Digital Commons Network^™

Prenatal Exposure To Maternal Disadvantage-Related Inflammatory Biomarkers: Associations With Neonatal White Matter Microstructure, Ashley F P Sanders, Brian Tirado, Nicole A Seider, Regina L Triplett, Rachel E Lean, Jeffrey J Neil, J Philip Miller, Rebecca Tillman, Tara A Smyser, Deanna M Barch, Joan L Luby, Cynthia E Rogers, Christopher D Smyser, Barbara B Warner, Et Al.

2020-Current year OA Pubs

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal …

The Bethesda Ercp Skills Assessment Tool (Besat) Can Reliably Differentiate Endoscopists Of Different Experience Levels, Kevin Liu, Vladimir Kushnir, Et Al.

2020-Current year OA Pubs

No abstract provided.

Circadian Immunity From Bench To Bedside: A Practical Guide, Huram Mok, Elaine Ostendorf, Alex Ganninger, Avi J. Adler, Guy Hazan, Jeffrey A. Haspel

2020-Current year OA Pubs

The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. The challenge is how to harness these biological rhythms to improve medical interventions. Here, we review recent literature documenting how circadian clocks organize fundamental innate and adaptive immune activities, the immunologic consequences of circadian rhythm and sleep disruption, and persisting knowledge gaps in the field. We then consider the evidence linking circadian rhythms to vaccination, …

Epidemiology And Preventability Of Hospital-Onset Bacteremia And Fungemia In 2 Hospitals In India, Sumanth Gandra, Dorothy Sinclair, Dustin Stwalley, Jacaranda Van Rheenen, David K Warren, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs).

DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to …

Core Requirements Of Frailty Screening In The Emergency Department: An International Delphi Consensus Study, Elizabeth Moloney, Christopher R Carpenter, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Frailty is associated with adverse outcomes among patients attending emergency departments (EDs). While multiple frailty screens are available, little is known about which variables are important to incorporate and how best to facilitate accurate, yet prompt ED screening. To understand the core requirements of frailty screening in ED, we conducted an international, modified, electronic two-round Delphi consensus study.

METHODS: A two-round electronic Delphi involving 37 participants from 10 countries was undertaken. Statements were generated from a prior systematic review examining frailty screening instruments in ED (logistic, psychometric and clinimetric properties). Reflexive thematic analysis generated a list of 56 statements …

Calorie Restriction Reduces Biomarkers Of Cellular Senescence In Humans, Zaira Aversa, Susan B Racette, Et Al.

2020-Current year OA Pubs

Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change …

Implementing Integrated Hypertension And Diabetes Management Using The World Health Organization's Hearts Model: Protocol For A Pilot Study In The Guatemalan National Primary Care System, Irmgardt Alicia Wellmann, Luis Fernando Ayala, José Javier Rodríguez, Timothy C Guetterman, Vilma Irazola, Eduardo Palacios, Mark D Huffman, Peter Rohloff, Michele Heisler, Manuel Ramírez-Zea, David Flood

2020-Current year OA Pubs

BACKGROUND: The HEARTS technical package was developed by the World Health Organization to address the implementation gap in cardiovascular disease prevention in low- and middle-income countries. Guatemala is a middle-income country that is currently implementing HEARTS. National authorities in Guatemala are interested in exploring how hypertension and diabetes management can be integrated in HEARTS implementation. The objective of this study is to conduct a feasibility and acceptability pilot trial of integrated hypertension and diabetes management based on HEARTS in the publicly funded primary care system in Guatemala.

METHODS: A single-arm pilot trial for 6 months will be carried out in …

Phase I Dose-Escalation Study Of The Safety And Pharmacokinetics Of Ags15e Monotherapy In Patients With Metastatic Urothelial Carcinoma, Daniel P Petrylak, Joel Picus, Et Al.

2020-Current year OA Pubs

PURPOSE: Effective treatment of locally advanced or metastatic urothelial carcinoma (mUC) remains an unmet need. Antibody-drug conjugates (ADC) providing targeted drug delivery have shown antitumor activity in this setting. AGS15E is an investigational ADC that delivers the cytotoxic drug monomethyl auristatin E to cells expressing SLITRK6, a UC-associated antigen.

PATIENTS AND METHODS: This was a multicenter, single-arm, phase I dose-escalation and expansion trial of AGS15E in patients with mUC (NCT01963052). During dose escalation, AGS15E was administered intravenously at six levels (0.10, 0.25, 0.50, 0.75, 1.00, 1.25 mg/kg), employing a continual reassessment method to determine dose-limiting toxicities (DLT) and the recommended …

Effects Of Cooking With Liquefied Petroleum Gas Or Biomass On Stunting In Infants, William Checkley, Lindsay J Underhill, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown.

METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length …

Process Evaluation Of A Double-Blind Randomized Controlled Trial To Assess The Efficacy And Safety Of A Quadruple Ultra-Low-Dose Treatment For Hypertension Within A Federally Qualified Health Center Network (Quartet Usa), Olutobi A Sanuade, Tyler A Jacobson, Adriana Quintana, Fallon M Flowers, Hiba Abbasi, My H Vu, Abigail S Baldridge, Jairo Mejia, Danielle Lazar, Jody D Ciolino, Mark D Huffman, Namratha R Kandula

2020-Current year OA Pubs

BACKGROUND: This convergent parallel-design mixed-methods process evaluation of the QUARTET USA (Quadruple Ultra-Low-Dose Treatment for Hypertension USA) clinical trial (NCT03640312) explores patient and health care professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management.

METHODS AND RESULTS: A survey of all 62 patients enrolled in the QUARTET USA trial was conducted. A subsample of 13 patients and 11 health care professionals, recruited via purposive sampling, took part in semistructured interviews. At enrollment, 68% of participants (mean [SD] age, 51.7 [11.5] years; 56% self-identified as Hispanic: Mexican ethnicity, 16% as Hispanic: other ethnicity, …

Breast Cancer Incidence Among Us Women Aged 20 To 49 Years By Race, Stage, And Hormone Receptor Status, Shuai Xu, Sara Murtagh, Yunan Han, Fei Wan, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Breast cancer in young women has a less favorable prognosis compared with older women. Yet, comprehensive data on recent trends and how period and cohort effects may affect these trends among young women are not well-known.

OBJECTIVE: To evaluate breast cancer incidence among young women in the US over a 20-year period by race and ethnicity, hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]), tumor stage, and age at diagnosis, as well as how period and cohort effects may affect these trends.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from Surveillance, Epidemiology, and End Results …

Washington University Magazine, December 2024

Washington University Magazine

No abstract provided.

Protocol For A Pilot Clinical Trial Of The Senolytic Drug Combination Dasatinib Plus Quercetin To Mitigate Age-Related Health And Cognitive Decline In Mental Disorders [Version 2; Peer Review: 1 Approved, 2 Approved With Reservations], Abigail Schweiger, Breno Diniz, Ginger Nicol, Julie Schweiger, Andes E Dasklakis-Perez, Eric J Lenze

2020-Current year OA Pubs

BACKGROUND: Major depressive disorder (MDD) and schizophrenia are linked to accelerated aging leading to reduced lifespan, health span and cognitive decline. Cellular senescence, in which cells lose proliferative capacity and develop a senescence-associated secretory phenotype (SASP), plays a role in this process. Emerging research suggests that the senolytic regimen of dasatinib+quercetin (D+Q) reduces senescent cells, potentially mitigating age-related health and cognitive decline. This pilot study aims to assess the feasibility and safety of D+Q in older adults with schizophrenia, schizoaffective disorder, and treatment-resistant depression (TRD).

METHODS: This single-center study will recruit 30 participants total aged 50 years or older with …

Is Multidimensional Poverty Associated To Dementia Risk? The Case Of Older Adults In Pakistan, Jean-François Trani, Yiqi Zhu, Soobin Park, Ganesh M Babulal

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Multidimensional poverty is associated with dementia. We aimed at establishing this association in Pakistan.

RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted in Punjab and Sindh, Pakistan, between March 30, 2002, and August 22, 2022, among adults aged 50 and older. Multidimensional poverty measures were composed of 6 dimensions and 15 indicators. Poverty was compared between adults with and without dementia using the Rowland Universal Dementia Assessment Scale, adjusting for sex, age, marital status, and household size. Associations between dementia and poverty were investigated using a multivariate logistic regression model.

RESULTS: We found that 594 (72.7%), …

Uropathogenic Escherichia Coli Wield Enterobactin-Derived Catabolites As Siderophores, Zongsen Zou, John I Robinson, Lindsey K Steinberg, Jeffrey P Henderson

2020-Current year OA Pubs

Uropathogenic Escherichia coli (UPEC) secrete multiple siderophore types to scavenge extracellular iron(III) ions during clinical urinary tract infections, despite the metabolic costs of biosynthesis. Here, we find the siderophore enterobactin (Ent) and its related products to be prominent components of the iron-responsive extracellular metabolome of a model UPEC strain. Using defined Ent biosynthesis and import mutants, we identify lower molecular weight dimeric exometabolites as products of incomplete siderophore catabolism, rather than prematurely released biosynthetic intermediates. In E. coli, iron acquisition from iron(III)-Ent complexes requires intracellular esterases that hydrolyze the siderophore. Although UPEC are equipped to consume the products of completely …

Adherence To Practice Parameters In Medicare Beneficiaries With Amyotrophic Lateral Sclerosis, Osvaldo J. Laurido-Soto, Irene M. Faust, Susan Searles Nielsen, Brad A. Racette

2020-Current year OA Pubs

OBJECTIVE: Physician adherence to evidence-based clinical practice parameters impacts outcomes of amyotrophic lateral sclerosis (ALS) patients. We sought to investigate compliance with the 2009 practice parameters for treatment of ALS patients in the United States, and sociodemographic and provider characteristics associated with adherence.

METHODS: In this population-based, retrospective cohort study of incident ALS patients in 2009-2014, we included all Medicare beneficiaries age ≥20 with ≥1 International Classification of Diseases, Ninth Revision, Clinical Modification ALS code (335.20) in 2009 and no prior years (N = 8,575). Variables of interest included race/ethnicity, sex, age, urban residence, Area Deprivation Index (ADI), and provider …

Bioactive Glycans In A Microbiome-Directed Food For Children With Malnutrition, Matthew C Hibberd, Daniel M Webber, Suzanne Henrissat, Robert Y Chen, Cyrus Zhou, Hannah M Lynn, Yi Wang, Hao-Wei Chang, Evan M Lee, Janaki Lelwala-Guruge, Ye Chen, Ishita Mostafa, Subhasish Das, Mustafa Mahfuz, Michael J Barratt, Tahmeed Ahmed, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition

A Global Scoping Review Of Adaptations In Nurturing Care Interventions During The Covid-19 Pandemic, Lidia Godoi, Simone Schenkman, Ana A Baumann, Aylene Bousquat, Gabriela Buccini

2020-Current year OA Pubs

BACKGROUND: During the COVID-19 pandemic, children faced a disproportionate burden of malnutrition and poor health outcomes. Nurturing care interventions (NCIs) including actions toward good health, adequate nutrition, responsive care, opportunities for early learning, and security and safety are critical for promoting equity. Due to the need for evidence-based responses and preparedness, we analyzed adaptations in NCIs' implementation strategies during COVID-19 according to the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS).

METHOD: We conducted a global scoping review including peer-reviewed and non-peer-reviewed literature. The databases searched were PubMed, Embase, Scopus, BVS, Scielo, and Web of Science. This …

Translatability Of Findings From Cynomolgus Monkey To Human Suggests A Mechanistic Role For Il-21 In Promoting Immunogenicity To An Anti-Pd-1/Il-21 Mutein Fusion Protein, Mark A Kroenke, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and a single IL-21 mutein domain on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that AMG 256 administration led to the development of immunogenicity-mediated responses and indicated that the IL-21 mutein domain of AMG 256 could enhance the anti-drug antibody response directed toward the monoclonal antibody domain. Anti-AMG 256 IgE were also observed in cynomolgus monkeys. A first-in-human (FIH) study in patients with advanced solid tumors was designed with these risks in mind. AMG 256 elicited ADA in 28 of 33 subjects (84.8%). However, ADA responses were …

Graceful Gait: Virtual Ballet Classes Improve Mobility And Reduce Falls More Than Wellness Classes For Older Women, Elinor C Harrison, Allison M Haussler, Lauren E Tueth, Sidney T Baudendistel, Gammon M Earhart

2020-Current year OA Pubs

INTRODUCTION: Dance is an effective and motivating form of exercise for older women, but few studies have quantified the benefits of virtual dance classes nor, specifically, ballet. This study tested the effectiveness of virtual ballet compared to virtual wellness classes, with the goal of reaching underserved populations. It is among the first to explore the effects of virtual classical ballet on functional gait mobility, balance, and quality of life measures in older women.

METHODS: Older women were recruited in two waves and randomized to two groups: a ballet class modified for older adults and a wellness-based control class. Both groups …

Lipin1 As A Therapeutic Target For Respiratory Insufficiency Of Duchenne Muscular Dystrophy, Alexandra Brown, Brooklyn Morris, John Karanja Kamau, Ryan J Rakoczy, Brian N Finck, Christopher N Wyatt, Hongmei Ren

2020-Current year OA Pubs

In Duchenne muscular dystrophy (DMD), diaphragm muscle dysfunction results in respiratory insufficiency which is a leading cause of death in patients. Mutations to the dystrophin gene result in myocyte membrane instability, contributing to the structural deterioration of the diaphragm muscle tissues. With previous works suggesting the importance of lipin1 for maintaining skeletal muscle membrane integrity, we explored the roles of lipin1 in the dystrophic diaphragm. We found that the protein expression levels of lipin1 were reduced by 60% in the dystrophic diaphragm. While further knockdown of lipin1 in the dystrophic diaphragm leads to increased necroptosis, restoration of lipin1 in the …

Protein Quality Malnutrition, Mark J Manary, Donna R Wegner, Kenneth Maleta

2020-Current year OA Pubs

Protein quality refers to the evaluation of a food or a diet based on its amino acid composition, protein digestibility, and protein bioavailability. When these parameters are specified, either through direct measurement or estimation, the amino acids provided by the diet are compared to those required by a healthy individual, and based on this comparison, an adequacy ratio or score is assigned. Two widely used protein quality scoring systems are the protein digestibility-corrected amino acid score (PDCAAS) and the digestible indispensable amino acid score (DIAAS), neither of which account for the dietary source of the protein. In malnourished children, metabolic …

Delayed Macrophage Targeting By Clodronate Liposomes Worsens The Progression Of Cytokine Storm Syndrome, Kunjan Khanna, Emily Eul, Hui Yan, Roberta Faccio

2020-Current year OA Pubs

Excessive macrophage activation and production of pro-inflammatory cytokines are hallmarks of the Cytokine Storm Syndrome (CSS), a lethal condition triggered by sepsis, autoimmune disorders, and cancer immunotherapies. While depletion of macrophages at disease onset protects from lethality in an infection-induced CSS murine model, patients are rarely diagnosed early, hence the need to characterize macrophage populations during CSS progression and assess the therapeutic implications of macrophage targeting after disease onset. In this study, we identified MHCII

Campylobacter Colonization And Undernutrition In Infants In Rural Eastern Ethiopia — A Longitudinal Community-Based Birth Cohort Study, Dehao Chen, Nurmohammad Shaik, Mark J Manary, Et Al.

2020-Current year OA Pubs

BACKGROUND:

METHODS: We followed a birth cohort of 106 infants in rural smallholder households in eastern Ethiopia up to 13 months of age. We measured anthropometry, surveyed sociodemographic determinants, and collected stool and urine samples. A short survey was conducted during monthly visits, infant stool samples were collected, and

RESULTS: The

CONCLUSION: This study found that most determinants associated with increased

Development, Usability, And Preliminary Efficacy Of A Virtual Reality Experience To Promote Healthy Lifestyle Behaviors In Children: Pilot Randomized Controlled Trial, Lauren A. Fowler, Melissa M. Vázquez, Bianca Depietro, Denise E. Wilfley, Ellen E. Fitzsimmons-Craft

2020-Current year OA Pubs

BACKGROUND: Virtual reality (VR) shows promise for supporting behavior change in children. This study used user-centered design to translate key tenets of behavioral health interventions into VR for children aged 6-12 years and their caregivers and examined the feasibility, acceptability, and preliminary efficacy of the VR experience in a pilot parallel, two-group randomized controlled trial (RCT).

METHODS: The VR experience incorporates psychoeducational content from evidence-based behavioral health interventions using voiceover and an interactive go-kart game related to the concepts of "food as fuel" and nutrition guidelines. Study 1 involved usability testing with n=5 child-caregiver dyads, which informed technical and content …

Perspectives From Public Health Practitioners And Advocates On Community Development For Active Living: What Are The Lasting Impacts?, Natalicio Serrano, Laurel Schmidt, Amy A Eyler, Ross C Brownson

2020-Current year OA Pubs

PURPOSE: Evidence suggests differential impacts of community development, including gentrification and displacement. Public health practitioners and advocates are key stakeholders involved in the community development process related to active living, yet little is known about their perceptions of its impacts. We explored the perspectives of relevant leaders of public health departments and key community and advocacy organizations on community development, gentrification, and displacement.

APPROACH: Purposive key informant interviews.

SETTING: CDC State Physical Activity and Nutrition (SPAN) funding recipients.

PARTICIPANTS: CDC SPAN recipient leadership (n = 10 of 16) and advocacy organizations they partnered with (n = 7 of 16).

METHOD: …

Effectively Communicating With Local Policymakers: A Randomized Trial Of Policy Brief Dissemination To Address Obesity, Elizabeth A Dodson, Renee G Parks, Rebekah R Jacob, Ruopeng An, Amy A Eyler, Nathan Lee, Alexandra B Morshed, Mary C Politi, Rachel G Tabak, Yan Yan, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: Evidence-based policies are a powerful tool for impacting health and addressing obesity. Effectively communicating evidence to policymakers is critical to ensure evidence is incorporated into policies. While all public health is local, limited knowledge exists regarding effective approaches for improving local policymakers' uptake of evidence-based policies.

METHODS: Local policymakers were randomized to view one of four versions of a policy brief (usual care, narrative, risk-framing, and narrative/risk-framing combination). They then answered a brief survey including questions about their impressions of the brief, their likelihood of using it, and how they determine legislative priorities.

RESULTS: Responses from 331 participants indicated …

Unmet Patient Needs In Monocarboxylate Transporter 8 (Mct8) Deficiency: A Review, Andrew J Bauer, Bethany Auble, Amy L Clark, Tina Y Hu, Amber Isaza, Kyle P Mcnerney, Daniel L Metzger, Lindsey Nicol, Samuel R Pierce, Richard Sidlow

2020-Current year OA Pubs

Monocarboxylate transporter 8 (MCT8) deficiency is a rare, X-linked disorder arising from mutations in the

Isoflurane Conditioning Improves Functional Outcomes After Peripheral Nerve Injury In A Sciatic Cut Repair Murine Model, Yameng Xu, Ying Yan, Gregory J Zipfel, Matthew Macewan, Wilson Z Ray, Umeshkumar Athiraman

2020-Current year OA Pubs

INTRODUCTION: Anesthetic conditioning has been shown to provide neuroprotection in several neurological disorders. Whether anesthetic conditioning provides protection against peripheral nerve injuries remains unknown. The aim of our current study is to investigate the impact of isoflurane conditioning on the functional outcomes after peripheral nerve injury (PNI) in a rodent sciatic nerve injury model.

METHODS: Adult male Lewis rats underwent sciatic nerve cut and repair and exposed to none (Group 1, sham), single isoflurane exposure (Group 2), three-time isoflurane exposure (Group 3), and six-time isoflurane exposure (Group 4). Isoflurane conditioning was established by administration of 2% isoflurane for 1 hour, …

Sexual Dimorphism In Hepatic Ppar Alpha And Cyp4a12a Expression Is Associated With Reduced Development Of Drug-Induced Non-Alcoholic Steatohepatitis In Female Il-33-/- Mice, Chloe Thomas, Dolores B Njoku

2020-Current year OA Pubs

Males are at higher risk for developing metabolic dysfunction-associated steatohepatitis (MASH) than females; however, mechanisms mediating sexual dimorphism in MASH development are not completely understood. Nutrition-based mouse models suggest that dysregulated fatty acid biosynthesis promotes MASH. Drugs recapitulate MASH without diet variabilities. This brief report investigates associations of sexual dimorphism with male susceptibility to MASH utilizing a drug-induced MASH model and focuses on very-long-chain fatty acid biosynthesis pathways. We assessed male and female mouse livers at 5 and 15 weeks following MASH induction by immunizations and age-matched un-immunized controls utilizing Western blot. Our results suggest that PPAR alpha and CYP4a12a …