kalpita R Karan, Anna S Monzel, Balaji Santhanam, Tanja Taivassalo, Céline Bris, Sarah A Ware, Marissa Cross, Atif Towheed, Albert Higgins-Chen, Meagan J Mcmanus, Andres Cardenas, Jue Lin, Elissa S Epel, Shamima Rahman, John Vissing, Bruno Grassi, Morgan Levine, Steve Horvath, Ronald G Haller, Guy Lenaers, Douglas C Wallace, Marie-Pierre St-Onge, Saeed Tavazoie, Vincent Procaccio, Brett A Kaufman, Erin L. Seifert, Michio Hirano, Martin Picard Jan 2023

Oxphos Defects Cause Hypermetabolism And Reduce Lifespan In Cells And In Patients With Mitochondrial Diseases, Gabriel Sturm, Kalpita R Karan, Anna S Monzel, Balaji Santhanam, Tanja Taivassalo, Céline Bris, Sarah A Ware, Marissa Cross, Atif Towheed, Albert Higgins-Chen, Meagan J Mcmanus, Andres Cardenas, Jue Lin, Elissa S Epel, Shamima Rahman, John Vissing, Bruno Grassi, Morgan Levine, Steve Horvath, Ronald G Haller, Guy Lenaers, Douglas C Wallace, Marie-Pierre St-Onge, Saeed Tavazoie, Vincent Procaccio, Brett A Kaufman, Erin L. Seifert, Michio Hirano, Martin Picard

Department of Pediatrics Faculty Papers

Patients with primary mitochondrial oxidative phosphorylation (OxPhos) defects present with fatigue and multi-system disorders, are often lean, and die prematurely, but the mechanistic basis for this clinical picture remains unclear. By integrating data from 17 cohorts of patients with mitochondrial diseases (n = 690) we find evidence that these disorders increase resting energy expenditure, a state termed hypermetabolism. We examine this phenomenon longitudinally in patient-derived fibroblasts from multiple donors. Genetically or pharmacologically disrupting OxPhos approximately doubles cellular energy expenditure. This cell-autonomous state of hypermetabolism occurs despite near-normal OxPhos coupling efficiency, excluding uncoupling as a general mechanism. Instead, hypermetabolism is associated …