bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual and Structural Environmental Influences on Utilization of Iron and Folic Acid Supplementation among Pregnant Women in Harare, Zimbabwe
Authors: Tinago Chiwoneso B. , Ingram Lucy Annang , Blake Christine E. , Frongillo Edward A. 
Published: November 2023

ObjectiveThe Ministry of Health and Child Care of Zimbabwe established a national policy for the prevention of maternal micronutrient deficiencies that centers on pregnant women receiving daily iron and folic acid (IFA) supplements at their first antenatal care visit and throughout pregnancy. Despite these efforts, utilization of IFA supplementation during pregnancy in Zimbabwe is low and no qualitative data existed to explain these low utilization rates. This study aimed to bridge this knowledge gap by investigating the experiences with and knowledge about IFA supplementation of pregnant women and healthcare workers in Harare, Zimbabwe, the health‐service and social environment in which IFA supplementation occurs, and how these influence utilization of IFA supplementation.MethodsSemi‐structured, in‐depth, qualitative interviews were conducted in both Shona and English with pregnant women (n=24) and healthcare workers (n=14) providing direct antenatal care services to pregnant women in two clinics located in two low‐income high‐density suburbs in Harare. Data were analyzed thematically using NVivo 10 software.ResultsInfluences on utilization from the perspectives of pregnant women and healthcare workers were at both the individual and structural environmental levels. Reasons for low utilization of IFA supplementation were side effects, misconceptions about IFA supplementation, limited access to nutrition information, delayed entry or non‐uptake of antenatal care services, and social norms of pregnant women for micronutrient supplementation. Utilization was enhanced by knowledge of risks and benefits of supplementation, fear of negative health complications with non‐utilization, family support, and healthcare‐provider recommendation for micronutrient supplementation.ConclusionsFuture approaches to improve maternal IFA supplementation utilization in Zimbabwe should address individual and structural environmental factors that begin before pregnancy, continue throughout pregnancy, and reach pregnant women who are currently not seeking antenatal care services. Study findings will be used to inform approaches to strengthen micronutrient supplementation utilization in order to improve the micronutrient status of pregnant women, decrease the micronutrient risk factors associated with maternal mortality, and improve overall maternal and child health in Zimbabwe.Support or Funding InformationThis study was supported by a SPARC Graduate Fellowship from the Office of the Vice President for Research at the University of South Carolina.
Physical Activity and Work Productivity in Response to Iron and Iodine Double‐Fortified Salt Trial in Indian Tea Estate Workers
Authors: Blakstad Mia M. , Nevins Julie E.H. , Venkatramanan Sudha , Przybyszewski Eric M. , Haas Jere D. 
Published: November 2023

IntroductionIron deficiency is the most common micronutrient deficiency in the world, with prevalence estimates for women in low‐income countries ranging between 15 and 50%. Iron is essential for oxygen transport through hemoglobin (Hb), and iron deficiency can lead to decreased physical work capacity. The relationship between iron and work capacity suggests that iron deficient individuals could experience reduced work productivity. We used accelerometry data to determine whether improvements in iron status from an intervention of salt double‐fortified with iron and iodine (DFS) increased the physical activity (PA) and efficiency of work performed by female tea pluckers.PopulationParticipants were 212 experienced tea pluckers between 18 and 55 years from a large tea estate in Darjeeling District of northern West Bengal, India.MethodsTwo groups were randomly assigned to receive either salt fortified with potassium iodate, or iodized salt that was additionally fortified with microencapsulated ferrous fumarate (3.3 mg/g salt). Over the 10‐month intervention, women received salt only from the study. All measurements were taken at both baseline and end line. Participants self‐reported ethnicity as Adivasi or Nepali. Weight, height, mid‐upper arm circumference (MUAC) and age were measured by trained research staff. Venous blood was analyzed for Hb, serum ferritin (sFt), and soluble transferrin receptor. Physical activity levels were assessed with ActiGraph GT3x tri‐axial accelerometers worn on the hip daily for six days, except when sleeping or bathing. Energy expenditure during the work day was estimated from heart rate, and productivity was measured as the amount of tea plucked (kg) from morning and afternoon weighing.ResultsMean (SD) change in minutes from baseline to endline spent at sedentary (<1 MET), light (1–3 MET), and moderate‐to‐rigorous (>3 MET) physical activity during plucking were 32.7 (160.8), 5.6 (75.5), and 6.7 (44.2) respectively. Neither the intervention, change in iron status, energy expenditure, energetic efficiency, nor amount of tea plucked were consistent predictors of PA, even after controlling for potential confounders.ConclusionWe found that, contradictory to previous findings, improvements in iron status did not improve physical performance or worker productivity in these Indian tea estate workers. The results should be interpreted in light of the very different tea plucking conditions observed during the study period. Our results may highlight the need for measures of work productivity that are more sensitive to changes in iron status.Support or Funding InformationFunded by the Micronutrient Initiative (MI) of Canada
Early Weight Gain, Linear Growth, and Mid‐childhood Blood Pressure
Authors: Perng Wei , Rifas‐Shiman Sheryl L , Kramer Michael S , Haugaard Line K , Oken Emily , Gillman Matthew W. , Belfort Mandy B. 
Published: November 2023

ObjectiveTo investigate relations of change in body mass index (BMI) and length/height during 4 early life age intervals (birth to 6mo, 6mo to 1y, 1 to 2y, and 2 to 3y) with mid‐childhood systolic blood pressure (SBP), and to evaluate for effect modification by birth size (birthweight‐for‐gestational age z‐score).MethodsWe studied 957 participants in Project Viva, an ongoing U.S. pre‐birth cohort. Using multivariable linear regression, we examined the associations of weight gain (change in body mass index [BMI] z‐score) change and linear growth (change in length/height z‐score) during each time period with mid‐childhood SBP, adjusting for maternal education, age, pre‐pregnancy BMI, and smoking; and child's age, sex, race/ethnicity, continuous birthweight‐for‐gestational age z‐score, and growth in preceding periods. We examined interaction of these growth measures with birth size according to small (<10th percentile of sex‐ and gestational‐age specific birthweight), appropriate (10th to <90th percentile), and large‐for‐gestational age (≥90th percentile).ResultsChildren were 7.9 ± 0.8 years at time of SBP assessment; 50.3% were girls and most were white (65%). Mean ± SD SBP was 94.4 ± 8.8 mmHg and DBP was 54.3 ± 5.7 mmHg. Each additional z‐score gain in BMI from birth to 6mo and 2 to 3y was associated with 0.81 (95% CI: 0.15, 1.46) and 1.61 (0.33, 2.89) mmHg higher systolic SBP, respectively. Gain in length from 1 to 2y was related to higher SBP among boys (2.24 [0.89, 3.60] mmHg per z‐score) but not girls (−0.18 [−1.60, 1.25] mmHg per z‐score). There was no evidence of effect modification by birth size.ConclusionsFaster gain in BMI during the first 6 postnatal months and in the preschool years may lead to higher SBP in mid‐childhood, regardless of size at birth. Strategies to reduce accrual of excess adiposity during early life may bring long‐term benefits for cardiovascular healthSupport or Funding InformationThis work was supported by the US National Institutes of Health (K24 HD069408, R37 HD 034568, P30 DK092924).
JAM‐C deficiency primes endothelial cells for a pro‐inflammatory state
Authors: Reglero Natalia , Beal Robert , Cabrera Claudia , Pickworth Catherine , Golding Matthew , Whiteford James , Nightingale Tom , Imhof Beat , Barnes Michael R , Nourshargh Sussan 
Published: November 2023

Endothelial cells (ECs) line the inner surface of all vascular walls and as such form a vital barrier between blood and interstitial tissues. Key to this function is the ability of ECs to form cell‐cell junctions that support the formation of a confluent EC monolayer, providing an effective gate‐keeper for the regulated vascular crossing of blood borne proteins and circulating immune cells. Junctional adhesion molecule‐C (JAM‐C) is a component of EC tight junctions and plays a key role in controlling numerous EC vascular and immune functions. Of note, previous work from our laboratory has shown that certain inflammatory conditions (e.g. ischemia‐reperfusion injury) can elicit reduced expression of EC JAM‐C, a phenomenon that can lead to disrupted neutrophil transendothelial cell migration (TEM) dynamics such as neutrophil reverse TEM (rTEM) (Woodfin et al., Nature Immunol., 2011; Colom et al., Immunity, 2015). To gain a better understanding of the role of JAM‐C in EC phenotype and functions, we conducted an unbiased gene expression analysis of ECs subjected to control or JAM‐C siRNA. Briefly, HUVECs were transfected with control or JAM‐C specific siRNA by nucleofection, with the latter achieving a consistently high (~90%) knockdown (KD) efficiency. Of note, JAM‐C (JAM3) KD did not affect the expression of other key EC junctional markers such as VE‐Cadherin or JAM‐A. The study revealed that JAM‐C KD HUVECs exhibit a pro‐inflammatory gene expression profile under basal conditions. Several genes implicated in leukocyte migration, such as the chemokine IL8 (p=6×10−5 fold change (FC) = 5.1) the adhesion molecules VCAM‐1 (p=9.4×10−6 FC= 16.7) and ICAM‐1 (p=0.0014; FC= 3.7), were significantly upregulated in JAM‐C KD cells. Furthermore, pathway analysis of the gene array data by Ingenuity (IPA) software indicated upregulation of numerous gene clusters associated with cell functions such as cellular homeostasis, leukocyte trafficking and several inflammatory signalling pathways. Regulation of key genes (e.g. IL8, VCAM‐1) was further validated by qPCR and at protein level. On‐going works are addressing the functional implications of these findings. Collectively, the present results have identified the crucial role of JAM‐C in maintaining ECs in a quiescent state, indicating that loss of EC JAM‐C could prime ECs for an enhanced and/or potentially aberrant inflammatory response. These findings provide novel insights into the consequences of reduced expression of JAM‐C under pathological conditions, such as that noted in response to ischemia‐reperfusion injury.Support or Funding InformationThis work was supported by generous funds from the The Wellcome Trust and Marie Curie Actions.
Cell‐type specific mechanisms regulate rhythmic leukocyte migration to tissues
Authors: He Wenyan , Kraus Kerstin , Druzd David , de Juan Alba , Ince Louise , Chen Chien‐Sin , Scheiermann Christoph 
Published: November 2023

Leukocyte recruitment from blood to tissues is a critical element of the immune system. However, the dynamics of leukocyte migration over the course of the day are unclear. Specifically, which leukocyte subtypes are being recruited to which specific tissue at what time during the daily cycle is unknown. Here, we screened the main leukocyte subpopulations in murine blood (neutrophils, B cells, CD4 T cells, CD8 T cells, natural killer (NK) cells, NKT cells, eosinophils, inflammatory as well non‐inflammatory monocytes) for oscillations in their migration behaviour. We examined surface protein expression levels of 28 adhesion molecules and chemokine receptors on these leukocyte subtypes in addition to 8 adhesion molecules expressed by endothelial cells in vascular beds of multiple organs using quantitative flow cytometry and imaging‐based approaches. Our data indicate the existence of a rhythmic leukocyte‐and tissue‐specific molecular signature in the expression of pro‐migratory factors. To test the relevance of these oscillations, we performed homing assays to investigate the recruitment capability of individual leukocyte subsets to tissues at specific times. These data revealed strong, >2‐fold time‐of‐day differences in the capacity of cells to emigrate out from blood. In addition, it exposed leukocyte‐distinct rhythms in their homing patterns to tissues, with the microenvironment and leukocyte‐autonomous oscillations co‐contributing in the recruitment process. Specifically, using B‐cell and T‐cell‐specific knockouts of the circadian gene Bmal1 demonstrated altered expression levels of specific oscillatory molecules and leukocyte numbers in tissues, which suggests that rhythmicity in these factors may be directly regulated by the circadian clock. Taken together, our data show discrete tissue and leukocyte mechanisms that control a broad and robustly rhythmic leukocyte recruitment process to organs.Support or Funding InformationFunded by the European Research Council (CIRCODE) and the German Research Foundation(EmmyNoether SCHE1645/2‐1 and SFB914 project B09).
OxLDL Exerts A Biphasic Effect on Endothelial Function: A Role for Oxidised Lipids in Angiogenesis and Inflammation
Authors: Olding Michael , Ardern‐Jones Michael R , Healy Eugene , Millar Timothy M 
Published: November 2023

Oxidised lipids are known to promote inflammation and are implicated in the pathophysiology of psoriasis, promoting cardiovascular disease. The deleterious effects of oxidised low‐density lipoprotein (oxLDL) are potentially mediated through vascular cell activation.We therefore tested the hypothesis that serum lipids, LDL and its oxidation products can modify endothelial cell function. The effects of serum lipids and oxLDL on primary human endothelial cells were assessed in assays for migration, angiogenesis, leukocyte recruitment and vascular cell surface receptor expression.Our results showed that at relatively high concentrations oxLDL inhibited angiogenesis and endothelial migration. However, lower concentrations of oxLDL stimulated endothelial migration. In contrast, oxLDL caused increased leukocyte recruitment to the endothelium under shear stress only at higher concentration. Native LDL was shown to have no effect at equivalent concentrations in these assays. Serum lipids were also shown to regulate endothelial function as their removal from cultures inhibited endothelial migration and angiogenesis. However, removal of serum lipids did not impair the ability of cytokine‐stimulated endothelial cells to recruit flowing leukocytes. Analysis of known oxLDL receptor‐1 (LOX‐1) and scavenger receptor B (CD36) showed minimal expression in these cells. A potential mechanism through which oxLDL mediates its activity involves the stimulation of sphingosine metabolism. Initial studies have revealed sphingosine‐1‐phosphate receptor (S1PR1) expression in endothelial cells and is currently under investigation for oxLDL mediated effects.In conclusion, these data suggest an important role for circulating lipids and lipoproteins in the regulation of endothelial function, which may have implications for psoriatic pathology and cardiovascular disease.Support or Funding InformationFunded by The Psoriasis Association, UK
Dysfunctional Mechanosensing of Extracellular Matrix in Thoracic Aortic Disease
Authors: Humphrey Jay D 
Published: November 2023

The ultimate fate of a compromised thoracic aorta – namely, progressive enlargement and acute dissection or rupture – depends upon the hemodynamic loads and mechanical properties of the wall. We have only limited understanding, however, of the mechanobiological processes that render the thoracic aorta vulnerable to such mechanical failures. Homeostasis requires the intramural cells to sense their local chemo‐mechanical environment and to establish, maintain, remodel, or repair the extracellular matrix to provide suitable compliance and yet sufficient strength. This sensing necessitates a mechanically competent extracellular matrix that can also sequester or present chemo‐ligands to the cells and functional membrane receptors that connect to intact actomyosin filaments of the cytoskeleton and regulate intracellular signaling. Diverse mutant genes associated with these thoracic aortic diseases affect extracellular matrix constituents, membrane receptors, or contractile proteins and associated signaling molecules and poorly controlled hypertension is the major risk factor for the disease. This constellation of mutant genes coupled with the fact that increased biomechanical forces drive the disease suggest that these thoracic aortic conditions result, in part, from a dysfunctional mechanosensing by the intramural cells, which in turn compromises the mechanoregulation of extracellular matrix that is needed to ensure sufficient structural integrity of the wall.Support or Funding InformationNIH U01 HL116323
Systems Mechanobiology and Multi‐Scale Modeling of Ventricular Hypertrophy and Failure
Authors: McCulloch Andrew D , Buchholz Kyle , Tan Philip , Dewan Sukriti , Saucerman Jeffrey , Omens Jeff H , Nigam Vishal 
Published: November 2023

Hypertrophic heart disease is a multi‐factorial, multi‐scale problem in which altered whole body hemodynamics and neurohormonal factors lead to a complex growth and remodeling response in the heart. The cells and extracellular matrix in the myocardium initially compensate to the abnormal environmental factors with altered gene expression, changes in contractile and mechanoenergetic function, cell and tissue structural remodeling, in turn further affecting circulatory dynamics and often leading to decompensation and failure.We have developed organ scale models of biomechanics growth and remodeling that suggest that a growth law in which myocytes respond differentially to transverse and longitudinal strains can explain many of the differences between ventricular hypertrophy associated with normal postnatal growth, aortic stenosis, mitral valve regurgitation and asymmetric electrical activation [1–3]. In‐vitro studies in micropatterned neonatal mouse ventricular myocytes subjected to anisotropic biaxial stretch show around differences in transcriptional responses when the major axis of stretch is longitudinal compared with transverse to the myofilament axis. Using transcriptomes measured by RNA‐seq in these preparations, we modified a network model of hypertrophic cell signaling [4] to include transverse and longitudinal stretch and transcriptional regulation of gene expression. The results revealed specific differences in cell signaling activated by transverse vs. longitudinal stretch with longitudinal stretch activating more pathways and regulators than transverse strain.Support or Funding InformationSupported by NIH grants 8 P41 GM103426‐19 (Amaro), P50 GM094503‐01A1 (Beard), 1R01HL105242‐01 (McCulloch/Bers) and 1R01HL121754‐01 (McCulloch/Omens)
Integrating Light‐Sheet and Hemodynamic Forces to Elucidate Cardiac Development, Injury and Repair
Authors: Hsiai Tzung 
Published: November 2023

Hemodynamic forces such as shear stress are intimately linked with cardiac morphogenesis. Mutations in Notch signaling components result in congenital heart defects in humans and mice. Hemodynamic shear stress induces vascular endothelial Notch signaling, and Notch pathway mediates differentiation and proliferation of trabecular myocytes. During heart development, the myocardium differentiates into two layers, an outer compact zone and an inner trabeculated zone. The trabeculae form a network of branching outgrowths from the ventricular wall, and both trabeculation and compaction are essential for normal cardiac contractile function. However, the mechanotransduction mechanisms underlying endocardial shear stress (ESS) and the initiation of trabeculation remain elusive. Our multi‐disciplinary approach has demonstrated that peristaltic contraction of the embryonic heart tube produces time‐varying shear stress (¶t/¶t) and pressure gradients (ÑP) across the atrioventricular (AV) canal in a zebrafish model of cardiac development. The advent of zebrafish genetic system has enabled the application of fli1 promoter to drive expression of enhanced green fluorescent protein (EGFP) in all vasculature throughout embryogenesis (Tg(fli1a:EGFP)y1); thereby, allowing for 3‐D visualization of the moving boundary conditions (2D + time) for computational fluid dynamics (CFD) simulation. However, 4‐D (3‐D + time) imaging to recapitulate the endocardium throughout the cardiac cycle requires fast tissue scanning and deep axial penetration. For these reasons, we have developed fluorescent Super‐Resolution Light‐Sheet Microscopy (SRLSM) to capture the 4‐D endocardial trabecular network in response to genetic manipulation of blood viscosity and Notch signaling pathway. Our multi‐disciplinary team aims to establish a fundamental direction at the interface of hemodynamic forces and cardiac development by introduction of a novel 4‐D SRLSM technique to elucidate ESS‐mediated Notch signaling with pathophysiological significance to cardiac development, injury, and repair.Support or Funding InformationNIH R01HL118650 NIH R01HL083015 NIH R01HL111437 NIH R01HL129727
Microscopic Anatomy and Pathology Laboratories: Design of an E‐Learning Atlas as an Evolving Response to Interdisciplinary Medical Curricular Needs
Authors: Jurjus Rosalyn A. , Wade Jenna , Moktan Varun , Davis Michelle S. , Mills Alexandra , Butera Gisela , Krum Janette , Latham Patricia 
Published: November 2023

Several institutions have integrated histology with other disciplines in team based laboratory approaches, but integration of histology and pathology instruction tools has been done to a lesser extent. Our aim was to develop an e‐learning atlas that integrates microanatomy and pathology laboratories for an interdisciplinary integrated medical curriculum. A multidisciplinary team is developing the online Microanatomy and Pathology Atlas (MAPA) (microanatomyatlas.com) that includes a library of histology and pathology images. Traditional laboratory manual instructions and study objectives are linked to specific labeled images that were made interactive to allow for self‐testing. Clinical case studies involving disease entities are being incorporated. Data is being collected on the number and frequency of medical students in the preclinical years using the atlas and a modified Likert‐style survey (1‐strongly agree to 4‐strongly disagree) is being used to assess student satisfaction and perceived learning. Preliminary data shows that 92%of students (score 1–2) would like to use the tool in the future, 62% strongly in favor (score 1). 92% of students (score 1–2) also stated they would advise their peers to use the MAPA. Data shows that the MAPA is positively correlated with material from lectures and is well suited for the level of student proficiency. In conclusion, MAPA is becoming an essential learning tool for students in our integrated curriculum at GWU‐SMHS.Support or Funding InformationSupported by AEIUCM