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Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.
Giri A, Hellwege JN, Keaton JM, Park J, Qiu C, Warren HR, Torstenson ES, Kovesdy CP, Sun YV, Wilson OD, Robinson-Cohen C, Roumie CL, Chung CP, Birdwell KA, Damrauer SM, DuVall SL, Klarin D, Cho K, Wang Y, Evangelou E, Cabrera CP, Wain LV, Shrestha R, Mautz BS, Akwo EA, Sargurupremraj M, Debette S, Boehnke M, Scott LJ, Luan J, Zhao JH, Willems SM, Thériault S, Shah N, Oldmeadow C, Almgren P, Li-Gao R, Verweij N, Boutin TS, Mangino M, Ntalla I, Feofanova E, Surendran P, Cook JP, Karthikeyan S, Lahrouchi N, Liu C, Sepúlveda N, Richardson TG, Kraja A, Amouyel P, Farrall M, Poulter NR, Understanding Society Scientific Group, International Consortium for Blood Pressure, Blood Pressure-International Consortium of Exome Chip Studies, Laakso M, Zeggini E, Sever P, Scott RA, Langenberg C, Wareham NJ, Conen D, Palmer CNA, Attia J, Chasman DI, Ridker PM, Melander O, Mook-Kanamori DO, Harst PV, Cucca F, Schlessinger D, Hayward C, Spector TD, Jarvelin MR, Hennig BJ, Timpson NJ, Wei WQ, Smith JC, Xu Y, Matheny ME, Siew EE, Lindgren C, Herzig KH, Dedoussis G, Denny JC, Psaty BM, Howson JMM, Munroe PB, Newton-Cheh C, Caulfield MJ, Elliott P, Gaziano JM, Concato J, Wilson PWF, Tsao PS, Velez Edwards DR, Susztak K, Million Veteran Program, O'Donnell CJ, Hung AM, Edwards TL
(2019) Nat Genet 51: 51-62
MeSH Terms: Adolescent, Animals, Blood Pressure, Ethnic Groups, Female, Gene Expression, Genome-Wide Association Study, Humans, Kidney Tubules, Male, Mice, Middle Aged, Polymorphism, Single Nucleotide, Transcriptome, Up-Regulation
Show Abstract · Added January 3, 2019
In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.
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1 Members
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15 MeSH Terms
Pancreas Volume Declines During the First Year After Diagnosis of Type 1 Diabetes and Exhibits Altered Diffusion at Disease Onset.
Virostko J, Williams J, Hilmes M, Bowman C, Wright JJ, Du L, Kang H, Russell WE, Powers AC, Moore DJ
(2019) Diabetes Care 42: 248-257
MeSH Terms: Adolescent, Adult, Atrophy, Autoantibodies, Case-Control Studies, Child, Child, Preschool, Cohort Studies, Diabetes Mellitus, Type 1, Female, Glucose Tolerance Test, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Pancreas, Time Factors, Young Adult
Show Abstract · Added December 18, 2018
OBJECTIVE - This study investigated the temporal dynamics of pancreas volume and microstructure in children and adolescents with recent-onset type 1 diabetes (T1D) and individuals without diabetes, including a subset expressing autoantibodies associated with the early stages of T1D.
RESEARCH DESIGN AND METHODS - MRI was performed in individuals with recent-onset stage 3 T1D ( = 51; median age 13 years) within 100 days after diagnosis (mean 67 days), 6 months, and 1 year postdiagnosis. Longitudinal MRI measurements were also made in similarly aged control participants ( = 57) and in autoantibody-positive individuals without diabetes ( = 20). The MRI protocol consisted of anatomical imaging to determine pancreas volume and quantitative MRI protocols interrogating tissue microstructure and composition.
RESULTS - Within 100 days of diabetes onset, individuals with T1D had a smaller pancreas (median volume 28.6 mL) than control participants (median volume 48.4 mL; < 0.001), including when normalized by individual weight ( < 0.001). Longitudinal measurements of pancreas volume increased in control participants over the year, consistent with adolescent growth, but pancreas volume declined over the first year after T1D diagnosis ( < 0.001). In multiple autoantibody-positive individuals, the pancreas volume was significantly larger than that of the T1D cohort ( = 0.017) but smaller than that of the control cohort ( = 0.04). Diffusion-weighted MRI showed that individuals with recent-onset T1D had a higher apparent diffusion coefficient ( = 0.012), suggesting a loss of cellular structural integrity, with heterogeneous pancreatic distribution.
CONCLUSIONS - These results indicate that pancreas volume is decreased in stages 1, 2, and 3 of T1D and decreases during the first year after diabetes onset and that this loss of pancreatic volume is accompanied by microstructural changes.
© 2018 by the American Diabetes Association.
1 Communities
3 Members
0 Resources
19 MeSH Terms
Serologic Response to Helicobacter pylori Proteins Associated With Risk of Colorectal Cancer Among Diverse Populations in the United States.
Butt J, Varga MG, Blot WJ, Teras L, Visvanathan K, Le Marchand L, Haiman C, Chen Y, Bao Y, Sesso HD, Wassertheil-Smoller S, Ho GYF, Tinker LE, Peek RM, Potter JD, Cover TL, Hendrix LH, Huang LC, Hyslop T, Um C, Grodstein F, Song M, Zeleniuch-Jacquotte A, Berndt S, Hildesheim A, Waterboer T, Pawlita M, Epplein M
(2019) Gastroenterology 156: 175-186.e2
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Bacterial, Bacterial Proteins, Biomarkers, Case-Control Studies, Colorectal Neoplasms, Female, Helicobacter Infections, Helicobacter pylori, Host-Pathogen Interactions, Humans, Incidence, Male, Middle Aged, Prospective Studies, Risk Factors, Seroepidemiologic Studies, United States, Virulence, Young Adult
Show Abstract · Added February 7, 2019
BACKGROUND & AIMS - Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States.
METHODS - We used H pylori multiplex serologic assays to analyze serum samples from 4063 incident cases of CRC, collected before diagnosis, and 4063 matched individuals without CRC (controls) from 10 prospective cohorts for antibody responses to 13 H pylori proteins, including virulence factors VacA and CagA. The association of seropositivity to H pylori proteins, as well as protein-specific antibody level, with odds of CRC was determined by conditional logistic regression.
RESULTS - Overall, 40% of controls and 41% of cases were H pylori-seropositive (odds ratio [OR], 1.09; 95% CI, 0.99-1.20). H pylori VacA-specific seropositivity was associated with an 11% increased odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds of CRC increased with level of VacA antibody in the overall cohort (P = .008) and specifically among African Americans (P = .007).
CONCLUSIONS - In an analysis of a large consortium of cohorts representing diverse populations, we found serologic responses to H pylori VacA to associate with increased risk of CRC risk, particularly for African Americans. Future studies should seek to understand whether this marker is related to virulent H pylori strains carried in these populations.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Neurological symptoms in Hypophosphatasia.
Colazo JM, Hu JR, Dahir KM, Simmons JH
(2019) Osteoporos Int 30: 469-480
MeSH Terms: Adolescent, Adult, Aged, Alkaline Phosphatase, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Hypophosphatasia, Male, Mental Disorders, Middle Aged, Nervous System Diseases, Prevalence, Retrospective Studies, United States, Vitamin B 6, Young Adult
Show Abstract · Added April 6, 2019
Hypophosphatasia (HPP) typically manifests with fractures, tooth loss, and muscle pain. Although mental health diagnoses and neurological symptoms have not been previously well documented in HPP, they occur commonly. The recognition of non-traditional symptoms may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and lead to further treatment options.
INTRODUCTION - Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of tissue non-specific alkaline phosphatase (TNSALP). It is traditionally characterized by rickets in children and osteomalacia in adults, along with fractures, tooth loss, and muscle pain. Neurological symptoms and mental health diagnoses have not been widely reported, and we therefore report their prevalence in a cohort of patients with HPP.
METHODS - A retrospective chart review was performed on a series of 82 HPP patients. Patient charts were reviewed to identify the possible presence and onset of 13 common neurological symptoms.
RESULTS - Median age was 36 years (2 to 79). Seventeen had adult onset HPP (> 18 years) and 65 had pediatric onset HPP (< 18 years). Median time from symptom onset to HPP diagnosis was 8 years (0 to 67). Seventy-four percent had a family history of bone disease, while 17% had a family history of neurologic disease. Bone problems occurred in 89%, dental problems in 77%, and muscle problems in 66%. Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in 35%, and hearing loss in 33%.
CONCLUSIONS - The extra-skeletal manifestations of HPP, specifically neurological symptoms, have not been previously well documented. However, mental health diagnoses and neurological symptoms such as headache and sleep disturbance occur commonly in patients with HPP. The recognition of non-traditional symptoms in HPP may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and may lead to further treatment options.
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1 Members
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19 MeSH Terms
Sleep in Teens With Type 1 Diabetes: Perspectives From Adolescents and Their Caregivers.
Bergner EM, Williams R, Hamburger ER, Lyttle M, Davis AC, Malow B, Simmons JH, Lybarger C, Capin R, Jaser SS
(2018) Diabetes Educ 44: 541-548
MeSH Terms: Adolescent, Caregivers, Diabetes Mellitus, Type 1, Female, Humans, Male, Perception, Qualitative Research, Sleep, Sleep Wake Disorders
Show Abstract · Added January 30, 2019
PURPOSE - The purpose of this study is to identify barriers, facilitators, and consequences of obtaining sufficient sleep in adolescents with type 1 diabetes.
METHODS - Semistructured interviews were conducted with 25 adolescents (52% female, mean age = 15.6 years) and 25 caregivers. Interviews were transcribed and coded using Atlas.ti. A thematic analytic approach was used to identify and organize significant patterns of meaning (themes) and interpret themes across the data.
RESULTS - Several barriers were identified, with the most common being the use of electronics before bed and sleep disturbances related to diabetes management. Caregivers described strategies for helping adolescents achieve sufficient sleep, such as enforcing bedtimes and limiting distractions, but many adolescents could not identify facilitators of sleep. Weekday/weekend discrepancies in sleep timing were commonly disclosed.
CONCLUSIONS - This study is the first to examine the perceptions of barriers and facilitators to obtaining sufficient sleep in adolescents with T1D and their caregivers. Results have the potential to inform providers' recommendations regarding sleep, including possible interventions to promote sleep in this high-risk population.
0 Communities
2 Members
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10 MeSH Terms
Associations among histological characteristics and patient outcomes in colorectal carcinoma with a mucinous component.
Gonzalez RS, Cates JMM, Washington K
(2019) Histopathology 74: 406-414
MeSH Terms: Adenocarcinoma, Mucinous, Adolescent, Adult, Aged, Aged, 80 and over, Child, Colorectal Neoplasms, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Proportional Hazards Models, Young Adult
Show Abstract · Added November 1, 2018
AIMS - Colorectal carcinoma (CRC) often has a mucinous component, with more than 50% mucin by volume defining the mucinous subtype of CRC. The prognostic impact of the mucinous phenotype remains unclear.
METHODS AND RESULTS - We evaluated 224 CRC with at least 5% mucinous component (herein 'mCRC') for patient sex, age, race and outcome; tumour size, location, stage and microsatellite instability (MSI) status; percentage of glands producing mucin; percentage of tumour volume composed of mucin; whether tumoral epithelium floated in mucin pools; tumour budding; signet ring cells (SRCs); and peritumoural inflammation (PI). We related these features to disease-specific survival and compared outcomes to 499 stage-matched, conventional colorectal adenocarcinomas. Factors predicting worse prognosis in mCRC on univariable analysis included non-MSI-high status (P = 0.0008), SRC (P = 0.0017) and lack of PI (P = 0.0034). No parameters were independently associated with outcome after adjusting for tumour stage in multivariate analysis. The percentage of glands producing mucin and percentage tumour volume composed of mucin did not affect prognosis, including at the recommended 50% cut-off for subtyping mCRC. Disease-specific survival for mCRC and adenocarcinomas were similar after accounting for stage.
CONCLUSIONS - Stage-matched mCRCs and adenocarcinomas have similar outcomes, with no prognostic significance to morphological subtyping. Histological characteristics of mCRC, including percentage of tumour volume comprised of mucin, were not predictive of outcome.
© 2018 John Wiley & Sons Ltd.
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1 Members
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14 MeSH Terms
Association of abdominal muscle composition with prediabetes and diabetes: The CARDIA study.
Granados A, Gebremariam A, Gidding SS, Terry JG, Carr JJ, Steffen LM, Jacobs DR, Lee JM
(2019) Diabetes Obes Metab 21: 267-275
MeSH Terms: Abdominal Muscles, Adipose Tissue, Adiposity, Adolescent, Adult, Body Composition, Cohort Studies, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Intra-Abdominal Fat, Male, Middle Aged, Physical Fitness, Prediabetic State, Prognosis, Risk Factors, Young Adult
Show Abstract · Added September 11, 2018
AIM - To evaluate the relationship of abdominal muscle lean tissue and adipose tissue volumes with prediabetes and diabetes.
RESEARCH DESIGN AND METHODS - We measured abdominal muscle composition in 3170 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent computed tomography (CT) at Year 25 of follow-up (ages, 43-55 years). Multinomial regression analysis was used to evaluate the associations of CT-measured intermuscular adipose tissue (IMAT), lean muscle tissue (lean) and visceral adipose tissue (VAT) volumes with diabetes at any point during the CARDIA study, newly detected prediabetes, prior history of prediabetes, and normal glucose tolerance. Models were adjusted for potential confounding factors: age, sex, race, height, smoking status, hypertension, hyperlipidaemia, cardiorespiratory fitness and study centre.
RESULTS - Higher IMAT, lean and VAT volumes were all separately associated with a higher prevalence of prediabetes and diabetes. Inclusion of VAT volume in models with both IMAT volume and lean volume attenuated the association of IMAT with both prediabetes and diabetes, but higher lean volume retained its association with prediabetes and diabetes. Individuals in the highest IMAT quartile, coupled with VAT in its lower three quartiles, had a higher prevalence of diabetes, but not of prediabetes, than those with both IMAT and VAT in their respective lower three quartiles. Adjusting for cardiorespiratory fitness did not substantially change the findings.
CONCLUSION - Higher IMAT volume was associated with a higher prevalence of diabetes even after adjustment for VAT volume. However, further study is warranted to understand the complicated relationship between abdominal muscle and adipose tissues.
© 2018 John Wiley & Sons Ltd.
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1 Members
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19 MeSH Terms
Impact of substance use disorder on gray matter volume in schizophrenia.
Quinn M, McHugo M, Armstrong K, Woodward N, Blackford J, Heckers S
(2018) Psychiatry Res Neuroimaging 280: 9-14
MeSH Terms: Adolescent, Adult, Amygdala, Cerebral Cortex, Diagnosis, Dual (Psychiatry), Female, Frontal Lobe, Gray Matter, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Occipital Lobe, Organ Size, Schizophrenia, Schizophrenic Psychology, Substance-Related Disorders, Young Adult
Show Abstract · Added March 26, 2019
Substance use may confound the study of brain structure in schizophrenia. We used voxel-based morphometry (VBM) to examine whether differences in regional gray matter volumes exist between schizophrenia patients with (n = 92) and without (n = 66) clinically significant cannabis and/or alcohol use histories compared to 88 healthy control subjects. Relative to controls, patients with schizophrenia had reduced gray matter volume in the bilateral precentral gyrus, right medial frontal cortex, right visual cortex, right occipital pole, right thalamus, bilateral amygdala, and bilateral cerebellum regardless of substance use history. Within these regions, we found no volume differences between patients with schizophrenia and a history of cannabis and/or alcohol compared to patients with schizophrenia without a clinically significant substance use history. Our data support the idea that a clinically meaningful history of alcohol or cannabis use does not significantly compound the gray matter deficits associated with schizophrenia.
Copyright © 2018. Published by Elsevier B.V.
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1 Members
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18 MeSH Terms
Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes.
Triolo TM, Fouts A, Pyle L, Yu L, Gottlieb PA, Steck AK, Type 1 Diabetes TrialNet Study Group
(2019) Diabetes Care 42: 192-199
MeSH Terms: Adolescent, Adult, Autoantibodies, Autoimmunity, Child, Child, Preschool, Diabetes Mellitus, Type 1, Disease Progression, Diseases in Twins, Environment, Female, Genetic Predisposition to Disease, Glutamate Decarboxylase, Humans, Insulin, Islets of Langerhans, Male, Mass Screening, Risk Factors, Seroepidemiologic Studies, Siblings, Twins, Twins, Dizygotic, Twins, Monozygotic, Young Adult
Show Abstract · Added August 15, 2018
OBJECTIVE - There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings.
RESEARCH DESIGN AND METHODS - Subjects from the TrialNet Pathway to Prevention Study ( = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years.
RESULTS - At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody-positive, 13% for single autoantibody-positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody-positive, 12% for single autoantibody-positive, and 0.5% for initially autoantibody-negative subjects.
CONCLUSIONS - Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody-positive identical twins and multiple autoantibody-positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.
© 2018 by the American Diabetes Association.
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2 Members
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25 MeSH Terms
Toileting Behaviors of Women-What is Healthy?
Kowalik CG, Daily A, Delpe S, Kaufman MR, Fowke J, Dmochowski RR, Reynolds WS
(2019) J Urol 201: 129-134
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Female, Health Behavior, Humans, Independent Living, Middle Aged, Self Report, Socioeconomic Factors, Surveys and Questionnaires, Urinary Bladder Diseases, Urination, Young Adult
Show Abstract · Added September 16, 2019
PURPOSE - The objective of this study was to assess toileting behaviors in community dwelling women.
MATERIALS AND METHODS - Women 18 years old or older were recruited through a national registry of research volunteers. They were asked to complete validated questionnaires assessing urinary symptoms and toileting behaviors, specifically place preference for voiding, convenience voiding, delayed voiding, straining during voiding and position preference for voiding. The PPBC (patient perception of bladder condition) was administered to assess the participant impression of bladder health. Analyses were done to determine the prevalence of each toileting behavior reported to occur sometimes or more often as well as differences in toileting behaviors in women with vs without self-perceived bladder problems based on the PPBC response.
RESULTS - The 6,695 women who completed the questionnaires were 18 to 89 years old (mean ± SD age 41.4 ± 15). Of the women 79.9% identified as white and 71.0% were college educated. Of the women 6,613 (98.8%) reported a place preference for voiding. The 3,552 women (53.1%) who reported a bladder problem were more likely to report convenience voiding, delayed voiding and strained voiding behaviors. While 6,657 women (99.4%) reported sitting to void at home only 5,108 (76.2%) reported sitting when using public toilets.
CONCLUSIONS - Certain toileting behaviors, of which some may be considered unhealthy, were common in this sample of women and most were associated with a perception of bladder problems. Voiding positions other than sitting were frequently used when away from home. These data have important implications for defining bladder health and implementing behavior based interventions for women with lower urinary tract symptoms.
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