Medicine and Health Sciences Commons^™

Leveraging Mhealth To Mitigate The Impact Of Covid-19 In Black American Communities: Qualitative Analysis, Kelly M Harris, Tilicia Mayo Gamble, Madelyn G Yoo, Lindsay A Spell, Timira N Minor, Holly Jones, Donald Lynch

2020-Current year OA Pubs

BACKGROUND: COVID-19 remains an ongoing public health crisis. Black Americans remain underrepresented among those vaccinated and overrepresented in both COVID-19 morbidity and mortality. Medical misinformation, specifically related to COVID-19, has exacerbated the impact of the disease in Black American communities. Communication tools and strategies to build relationships and disseminate credible and trustworthy diagnostic and preventative health information are necessary to improve outcomes and equity for historically oppressed populations.

OBJECTIVE: As the initial phase of a larger mixed methods project to develop, pilot, and evaluate a mobile health (mHealth) intervention among a population at high risk for COVID-19 and cardiovascular comorbidities, …

Comparative Genomics Reveals The Correlations Of Stress Response Genes And Bacteriophages In Developing Antibiotic Resistance Of Staphylococcus Saprophyticus, Kailun Zhang, Robert F Potter, Jamie Marino, Carol E Muenks, Matthew G Lammers, Jennifer Dien Bard, Tanis C Dingle, Romney Humphries, Lars F Westblade, Carey-Ann D Burnham, Gautam Dantas

2020-Current year OA Pubs

No abstract provided.

A Patterned Human Primitive Heart Organoid Model Generated By Pluripotent Stem Cell Self-Organization, Brett Volmert, Chao Zhou, Et Al.

2020-Current year OA Pubs

Pluripotent stem cell-derived organoids can recapitulate significant features of organ development in vitro. We hypothesized that creating human heart organoids by mimicking aspects of in utero gestation (e.g., addition of metabolic and hormonal factors) would lead to higher physiological and anatomical relevance. We find that heart organoids produced using this self-organization-driven developmental induction strategy are remarkably similar transcriptionally and morphologically to age-matched human embryonic hearts. We also show that they recapitulate several aspects of cardiac development, including large atrial and ventricular chambers, proepicardial organ formation, and retinoic acid-mediated anterior-posterior patterning, mimicking the developmental processes found in the post-heart tube stage …

Overall Survival Of Patients With Chl Who Progress After Autologous Stem Cell Transplant: Results In The Novel Agent Era, Sanjal H Desai, Brad Kahl, Raya Saba, Et Al.

2020-Current year OA Pubs

In the pre-novel agent era, the median postprogression overall survival (PPS) of patients with classic Hodgkin lymphoma (cHL) who progress after autologous stem cell transplant (ASCT) was 2 to 3 years. Recently, checkpoint inhibitors (CPI) and brentuximab vedotin (BV) have improved the depth and durability of response in this population. Here, we report the estimate of PPS in patients with relapsed cHL after ASCT in the era of CPI and BV. In this multicenter retrospective study of 15 participating institutions, adult patients with relapsed cHL after ASCT were included. Study objective was postprogression overall survival (PPS), defined as the time …

A Multilevel Mhealth Intervention Boosts Adherence To Hydroxyurea In Individuals With Sickle Cell Disease, Jane S Hankins, Allison A King, Ana A Baumann, Lisa M Klesges, Et Al.

2020-Current year OA Pubs

Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSβ0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P < 0.001) and sustained (39.7% to 51.4%, P < 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P < 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU Toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167.

Reproductive Decision Making In Women With Medical Comorbidities: A Qualitative Study, Elena M Kraus, Niraj R Chavan, Victoria Whelan, Jennifer Goldkamp, James M Dubois

2020-Current year OA Pubs

BACKGROUND: A growing number of reproductive-age women in the U.S. have chronic medical conditions, increasing their risk of perinatal morbidity and mortality. Still, they experience unintended pregnancies at similar rates to low-risk mothers. We have limited understanding of how these individuals consider decisions about pregnancy and contraceptive use. The purpose of this study was to understand factors that influence reproductive decision-making among pregnant women with chronic medical conditions.

METHODS: We conducted 28 semi-structured interviews with pregnant women with pre-existing medical conditions admitted to a tertiary maternal hospital to examine factors influencing reproductive decision making. Maternal demographic characteristics, medical history, and …

Trends In Ductus Arteriosus Stent Versus Blalock-Taussig-Thomas Shunt Use And Comparison Of Cost, Length Of Stay, And Short-Term Outcomes In Neonates With Ductal-Dependent Pulmonary Blood Flow: An Observational Study Using The Pediatric Health Information Systems Database, Bethan A Lemley, Lezhou Wu, Amy L Roberts, Russell T Shinohara, William O Quarshie, Athar M Qureshi, Christopher L Smith, Yoav Dori, Matthew J Gillespie, Jonathan J Rome, Andrew C Glatz, Sandra Amaral, Michael L O'Byrne

2020-Current year OA Pubs

BACKGROUND: The modified Blalock-Taussig-Thomas shunt is the gold standard palliation for securing pulmonary blood flow in infants with ductal-dependent pulmonary blood flow. Recently, the ductus arteriosus stent (DAS) has become a viable alternative.

METHODS AND RESULTS: This was a retrospective multicenter study of neonates ≤30 days undergoing DAS or Blalock-Taussig-Thomas shunt placement between January 1, 2017 and December 31, 2020 at hospitals reporting to the Pediatric Health Information Systems database. We performed generalized linear mixed-effects modeling to evaluate trends in intervention and intercenter variation, propensity score adjustment and inverse probability weighting with linear mixed-effects modeling to analyze length of stay …

Maternal Diet During Early Gestation Influences Postnatal Taste Activity-Dependent Pruning By Microglia, Chengsan Sun, Shuqiu Zheng, Justin S A Perry, Geoffrey T Norris, Mei Cheng, Fanzhen Kong, Rolf Skyberg, Jianhua Cang, Alev Erisir, Jonathan Kipnis, David L Hill

2020-Current year OA Pubs

A key process in central sensory circuit development involves activity-dependent pruning of exuberant terminals. Here, we studied gustatory terminal field maturation in the postnatal mouse nucleus of the solitary tract (NST) during normal development and in mice where their mothers were fed a low NaCl diet for a limited period soon after conception. Pruning of terminal fields of gustatory nerves in controls involved the complement system and is likely driven by NaCl-elicited taste activity. In contrast, offspring of mothers with an early dietary manipulation failed to prune gustatory terminal fields even though peripheral taste activity developed normally. The ability to …

Core Warming Of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study, Nathaniel P Bonfanti, Nicholas M Mohr, David C Willms, Roger J Bedimo, Emily Gundert, Kristina L Goff, Erik B Kulstad, Anne M Drewry

2020-Current year OA Pubs

Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial (RCT) showing lower mortality by warming afebrile sepsis patients in the intensive care unit (ICU). The objective of this prospective single-site RCT was to determine if core warming improves respiratory physiology of mechanically ventilated patients with coronavirus disease 2019 (COVID-19), allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean …

The Persistency Index: A Novel Screening Tool For Identifying Myofascial Pelvic Floor Dysfunction In Patients Seeking Care For Lower Urinary Tract Symptoms, A Lenore Ackerman, Michele Torosis, Nicholas J Jackson, Ashley T Caron, Melissa R Kaufman, Jerry L Lowder, Jonathan C Routh

2020-Current year OA Pubs

BACKGROUND: Patients with myofascial pelvic floor dysfunction often present with lower urinary tract symptoms, such as urinary frequency, urgency, and bladder pressure. Often confused with other lower urinary tract disorders, this constellation of symptoms, recently termed myofascial urinary frequency syndrome, is distinct from other lower urinary tract symptoms and optimally responds to pelvic floor physical therapy. A detailed pelvic floor myofascial examination performed by a skilled provider is currently the only method to identify myofascial urinary frequency syndrome. Despite a high influence on quality of life, low awareness of this condition combined with no objective diagnostic testing leads to the …

The Persistency Index: A Novel Screening Tool For Identifying Myofascial Pelvic Floor Dysfunction In Patients Seeking Care For Lower Urinary Tract Symptoms, A Lenore Ackerman, Michele Torosis, Nicholas J Jackson, Ashley T Caron, Melissa R Kaufman, Jerry L Lowder, Jonathan C Routh

2020-Current year OA Pubs

BACKGROUND: Patients with myofascial pelvic floor dysfunction often present with lower urinary tract symptoms, such as urinary frequency, urgency, and bladder pressure. Often confused with other lower urinary tract disorders, this constellation of symptoms, recently termed myofascial urinary frequency syndrome, is distinct from other lower urinary tract symptoms and optimally responds to pelvic floor physical therapy. A detailed pelvic floor myofascial examination performed by a skilled provider is currently the only method to identify myofascial urinary frequency syndrome. Despite a high influence on quality of life, low awareness of this condition combined with no objective diagnostic testing leads to the …

Blockade Of Il-6r Prevents Preterm Birth And Adverse Neonatal Outcomes, Marcelo Farias-Jofre, Valeria Garcia-Flores, Nardhy Gomez-Lopez, Et Al.

2020-Current year OA Pubs

BACKGROUND: Preterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks treatment.

METHODS: Proteomic and scRNA-seq human data were analysed to evaluate the role of IL-6 and IL-1α in SIAI. A C57BL/6 murine model of SIAI-induced preterm birth was developed by the ultrasound-guided intra-amniotic injection of IL-1α. The blockade of IL-6R by using an aIL-6R was tested as prenatal treatment for preterm birth and adverse neonatal outcomes. QUEST-MRI evaluated brain oxidative stress in utero. Targeted transcriptomic profiling assessed maternal, foetal, and neonatal inflammation. Neonatal biometrics and neurodevelopment …

Enlarged Perivascular Spaces In Infancy And Autism Diagnosis, Cerebrospinal Fluid Volume, And Later Sleep Problems, Dea Garic, Robert C Mckinstry, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume.

OBJECTIVE: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep …

Lasofoxifene Versus Fulvestrant For Er+/Her2- Metastatic Breast Cancer With An Esr1 Mutation: Results From The Randomized, Phase Ii Elaine 1 Trial, M P Goetz, N A Bagegni, Et Al.

2020-Current year OA Pubs

BACKGROUND: Acquired estrogen receptor alpha (ER/ESR1) mutations commonly cause endocrine resistance in ER+ metastatic breast cancer (mBC). Lasofoxifene, a novel selective ER modulator, stabilizes an antagonist conformation of wild-type and ESR1-mutated ER-ligand binding domains, and has antitumor activity in ESR1-mutated xenografts.

PATIENTS AND METHODS: In this open-label, randomized, phase II, multicenter, ELAINE 1 study (NCT03781063), we randomized women with ESR1-mutated, ER+/human epidermal growth factor receptor 2 negative (HER2-) mBC that had progressed on an aromatase inhibitor (AI) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to oral lasofoxifene 5 mg daily or IM fulvestrant 500 mg (days 1, 15, and 29, …

Greater Socioenvironmental Risk Factors And Higher Chronic Pain Stage Are Associated With Thinner Bilateral Temporal Lobes, Lisa H Antoine, Burel R Goodin, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is …

Longitudinal Lipidomic Profiles During Pregnancy And Associations With Neonatal Anthropometry: Findings From A Multiracial Cohort, Yiqing Song, Ruijin Lu, Guoqi Yu, Mohammad L Rahman, Liwei Chen, Yeiyi Zhu, Michael Y Tsai, Oliver Fiehn, Zhen Chen, Cuilin Zhang

2020-Current year OA Pubs

BACKGROUND: Maternal lipidomic profiling offers promise for characterizing lipid metabolites during pregnancy, but longitudinal data are limited. This study aimed to examine associations of longitudinal lipidomic profiles during pregnancy with multiple neonatal anthropometry using data from a multiracial cohort.

METHODS: We measured untargeted plasma lipidome profiles among 321 pregnant women from the NICHD Fetal Growth Study-Singletons using plasma samples collected longitudinally during four study visits at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39, respectively. We evaluated individual lipidomic metabolites at each study visit in association with neonatal anthropometry. We also evaluated the associations longitudinally by constructing lipid networks using …

Obesity And Outcomes Of Kawasaki Disease And Covid-19-Related Multisystem Inflammatory Syndrome In Children, Michael Khoury, William B Orr, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Obesity may affect the clinical course of Kawasaki disease (KD) in children and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19.

OBJECTIVE: To compare the prevalence of obesity and associations with clinical outcomes in patients with KD or MIS-C.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, analysis of International Kawasaki Disease Registry (IKDR) data on contemporaneous patients was conducted between January 1, 2020, and July 31, 2022 (42 sites, 8 countries). Patients with MIS-C (defined by Centers for Disease Control and Prevention criteria) and patients with KD (defined by American Heart Association criteria) were included. Patients with …

Sex-Associated Differences In Frequencies And Prognostic Impact Of Recurrent Genetic Alterations In Adult Acute Myeloid Leukemia (Alliance, Amlcg), Michael Ozga, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Clinical outcome of patients with acute myeloid leukemia (AML) is associated with demographic and genetic features. Although the associations of acquired genetic alterations with patients' sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols. A validation cohort comprised 465 women and 489 men treated on frontline protocols of the German AML Cooperative Group. Compared with men, women more often had normal …

Stratification Of Risk For Emergent Intracranial Abnormalities In Children With Headaches: A Pediatric Emergency Care Applied Research Network (Pecarn) Study Protocol, Daniel S Tsze, Kimberly S Quayle, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA …

Mycoplasma Genitalium In The Us (Mygenius): Surveillance Data From Sexual Health Clinics In 4 Us Regions, Lisa E Manhart, Gina Leipertz, Olusegun O Soge, Stephen J Jordan, Candice Mcneil, Preeti Pathela, Hilary Reno, Karen Wendel, Anika Parker, William M Geisler, Damon Getman, Matthew R Golden, Mygenius Study Team

2020-Current year OA Pubs

BACKGROUND: Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.

METHODS: We initiated surveillance in sexual health clinics in 6 cities, selecting a quota sample of urogenital specimens tested for gonorrhea and/or chlamydia. We abstracted patient data from medical records and detected MG and macrolide-resistance mutations (MRMs) by nucleic acid amplification testing. We used Poisson regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs, adjusting for sampling criteria (site, birth sex, symptom status).

RESULTS: From October-December 2020 we tested 1743 urogenital specimens: 57.0% from males, 46.1% …

Association Between User Interaction And Treatment Response Of A Voice-Based Coach For Treating Depression And Anxiety: Secondary Analysis Of A Pilot Randomized Controlled Trial, Nan Lv, Thomas Kannampallil, Lan Xiao, Corina R Ronneberg, Vikas Kumar, Nancy E Wittels, Olusola A Ajilore, Joshua M Smyth, Jun Ma

2020-Current year OA Pubs

BACKGROUND: The quality of user interaction with therapeutic tools has been positively associated with treatment response; however, no studies have investigated these relationships for voice-based digital tools.

OBJECTIVE: This study evaluated the relationships between objective and subjective user interaction measures as well as treatment response on Lumen, a novel voice-based coach, delivering problem-solving treatment to patients with mild to moderate depression or anxiety or both.

METHODS: In a pilot trial, 42 adults with clinically significant depression (Patient Health Questionnaire-9 [PHQ-9]) or anxiety (7-item Generalized Anxiety Disorder Scale [GAD-7]) symptoms or both received Lumen, a voice-based coach delivering 8 problem-solving treatment …

Evaluation Of The Efficacy And Safety Of Bempedoic Acid In Women And Men: Pooled Analyses From Phase 3 Trials, Anne C Goldberg, Maciej Banach, Alberico L Catapano, P Barton Duell, Lawrence A Leiter, Jeffrey C Hanselman, Lei Lei, G B John Mancini

2020-Current year OA Pubs

BACKGROUND AND AIMS: Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid.

METHODS: Patients were grouped into two pools: 1) atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) "on statins" and 2) "low-dose or no statin". Percent changes from baseline to at least week 12 in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed …

Regional Vulnerability Indices In Youth With Persistent And Distressing Psychoticlike Experiences, Nicole R Karcher, Hailey Modi, Peter Kochunov, Si Gao, Deanna M Barch

2020-Current year OA Pubs

IMPORTANCE: Distressing and persistent psychoticlike experiences (PLEs) in youth are associated with greater odds of developing psychiatric conditions in adulthood. Despite this risk, it is unclear whether early PLEs show similar brain patterns compared with adults with psychiatric and neurologic conditions.

OBJECTIVE: To examine the degree to which persistent and distressing PLEs exhibit neural metrics that show similarity to adults with chronic psychiatric and neurologic conditions.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Adolescent Brain Cognitive Development (ABCD) Study examining the persistence and distress associated with PLEs across the first 3 waves of data with baseline structural magnetic resonance …

Molecular Diagnostic Yield Of Exome Sequencing In Patients With Congenital Hydrocephalus: A Systematic Review And Meta-Analysis, Ana B W Greenberg, Neel H Mehta, Garrett Allington, Sheng Chih Jin, Andrés Moreno-De-Luca, Kristopher T Kahle

2020-Current year OA Pubs

IMPORTANCE: Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH).

OBJECTIVE: To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH.

DATA SOURCES: PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, …

Repeated Measures Of Mammographic Density And Texture To Evaluate Prediction And Risk Of Breast Cancer: A Systematic Review Of The Methods Used In The Literature, Akila Anandarajah, Yongzhen Chen, Carolyn Stoll, Angela Hardi, Shu Jiang, Graham A Colditz

2020-Current year OA Pubs

PURPOSE: It may be important for women to have mammograms at different points in time to track changes in breast density, as fluctuations in breast density can affect breast cancer risk. This systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk.

METHODS: The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021. Eligibility criteria included published articles in English describing the relationship of change in mammographic features with risk of breast cancer. Risk of bias was assessed using the …

A Human Mitofusin 2 Mutation Can Cause Mitophagic Cardiomyopathy, Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina De Guzman Strong, Gerald W Dorn

2020-Current year OA Pubs

Cardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is 15-20× over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical, and functional characteristics of MFN2 Q400 versus wild-type and CMT2A-causing MFN2 mutants. All MFN2 mutants had impaired mitochondrial fusion, the canonical MFN2 function. Compared to MFN2 T105M that lacked catalytic GTPase activity and exhibited normal …

Infants Exposed In Utero To Hurricane Maria Have Gut Microbiomes With Reduced Diversity And Altered Metabolic Capacity, Ai Zhang, David De Ángel Solá, Midnela Acevedo Flores, Lijuan Cao, Leran Wang, Josh G Kim, Phillip I Tarr, Barbara B Warner, Nicolás Rosario Matos, Leyao Wang

2020-Current year OA Pubs

The gut microbiome is a potentially important mechanism that links prenatal disaster exposures with increased disease risks. However, whether prenatal disaster exposures are associated with alterations in the infant's gut microbiome remains unknown. We established a birth cohort study named Hurricane as the Origin of Later Alterations in Microbiome (HOLA) after Hurricane Maria struck Puerto Rico in 2017. We enrolled vaginally born Latino term infants aged 2 to 6 months, including

Development Of Novel Composite Data Quality Scores To Evaluate Facility-Level Data Quality In Electronic Data In Kenya: A Nationwide Retrospective Cohort Study, Beryne M Odeny, Anne Njoroge, Steve Gloyd, James P Hughes, Bradley H Wagenaar, Jacob Odhiambo, Lilly M Nyagah, Ayub Manya, Ooga Wesley Oghera, Nancy Puttkammer

2020-Current year OA Pubs

BACKGROUND: In this evaluation, we aim to strengthen Routine Health Information Systems (RHIS) through the digitization of data quality assessment (DQA) processes. We leverage electronic data from the Kenya Health Information System (KHIS) which is based on the District Health Information System version 2 (DHIS2) to perform DQAs at scale. We provide a systematic guide to developing composite data quality scores and use these scores to assess data quality in Kenya.

METHODS: We evaluated 187 HIV care facilities with electronic medical records across Kenya. Using quarterly, longitudinal KHIS data from January 2011 to June 2018 (total N = 30 quarters), …

Lipidome Of Mammographic Breast Density In Premenopausal Women, Kayla R Getz, Myung Sik Jeon, Chongliang Luo, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women.

METHODS: Premenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon …

Multivariate Gwas Of Alzheimer's Disease Csf Biomarker Profiles Implies Grin2d In Synaptic Functioning, Alexander Neumann, Jigyasha Timsina, Thomas W Marsh, Priyanka Gorijala, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.

METHODS: We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD …