Medicine and Health Sciences Commons^™

Shared Genetic Architecture Of Non-Viral Cirrhosis With Several Pleiotropic Traits: A Nested Case-Control Study In The Uk Biobank, Jinyoung Byun, Hyun-Seok Kim, Younghun Han, Aaron P Thrift, Sabrina M Lin, Xiangjun Xiao, Hyeyeun Lim, Goo Jun, Stacia M Desantis, Hashem B El-Serag, Fasiha Kanwal, Christopher I Amos

Faculty, Staff and Students Publications

Background & aims: Cirrhosis is a leading cause of liver-related mortality and a multifactorial disease. To date, the complex genetic architecture of non-viral cirrhosis has not been fully explored. Cross-trait genetic correlations can elucidate the common genetic etiology of genetically correlated phenotypes. This study aims to identify polygenic and pleiotropic traits associated with cirrhosis using the linkage disequilibrium score regression analysis.

Methods: We conducted genome-wide association analysis of 9,622,842 imputed SNPs on 3,368 non-viral cirrhosis cases and 258,258 controls, and cross-trait analysis between non-viral cirrhosis and various polygenic and pleiotropic traits using the UK Biobank cohort study. We further performed …

Corrigendum To “The Systemic Availability Of Indispensable Amino Acids From Orally Ingested Algal And Legume Protein In Young Children At Risk Of Environmental Enteric Dysfunction” [Am J Clin Nutr 188 (2024) 96–102], Nirupama Shivakumar, Sindhu Kashyap, Farook Jahoor, Sarita Devi, Thomas Preston, Tinku Thomas, Anura V Kurpad

Faculty, Staff and Students Publications

The authors would like to add a second affiliation for Dr Nirupama Shivakumar. It is as follows: Center for Doctoral Studies, Manipal Academy of Higher Education, Manipal, India.

Understanding Health-Related Quality Of Life After Hypospadias Repair: A Qualitative Study With Pre-Adolescent Males And Parents, Vinaya Bhatia, Shannon Cannon, Anjali N Patel, Heidi W Brown, Walid A Farhat, Marisa E Hilliard

Faculty, Staff and Students Publications

Introduction: Hypospadias is a common disease that affects approximately 1 in every 200 live male births in the United States, and long-term studies of individuals who have undergone repair demonstrate complication rates of 15%-70%. The Hypospadias-Specific Health-related Quality of Life (HRQOL) Conceptual Framework for youth and adults suggests that additional morbidity may be incurred from poor psychological, social, and sexual health. The current study sought to clarify hypospadias-specific HRQOL and care priorities in a pre-pubertal population.

Material and methods: This IRB-approved, semi-structured interview study used rigorous qualitative research methods. Eligible patients were English-speaking 8-12-year-old males with hypospadias and their parents. …

Mecp2 Variants In Males: More Common Than Previously Appreciated, Amitha Ananth, Cary Fu, Jeffrey L Neul, Tim Benke, Eric Marsh, Bernhard Suter, Kathleen Ferdinandsen, Steven A Skinner, Fran Annese, Alan K Percy

Faculty, Staff and Students Publications

Background: To assess the age and MECP2 variants of recently identified males and set the stage for further study of clinical features in males.

Methods: Genetic information on the specific MECP2 variant was acquired from the coordinator (K.F.) of the Parent Group for Males. Data were collected indicating whether these variants were de novo or transmitted from the mother and whether males who appeared to meet the diagnostic criteria for Rett syndrome had mosaicism for the MECP2 variant.

Results: Fifty-nine males were identified through the parent group. Their ages ranged from 2 to 28 years, with the median age being …

Pediatric High Blood Pressure Recognition Associated With Electronic Decision Support: A Cohort Analysis, Justin P Zachariah, Tavleen Singh, Shannon Collinson, Justin Rahman, Alisa A Acosta, Jessica F Campbell, Mary Hoang, Katharine E Sigler, Elizabeth A Onugha, Shweta S Shah, S Kristen Sexson-Tejtel, Mark Farrior, Scott Watson

Faculty, Staff and Students Publications

Background: Pediatric high blood pressure (BP) predicts future cardiovascular disease events. High BP is improperly measured, underrecognized, and undermanaged especially in disadvantaged populations. In a large, diverse, academic pediatric practice, we detail the associations of a comprehensive initiative with high BP provider recognition.

Methods: A comprehensive BP initiative was promulgated including (1) retraining providers and staff on BP management; (2) deploying equipment at 55+ sites; and (3) electronic decision support tool alerting staff and clinicians and suggesting management. During the 14-month preintervention and 14-month postintervention periods, data on BP and patient characteristics were collected. The outcome was incident BP recognition …

International Classification System For Ocular Complications Of Anti-Vegf Agents In Clinical Trials, Marko M Popovic, Michael Balas, Srinivas R Sadda, David Sarraf, Ryan Huang, Sophie J Bakri, Audina Berrocal, Andrew Chang, Chui Ming Gemmy Cheung, Sunir Garg, Roxane J Hillier, Frank G Holz, Mark W Johnson, Peter K Kaiser, Peter J Kertes, Timothy Y Y Lai, Jason Noble, Susanna S Park, Yannis M Paulus, Giuseppe Querques, Aleksandra Rachitskaya, Paisan Ruamviboonsuk, Shohista Saidkasimova, Maria Teresa Sandinha, David H Steel, Hiroko Terasaki, Christina Y Weng, Basil K Williams, Lihteh Wu, Rajeev H Muni

Faculty, Staff and Students Publications

Purpose: Complications associated with intravitreal anti-VEGF therapies are reported inconsistently in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process.

Design: Systematic review and Delphi consensus process.

Participants: Twenty-five international retinal specialists participated in the Delphi consensus survey.

Methods: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to …

The Long Road Of Drug Development For Endometriosis – Pains, Gains, And Hopes, Zian Liao, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Endometriosis, defined by the growth of endometrial tissues outside of the uterine cavity, is a global health burden for ∼200 million women. Patients with endometriosis usually present with chronic pain and are often diagnosed with infertility. The pathogenesis of endometriosis is still an open question; however, tissue stemness and immunological and genetic factors have been extensively discussed in the establishment of endometriotic lesions. Current treatments for endometriosis can be categorized into pharmacological management of hormone levels and surgical removal of the lesions. Both approaches have limited efficacy, with recurrences often encountered; thus, there is no complete cure for the disease …

Association Of Left Atrial Function With Frailty: The Atherosclerosis Risk In Communities (Aric) Study, Daokun Sun, Romil R Parikh, Wendy Wang, Anne Eaton, Pamela L Lutsey, B Gwen Windham, Riccardo M Inciardi, Scott D Solomon, Christie M Ballantyne, Amil M Shah, Lin Yee Chen

Faculty, Staff and Students Publications

Background: Frailty is common in people with cardiovascular disease. Worse left atrial (LA) function is an independent risk factor for cardiovascular disease. However, whether worse LA function is associated with frailty is unclear.

Methods: We included 3292 older adults from the Atherosclerosis Risk in Communities study who were non-frail at baseline (visit 5, 2011-2013) and had LA function (reservoir, conduit, and contractile strain) measured from two-dimensional speckle-tracking echocardiography. LA stiffness index was calculated as a ratio of E/e' to LA reservoir strain. Frailty was defined using the validated Fried frailty phenotype. Incident frailty was assessed between 2016 and 2019 during …

Molecular Imaging Of Macrophage Composition And Dynamics In Masld, Bin Q Yang, Mandy M Chan, Gyu Seong Heo, Lanlan Lou, Hannah Luehmann, Christopher Park, Alexandria Li, Divangana Lahad, Deborah Sultan, Peter Voller, Kathleen Byrnes, Christina Fu, Yongjian Liu, Joel D Schilling

2020-Current year OA Pubs

BACKGROUND & AIMS: Metabolic-dysfunction associated steatohepatitis (MASH) is associated with obesity and diabetes, and is linked to liver fibrosis and cardiovascular disease. Identification of patients who have MASH is challenging and the development of non-invasive strategies to diagnose and follow this condition is an important unmet need. Recent studies in mouse and humans have identified that significant changes occur in liver macrophage composition during MASH progression; namely, resident Kupffer cells decrease in number while recruited monocyte-derived macrophages increase.

METHODS: We developed peptide radiotracers targeted to C-C motif chemokine receptor 2 (CCR2) and CD163 to conduct positron emission tomography (PET) imaging …

Molecular Imaging In Experimental Pulmonary Fibrosis Reveals That Nintedanib Unexpectedly Modulates Ccr2 Immune Cell Infiltration, Hasan Farooq, Hannah P Luehmann, Jeffrey R Koenitzer, Gyu Seong Heo, Deborah H Sultan, Devesha H Kulkarni, Sean P Gunsten, Rekha M Sashti, Tao Huang, Amanda R Keller, Kory J Lavine, Jeffrey J Atkinson, Laura M Wingler, Yongjian Liu, Steven L Brody

2020-Current year OA Pubs

BACKGROUND: Pulmonary fibrosis is a challenging clinical problem with lung pathology featuring immune cell infiltrates, fibroblast expansion, and matrix deposition. Molecular analysis of diseased lungs and preclinical models have uncovered C-C chemokine receptor type 2 (CCR2)+ monocyte egress from the bone marrow into the lung, where they acquire profibrotic activities. Current drug treatment is focused on fibroblast activity. Alternatively, therapeutic targeting and monitoring CCR2+ cells may be an effective patient management strategy.

METHODS: Inhibition of CCR2+ cells and, as a benchmark, the clinical antifibrotic agent, nintedanib, were used in mouse lung fibrosis models. Lungs were evaluated directly for CCR2+ cell …

Tyk2 Regulates Tau Levels, Phosphorylation And Aggregation In A Tauopathy Mouse Model, Jiyoen Kim, Bakhos Tadros, Yan Hong Liang, Youngdoo Kim, Cristian Lasagna-Reeves, Jun Young Sonn, Dah-Eun Chloe Chung, Bradley Hyman, David M Holtzman, Huda Yahya Zoghbi

2020-Current year OA Pubs

Alzheimer's disease is one of at least 26 diseases characterized by tau-positive accumulation in neurons, glia or both. However, it is still unclear what modifications cause soluble tau to transform into insoluble aggregates. We previously performed genetic screens that identified tyrosine kinase 2 (TYK2) as a candidate regulator of tau levels. Here we verified this finding and found that TYK2 phosphorylates tau at tyrosine 29 (Tyr29) leading to its stabilization and promoting its aggregation in human cells. We discovered that TYK2-mediated Tyr29 phosphorylation interferes with autophagic clearance of tau. We also show that TYK2-mediated phosphorylation of Tyr29 facilitates pathological tau …

Pet Clinical Study Of Novel Antipsychotic Lb-102 Demonstrates Unexpectedly Prolonged Dopamine Receptor Target Engagement, Dean F Wong, Ganesh B Chand, Nicole Caito, Anna Eramo, Vincent T Grattan, Mark S Hixon, Ginger Nicol, Erin Lessie, Zachary Prensky, Hiroto Kuwabara, Lucy Tian, Ines Valenta, Thomas H Schindler, Gerhard Gründer, Andrew R Vaino

2020-Current year OA Pubs

Regulation of dopamine activity has important clinical consequences, most notably in schizophrenia. LB-102, N-methyl amisulpride, is a novel dopamine D

Volumetric Breast Density Estimation From Three-Dimensional Reconstructed Digital Breast Tomosynthesis Images Using Deep Learning, Vinayak S Ahluwalia, Nehal Doiphode, Walter C Mankowski, Eric A Cohen, Sarthak Pati, Lauren Pantalone, Spyridon Bakas, Ari Brooks, Celine M Vachon, Emily F Conant, Aimilia Gastounioti, Despina Kontos

2020-Current year OA Pubs

PURPOSE: Breast density is a widely established independent breast cancer risk factor. With the increasing utilization of digital breast tomosynthesis (DBT) in breast cancer screening, there is an opportunity to estimate volumetric breast density (VBD) routinely. However, current available methods extrapolate VBD from two-dimensional (2D) images acquired using DBT and/or depend on the existence of raw DBT data, which is rarely archived by clinical centers because of storage constraints.

METHODS: We retrospectively analyzed 1,080 nonactionable three-dimensional (3D) reconstructed DBT screening examinations acquired between 2011 and 2016. Reference tissue segmentations were generated using previously validated software that uses 3D reconstructed slices …

Three Techniques For 360-Degree Gonioscopy-Assisted Transluminal Trabeculotomy With Itrack Advance, Sean Smith, Jessie Wang, Shivani Kamat, Arsham Sheybani, Ian Patterson, Mary Qiu

2020-Current year OA Pubs

PURPOSE: 360-degree gonioscopy-assisted transluminal trabeculotomy (GATT) is a safe and effective angle-based intervention to lower IOP. Use of the iTrack Advance allows the surgeon to efficiently advance the microcatheter in one continuous motion with a slider, an improvement upon previous techniques in which microcatheters or sutures which had to be manually threaded through Schlemm's canal with microforceps. This report demonstrates three variations in surgical technique for successful 360-degree GATT using the iTrack Advance.

OBSERVATIONS: The first technique requires retrieval of the tip of the microcatheter and requires an assistant to hold the gonioprism. The second method also requires retrieval of …

Mucosal Single-Cell Profiling Of Crohn's-Like Disease Of The Pouch Reveals Unique Pathogenesis And Therapeutic Targets, Siyan Cao, Khai M Nguyen, Kaiming Ma, Xiaotang Du, Xiuli Liu, Alina Ulezko Antonova, Richard P Rood, Anas Gremida, Chien-Huan Chen, Alexandra Gutierrez, Deborah C Rubin, Martin H Gregory, Mate Gergely, Guadalupe Oliva Escudero, Katherine Huang, Natalia Jaeger, Marina Cella, Rodney D Newberry, Nicholas O Davidson, Matthew A Ciorba, Parakkal Deepak, Marco Colonna

2020-Current year OA Pubs

BACKGROUND & AIMS: The pathophysiology of Crohn's-like disease of the pouch (CDP) in patients with a history of ulcerative colitis (UC) is unknown. We examined mucosal cells from patients with and without CDP using single-cell analyses.

METHODS: Endoscopic samples were collected from pouch body and prepouch ileum (pouch/ileum) of 50 patients with an ileal pouch-anal anastomosis. Single-cell RNA sequencing was performed on pouch/ileal tissues of patients with normal pouch/ileum and CDP. Mass cytometry was performed on mucosal immune cells from patients with UC with normal pouch/ileum, CDP, pouchitis, and those with familial adenomatous polyposis after pouch formation. Findings were independently …

A Genetically Inducible Endothelial Niche Enables Vascularization Of Human Kidney Organoids With Multilineage Maturation And Emergence Of Renin Expressing Cells, Joseph C Maggiore, Haojia Wu, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Vascularization plays a critical role in organ maturation and cell-type development. Drug discovery, organ mimicry, and ultimately transplantation hinge on achieving robust vascularization of in vitro engineered organs. Here, focusing on human kidney organoids, we overcame this hurdle by combining a human induced pluripotent stem cell (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing a role in endothelial cell development) that directs endothelial differentiation in vitro, with a non-transgenic iPSC line in suspension organoid culture. The resulting human kidney organoids show extensive endothelialization with a cellular identity most closely related to human kidney endothelia. …

Review And Metabolomic Profiling Of Unsolved Case Reveals Newly Reported Autosomal Dominant Congenital Disorder Of Glycosylation, Type Iw Formerly Thought To Only Be An Autosomal Recessive Condition, Kimberly M Ezell, Yutaka Furuta, Devin Oglesbee, Eniko K Pivnick, David Rinker, Jonathan H Sheehan, Rory J Tinker, Rizwan Hamid, Joy D Cogan, Lynette Rives, Serena Neumann, Brian Corner, Mary Koziura, John A Phillips 3rd, Undiagnosed Diseases Network

2020-Current year OA Pubs

Autosomal dominant congenital disorder of glycosylation (CDG) type Iw (OMIM# 619714) is caused by a heterozygous mutation in the

Acral Fibrochondromyxoid Tumor: A Clinicopathologic And Molecular Genetic Study Of 37 Cases, Carina A Dehner, Jonathan C Baker, John S A Chrisinger, Et Al.

2020-Current year OA Pubs

Acral fibrochondromyxoid tumor (AFCMT) is a recently described likely benign mesenchymal neoplasm arising in the distal extremities with distinctive histologic features and a recurrent THBS1::ADGRF5 fusion. We studied an additional 37 cases of AFCMT and expanded on the so-far reported clinicopathologic and molecular findings. Tumors occurred in 21 females and 16 males, ranging in age from 17 to 78 years (median age: 47), and solely involved the hands (24/37, 65%) or feet (13/37, 35%). Histologic examination revealed well-delineated uni- or multinodular tumors with prominent vasculature-rich septa and bland, chondrocyte-like tumor cells set within abundant chondromyxoid stroma. Immunohistochemical studies showed that …

Development Of A Deep Learning Algorithm For Paneth Cell Density Quantification For Inflammatory Bowel Disease, Liang-I Kang, Kathryn Sarullo, Jon N Marsh, Liang Lu, Pooja Khonde, Changqing Ma, Talin Haritunians, Angela Mujukian, Emebet Mengesha, Dermot P B Mcgovern, Thaddeus S Stappenbeck, S Joshua Swamidass, Ta-Chiang Liu

2020-Current year OA Pubs

BACKGROUND: Alterations in ileal Paneth cell (PC) density have been described in gut inflammatory diseases such as Crohn's disease (CD) and could be used as a biomarker for disease prognosis. However, quantifying PCs is time-intensive, a barrier for clinical workflow. Deep learning (DL) has transformed the development of robust and accurate tools for complex image evaluation. Our aim was to use DL to quantify PCs for use as a quantitative biomarker.

METHODS: A retrospective cohort of whole slide images (WSI) of ileal tissue samples from patients with/without inflammatory bowel disease (IBD) was used for the study. A pathologist-annotated training set …

Development And Validation Of A Prechiasmatic Mouse Model Of Subarachnoid Hemorrhage To Measure Long-Term Cognitive Deficits, Deepti Diwan, Jogender Mehla, James W Nelson, James D Quirk, Sheng-Kwei Song, Sarah Cao, Benjamin Meron, Aminah Mostofa, Gregory J Zipfel

2020-Current year OA Pubs

Controllable and reproducible animal models of aneurysmal subarachnoid hemorrhage (SAH) are crucial for the systematic study of the pathophysiology and treatment of this debilitating condition. However, current animal models have not been successful in replicating the pathology and disabilities seen in SAH patients, especially the long-term neurocognitive deficits that affect the survivor's quality of life. Therefore, there is an unmet need to develop experimental models that reliably replicate the long-term clinical ramifications of SAH - especially in mice where genetic manipulations are straightforward and readily available. To address this need, a standardized mouse SAH model is developed that reproducibly produced …

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al.

2020-Current year OA Pubs

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a …

Research Priorities For Children With Hypoxic-Ischemic Encephalopathy Or Myelomeningocele: A Survey Of Parents, Renée A Shellhaas, Betsy Pilon, Judy Thibadeau, Stephanie M D Rau, John D E Barks, Ronald D Chervin

2020-Current year OA Pubs

No abstract provided.

Pathogenicity And Virulence Of Human Respiratory Syncytial Virus: Multifunctional Nonstructural Proteins Ns1 And Ns2, Trudy N Merritt, Jingjing Pei, Daisy W Leung

2020-Current year OA Pubs

Human respiratory syncytial virus (hRSV) is a major cause of lower respiratory tract infections in young children, the elderly, and immunocompromised. Despite its discovery over 60 years ago and the global impact on human health, limited effective prophylactic or therapeutic options have been available for hRSV infections. This has largely been attributed to the legacy of vaccine failure in the 1960s using a formalin-inactivated RSV , which led to enhancement of disease post exposure to hRSV infection and hampered subsequent development of vaccine candidates. Recent FDA approval of vaccines for older adults and pregnant individuals are major advancements but leaves …

Caesarean Section And Associated Factors In Nigeria: Assessing Inequalities Between Rural And Urban Areas—Insights From The Nigeria Demographic And Health Survey 2018, Emmanuel O. Adewuyi, Wole Akosile, Victory Olutuase, Aaron Akpu Philip, Rhoda Olaleru, Mary I. Adewuyi, Asa Auta, Vishnu Khanal

Research outputs 2022 to 2026

Introduction: When medically indicated, caesarean section (CS) can be a life-saving intervention for mothers and their newborns. This study assesses the prevalence of CS and its associated factors, focussing on inequalities between rural and urban areas in Nigeria. Methods: We disaggregated the Nigeria Demographic and Health Survey 2018 and performed analyses separately for Nigeria’s overall, rural, and urban residences. We summarised data using frequency tabulations and identified factors associated with CS through multivariable logistic regression analysis. Results: CS prevalence was 2.7% in Nigeria (overall), 5.2% in urban and 1.2% in rural areas. The North-West region had the lowest prevalence of …

Co-Designing A Digital Family-Led Intervention For Delirium Prevention And Management In Adult Critically Ill Patients: An Application Of The Double Diamond Design Process, Gideon U. Johnson, Amanda Towell-Barnard, Christopher Mclean, Glenn Robert, Beverley Ewens

Research outputs 2022 to 2026

Background: Co-designing healthcare interventions is gaining recognition as a novel and collaborative method. Co-design involves end-users from the start, ensuring that an intervention best meets their needs. Despite its potential benefits, this approach is not yet widely used in developing clinical interventions within intensive care units where the perspectives of patients, family members, and clinicians are crucial. Objective: To describe the application, benefits and challenges of the Double Diamond model to co-design a digital family-led voice reorientation intervention for delirium prevention and management in critically ill adult patients. Methods: The co-design process was guided by the Double Diamond model over …

Nursing And Medical Students’ Views Before And After Participation In A Simulated Ward-Based Interprofessional Learning Activity: An Exploratory Study, Hugh Davies, Olivia Gallagher, Amanda Cole, Carol Crevacore, Evelyn Kang, Kate Jutsum

Research outputs 2022 to 2026

Background: The complex nature of delivering healthcare requires teamwork within and between disciplines. None as important is teamwork between registered nurses and junior doctors. Understanding each other perspectives, practices and purpose offers the prospect of improved patient care. Opportunities for undergraduate interprofessional education allows the exchange of discipline specific knowledge to inform practice. Aim: To explore the views and attitudes of nursing and medical students before and after participation in a simulated ward-based interprofessional activity. Method: Final semester nursing and medical students from different universities were invited to record their views and attitudes before and after participation in an interprofessional …

The Expanding Role Of Exercise Oncology In Cancer Care: An Editorial Highlighting Emerging Research, David Mizrahi, Erika Rees-Punia, Robert U. Newton, Carolina X. Sandler

Research outputs 2022 to 2026

No abstract provided.

Higher Habitual Intakes Of Flavonoids And Flavonoid-Rich Foods Are Associated With A Lower Incidence Of Type 2 Diabetes In The Uk Biobank Cohort, Alysha S. Thompson, Amy Jennings, Nicola P. Bondonno, Anna Tresserra-Rimbau, Benjamin H. Parmenter, Claire Hill, Aurora Perez-Cornago, Tilman Kühn, Aedín Cassidy

Research outputs 2022 to 2026

Aim: To examine the associations of a diet high in flavonoid-rich foods, as reflected by a “Flavodiet Score” (FDS), the major individual food contributors to flavonoid intake, and flavonoid subclasses with type 2 diabetes (T2D) risk in the UK Biobank cohort. Materials and methods: Flavonoid intakes were estimated from ≥2 dietary assessments among 113,097 study participants [age at enrolment: 56 ± 8 years; 57% female] using the U.S Department of Agriculture (USDA) databases. Multivariable Cox proportional hazards models were used to investigate associations between dietary exposures and T2D. Results: During 12 years of follow-up, 2628 incident cases of T2D were …

Associations Of Metabolic Changes And Polygenic Risk Scores With Cardiovascular Outcomes And All-Cause Mortality Across Bmi Categories: A Prospective Cohort Study, Cancan Li, Xiaoni Meng, Jie Zhang, Haotian Wang, Huimin Lu, Meiling Cao, Shengzhi Sun, Youxin Wang

Research outputs 2022 to 2026

Background: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories. Methods: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories. Results: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed. Conclusions: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved. Graphical abstract: (Figure presented.)

Dual-Trajectory Of Tyg Levels And Lifestyle Scores And Their Associations With Ischemic Stroke In A Non-Diabetic Population: A Cohort Study, Hui Zhou, Xiong Ding, Yulong Lan, Wei Fang, Xiaojie Yuan, Yan Tian, Shuohua Chen, Shouling Wu, Dan Wu

Research outputs 2022 to 2026

Background: The Triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been implicated in the risk of ischemic stroke. However, the interplay between TyG levels, lifestyle factors, and their collective impact on stroke risk in non-diabetic populations remains inadequately explored. This study aims to evaluate the association of ischemic stroke with the joint development of the TyG index and lifestyle in the non-diabetic population. Methods: In this prospective cohort study, data was collected across three consecutive biennial surveys of the Kailuan Study from 2006 to 2011. The dual-trajectory model was used to determine the temporal development of TyG levels …