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Article ; Online: Leukocyte telomere length predicts subsequent infectious morbidity among Colombian schoolchildren.

Lee, Gwenyth O / Mora-Plazas, Mercedes / Marín, Constanza / Villamor, Eduardo

American journal of human biology : the official journal of the Human Biology Council

2023 Volume 35, Issue 10, Page(s) e23966

Abstract: Objective: Telomere length (TL) attrition is related to chronic disease risk. However, less is known on whether TL predicts infectious outcomes, especially in childhood. We examined whether leukocyte TL (LTL) was associated with subsequent infectious ... ...

Abstract	Objective: Telomere length (TL) attrition is related to chronic disease risk. However, less is known on whether TL predicts infectious outcomes, especially in childhood. We examined whether leukocyte TL (LTL) was associated with subsequent infectious morbidity in schoolchildren. Methods: We assessed LTL in 717 Colombian children 5-12 years-old at the beginning of a school year and followed them through the year for daily occurrence of common infection symptoms and doctor visits. We estimated adjusted incidence rate ratios (IRR) with 95% confidence intervals (CI) of gastrointestinal and respiratory syndromes for quartiles of standardized LTL Z score and per unit LTL Z score. Results: A longer LTL was associated with increased incidence of all infectious morbidity syndromes considered. Adjusted IRR (95% CI) per unit LTL Z score were 1.55 (1.20, 2.00) for diarrhea with vomiting, 1.34 (1.13, 1.60) for cough with fever, 1.70 (1.28, 2.28) for ear infection, and 1.66 (1.36, 2.02) for doctor visits with symptoms. Conclusions: Longer LTL is related to increased incidence of common infectious morbidities in middle childhood.
Language	English
Publishing date	2023-07-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1025339-7
ISSN	1520-6300 ; 1042-0533
ISSN (online)	1520-6300
ISSN	1042-0533
DOI	10.1002/ajhb.23966
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Article ; Online: Short-term dynamics of linear growth among Peruvian infants in the first year of life in a population with linear growth faltering.

Lee, Gwenyth O / McCormick, Benjamin J J / Yori, Pablo P / Paredes-Olortegui, Maribel / Caulfield, Laura E / Kosek, Margaret N

American journal of human biology : the official journal of the Human Biology Council

2024 , Page(s) e24039

Abstract: Objectives: Infant growth is recognized to vary over the short term, with periods of greater and lesser linear growth velocity. Our objectives were to (1) examine the potential differences in overall growth profiles between children who experienced ... ...

Abstract	Objectives: Infant growth is recognized to vary over the short term, with periods of greater and lesser linear growth velocity. Our objectives were to (1) examine the potential differences in overall growth profiles between children who experienced cumulative growth faltering in the first year of life consistent with that seen by many children living in poverty in low- and middle-income countries, versus children without growth faltering and (2) test whether biological factors were associated with the timing of magnitude of growth saltations. Methods: Thrice-weekly measurements of length were recorded for n = 61 Peruvian infants (28 boys and 33 girls) enrolled from birth to 1 year. A total of 6040 measurements were analyzed. We tested for the evidence of saltatory growth and used hurdle models to test whether the timing and magnitude of saltations varied between children with greater or lesser growth faltering. Results: There were no differences in the duration of stasis periods or magnitude of growth saltations between children who were stunted at 1 year old (N = 18) versus those who were not stunted (N = 43). Children who experienced greater declines in LAZ in the first year of life trended toward longer periods between saltations than those with less of a decline (14.5 days vs. 13.4 days, p = .0512). A 1-unit increase in mid upper arm circumference for age Z-score in the 21 days prior was associated with 35% greater odds of a saltation occurring (p < .001), and a 0.128 cm greater saltation (p < .001). Conclusions: After characterizing infant growth into periods of saltation and stasis, our results suggest that increases in weight preceded increases in length.
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1025339-7
ISSN	1520-6300 ; 1042-0533
ISSN (online)	1520-6300
ISSN	1042-0533
DOI	10.1002/ajhb.24039
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Article: Performance of empirical and model-based classifiers for detecting sucrase-isomaltase inhibition using the

Van Wyk, Hannah / Lee, Gwenyth O / Schillinger, Robert J / Edwards, Christine A / Morrison, Douglas J / Brouwer, Andrew F

medRxiv : the preprint server for health sciences

2024

Abstract: Background: Environmental enteric dysfunction (EED) is a syndrome characterized by epithelial damage including blunting of the small intestinal villi and altered digestive and absorptive capacity which may negatively impact linear growth in children. ... ...

Abstract	Background: Environmental enteric dysfunction (EED) is a syndrome characterized by epithelial damage including blunting of the small intestinal villi and altered digestive and absorptive capacity which may negatively impact linear growth in children. The Methods: We leveraged SBT data from a cross-over study in 16 adults who received 0, 100, and 750 mg of Reducose, a natural SIM inhibitor. We evaluated the performance of a pharmacokinetic-model-based classifier, Results: Test durations of less than 2 hours generally failed to accurately predict later breath curve dynamics. The cPDR90 classifier had the highest area-under-the-curve and, by design, was robust to shorter test durations. For detecting mild SIM inhibition, Conclusions: We recommend SBT tests run for at least a 2-hour duration. Although cPDR90 was the classifier with highest accuracy and robustness to test duration in this application, concerns remain about its sensitivity to misspecification of CO
Language	English
Publishing date	2024-05-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.05.01.24306704
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Article ; Online: Stool biomarkers as measures of enteric pathogen infection in infants from Addis Ababa informal settlements.

Espira, Leon M / Lee, Gwenyth O / Baye, Kaleab / Jones, Andrew D / Love, Nancy G / Eisenberg, Joseph N S

PLoS neglected tropical diseases

2023 Volume 17, Issue 2, Page(s) e0011112

Abstract: Frequent enteric infections in children may be an important cause of growth faltering; however, we do not fully understand the mechanisms by which pathogen infections and the physiological responses to these infections result in poorer growth. Commonly ... ...

Abstract	Frequent enteric infections in children may be an important cause of growth faltering; however, we do not fully understand the mechanisms by which pathogen infections and the physiological responses to these infections result in poorer growth. Commonly used protein fecal biomarkers (anti-alpha trypsin, neopterin, and myeloperoxidase) provide broad immunological information on an inflammatory response; however, they do not provide information on non-immune processes (e.g., gut integrity) that may be important indicators of chronic end states such as environmental enteric dysfunction (EED). To explore how additional biomarkers will better inform which physiological pathways (both immune and non-immune) are impacted by pathogen exposure we added to the traditional panel of 3 protein fecal biomarkers 4 novel fecal mRNA transcript biomarkers (sucrase isomaltase, caudal homeobox 1, S100A8, and mucin 12) and analyzed stool samples from infants living in informal settlements in Addis Ababa, Ethiopia. To test how this expanded biomarker panel captures distinct pathogen exposure processes we used two different scoring systems. First, we used a theory-based approach to assign each biomarker to specific physiological attributes based on prior understanding of each biomarker. Second, we used data reduction methods to categorize biomarkers and then assign physiological attributes to those categories. We used linear models to examine the association between the derived biomarker scores (based on mRNA and protein levels) and stool pathogen gene counts to determine pathogen specific effects on gut physiology and immune responses. Inflammation scores were positively associated with Shigella and enteropathogenic E.Coli (EPEC) infection, while gut integrity scores were negatively associated with Shigella, EPEC and, shigatoxigenic E.coli (STEC) infection. Our expanded panel of biomarkers hold promise as tools to measure systemic outcomes of enteric pathogen infection. mRNA biomarkers complement established protein biomarkers by providing important cell-specific physiological and immunological consequences of pathogen carriage that can lead to chronic end states such as EED.
MeSH term(s)	Child ; Humans ; Infant ; Ethiopia ; Inflammation ; Intestine, Small ; Intestinal Diseases/pathology ; Escherichia coli Infections ; Biomarkers/metabolism ; RNA, Messenger ; Feces
Chemical Substances	Biomarkers ; RNA, Messenger
Language	English
Publishing date	2023-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0011112
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Article ; Online: A Qualitative Study of Food Choice in Urban Coastal Esmeraldas, Ecuador.

Uruchima, Jessica / Renehan, Cala / Castro, Nancy / Cevallos, William / Levy, Karen / Eisenberg, Joseph Ns / Lee, Gwenyth O

Current developments in nutrition

2023 Volume 7, Issue 5, Page(s) 100093

Abstract: Background: Constraints on food choice increase risk of malnutrition worldwide. Residents of secondary cities within low- and middle-income countries are a population of particular concern because they often face high rates of food insecurity and ... ...

Abstract	Background: Constraints on food choice increase risk of malnutrition worldwide. Residents of secondary cities within low- and middle-income countries are a population of particular concern because they often face high rates of food insecurity and multiple nutritional burdens. Within this context, effective and equitable interventions to support healthy diets must be based on an understanding of the lived experience of individuals and their interactions with the food environment. Objectives: The primary objectives of this study were to describe considerations that drive household decision making around food choice in the city of Esmeraldas, Ecuador; to identify trade-offs between these considerations; and to understand how an evolving urban environment influences these trade-offs. Methods: Semistructured interviews were conducted with 20 mothers of young children to explore drivers in food choice throughout the purchase, preparation, and consumption chain. Interviews were transcribed and coded to identify key themes. Results: Personal preference, economic access (costs), convenience, and perceptions of food safety were key influencers of decision making related to food. In addition, concerns about personal safety in the urban environment limited physical access to food. This, combined with the need to travel long distances to obtain desirable foods, increased men's participation in food purchasing. Women's increasing engagement in the workforce also increased men's participation in food preparation. Conclusions: Policies to promote healthy food behavior in this context should focus on increasing access to health foods, such as affordable fresh produce, in convenient and physically safe locations.
Language	English
Publishing date	2023-04-26
Publishing country	United States
Document type	Journal Article
ISSN	2475-2991
ISSN (online)	2475-2991
DOI	10.1016/j.cdnut.2023.100093
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Article ; Online: Nutrient intakes from complementary foods are associated with cardiometabolic biomarkers among undernourished Peruvian children.

Lee, Gwenyth O / Caulfield, Laura E / Paredes-Olortegui, Maribel / Penataro-Yori, Pablo / Salas, Mery Sigas / Kosek, Margaret N

Journal of nutritional science

2023 Volume 12, Page(s) e80

Abstract: Relatively little is known about how the diet of chronically undernourished children may impact cardiometabolic biomarkers. The objective of this exploratory study was to characterise relationships between dietary patterns and the cardiometabolic profile ...

Abstract	Relatively little is known about how the diet of chronically undernourished children may impact cardiometabolic biomarkers. The objective of this exploratory study was to characterise relationships between dietary patterns and the cardiometabolic profile of 153 3-5-year-old Peruvian children with a high prevalence of chronic undernutrition. We collected monthly dietary recalls from children when they were 9-24 months old. At 3-5 years, additional dietary recalls were collected, and blood pressure, height, weight, subscapular skinfolds and fasting plasma glucose, insulin and lipid profiles were assessed. Nutrient intakes were expressed as average density per 100 kcals (i) from 9 to 24 months and (ii) at follow-up. The treelet transform and sparse reduced rank regress'ion (RRR) were used to summarize nutrient intake data. Linear regression models were then used to compare these factors to cardiometabolic outcomes and anthropometry. Linear regression models adjusting for subscapular skinfold-for-age
MeSH term(s)	Humans ; Child ; Child, Preschool ; Infant ; Peru ; Cardiovascular Diseases/epidemiology ; Eating ; Cholesterol ; Biomarkers ; Insulin
Chemical Substances	Cholesterol (97C5T2UQ7J) ; Biomarkers ; Insulin
Language	English
Publishing date	2023-07-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2656288-1
ISSN	2048-6790 ; 2048-6790
ISSN (online)	2048-6790
ISSN	2048-6790
DOI	10.1017/jns.2023.66
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Article ; Online: Characterizing dengue transmission in rural areas: A systematic review.

Man, Olivia / Kraay, Alicia / Thomas, Ruth / Trostle, James / Lee, Gwenyth O / Robbins, Charlotte / Morrison, Amy C / Coloma, Josefina / Eisenberg, Joseph N S

PLoS neglected tropical diseases

2023 Volume 17, Issue 6, Page(s) e0011333

Abstract: Dengue has historically been considered an urban disease associated with dense human populations and the built environment. Recently, studies suggest increasing dengue virus (DENV) transmission in rural populations. It is unclear whether these reports ... ...

Abstract	Dengue has historically been considered an urban disease associated with dense human populations and the built environment. Recently, studies suggest increasing dengue virus (DENV) transmission in rural populations. It is unclear whether these reports reflect recent spread into rural areas or ongoing transmission that was previously unnoticed, and what mechanisms are driving this rural transmission. We conducted a systematic review to synthesize research on dengue in rural areas and apply this knowledge to summarize aspects of rurality used in current epidemiological studies of DENV transmission given changing and mixed environments. We described how authors defined rurality and how they defined mechanisms for rural dengue transmission. We systematically searched PubMed, Web of Science, and Embase for articles evaluating dengue prevalence or cumulative incidence in rural areas. A total of 106 articles published between 1958 and 2021 met our inclusion criteria. Overall, 56% (n = 22) of the 48 estimates that compared urban and rural settings reported rural dengue incidence as being as high or higher than in urban locations. In some rural areas, the force of infection appears to be increasing over time, as measured by increasing seroprevalence in children and thus likely decreasing age of first infection, suggesting that rural dengue transmission may be a relatively recent phenomenon. Authors characterized rural locations by many different factors, including population density and size, environmental and land use characteristics, and by comparing their context to urban areas. Hypothesized mechanisms for rural dengue transmission included travel, population size, urban infrastructure, vector and environmental factors, among other mechanisms. Strengthening our understanding of the relationship between rurality and dengue will require a more nuanced definition of rurality from the perspective of DENV transmission. Future studies should focus on characterizing details of study locations based on their environmental features, exposure histories, and movement dynamics to identify characteristics that may influence dengue transmission.
MeSH term(s)	Child ; Humans ; Dengue ; Dengue Virus ; Seroepidemiologic Studies ; Longitudinal Studies ; Rural Population
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0011333
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Article ; Online: The biting rate of Aedes aegypti and its variability: A systematic review (1970-2022).

Zahid, Mondal Hasan / Van Wyk, Hannah / Morrison, Amy C / Coloma, Josefina / Lee, Gwenyth O / Cevallos, Varsovia / Ponce, Patricio / Eisenberg, Joseph N S

PLoS neglected tropical diseases

2023 Volume 17, Issue 8, Page(s) e0010831

Abstract: Background: Transmission models have a long history in the study of mosquito-borne disease dynamics. The mosquito biting rate (MBR) is an important parameter in these models, however, estimating its value empirically is complex. Modeling studies obtain ... ...

Abstract	Background: Transmission models have a long history in the study of mosquito-borne disease dynamics. The mosquito biting rate (MBR) is an important parameter in these models, however, estimating its value empirically is complex. Modeling studies obtain biting rate values from various types of studies, each of them having its strengths and limitations. Thus, understanding these study designs and the factors that contribute to MBR estimates and their variability is an important step towards standardizing these estimates. We do this for an important arbovirus vector Aedes aegypti. Methodology/principal findings: We perform a systematic review using search terms such as 'biting rate' and 'biting frequency' combined with 'Aedes aegypti' ('Ae. aegypti' or 'A. aegypti'). We screened 3,201 articles from PubMed and ProQuest databases, of which 21 met our inclusion criteria. Two broader types of studies are identified: human landing catch (HLC) studies and multiple feeding studies. We analyze the biting rate data provided as well as the methodologies used in these studies to characterize the variability of these estimates across temporal, spatial, and environmental factors and to identify the strengths and limitations of existing methodologies. Based on these analyses, we present two approaches to estimate population mean per mosquito biting rate: one that combines studies estimating the number of bites taken per gonotrophic cycle and the gonotrophic cycle duration, and a second that uses data from histological studies. Based on one histological study dataset, we estimate biting rates of Ae. aegypti (0.41 and 0.35 bite/mosquito-day in Thailand and Puerto Rico, respectively). Conclusions/significance: Our review reinforces the importance of engaging with vector biology when using mosquito biting rate data in transmission modeling studies. For Ae. aegypti, this includes understanding the variation of the gonotrophic cycle duration and the number of bites per gonotrophic cycle, as well as recognizing the potential for spatial and temporal variability. To address these variabilities, we advocate for site-specific data and the development of a standardized approach to estimate the biting rate.
MeSH term(s)	Animals ; Humans ; Mosquito Vectors ; Aedes ; Insect Bites and Stings/epidemiology ; Thailand/epidemiology ; Feeding Behavior
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Systematic Review ; Journal Article
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0010831
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Article ; Online: A Model-Based

Brouwer, Andrew F / Lee, Gwenyth O / Van Wyk, Hannah / Schillinger, Robert J / Edwards, Christine A / Morrison, Douglas J

The Journal of nutrition

2023 Volume 154, Issue 3, Page(s) 815–825

Abstract: Background: Environmental enteric dysfunction (EED) causes malnutrition in children in low-resource settings. Stable-isotope breath tests have been proposed as noninvasive tests of altered nutrient metabolism and absorption in EED, but uncertainty over ... ...

Abstract	Background: Environmental enteric dysfunction (EED) causes malnutrition in children in low-resource settings. Stable-isotope breath tests have been proposed as noninvasive tests of altered nutrient metabolism and absorption in EED, but uncertainty over interpreting the breath curves has limited their use. The activity of sucrose-isomaltase, the glucosidase enzyme responsible for sucrose hydrolysis, may be reduced in EED. We previously developed a mechanistic model describing the dynamics of the Objectives: This study aimed to determine which breath test curve dynamics are associated with sucrose hydrolysis and with the transport and metabolism of the fructose and glucose moieties and to propose and evaluate a model-based diagnostic for the loss of activity of sucrase-isomaltase. Methods: We applied the mechanistic model to 2 sets of exploratory Results: Sucrose hydrolysis and the transport and metabolism of the fructose and glucose moieties were reflected in the same mechanistic process. The model distinguishes these processes from the fraction of tracer exhaled and an exponential metabolic process. The model-based diagnostic performed as well as the conventional summary statistics in distinguishing between no and low inhibition [area under the curve (AUC): 0.77 vs. 0.66-0.79] and for low vs. high inhibition (AUC 0.92 vs. 0.91-0.99). Conclusions: Current summary approaches to interpreting
MeSH term(s)	Child ; Adult ; Humans ; Sucrose ; Sucrase-Isomaltase Complex ; Cross-Over Studies ; Carbohydrate Metabolism, Inborn Errors/diagnosis ; Carbohydrate Metabolism, Inborn Errors/metabolism ; Glucose/metabolism ; Oligo-1,6-Glucosidase ; Breath Tests ; Fructose
Chemical Substances	Sucrose (57-50-1) ; Sucrase-Isomaltase Complex (EC 3.2.1.-) ; Glucose (IY9XDZ35W2) ; Oligo-1,6-Glucosidase (EC 3.2.1.10) ; Fructose (30237-26-4)
Language	English
Publishing date	2023-11-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1016/j.tjnut.2023.11.017
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Article ; Online: Mechanistic inference of the metabolic rates underlying [Formula: see text]C breath test curves.

Brouwer, Andrew F / Lee, Gwenyth O / Schillinger, Robert J / Edwards, Christine A / Van Wyk, Hannah / Yazbeck, Roger / Morrison, Douglas J

Journal of pharmacokinetics and pharmacodynamics

2023 Volume 50, Issue 3, Page(s) 203–214

Abstract: Carbon stable isotope breath tests offer new opportunities to better understand gastrointestinal function in health and disease. However, it is often not clear how to isolate information about a gastrointestinal or metabolic process of interest from a ... ...

Abstract	Carbon stable isotope breath tests offer new opportunities to better understand gastrointestinal function in health and disease. However, it is often not clear how to isolate information about a gastrointestinal or metabolic process of interest from a breath test curve, and it is generally unknown how well summary statistics from empirical curve fitting correlate with underlying biological rates. We developed a framework that can be used to make mechanistic inference about the metabolic rates underlying a
MeSH term(s)	Adult ; Humans ; Pilot Projects ; Breath Tests/methods ; Carbon Isotopes
Chemical Substances	Carbon Isotopes
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2041601-5
ISSN	1573-8744 ; 1567-567X
ISSN (online)	1573-8744
ISSN	1567-567X
DOI	10.1007/s10928-023-09847-x
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