Medicine and Health Sciences Commons^™

Myocardial Relaxation Is Accelerated By Fast Stretch, Not Reduced Afterload, Charles S. Chung, Charles W. Hoopes, Kenneth S. Campbell

Physiology Faculty Publications

Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction. Therefore, we reevaluated the protocols that suggest reducing afterload accelerates the relaxation rate and identified that myocardial relengthening was a potential confounding factor. We hypothesized that the …

Does Mental Status Impact Therapist And Patient Communication In Emergency Department Brief Interventions Addressing Alcohol Use?, Brian Borsari, Timothy R. Apodaca, Ali Yurasek, Peter M. Monti

Manuscripts, Articles, Book Chapters and Other Papers

Motivational interviewing (MI) is often incorporated into screening, brief intervention, and referral to treatment (SBIRT) interventions in critical care settings to address alcohol and other drug use. However, cognitive status has been linked to differential response to MI sessions in emergency department (ED) settings. The current study examined one possible explanation for this differential response: whether higher versus lower mental status impacts patient response to clinician statements during MI sessions conducted in an ED. Participants were 126 patients receiving an MI-based single-session alcohol brief intervention, and 13 therapists who provided treatment. Participants completed a mental status exam (MSE) as part …

Interhospital Transfer Of Children In Respiratory Failure: A Clinician Interview Qualitative Study., Folafoluwa O. Odetola, Renee R. Anspach, Yong Y. Han, Sarah J. Clark

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To investigate the decision making underlying transfer of children with respiratory failure from level II to level I pediatric intensive care unit care.

METHODS: Interviews with 19 eligible level II pediatric intensive care unit physicians about a hypothetical scenario of a 2-year-old girl in respiratory failure: RESULTS: At baseline, indices critical to management were as follows: OI (53%), partial pressure of oxygen in arterial blood (Pao

CONCLUSION: Interhospital transfer of children in respiratory failure is triggered by poor response to escalation of locally available care modalities. This finding provides new insight into decision making underlying interhospital transfer of children …

Large-Scale Behavior-Change Initiative For Infant And Young Child Feeding Advanced Language And Motor Development In A Cluster-Randomized Program Evaluation In Bangladesh, Edward A. Frongillo Jr., Phuong H. Nguyen, Kuntal K. Saha, Tina Sanghvi, Kaosar Afsana, Raisul Haque, Jean Baker, Marie T. Ruel, Rahul Rawat, Purnima Menon

Faculty Publications

Background: Promoting adequate nutrition through interventions to improve infant and young child feeding (IYCF) has the potential to contribute to child development.

Objective: We examined whether an intensive intervention package that was aimed at improving IYCF at scale through the Alive & Thrive initiative in Bangladesh also advanced language and gross motor development, and whether advancements in language and gross motor development were explained through improved complementary feeding.

Methods: A cluster-randomized design compared 2 intervention packages: intensive interpersonal counseling on IYCF, mass media campaign, and community mobilization (intensive) compared with usual nutrition counseling and mass media campaign (nonintensive). Twenty subdistricts …

Newborn Sequencing In Genomic Medicine And Public Health., Jonathan S. Berg, Pankaj B. Agrawal, Donald B. Bailey, Alan H. Beggs, Steven E. Brenner, Amy M. Brower, Julie A. Cakici, Ozge Ceyhan-Birsoy, Kee Chan, Flavia Chen, Robert J. Currier, Dmitry Dukhovny, Robert C. Green, Julie Harris-Wai, Ingrid A. Holm, Brenda Iglesias, Galen Joseph, Stephen F. Kingsmore, Barbara A. Koenig, Pui-Yan Kwok, John Lantos, J Steven Leeder, Megan A. Lewis, Amy L. Mcguire, Laura V. Milko, Sean D. Mooney, Richard B. Parad, Stacey Pereira, Josh E. Petrikin, Bradford C. Powell, Cynthia M. Powell, Jennifer M. Puck, Heidi L. Rehm, Neil Risch, Myra Roche, Joseph T. Shieh, Narayanan Veeraraghavan, Michael S. Watson, Laurel K. Willig, Timothy W. Yu, Tiina Urv, Anastasia L. Wise

Manuscripts, Articles, Book Chapters and Other Papers

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing …

Family Strategies To Support Siblings Of Pediatric Hematopoietic Stem Cell Transplant Patients., Taylor E. White, Kristopher A. Hendershot, Margie D. Dixon, Wendy Pelletier, Ann Haight, Kristin Stegenga, Melissa A. Alderfer, Lydia Cox, Jeffrey M. Switchenko, Pamela Hinds, Rebecca D. Pentz

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To describe the strategies families report using to address the needs and concerns of siblings of children, adolescents, and young adults undergoing hematopoietic stem cell transplant (HSCT).

METHODS: A secondary semantic analysis was conducted of 86 qualitative interviews with family members of children, adolescents, and young adults undergoing HSCT at 4 HSCT centers and supplemented with a primary analysis of 38 additional targeted qualitative interviews (23 family members, 15 health care professionals) conducted at the primary center. Analyses focused on sibling issues and the strategies families use to address these issues.

RESULTS: The sibling issues identified included: (1) feeling …

Reexamining The Hypoglycemia Fear Survey For Parents Of Young Children In A Sample Of Children Using Insulin Pumps., Susana R. Patton, Amy E. Noser, Mark A. Clements, Lawrence M. Dolan, Scott W. Powers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We update the psychometric properties of the Hypoglycemia Fear Survey-Parents of Young Children (HFS-PYC), a 26-item measure of parents' hypoglycemia fear for young children using an insulin pump.

METHODS: We combined three similar datasets for the analyses. The data analyzed included parents' responses to the HFS-PYC and a demographic form. For a subset of children (n = 91), we also analyzed self-monitoring of blood glucose data. We used confirmatory factor analysis (CFA) to confirm the measure's original factor structure. Additional analyses examined reliability and validity of a revised HFS-PYC for parents of young children using pumps.

RESULTS: We analyzed …

Metronidazole Metabolism In Neonates And The Interplay Between Ontogeny And Genetic Variation., Laura A. Wang, Daniel Gonzalez, J Steven Leeder, Rachel F. Tyndale, Robin E. Pearce, Daniel K. Benjamin, Gregory L. Kearns, Michael Cohen-Wolkowiez, Best Pharmaceuticals For Children Act-Pediatric Trials Network Steering Committee

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Surrogate Pregnancy After Prenatal Diagnosis Of Spina Bifida., Lynnette J. Mazur, Mary Kay Kisthardt, Helen H. Kim, Laura M. Rosas, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Some pregnancies today involve infertile individuals or couples who contract with a fertile woman to carry a pregnancy for them. The woman who carries the pregnancy is referred to as a "gestational carrier." The use of such arrangements is increasing. Most of the time, these arrangements play out as planned; sometimes, however, problems arise. This article discusses a case in which a fetal diagnosis of spina bifida led the infertile couple to request that the gestational carrier terminate the pregnancy, and the gestational carrier did not wish to do so. Experts in the medical and legal issues surrounding surrogacy discuss …

Use Of The Ketogenic Diet In The Neonatal Intensive Care Unit-Safety And Tolerability., Lindsey M. Thompson, Erin Day Fecske, Mohammad Salim, Ara Hall

Manuscripts, Articles, Book Chapters and Other Papers

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common …

Outcomes From A 12-Week, Open-Label, Multicenter Clinical Trial Of Teduglutide In Pediatric Short Bowel Syndrome., Beth A. Carter, Valeria C. Cohran, Conrad R. Cole, Mark R. Corkins, Reed A. Dimmitt, Christopher Duggan, Susan Hill, Simon Horslen, Joel D. Lim, David F. Mercer, Russell J. Merritt, Peter F. Nichol, Luther Sigurdsson, Daniel H. Teitelbaum, John Thompson, Charles Vanderpool, Juliana F. Vaughan, Benjamin Li, Nader N. Youssef, Robert S. Venick, Samuel A. Kocoshis

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF).

STUDY DESIGN: This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used.

RESULTS: All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related …

Interdisciplinary Care Of Children With Severe Bronchopulmonary Dysplasia., Steven H. Abman, Joseph M. Collaco, Edward G. Shepherd, Martin Keszler, Milenka Cuevas-Guaman, Stephen E. Welty, William E. Truog, Sharon A. Mcgrath-Morrow, Paul E. Moore, Lawrence M. Rhein, Haresh Kirpalani, Huayan Zhang, Linda L. Gratny, Susan K. Lynch, Jennifer Curtiss, Barbara S. Stonestreet, Robin L. Mckinney, Kevin C. Dysart, Jason Gien, Christopher D. Baker, Pamela K. Donohue, Eric Austin, Candice Fike, Leif D. Nelin, Bronchopulmonary Dysplasia Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Metronidazole Metabolism In Neonates And The Interplay Between Ontogeny And Genetic Variation., Laura A. Wang, Daniel Gonzalez, J Steven Leeder, Rachel F. Tyndale, Robin E. Pearce, Daniel K. Benjamin, Gregory L. Kearns, Michael Cohen-Wolkowiez, Best Pharmaceuticals For Children Act-Pediatric Trials Network Steering Committee

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Age-Dependent Absolute Abundance Of Hepatic Carboxylesterases (Ces1 And Ces2) By Lc-Ms/Ms Proteomics: Application To Pbpk Modeling Of Oseltamivir In Vivo Pharmacokinetics In Infants., Mikael Boberg, Marc Vrana, Aanchal Mehrotra, Robin E. Pearce, Andrea Gaedigk, Deepak Kumar Bhatt, J Steven Leeder, Bhagwat Prasad

Manuscripts, Articles, Book Chapters and Other Papers

The age-dependent absolute protein abundance of carboxylesterase (CES) 1 and CES2 in human liver was investigated and applied to predict infant pharmacokinetics (PK) of oseltamivir. The CES absolute protein abundance was determined by liquid chromatography-tandem mass spectrometry proteomics in human liver microsomal and cytosolic fractions prepared from tissue samples obtained from 136 pediatric donors and 35 adult donors. Two surrogate peptides per protein were selected for the quantification of CES1 and CES2 protein abundance. Purified CES1 and CES2 protein standards were used as calibrators, and the heavy labeled peptides were used as the internal standards. In hepatic microsomes, CES1 and …

Cystatin C And Cardiac Measures In Children And Adolescents With Ckd., Tammy M. Brady, Kelly Townsend, Michael F. Schneider, Christopher Cox, Thomas Kimball, Peace Madueme, Bradley A. Warady, Susan Furth, Mark Mitsnefes

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. …

Moderating Effects Of Immunosuppressive Medications And Risk Factors For Post-Operative Joint Infection Following Total Joint Arthroplasty In Patients With Rheumatoid Arthritis Or Osteoarthritis, Elizabeth G. Salt, Amanda T. Wiggins, Mary Kay Rayens, Brent J. Morris, David M. Mannino, Andrew Hoellein, Ryan P. Donegan, Leslie J. Crofford

Nursing Faculty Publications

Objective—Inconclusive findings about infection risks, importantly the use of immunosuppressive medications, in patients who have undergone large-joint total joint arthroplasty challenge efforts to provide evidenced-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a postoperative infection in patients undergoing TJA of a large joint [total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty] by identifying clinical and demographic factors, including the use of high risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses (i.e., rheumatoid arthritis [RA], osteoarthritis [OA], gout, obesity, diabetes mellitus), that …

Treatment Outcomes For Inpatients With Obsessive-Compulsive Personality Disorder: An Open Comparison Trial, Ryan Smith, Christopher Shepard, Anika Wiltgen, Katrina Rufino, J Christopher Fowler

Staff and Researcher Publications

Background: The current case-control study compared rates of clinically significant and reliable change in psychopathology and global functioning, prevalence of clinical deterioration, and rates of symptom remission among adult patients with obsessive compulsive personality disorder OCPD (n=52) and well-matched inpatients with any other personality disorder (n=56) and no personality disorder (n=53).

Methods: Propensity score matching (PSM) was utilized to select patients matched on specific criteria present in the OCPD group. Multivariate analysis of variance models measured differences in admission functioning and RCI change across depression and anxiety severity, emotion dysregulation and suicidal ideation.

Results: Patients diagnosed with OCPD admit to …

Fare Thee Well, Dr Cooley, Herbert L Fred, James T Willerson

The Texas Heart Institute Journal

No abstract provided.

Clinical Risk Factors For Infective Endocarditis In Staphylococcus Aureus Bacteremia, Vincent Bryan D Salvador, Bikash Chapagain, Astha Joshi, Debra J Brennessel

The Texas Heart Institute Journal

Crucial to the management of staphylococcal bacteremia is an accurate evaluation of associated endocarditis, which has both therapeutic and prognostic implications. Because the clinical presentation of endocarditis can be nonspecific, the judicious use of echocardiography is important in distinguishing patients at high risk of developing endocarditis. In the presence of high-risk clinical features, an early transesophageal echocardiogram is warranted without prior transthoracic echocardiography.

The purpose of this study was to investigate the clinical risk factors for staphylococcal infective endocarditis that might warrant earlier transesophageal echocardiography and to describe the incidence of endocarditis in cases of methicillin-resistant and methicillin-sensitive Staphylococcus aureus …

Titanium Plug Closure After Heartware Ventricular Assist Device Explantation In A 15-Year-Old Girl: First Us Experience, Diego A Lara, Aamir Jeewa, Barbara A Elias, Elizabeth O Mccullum, Susan W Denfield, William J Dreyer, Iki Adachi

The Texas Heart Institute Journal

We describe the case of a teenage girl with anthracycline-induced cardiomyopathy who received a HeartWare ventricular assist device and underwent successful device explantation after cardiac recovery. During device support, the patient's cardiac function returned to normal. Twelve months after implantation, we explanted the device via repeat median sternotomy. To close the hole in the left ventricular apex and preserve the sewing ring in case future device support is needed, we used a German-manufactured titanium plug, developed specifically for this purpose. To our knowledge, this is the first use of this plug in the United States. The patient recovered uneventfully and …

Percutaneous Valvuloplasty For Bioprosthetic Tricuspid Valve Stenosis, Gaurav Rana, Rohit Malhotra, Anjali Sharma, Nikolaos Kakouros

The Texas Heart Institute Journal

Percutaneous transcatheter tricuspid balloon valvuloplasty (PTTBV) is an accepted treatment option for symptomatic severe native tricuspid valve stenosis, although surgical tricuspid valve replacement remains the treatment of choice. There have been few reports of successful PTTBV for bioprosthetic tricuspid valve stenosis. We present case reports of 3 patients from our hospital experience. Two of the 3 cases were successful, with lasting clinical improvement, whereas the 3rd patient failed to show a reduction in valve gradient. We describe the standard technique used for PTTBV. We present results from a literature review that identified 16 previously reported cases of PTTBV for bioprosthetic …

Cancer Antigen 125 Is Associated With Length Of Stay In Patients With Acute Heart Failure, Hakki Kaya, Recep Kurt, Osman Beton, Ali Zorlu, Hasan Yucel, Hakan Gunes, Didem Oguz, Mehmet Birhan Yilmaz

The Texas Heart Institute Journal

Length of stay is the primary driver of heart-failure hospitalization costs. Because cancer antigen 125 has been associated with poor morbidity and mortality rates in heart failure, we investigated the relationship between admission cancer antigen 125 levels and lengths of stay in heart-failure patients. A total of 267 consecutive patients (184 men, 83 women) with acute decompensated heart failure were evaluated prospectively. The median length of stay was 4 days, and the patients were classified into 2 groups: those with lengths of stay ≤4 days and those with lengths of stay >4 days. Patients with longer lengths of stay had …

Safety And Improvement Of Movement Function After Stroke With Atomoxetine: A Pilot Randomized Trial, Andrea Ward, Cheryl Carrico, Elizabeth Powell, Philip M. Westgate, Laurie Nichols, Anne Fleischer, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

Background: Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention.

Objective: Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke.

Methods: In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, …

Qualitative Study Of Primary Care Clinicians' Views On Point-Of-Care Testing For C-Reactive Protein For Acute Respiratory Tract Infections In Family Medicine., Victoria Hardy, Matthew Thompson, Gina A Keppel, William Alto, M Ashworth Dirac, Jon Neher, Christopher Sanford, Jaime Hornecker, Allison Cole

Articles, Abstracts, and Reports

OBJECTIVE: To explore clinicians views of the barriers and facilitators to use of C-reactive protein (CRP) point-of-care tests (POCT) in US family medicine clinics for the management of acute respiratory tract infections (ARTIs) in adults.

SETTING: Five family medicine clinics across two US states.

PARTICIPANTS: 30 clinicians including 18 physicians, 9 physician residents, 2 physician assistants and 1 nurse practitioner, took part in the study.

DESIGN: A qualitative study using a grounded theory approach to thematically analyse focus group interviews.

RESULTS: These clinicians had limited access to diagnostic tests for patients with ARTI, and very little knowledge of CRP POCT. …

Caesarean Sections And For-Profit Status Of Hospitals: Systematic Review And Meta-Analysis, Ilir Hoxha, Lamprini Syrogiannouli, Xhyljeta Luta, Kali Tal, David C. Goodman

Dartmouth Scholarship

Objective: Financial incentives may encourage private for-profit providers to perform more caesarean section (CS) than non-profit hospitals. We therefore sought to determine the association of for-profit status of hospital and odds of CS.

Design: Systematic review and meta-analysis. Data sources: MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from the first year of records through February 2016. Eligibility criteria: To be eligible, studies had to report data to allow the calculation of ORs of CS comparing private for-profit hospitals with public or private non-profit hospitals in a specific geographic area. Outcomes: The prespecified primary outcome was the adjusted OR …

A Cognitive Electrophysiological Signature Differentiates Amnestic Mild Cognitive Impairment From Normal Aging, Juan Li, Lucas S. Broster, Gregory A. Jicha, Nancy B. Munro, Frederick A. Schmitt, Erin L. Abner, Richard J. Kryscio, Charles D. Smith, Yang Jiang

Behavioral Science Faculty Publications

Background: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education.

Methods: Eighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be …

Crispr-Cas9 Mediated Nox4 Knockout Inhibits Cell Proliferation And Invasion In Hela Cells, Naser Jafari, Hyunju Kim, Rackhyun Park, Liqing Li, Minsu Jang, Andrew J. Morris, Junsoo Park, Cai Huang

Markey Cancer Center Faculty Publications

Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood. We generated NOX4 knockout HeLa cell lines using the CRISPR-Cas9 gene editing system to explore the cellular functions of NOX4. After transfection of CRISPR-Cas9 construct, we performed T7 endonuclease 1 assays and DNA sequencing to generate and identify insertion and deletion of the NOX4 locus. We confirmed the knockout of NOX4 by Western blotting. NOX4 knockout cell lines showed reduced cell proliferation with an increase of sub-G1 cell population and the decrease of S/G2/M …

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …

Supporting Shared Decision-Making For Older People With Multiple Health And Social Care Needs: A Protocol For A Realist Synthesis To Inform Integrated Care Models, Frances Bunn, Claire Goodman, Jill Manthorpe, Marie-Anne Durand, Isabel Hodkinson, Greta Rait, Paul Millac, Sue L. Davies, Bridget Russell, Patricia Wilson

Dartmouth Scholarship

Introduction: Including the patient or user perspective is a central organising principle of integrated care. Moreover, there is increasing recognition of the importance of strengthening relationships among patients, carers and practitioners, particularly for individuals receiving substantial health and care support, such as those with long-term or multiple conditions. The overall aims of this synthesis are to provide a context-relevant understanding of how models to facilitate shared decision-making (SDM) might work for older people with multiple health and care needs, and how they might be applied to integrated care models.

Methods and analysis: The synthesis draws on the principles of realist …

Neutralization Of Diverse Human Cytomegalovirus Strains Conferred By Antibodies Targeting Viral Gh/Gl/Pul128-131 Pentameric Complex, Sha Ha, Fengsheng Li, Matthew C. Troutman, Daniel C. Freed, Aimin Tang, John W. Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C. Nickle, Richard R. Rustandi, Melissa Hamm, Pete A. Dephillips, Ningyan Zhang, Jason S. Mclellan, Stuart P. Adler, Michael A. Mcvoy, Zhiqiang An, Tong-Ming Fu

Dartmouth Scholarship

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a …