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Article ; Online: Prevalence of genetic causes of obesity in clinical practice

Jaclyn Tamaroff / Dylan Williamson / James C. Slaughter / Meng Xu / Gitanjali Srivastava / Ashley H. Shoemaker

Obesity Science & Practice, Vol 9, Iss 5, Pp 508-

2023 Volume 515

Abstract: Abstract Background While obesity is common in the United States, monogenic obesity is rare, accounting for approximately 5% of individuals with obesity. New targeted therapies for genetic forms of obesity are available but there is limited guidance on ... ...

Abstract	Abstract Background While obesity is common in the United States, monogenic obesity is rare, accounting for approximately 5% of individuals with obesity. New targeted therapies for genetic forms of obesity are available but there is limited guidance on who requires testing. The aims of this study were to evaluate the prevalence of potentially clinically significant variants among individuals in Pediatric Endocrinology or Medical Weight Center clinics at a single center and to identify clinical characteristics that may make genetic obesity more likely. Methods Children and adults who had a genetic test for obesity, Uncovering Rare Obesity Gene panel, ordered during routine clinic visits from December 2019 to March 2021 were identified. Results Of the 139 patients with testing ordered, 117 had available results and clinical data. Over 40% (52/117, 44%) had at least one positive result (variant) with a variant that is considered pathogenic, likely pathogenic, or a variant of uncertain significance. No association was detected between age, sex, race, and body mass index (BMI) or BMI z‐score with a variant. Twenty‐six individuals (22%) had one or more variants in genes associated with Bardet Biedl Syndrome, and 8 (6.8%) of them had pathogenic variants, higher than expected. Conclusion Overall, clinical suspicion for genetic obesity is important in determining who requires genetic testing but no clinical factors were found to predict results. While obesity is multifactorial, novel medications for genetic forms of obesity indicate the need for evidence‐based guidelines for who requires genetic testing for obesity.
Keywords	body mass index ; genetic testing ; genetics ; obesity ; pediatric obesity ; Internal medicine ; RC31-1245
Subject code	616
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: 4486 Assessing the Validity of an ICD-9 and ICD-10 Coding Algorithm for Identifying Cervical Premalignant Lesions Using Administrative Claims Data

Jaimie Zhi Shing / Marie Griffin / James C Slaughter / Manideepthi Pemmaraju / Edward F Mitchel / Rachel S Chang / Pamela C Hull

Journal of Clinical and Translational Science, Vol 4, Pp 45-

2020 Volume 45

Abstract: OBJECTIVES/GOALS: We compared the validity of an International Classification of Diseases, Clinical Modification (ICD) algorithm for identifying high-grade cervical intraepithelial neoplasia and adenocarcinoma in situ (together referred to as CIN2+) from ...

Abstract	OBJECTIVES/GOALS: We compared the validity of an International Classification of Diseases, Clinical Modification (ICD) algorithm for identifying high-grade cervical intraepithelial neoplasia and adenocarcinoma in situ (together referred to as CIN2+) from ICD 9th revision (ICD-9) and 10th revision (ICD-10) codes. METHODS/STUDY POPULATION: Using Tennessee Medicaid data, we identified cervical diagnostic procedures in 2008-2017 among females aged 18-39 years in Davidson County, TN. Gold-standard cases were pathology-confirmed CIN2+ diagnoses validated by HPV-IMPACT, a population-based surveillance project in catchment areas of five US states. Procedures in the ICD transition year (2015) were excluded to account for implementation lag. We pre-grouped diagnosis and procedure codes by theme. We performed feature selection using least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross validation and validated models by ICD-9 era (2008-2014, N = 6594) and ICD-10 era (2016-2017, N = 1270). RESULTS/ANTICIPATED RESULTS: Of 7864 cervical diagnostic procedures, 880 (11%) were true CIN2+ cases. LASSO logistic regression selected the strongest features of case status: Having codes for a CIN2+ tissue diagnosis, non-specific CIN tissue diagnosis, high-grade squamous intraepithelial lesion, receiving a cervical treatment procedure, and receiving a cervical/vaginal biopsy. Features of non-case status were codes for a CIN1 tissue diagnosis, Pap test, and HPV DNA test. The ICD-9 vs ICD-10 algorithms predicted case status with 68% vs 63% sensitivity, 95% vs 94% specificity, 63% vs 64% positive predictive value, 96% vs 94% negative predictive value, 92% vs 89% accuracy, and C-indices of 0.95 vs 0.92, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, the algorithm’s validity for identifying CIN2+ case status was similar between coding versions. ICD-9 had slightly better discriminative ability. Results support a prior study concluding that ICD-10 implementation has not substantially improved ...
Keywords	Medicine ; R
Subject code	310
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Cambridge University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Environmental Interactions and Epistasis Are Revealed in the Proteomic Responses to Complex Stimuli.

Parimal Samir / Rahul / James C Slaughter / Andrew J Link

PLoS ONE, Vol 10, Iss 8, p e

2015 Volume 0134099

Abstract: Ultimately, the genotype of a cell and its interaction with the environment determine the cell's biochemical state. While the cell's response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple ... ...

Abstract	Ultimately, the genotype of a cell and its interaction with the environment determine the cell's biochemical state. While the cell's response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple environmental stimuli applied concurrently is not as well developed. In this study, we developed the concepts of environmental interactions and epistasis to explain the responses of the S. cerevisiae proteome to simultaneous environmental stimuli. We hypothesize that, as an abstraction, environmental stimuli can be treated as analogous to genetic elements. This would allow modeling of the effects of multiple stimuli using the concepts and tools developed for studying gene interactions. Mirroring gene interactions, our results show that environmental interactions play a critical role in determining the state of the proteome. We show that individual and complex environmental stimuli behave similarly to genetic elements in regulating the cellular responses to stimuli, including the phenomena of dominance and suppression. Interestingly, we observed that the effect of a stimulus on a protein is dominant over other stimuli if the response to the stimulus involves the protein. Using publicly available transcriptomic data, we find that environmental interactions and epistasis regulate transcriptomic responses as well.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Etiology of acute gastroenteritis among children less than 5 years of age in Bucaramanga, Colombia

Ana E Farfán-García / Aamer Imdad / Chengxian Zhang / Mónica Y Arias-Guerrero / Nayibe T Sánchez-Álvarez / Junaid Iqbal / Adriana E Hernández-Gamboa / James C Slaughter / Oscar G Gómez-Duarte

PLoS Neglected Tropical Diseases, Vol 14, Iss 6, p e

A case-control study.

2020 Volume 0008375

Abstract: Background Acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children aged less than 5 years in low- and middle-income countries where limited access to potable water, poor sanitation, deficient hygiene, and food product ... ...

Abstract	Background Acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children aged less than 5 years in low- and middle-income countries where limited access to potable water, poor sanitation, deficient hygiene, and food product contamination are prevalent. Research on the changing etiology of AGE and associated risk factors in Latin America, including Colombia, is essential to understand the epidemiology of these infections. The primary objectives of this study were to describe etiology of moderate to severe AGE in children less than 5 years of age from Bucaramanga, Colombia, a middle-income country in Latin American, and to identify the presence of emerging E. coli pathotypes. Methodology/principal findings This was a prospective, matched for age, case-control study to assess the etiology of moderate to severe AGE in children less than 5 years of age in Bucaramanga, Colombia, South America. We tested for 24 pathogens using locally available diagnostic testing, including stool culture, polymerase chain reaction, microscopy and enzyme-linked immunoassay. Adjusted attributable fractions were calculated to assess the association between AGE and each pathogen in this study population. The study included 861 participants, 431 cases and 430 controls. Enteric pathogens were detected in 71% of cases and in 54% of controls (p = <0.001). Co-infection was identified in 28% of cases and in 14% of controls (p = <0.001). The adjusted attributable fraction showed that Norovirus GII explained 14% (95% CI: 10-18%) of AGE, followed by rotavirus 9.3% (6.4-12%), adenovirus 3% (1-4%), astrovirus 2.9% (0.6-5%), enterotoxigenic Escherichia coli (ETEC) 2.4% (0.4-4%), Cryptosporidium sp. 2% (0.5-4%), Campylobacter sp. 2% (0.2-4%), and Salmonella sp.1.9% (0.3 to 3.5%). Except for Cryptosporidium, all parasite infections were not associated with AGE. Three emergent diarrheagenic E. coli pathotypes were identified in cases (0.7%), including an enteroaggregative/enterotoxigenic E.coli (EAEC/ETEC), an ...
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	360
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease.

Laura A Powell / Julie M Fox / Nurgun Kose / Arthur S Kim / Mahsa Majedi / Robin Bombardi / Robert H Carnahan / James C Slaughter / Thomas E Morrison / Michael S Diamond / James E Crowe

PLoS Pathogens, Vol 16, Iss 5, p e

2020 Volume 1008517

Abstract: Ross River fever is a mosquito-transmitted viral disease that is endemic to Australia and the surrounding Pacific Islands. Ross River virus (RRV) belongs to the arthritogenic group of alphaviruses, which largely cause disease characterized by ... ...

Abstract	Ross River fever is a mosquito-transmitted viral disease that is endemic to Australia and the surrounding Pacific Islands. Ross River virus (RRV) belongs to the arthritogenic group of alphaviruses, which largely cause disease characterized by debilitating polyarthritis, rash, and fever. There is no specific treatment or licensed vaccine available, and the mechanisms of protective humoral immunity in humans are poorly understood. Here, we describe naturally occurring human mAbs specific to RRV, isolated from subjects with a prior natural infection. These mAbs potently neutralize RRV infectivity in cell culture and block infection through multiple mechanisms, including prevention of viral attachment, entry, and fusion. Some of the most potently neutralizing mAbs inhibited binding of RRV to Mxra8, a recently discovered alpahvirus receptor. Epitope mapping studies identified the A and B domains of the RRV E2 protein as the major antigenic sites for the human neutralizing antibody response. In experiments in mice, these mAbs were protective against cinical disease and reduced viral burden in multiple tissues, suggesting a potential therapeutic use for humans.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: In vivo Raman spectral analysis of impaired cervical remodeling in a mouse model of delayed parturition

Christine M. O’Brien / Jennifer L. Herington / Naoko Brown / Isaac J. Pence / Bibhash C. Paria / James C. Slaughter / Jeff Reese / Anita Mahadevan-Jansen

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 14

Abstract: Abstract Monitoring cervical structure and composition during pregnancy has high potential for prediction of preterm birth (PTB), a problem affecting 15 million newborns annually. We use in vivo Raman spectroscopy, a label-free, light-based method that ... ...

Abstract	Abstract Monitoring cervical structure and composition during pregnancy has high potential for prediction of preterm birth (PTB), a problem affecting 15 million newborns annually. We use in vivo Raman spectroscopy, a label-free, light-based method that provides a molecular fingerprint to non-invasively investigate normal and impaired cervical remodeling. Prostaglandins stimulate uterine contractions and are clinically used for cervical ripening during pregnancy. Deletion of cyclooxygenase-1 (Cox-1), an enzyme involved in production of these prostaglandins, results in delayed parturition in mice. Contrary to expectation, Cox-1 null mice displayed normal uterine contractility; therefore, this study sought to determine whether cervical changes could explain the parturition differences in Cox-1 null mice and gestation-matched wild type (WT) controls. Raman spectral changes related to extracellular matrix proteins, lipids, and nucleic acids were tracked over pregnancy and found to be significantly delayed in Cox-1 null mice at term. A cervical basis for the parturition delay was confirmed by other ex vivo tests including decreased tissue distensibility, hydration, and elevated progesterone levels in the Cox-1 null mice at term. In conclusion, in vivo Raman spectroscopy non-invasively detected abnormal remodeling in the Cox-1 null mouse, and clearly demonstrated that the cervix plays a key role in their delayed parturition.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice

Chunxian Zhang / Michael P. Sherman / Lawrence S. Prince / David Bader / Jörn-Hendrik Weitkamp / James C. Slaughter / Steven J. McElroy

Disease Models & Mechanisms, Vol 5, Iss 4, Pp 522-

2012 Volume 532

Abstract: SUMMARY Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. During NEC pathogenesis, bacteria are able to penetrate innate immune defenses and invade the intestinal epithelial layer, causing subsequent ... ...

Abstract	SUMMARY Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. During NEC pathogenesis, bacteria are able to penetrate innate immune defenses and invade the intestinal epithelial layer, causing subsequent inflammation and tissue necrosis. Normally, Paneth cells appear in the intestinal crypts during the first trimester of human pregnancy. Paneth cells constitute a major component of the innate immune system by producing multiple antimicrobial peptides and proinflammatory mediators. To better understand the possible role of Paneth cell disruption in NEC, we quantified the number of Paneth cells present in infants with NEC and found that they were significantly decreased compared with age-matched controls. We were able to model this loss in the intestine of postnatal day (P)14-P16 (immature) mice by treating them with the zinc chelator dithizone. Intestines from dithizone-treated animals retained approximately half the number of Paneth cells compared with controls. Furthermore, by combining dithizone treatment with exposure to Klebsiella pneumoniae, we were able to induce intestinal injury and inflammatory induction that resembles human NEC. Additionally, this novel Paneth cell ablation model produces NEC-like pathology that is consistent with other currently used animal models, but this technique is simpler to use, can be used in older animals that have been dam fed, and represents a novel line of investigation to study NEC pathogenesis and treatment.
Keywords	Medicine ; R ; Pathology ; RB1-214
Subject code	690
Language	English
Publishing date	2012-07-01T00:00:00Z
Publisher	The Company of Biologists
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Immunogenicity and efficacy of alphavirus-derived replicon vaccines for respiratory syncytial virus and human metapneumovirus in nonhuman primates

Bates, John T / Frances Smith-House / James C. Slaughter / James E. Crowe / Jennifer A. Pickens / Jennifer E. Schuster / John V. Williams / Monika Johnson / Nancy L. Davis / Nancy Schultz-Darken / Robert E. Johnston / Sharon J. Tollefson

Vaccine. 2016 Feb. 10, v. 34, no. 7

2016

Abstract: Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ... ...

Abstract	Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development.
Keywords	antibodies ; blood serum ; Cercopithecus aethiops ; children ; elderly ; encephalitis ; genome ; horses ; Human metapneumovirus ; Human respiratory syncytial virus ; immune response ; neutralization ; replicon ; respiratory mucosa ; vaccines ; viral load ; viruses
Language	English
Dates of publication	2016-0210
Size	p. 950-956.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2015.12.045
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.

Dawn M Wiese / Sara N Horst / Caroline T Brown / Margaret M Allaman / Mallary E Hodges / James C Slaughter / Jennifer P Druce / Dawn B Beaulieu / David A Schwartz / Keith T Wilson / Lori A Coburn

PLoS ONE, Vol 11, Iss 5, p e

2016 Volume 0156387

Abstract: Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum ... ...

Abstract	Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines.Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography.UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations.In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: POWERLIB

Jacqueline L. Johnson / Keith E. Muller / James C. Slaughter / Matthew J. Gurka / Matthew J. Gribbin Sano / Sean L. Simpson

Journal of Statistical Software, Vol 30, Iss

SAS/IML Software for Computing Power in Multivariate Linear Models

2009 Volume 5

Abstract: The POWERLIB SAS/IML software provides convenient power calculations for a widerange of multivariate linear models with Gaussian errors. The software includes the Box,Geisser-Greenhouse, Huynh-Feldt, and uncorrected tests in the univariate" approach ... ...

Abstract	The POWERLIB SAS/IML software provides convenient power calculations for a widerange of multivariate linear models with Gaussian errors. The software includes the Box,Geisser-Greenhouse, Huynh-Feldt, and uncorrected tests in the univariate" approach torepeated measures (UNIREP), the Hotelling Lawley Trace, Pillai-Bartlett Trace, andWilks Lambda tests in multivariate" approach (MULTIREP), as well as a limited butuseful range of mixed models. The familiar univariate linear model with Gaussian errorsis an important special case. For estimated covariance, the software provides condencelimits for the resulting estimated power. All power and condence limits values canbe output to a SAS dataset, which can be used to easily produce plots and tables formanuscripts.
Keywords	power ; multivariate linear models ; mixed models ; Gaussian errors ; SAS ; Statistics ; HA1-4737 ; Social Sciences ; H ; DOAJ:Statistics ; DOAJ:Mathematics and Statistics
Language	English
Publishing date	2009-04-01T00:00:00Z
Publisher	University of California, Los Angeles
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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