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Nutritional Considerations For A New Era: A Cf Foundation Position Paper, Amanda Leonard, Marina Litvin, Et Al. Sep 2023

Nutritional Considerations For A New Era: A Cf Foundation Position Paper, Amanda Leonard, Marina Litvin, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To provide interim advice and considerations to the CF Community around CF nutrition in the current era.

METHODS: The Cystic Fibrosis (CF) Foundation organized a multidisciplinary committee to develop a Nutrition Position Paper based on the rapidly changing nutrition landscape in CF, due in part to widespread use of cystic fibrosis transmembrane regulator highly effective modulator therapy (HEMT). Four workgroups were formed: Weight Management, Eating Behavior/Food Insecurity, Salt Homeostasis and Pancreatic Enzyme use. Each workgroup conducted their own focused review of the literature.

RESULTS: The committee summarized current understanding of issues pertaining to the four workgroup topics and provided …


The Pyruvate Dehydrogenase Complex Regulates Mitophagic Trafficking And Protein Phosphorylation, Panagiota Kolitsida, Vladimir Nolic, Jianwen Zhou, Michael Stumpe, Natalie M Niemi, Jörn Dengjel, Hagai Abeliovich Sep 2023

The Pyruvate Dehydrogenase Complex Regulates Mitophagic Trafficking And Protein Phosphorylation, Panagiota Kolitsida, Vladimir Nolic, Jianwen Zhou, Michael Stumpe, Natalie M Niemi, Jörn Dengjel, Hagai Abeliovich

2020-Current year OA Pubs

The mitophagic degradation of mitochondrial matrix proteins in


The Emerging Importance Of Lymphatics In Health And Disease: An Nih Workshop Report, Babak J. Mehrara, Andrea J. Radtke, Gwendalyn J. Randolph, Brianna T. Wachter, Patricia Greenwel, Ilsa I. Rovira, Zorina S. Galis, Selen C. Muratoglu Sep 2023

The Emerging Importance Of Lymphatics In Health And Disease: An Nih Workshop Report, Babak J. Mehrara, Andrea J. Radtke, Gwendalyn J. Randolph, Brianna T. Wachter, Patricia Greenwel, Ilsa I. Rovira, Zorina S. Galis, Selen C. Muratoglu

2020-Current year OA Pubs

The lymphatic system (LS) is composed of lymphoid organs and a network of vessels that transport interstitial fluid, antigens, lipids, cholesterol, immune cells, and other materials in the body. Abnormal development or malfunction of the LS has been shown to play a key role in the pathophysiology of many disease states. Thus, improved understanding of the anatomical and molecular characteristics of the LS may provide approaches for disease prevention or treatment. Recent advances harnessing single-cell technologies, clinical imaging, discovery of biomarkers, and computational tools have led to the development of strategies to study the LS. This Review summarizes the outcomes …


The Role Of Bmi In Allostatic Load And Risk Of Cancer Death, Sydney E Andrzejak, Marquita W Lewis-Thames, Marvin E Langston, Yunan Han, Saira Khan, Darryl A Nettles, Lindsay N Fuzzell, Martha S Tingen, Justin X Moore Sep 2023

The Role Of Bmi In Allostatic Load And Risk Of Cancer Death, Sydney E Andrzejak, Marquita W Lewis-Thames, Marvin E Langston, Yunan Han, Saira Khan, Darryl A Nettles, Lindsay N Fuzzell, Martha S Tingen, Justin X Moore

2020-Current year OA Pubs

INTRODUCTION: Obesity and proinflammatory conditions are associated with increased risks of cancer. The associations of baseline allostatic load with cancer mortality and whether this association is modified by body mass index (BMI) were examined.

METHODS: A retrospective analysis was performed in March-September 2022 using National Health and Nutrition Examination Survey years 1988 through 2010 linked with the National Death Index through December 31, 2019. Fine and Gray Cox proportional hazard models were stratified by BMI status to estimate subdistribution hazard ratios of cancer death between high and low allostatic load status (adjusted for age, sociodemographics, and health factors).

RESULTS: In …


Defining The Roles Of Pyruvate Oxidation, Tca Cycle, And Mannitol Metabolism In Methicillin-Resistant Staphylococcus Aureus Catheter-Associated Urinary Tract Infection, Santosh Paudel, Sarah Guedry, Chloe L P Obernuefemann, Scott J. Hultgren, Jennifer N. Walker, Ritwij Kulkarni Aug 2023

Defining The Roles Of Pyruvate Oxidation, Tca Cycle, And Mannitol Metabolism In Methicillin-Resistant Staphylococcus Aureus Catheter-Associated Urinary Tract Infection, Santosh Paudel, Sarah Guedry, Chloe L P Obernuefemann, Scott J. Hultgren, Jennifer N. Walker, Ritwij Kulkarni

2020-Current year OA Pubs

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of complicated urinary tract infection (UTI) associated with the use of indwelling urinary catheters. Previous reports have revealed host and pathogen effectors critical for MRSA uropathogenesis. Here, we sought to determine the significance of specific metabolic pathways during MRSA UTI. First, we identified four mutants from the Nebraska transposon mutant library in the MRSA JE2 background that grew normally in rich medium but displayed significantly reduced growth in pooled human urine (HU). This prompted us to transduce the uropathogenic MRSA 1369 strain with the transposon mutants in


The Effects Of Advanced Factor Analysis Approaches On Outcomes In Randomised Trials For Depression: Protocol For Secondary Analysis Of Individual Participant Data, Frank Doyle, David Byrne, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Shane Kelly, Stephen Mcbride, Emma Wallace, Fiona Boland Aug 2023

The Effects Of Advanced Factor Analysis Approaches On Outcomes In Randomised Trials For Depression: Protocol For Secondary Analysis Of Individual Participant Data, Frank Doyle, David Byrne, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Shane Kelly, Stephen Mcbride, Emma Wallace, Fiona Boland

2020-Current year OA Pubs

BACKGROUND: Modern psychometric methods make it possible to eliminate nonperforming items and reduce measurement error. Application of these methods to existing outcome measures can reduce variability in scores, and may increase treatment effect sizes in depression treatment trials.

AIMS: We aim to determine whether using confirmatory factor analysis techniques can provide better estimates of the true effects of treatments, by conducting secondary analyses of individual patient data from randomised trials of antidepressant therapies.

METHOD: We will access individual patient data from antidepressant treatment trials through Clinicalstudydatarequest.com and Vivli.org, specifically targeting studies that used the Hamilton Rating Scale for Depression (HRSD) …


Harm Reduction: A Missing Piece To The Holistic Care Of Patients Who Inject Drugs, Nathanial S Nolan, Sarah M Fracasso Francis, Laura R Marks, Susan E Beekmann, Philip M Polgreen, Stephen Y Liang, Michael J Durkin Aug 2023

Harm Reduction: A Missing Piece To The Holistic Care Of Patients Who Inject Drugs, Nathanial S Nolan, Sarah M Fracasso Francis, Laura R Marks, Susan E Beekmann, Philip M Polgreen, Stephen Y Liang, Michael J Durkin

2020-Current year OA Pubs

BACKGROUND: The rise in injection drug use (IDU) has led to an increase in drug-related infections. Harm reduction is an important strategy for preventing infections among people who inject drugs (PWID). We attempted to evaluate the harm reduction counseling that infectious diseases physicians provide to PWID presenting with infections.

METHODS: An electronic survey was distributed to physician members of the Emerging Infections Network to inquire about practices used when caring for patients with IDU-related infections.

RESULTS: In total, 534 ID physicians responded to the survey. Of those, 375 (70%) reported routinely caring for PWID. Most respondents report screening for human …


Engaging Adolescents In Using Online Patient Portals, Bryan A Sisk, Alison L Antes, Christine Bereitschaft, Madi Enloe, Sunny Lin, Meghana Srinivas, Fabienne Bourgeois, James M Dubois Aug 2023

Engaging Adolescents In Using Online Patient Portals, Bryan A Sisk, Alison L Antes, Christine Bereitschaft, Madi Enloe, Sunny Lin, Meghana Srinivas, Fabienne Bourgeois, James M Dubois

2020-Current year OA Pubs

IMPORTANCE: Many health care systems offer adolescents access to health information through online patient portals, but few studies have explored how to engage adolescents in using and benefiting from online portals.

OBJECTIVE: To determine how US children's hospitals have attempted to encourage adolescent portal use, barriers to engaging adolescents, and ideal future goals for engagement.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study performed structured qualitative interviews with informatics administrators from children's hospitals across the US between February and July 2022. Informatics administrators were employed by US health care systems that managed a children's hospital with at least 50 dedicated pediatrics …


Effect Of Fecal Microbiota, Live-Jslm (Rebyota [Rbl]) On Health-Related Quality Of Life In Patients With Recurrent Clostridioides Difficile Infection: Results From The Punch Cd3 Clinical Trial, Kevin W Garey, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana García-Horton, Mirko Fillbrunn, Hongjue Wang, Glenn S Tillotson, Lindy L Bancke, Paul Feuerstadt Aug 2023

Effect Of Fecal Microbiota, Live-Jslm (Rebyota [Rbl]) On Health-Related Quality Of Life In Patients With Recurrent Clostridioides Difficile Infection: Results From The Punch Cd3 Clinical Trial, Kevin W Garey, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana García-Horton, Mirko Fillbrunn, Hongjue Wang, Glenn S Tillotson, Lindy L Bancke, Paul Feuerstadt

2020-Current year OA Pubs

BACKGROUND: Recurrence of

METHODS: This was a secondary analysis of a randomized, double-blind, placebo-controlled phase 3 study (PUNCH CD3). The disease-specific

RESULTS: Findings were analyzed in a total of 185 patients (RBL, n = 128 [69.2%]; placebo, n = 57 [30.8%]) with available Cdiff32 data. Patients from both arms showed significant improvements in Cdiff32 scores relative to baseline across all outcomes and at all time points (all

CONCLUSIONS: In a phase 3 double-blinded clinical trial, RBL-treated patients reported more substantial and sustained disease-specific HRQL improvements than placebo-treated patients.

CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).


Symbiotic Bacteria, Immune-Like Sentinel Cells, And The Response To Pathogens In A Social Amoeba, Trey J. Scott, Tyler J. Larsen, Debra A. Brock, So Yeon Stacey Uhm, David C. Queller, Joan E. Strassmann Aug 2023

Symbiotic Bacteria, Immune-Like Sentinel Cells, And The Response To Pathogens In A Social Amoeba, Trey J. Scott, Tyler J. Larsen, Debra A. Brock, So Yeon Stacey Uhm, David C. Queller, Joan E. Strassmann

2020-Current year OA Pubs

Some endosymbionts living within a host must modulate their hosts' immune systems in order to infect and persist. We studied the effect of a bacterial endosymbiont on a facultatively multicellular social amoeba host. Aggregates of the amoeba


Courage-Als: A Randomized, Double-Blind Phase 3 Study Designed To Improve Participant Experience And Increase The Probability Of Success, Jeremy M Shefner, Timothy M Miller, Et Al. Aug 2023

Courage-Als: A Randomized, Double-Blind Phase 3 Study Designed To Improve Participant Experience And Increase The Probability Of Success, Jeremy M Shefner, Timothy M Miller, Et Al.

2020-Current year OA Pubs

No abstract provided.


Alcohol Consumption Among Adults With A Cancer Diagnosis In The All Of Us Research Program, Mengyao Shi, Chongliang Luo, Oluseye K Oduyale, Xiaoyu Zong, Noelle K Loconte, Yin Cao Aug 2023

Alcohol Consumption Among Adults With A Cancer Diagnosis In The All Of Us Research Program, Mengyao Shi, Chongliang Luo, Oluseye K Oduyale, Xiaoyu Zong, Noelle K Loconte, Yin Cao

2020-Current year OA Pubs

IMPORTANCE: Alcohol consumption is associated with adverse oncologic and treatment outcomes among individuals with a diagnosis of cancer. As a key modifiable behavioral factor, alcohol consumption patterns among cancer survivors, especially during treatment, remain underexplored in the United States.

OBJECTIVE: To comprehensively characterize alcohol consumption patterns among US cancer survivors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from May 6, 2018, to January 1, 2022, from the National Institutes of Health All of Us Research Program, a diverse US cohort with electronic health record (EHR) linkage, and included 15 199 participants who reported a cancer diagnosis and 1839 …


Landscape Of Team-Based Care To Manage Hypertension: Results From Two Surveys In Low/Middle-Income Countries, Oluwabunmi Ogungbe, Mark D Huffman, Et Al. Jul 2023

Landscape Of Team-Based Care To Manage Hypertension: Results From Two Surveys In Low/Middle-Income Countries, Oluwabunmi Ogungbe, Mark D Huffman, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Team-based care is essential for improving hypertension outcomes in low-resource settings. We assessed perceptions of country representatives and healthcare workers (HCWs) on team-based hypertension care in low/middle-income countries.

DESIGN: Two cross-sectional surveys.

SETTING: The first survey (Country Profile Survey) was conducted in 17 countries and eight in-country regions: Algeria, Bangladesh, Burundi, Chile, China (Beijing, Henan, Shandong), Cuba, Ethiopia, India (Kerala, Madhya Pradesh, Maharashtra, Punjab, Telangana), Nepal, Nigeria, Philippines, Saint Lucia, Sri Lanka, Thailand, Turkey, Uganda and Vietnam. The second survey (HCW Survey) was conducted in four countries: Bangladesh, China, Ethiopia and Nigeria.

PARTICIPANTS: Using convenience sampling, participants for the …


Engineered Reporter Phages For Detection Of Escherichia Coli, Enterococcus, And Klebsiella In Urine, Susanne Meile, Jonas Marschall, Et Al. Jul 2023

Engineered Reporter Phages For Detection Of Escherichia Coli, Enterococcus, And Klebsiella In Urine, Susanne Meile, Jonas Marschall, Et Al.

2020-Current year OA Pubs

The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, …


Deletion Of Taf1 And Taf5 In Zebrafish Capitulate Cardiac And Craniofacial Abnormalities Associated With Tafopathies Through Perturbations In Metabolism, Jamison Leid, Ryan Gray, Peter Rakita, Andrew L Koenig, Rohan Tripathy, James A J Fitzpatrick, Charles Kaufman, Lilianna Solnica-Krezel, Kory J Lavine Jul 2023

Deletion Of Taf1 And Taf5 In Zebrafish Capitulate Cardiac And Craniofacial Abnormalities Associated With Tafopathies Through Perturbations In Metabolism, Jamison Leid, Ryan Gray, Peter Rakita, Andrew L Koenig, Rohan Tripathy, James A J Fitzpatrick, Charles Kaufman, Lilianna Solnica-Krezel, Kory J Lavine

2020-Current year OA Pubs

Intellectual disability is a neurodevelopmental disorder that affects 2-3% of the general population. Syndromic forms of intellectual disability frequently have a genetic basis and are often accompanied by additional developmental anomalies. Pathogenic variants in components of TATA-binding protein associated factors (TAFs) have recently been identified in a subset of patients with intellectual disability, craniofacial hypoplasia, and congenital heart disease. This syndrome has been termed as a TAFopathy and includes mutations in TATA binding protein (TBP), TAF1, TAF2, and TAF6. The underlying mechanism by which TAFopathies give rise to neurodevelopmental, craniofacial, and cardiac abnormalities remains to be defined. Through a forward …


Baseline Features And Reasons For Nonparticipation In The Colonoscopy Versus Fecal Immunochemical Test In Reducing Mortality From Colorectal Cancer (Confirm) Study, A Colorectal Cancer Screening Trial, Douglas J Robertson, Jill Elwing, Et Al. Jul 2023

Baseline Features And Reasons For Nonparticipation In The Colonoscopy Versus Fecal Immunochemical Test In Reducing Mortality From Colorectal Cancer (Confirm) Study, A Colorectal Cancer Screening Trial, Douglas J Robertson, Jill Elwing, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy.

OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs …


Glp-1r Agonists Demonstrate Potential To Treat Wolfram Syndrome In Human Preclinical Models, Vyron Gorgogietas, Cris Brown, Fumihiko Urano, Et Al. Jul 2023

Glp-1r Agonists Demonstrate Potential To Treat Wolfram Syndrome In Human Preclinical Models, Vyron Gorgogietas, Cris Brown, Fumihiko Urano, Et Al.

2020-Current year OA Pubs

AIMS/HYPOTHESIS: Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene. It is characterised by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss and neurodegeneration. Considering the unmet treatment need for this orphan disease, this study aimed to evaluate the therapeutic potential of glucagon-like peptide 1 receptor (GLP-1R) agonists under wolframin (WFS1) deficiency with a particular focus on human beta cells and neurons.

METHODS: The effect of the GLP-1R agonists dulaglutide and exenatide was examined in Wfs1 knockout mice and in an array of human preclinical models of Wolfram syndrome, including WFS1-deficient …


Dietary Patterns Are Not Associated With Disease Activity Among Patients With Inflammatory Conditions Of The Pouch In A Prospective Cohort, Edward L Barnes, Poonam Beniwal-Patel, Parakkal Deepak, Laura Raffals, Maia Kayal, Marla Dubinsky, Shannon Chang, Peter D R Higgins, Jennifer I Barr, Chelsea Anderson, Raymond K Cross, Millie D Long, Hans H Herfarth Jul 2023

Dietary Patterns Are Not Associated With Disease Activity Among Patients With Inflammatory Conditions Of The Pouch In A Prospective Cohort, Edward L Barnes, Poonam Beniwal-Patel, Parakkal Deepak, Laura Raffals, Maia Kayal, Marla Dubinsky, Shannon Chang, Peter D R Higgins, Jennifer I Barr, Chelsea Anderson, Raymond K Cross, Millie D Long, Hans H Herfarth

2020-Current year OA Pubs

BACKGROUND: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited.

METHODS: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients …


Exploring The Natural History Of Intrinsic Capacity Impairments: Longitudinal Patterns In The 10/66 Study, Emmanuel Gonzalez-Bautista, Jorge Jesus Llibre-Guerra, Ana L Sosa, Isaac Acosta, Sandrine Andrieu, Daisy Acosta, Juan De Jesús Llibre-Rodríguez, Matthew Prina Jul 2023

Exploring The Natural History Of Intrinsic Capacity Impairments: Longitudinal Patterns In The 10/66 Study, Emmanuel Gonzalez-Bautista, Jorge Jesus Llibre-Guerra, Ana L Sosa, Isaac Acosta, Sandrine Andrieu, Daisy Acosta, Juan De Jesús Llibre-Rodríguez, Matthew Prina

2020-Current year OA Pubs

BACKGROUND: intrinsic capacity (IC) is a construct encompassing people's physical and mental abilities. There is an implicit link amongst IC domains: cognition, locomotion, nutrition, sensory and psychological. However, little is known about the integration of the domains.

OBJECTIVES: to investigate patterns in the presentation and evolution of IC domain impairments in low-and-middle-income countries and if such patterns were associated with adverse outcomes.

METHODS: secondary analyses of the first two waves of the 10/66 study (population-based surveys conducted in eight urban and four rural catchment areas in Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico and China). We applied latent transition …


Provider Perspectives On Patient-Centredness: Participatory Formative Research And Rapid Analysis Methods To Inform The Design And Implementation Of A Facility-Based Hiv Care Improvement Intervention In Zambia, Chanda Mwamba, Laura K Beres, Njekwa Mukamba, Lazarus Jere, Marksman Foloko, Kasapo Lumbo, Kombatende Sikombe, Sandra Simbeza, Aaloke Mody, Jake M Pry, Charles B Holmes, Izukanji Sikazwe, Carolyn Bolton Moore, Katerina Christopoulos, Anjali Sharma, Elvin H Geng Jul 2023

Provider Perspectives On Patient-Centredness: Participatory Formative Research And Rapid Analysis Methods To Inform The Design And Implementation Of A Facility-Based Hiv Care Improvement Intervention In Zambia, Chanda Mwamba, Laura K Beres, Njekwa Mukamba, Lazarus Jere, Marksman Foloko, Kasapo Lumbo, Kombatende Sikombe, Sandra Simbeza, Aaloke Mody, Jake M Pry, Charles B Holmes, Izukanji Sikazwe, Carolyn Bolton Moore, Katerina Christopoulos, Anjali Sharma, Elvin H Geng

2020-Current year OA Pubs

INTRODUCTION: Implementation of patient-centred care (PCC) practices in HIV treatment depends on healthcare workers' (HCWs) perceptions of the acceptability, appropriateness and feasibility of such practices (e.g. use of intentional, metric-driven activities to improve patient experiences).

METHODS: We applied rapid, rigorous formative research methods to refine a PCC intervention for future trial. In 2018, we conducted focus group discussions (FGDs) with 46 HCWs purposefully selected from two pilot sites. We elicited HCW perceptions of HIV service delivery, HCW motivation and perceived value of patient experience measures intended to improve PCC. FGDs utilized participatory methods to understand HCW responses to patient-reported care …


Postmortem Diagnosis Of Very Long Chain Acyl-Coa Dehydrogenase (Vlcad) Deficiency In A Neonate With Sudden Cardiac Death, Prapti Singh, Deirdre Amaro, Olugbemisola Obi, Fnu Kiran, Erin Hediger, Tomi L Toler, Patricia I Dickson, Dorothy K Grange Jul 2023

Postmortem Diagnosis Of Very Long Chain Acyl-Coa Dehydrogenase (Vlcad) Deficiency In A Neonate With Sudden Cardiac Death, Prapti Singh, Deirdre Amaro, Olugbemisola Obi, Fnu Kiran, Erin Hediger, Tomi L Toler, Patricia I Dickson, Dorothy K Grange

2020-Current year OA Pubs

Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive long chain fatty acid β-oxidation disorder with a variable clinical spectrum, ranging from an acute neonatal presentation with cardiac and hepatic failure to childhood or adult onset of symptoms with hepatomegaly or rhabdomyolysis provoked by illness or exertion. Neonatal cardiac arrest or sudden unexpected death can be the presenting phenotype in some patients, emphasizing the importance of early clinical suspicion and intervention. We report a patient who had a cardiac arrest and died at one day of age. Following her death, the newborn screen reported biochemical evidence of VLCAD …


Β Cell Function After Roux-En-Y Gastric Bypass Surgery Or Reduced Energy Intake Alone In People With Obesity, Bettina Mittendorfer, Bruce W. Patterson, Faidon Magkos, Mihoko Yoshino, David P. Bradley, J. Christopher Eagon, Samuel Klein Jun 2023

Β Cell Function After Roux-En-Y Gastric Bypass Surgery Or Reduced Energy Intake Alone In People With Obesity, Bettina Mittendorfer, Bruce W. Patterson, Faidon Magkos, Mihoko Yoshino, David P. Bradley, J. Christopher Eagon, Samuel Klein

2020-Current year OA Pubs

BackgroundThe effects of diet-induced weight loss (WL) and WL after Roux-en-Y gastric bypass (RYGB) surgery on β cell function (BCF) are unclear because of conflicting results from different studies, presumably because of differences in the methods used to measure BCF, the amount of WL between treatment groups, and baseline BCF. We evaluated the effect of WL after RYGB surgery or reduced energy intake alone on BCF in people with obesity with and without type 2 diabetes.MethodsBCF (insulin secretion in relationship to plasma glucose) was assessed before and after glucose or mixed-meal ingestion before and after (a) progressive amounts (6%, 11%, …


Defining Diurnal Fluctuations In Mouse Choroid Plexus And Csf At High Molecular, Spatial, And Temporal Resolution, Ryann M Fame, Yong Zhang, Michael J Holtzman, Et Al. Jun 2023

Defining Diurnal Fluctuations In Mouse Choroid Plexus And Csf At High Molecular, Spatial, And Temporal Resolution, Ryann M Fame, Yong Zhang, Michael J Holtzman, Et Al.

2020-Current year OA Pubs

Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene …


Heterogeneity In The Effect Of Marked Weight Loss On Metabolic Function In Women With Obesity, Bettina Mittendorfer, Brandon D. Kayser, Mihoko Yoshino, Jun Yoshino, Jeramie D. Watrous, Mohit Jain, J. Christopher Eagon, Bruce W. Patterson, Samuel Klein Jun 2023

Heterogeneity In The Effect Of Marked Weight Loss On Metabolic Function In Women With Obesity, Bettina Mittendorfer, Brandon D. Kayser, Mihoko Yoshino, Jun Yoshino, Jeramie D. Watrous, Mohit Jain, J. Christopher Eagon, Bruce W. Patterson, Samuel Klein

2020-Current year OA Pubs

BACKGROUNDThere is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODSWe evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as "Responders" (n = 11) or "Non-responders" (n = 11), defined as the top (>75% increase) and bottom (<5% increase) quartiles of the weight loss-induced increase in glucose disposal rate (GDR) during a hyperinsulinemic-euglycemic clamp procedure, among 43 women with obesity (BMI: 44.1 ± 7.9 kg/m2).RESULTSAt baseline, GDR, which provides an index of muscle insulin sensitivity, and the hepatic insulin sensitivity index were more than 50% lower in Responders than Non-responders, but both increased much more after weight loss in Responders than Non-responders, which eliminated the differences between groups. Weight loss also caused greater decreases in intrahepatic triglyceride content and plasma adiponectin and PAI-1 concentrations in Responders than Non-responders and greater insulin-mediated suppression of plasma free fatty acids, branched-chain amino acids, and C3/C5 acylcarnitines in Non-responders than Responders, so that differences between groups at baseline were no longer present after weight loss. The effect of weight loss on total body fat mass, intra-abdominal adipose tissue volume, adipocyte size, and circulating inflammatory markers were not different between groups.CONCLUSIONThe results from our study demonstrate that the heterogeneity in the effects of marked weight loss on muscle and hepatic insulin sensitivity in people with obesity is determined by baseline insulin action, and reaches a ceiling when "normal" insulin action is achieved.TRIAL REGISTRATIONNCT00981500, NCT01299519, NCT02207777.FUNDINGNIH grants P30 DK056341, P30 DK020579, P30 DK052574, UL1 TR002345, and T32 HL13035, the American Diabetes Association (1-18-ICTS-119), the Longer Life Foundation (2019-011), and the Atkins Philanthropic Trust.


Safety Of Fecal Microbiota, Live-Jslm (Rebyota™) In Individuals With Recurrent Clostridioides Difficile Infection: Data From Five Prospective Clinical Trials, Christine Lee, Thomas Louie, Lindy Bancke, Beth Guthmueller, Adam Harvey, Paul Feuerstadt, Sahil Khanna, Robert Orenstein, Erik R Dubberke Jun 2023

Safety Of Fecal Microbiota, Live-Jslm (Rebyota™) In Individuals With Recurrent Clostridioides Difficile Infection: Data From Five Prospective Clinical Trials, Christine Lee, Thomas Louie, Lindy Bancke, Beth Guthmueller, Adam Harvey, Paul Feuerstadt, Sahil Khanna, Robert Orenstein, Erik R Dubberke

2020-Current year OA Pubs

BACKGROUND: Microbiota-based treatments reduce the incidence of recurrent

OBJECTIVES: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) - the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration - for preventing rCDI in adults.

DESIGN: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL.

METHODS: Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or …


Adaptation Of A Mobile Interactive Obesity Treatment Approach For Early Severe Mental Illness: Protocol For A Mixed Methods Implementation And Pilot Randomized Controlled Trial, Ginger E Nicol, Madeline O Jansen, Amanda R Ricchio, Julia A Schweiger, Katie E Keenoy, J Philip Miller, Elaine H Morrato, Zhaohua Guo, Bradley A Evanoff, Joseph J Parks, John W Newcomer Jun 2023

Adaptation Of A Mobile Interactive Obesity Treatment Approach For Early Severe Mental Illness: Protocol For A Mixed Methods Implementation And Pilot Randomized Controlled Trial, Ginger E Nicol, Madeline O Jansen, Amanda R Ricchio, Julia A Schweiger, Katie E Keenoy, J Philip Miller, Elaine H Morrato, Zhaohua Guo, Bradley A Evanoff, Joseph J Parks, John W Newcomer

2020-Current year OA Pubs

BACKGROUND: Obesity is common in individuals with severe mental illness (SMI), contributing to a significantly shortened lifespan when compared to the general population. Available weight loss treatments have attenuated efficacy in this population, underscoring the importance of prevention and early intervention.

OBJECTIVE: Here, we describe a type 1 hybrid study design for adapting and pilot-testing an existing mobile health intervention for obesity prevention in individuals with early SMI and Class I or early-stage obesity, defined as a BMI of 30-35.

METHODS: An existing, evidence-based interactive obesity treatment approach using low-cost, semiautomated SMS text messaging was selected for adaptation. Community mental …


Validation Of The Adolescent Binge Eating Disorder Measure (Ado-Bed) Among Transgender Youth And Young Adults, Whitney Linsenmeyer, Dana Stiles, Sarah Garwood, Andrea Giedinghagen, Christopher Lewis, Gretta Strand Jun 2023

Validation Of The Adolescent Binge Eating Disorder Measure (Ado-Bed) Among Transgender Youth And Young Adults, Whitney Linsenmeyer, Dana Stiles, Sarah Garwood, Andrea Giedinghagen, Christopher Lewis, Gretta Strand

2020-Current year OA Pubs

BACKGROUND: Transgender youth and young adults are at increased risk for eating disorders, including binge eating disorder, yet few measures have been validated for screening purposes with the transgender population.

METHODS: The purpose of this study was to provide initial evidence for the internal consistency and convergent validity of the Adolescent Binge Eating Disorder questionnaire (ADO-BED) in a sample of transgender youth and young adults. 208 participants completed the ADO-BED as part of a routine nutrition screening protocol at a gender center. Exploratory factor analysis and confirmatory factor analysis was used to establish the factor structure of the ADO-BED. Relationships …


Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, C Charles Gu, Et Al. Jun 2023

Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, C Charles Gu, Et Al.

2020-Current year OA Pubs

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs …


Associations Between Socioeconomic Status, Obesity, Cognition, And White Matter Microstructure In Children, Zhaolong Adrian Li, Yuqi Cai, Rita L Taylor, Sarah A Eisenstein, Deanna M Barch, Scott Marek, Tamara Hershey Jun 2023

Associations Between Socioeconomic Status, Obesity, Cognition, And White Matter Microstructure In Children, Zhaolong Adrian Li, Yuqi Cai, Rita L Taylor, Sarah A Eisenstein, Deanna M Barch, Scott Marek, Tamara Hershey

2020-Current year OA Pubs

IMPORTANCE: Lower neighborhood and household socioeconomic status (SES) are associated with negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter and via what mechanisms.

OBJECTIVE: To assess whether and how neighborhood and household SES are independently associated with children's white matter microstructure and examine whether obesity and cognitive performance (reflecting environmental cognitive and sensory stimulation) are plausible mediators.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from participants in the Adolescent Brain Cognitive Development (ABCD) study. Data were collected at 21 US sites, and school-based recruitment was used …


Protein Kinetics Of Superoxide Dismutase-1 In Familial And Sporadic Amyotrophic Lateral Sclerosis, Cindy V Ly, Margaret D Ireland, Wade K Self, James Bollinger, Jennifer Jockel-Balsarotti, Hillary Herzog, Peggy Allred, Leah Miller, Michael Doyle, Isabel Anez-Bruzual, Bhavesh Trikamji, Ted Hyman, Tyler Kung, Katherine Nicholson, Robert C Bucelli, Bruce W Patterson, Randall J Bateman, Timothy M Miller Jun 2023

Protein Kinetics Of Superoxide Dismutase-1 In Familial And Sporadic Amyotrophic Lateral Sclerosis, Cindy V Ly, Margaret D Ireland, Wade K Self, James Bollinger, Jennifer Jockel-Balsarotti, Hillary Herzog, Peggy Allred, Leah Miller, Michael Doyle, Isabel Anez-Bruzual, Bhavesh Trikamji, Ted Hyman, Tyler Kung, Katherine Nicholson, Robert C Bucelli, Bruce W Patterson, Randall J Bateman, Timothy M Miller

2020-Current year OA Pubs

OBJECTIVE: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts.

METHODS: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured.

RESULTS: In …