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To compare rates of clinical response in children with Clostridioides difficile infection (CDI) treated with metronidazole vs vancomycin.
Design:
Retrospective cohort study was performed as a secondary analysis of a previously established prospective cohort of hospitalized children with CDI. For 187 participants 2–17 years of age who were treated with metronidazole and/or vancomycin, the primary outcome of clinical response (defined as resolution of diarrhea within 5 days of treatment initiation) was identified retrospectively. Baseline variables associated with the primary outcome were included in a logistic regression propensity score model estimating the likelihood of receiving metronidazole vs vancomycin. Logistic regression using inverse probability of treatment weighting (IPTW) was used to estimate the effect of treatment on clinical response.
Results:
One hundred seven subjects received metronidazole and 80 subjects received vancomycin as primary treatment. There was no univariable association between treatment group and clinical response; 78.30% (N = 83) of the metronidazole treatment group and 78.75% (N = 63) of the vancomycin group achieved clinical response (P = 0.941). After adjustment using propensity scores with IPTW, the odds of a clinical response for participants who received metronidazole was 0.554 (95% CI: 0.272, 1.131) times the odds of those who received vancomycin (P = 0.105).
Conclusions:
In this observational cohort study of pediatric inpatients with CDI, the rate of resolution of diarrhea after 5 days of treatment did not differ among children who received metronidazole vs vancomycin.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Oxygen isotopic compositions were determined for coexisting mixed-layer serpentine-chlorite (Sp-Ch) and illite-smectite (I-S) from 5 Tuscaloosa Formation sandstone cores sampled between 1937 and 5470 m burial depth. High gradient magnetic separation (HGMS) was used to concentrate Sp-Ch and I-S from the <0.5 μm fraction of each core sample into fractions with a range in the Sp-Ch: I-S ratio, and end-member δ18O compositions were determined by extrapolation. The Sp-Ch δ18O values range from + 10.4 to 13.7% and increase with burial between 3509 and 5470 m. The only exception is Sp-Ch from 1937 m, which has an anomalously high δ18O value of +12.6‰ The I-S δ18O values range from +16.1 to 17.3% and do not change significantly between 3509 and 5470 m burial depth.
Pore water δ18O compositions calculated from Sp-Ch and I-S values and measured borehole temperatures range from −2.6 to +10.3‰ The isotopically light values indicate that Sp-Ch formed at shallow burial depths in the presence of brackish to marine water and/or meteoric water. The depth-related increase in δ18O of Sp-Ch is attributed to oxygen exchange between mineral and pore water during diagenetic mineral reactions. Increasing δ18O values, in conjunction with XRD and SEM data, indicate that transformation of serpentine layers to chlorite layers and Ibb polytype layers to Iaa polytype layers occurred on a layer-by-layer basis when individual layers dissolved and recrystallized within the confines of coherent crystals. Possible explanations for the variation in I-S δ18O values include depth-related differences in pore water δ18O values present at the time of I-S crystallization, contamination by detrital 2M, mica and 1M polytype rotations that facilitated oxygen exchange.
Recent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anaemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modelling framework to estimate the cost and cost-effectiveness of SQ-LNS and applied the framework in the context of rural Uganda.
Design:
We adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anaemia and developmental disability.
Setting:
Rural Uganda.
Participants:
Not applicable.
Results:
Providing SQ-LNS daily to all children in rural Uganda (> 1 million) for 12 months (from 6 to 18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars) or ∼$58·7 million annually. SQ-LNS could avert an average of > 242 000 disability-adjusted life years (DALYs) annually as a result of preventing 3689 deaths, > 160 000 cases of moderate or severe anaemia and ∼6000 cases of developmental disability. The estimated cost per DALY averted is $242.
Conclusions:
In this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a programme including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility.
This study investigates the religious origins of the American temperance and antislavery movements in New York State. We introduce new county-level longitudinal data between 1828 and 1838 to document the onset and growth of New York temperance and antislavery societies during the movements’ early stages. Data are compiled from numerous historical sources and document counts of temperance societies in 55 New York counties in years 1828, 1829, 1831, 1833, and 1834; and county-level counts of antislavery societies in years 1835, 1836, 1837, and 1838. The early growth of temperance and antislavery societies across New York counties are examined as outcomes of state building, market changes, and religious activism associated with the Second Great Awakening. We hypothesize that religious activism was positively associated with the establishment of temperance and antislavery societies in New York counties between 1828 and 1834 and between 1835 and 1838, respectively, as well as positively associated with growth in temperance and antislavery societies during these times. Results support our hypotheses with findings suggesting that evangelist activities were substantially influencing both the onset and growth of temperance and antislavery societies during the early stages of these social movements. The evidence is consistent with a “life politics” perspective of social movements and with the argument that US temperance and abolitionism were confessional protests with deep ties to the Second Great Awakening.
Background: Spinal cord compression from degenerative cervical myelopathy is characterized by progressive loss of hand dexterity, alongside changes in the metabolite profiles in the brain and spinal cord. Correlating the changing metabolite profile with measures of dexterity following decompression surgery may assist in identifying which patients may benefit most from surgery. Methods: Thirty operative myelopathy patients consented to receive spectroscopy and GRASSP-M dexterity assessments both preoperatively and 6-weeks postoperatively. Magnetic resonance spectroscopy (TE=135) was performed in the motor cortex using a 3 Tesla Siemens MRI scanner at Robarts Research Institute. Spearman correlations were used to evaluate associations between metabolite levels and dexterity (p<0.05 was considered significant). Paired two-tailed Student t-tests were used to assess for postoperative changes in metabolite levels. Results: Postoperatively, we observed a statistically significant (p<0.05) negative correlation (r=-0.44) between the N-acetylaspartate-to-creatine ratio (NAA/Cr) and GRASSP-M dexterity scores. There was no significant difference in NAA, Cr, or NAA/Cr postoperatively. Conclusions: These findings demonstrate that patients with lower postoperative NAA/Cr usually have better recovery of dexterity. This link between the myelopathic metabolite profile and clinically meaningful dexterity values requires further investigation to understand the role of both NAA and Cr in mechanisms of postoperative recovery from myelopathy.
The current study argues that population prevalence estimates for mental health disorders, or changes in mean scores over time, may not adequately reflect the heterogeneity in mental health response to the COVID-19 pandemic within the population.
Methods
The COVID-19 Psychological Research Consortium (C19PRC) Study is a longitudinal, nationally representative, online survey of UK adults. The current study analysed data from its first three waves of data collection: Wave 1 (March 2020, N = 2025), Wave 2 (April 2020, N = 1406) and Wave 3 (July 2020, N = 1166). Anxiety-depression was measured using the Patient Health Questionnaire Anxiety and Depression Scale (a composite measure of the PHQ-9 and GAD-7) and COVID-19-related posttraumatic stress disorder (PTSD) with the International Trauma Questionnaire. Changes in mental health outcomes were modelled across the three waves. Latent class growth analysis was used to identify subgroups of individuals with different trajectories of change in anxiety-depression and COVID-19 PTSD. Latent class membership was regressed on baseline characteristics.
Results
Overall prevalence of anxiety-depression remained stable, while COVID-19 PTSD reduced between Waves 2 and 3. Heterogeneity in mental health response was found, and hypothesised classes reflecting (i) stability, (ii) improvement and (iii) deterioration in mental health were identified. Psychological factors were most likely to differentiate the improving, deteriorating and high-stable classes from the low-stable mental health trajectories.
Conclusions
A low-stable profile characterised by little-to-no psychological distress (‘resilient’ class) was the most common trajectory for both anxiety-depression and COVID-19 PTSD. Monitoring these trajectories is necessary moving forward, in particular for the ~30% of individuals with increasing anxiety-depression levels.
ABSTRACT IMPACT: Current practice guidelines offer a variety of treatment options for sternal reconstruction but complications and infections remain a serious surgical problem. This work seeks to provide a comprehensive picture of the com-morbidities and reconstructive methods that lead to success and improve patient outcomes. OBJECTIVES/GOALS: Patients that undergo cardiac surgery via the median sternotomy approach are at risk of wound complications that require repair. We seek to evaluate how outcomes of sternal reconstruction are influenced by patient comorbidities, flap usage and internal mammary artery grafts and methods of sternal closure. METHODS/STUDY POPULATION: We identified patients between 2005 and 2020 who underwent sternotomy followed by debridement and flap coverage at our institution. Comorbidities, method of reconstruction, demographic data, surgical history, and other factors pertaining to mortality and morbidity were collected. The data will then be analyzed to identify population characteristics using logistic regression variables to determine univariate and adjusted multivariable measures of association with mortality. We present the pre-liminary data analyzed using chi-square and one-way anova in R. RESULTS/ANTICIPATED RESULTS: In this study we present a preliminary characterization of one institution’s sternal reconstruction patient outcomes with a variety of reconstruction methods including pectoralis advancement flaps, omental flaps and latissumus dorsi flaps. Notable preoperative comorbidities include 50% of patients > age 60, 18% with diabetes mellitus, 18 % with diagnosed hypertension, 18% with COPD, and 9% with a smoking history DISCUSSION/SIGNIFICANCE OF FINDINGS: In an evolving cardiothoracic landscape, clinical characteristics of patients being treated for sternal reconstructive surgery present a moving target. Understanding current risk factors, preoperative management and timing for aggressive surgical treatment offers an opportunity to update treatment protocol and maximize successful outcomes.
Toxoplasma gondii (T. gondii) is an important human disease-causing parasite. In the USA, T. gondii infects >10% of the population, accrues economic losses of US$3.6 billion/year, and ranks as the second leading culprit of foodborne illness-related fatalities. We assessed toxoplasmosis risk among the Old Order Amish, a mostly homogenous population with a high prevalence of T. gondii seropositivity, using a questionnaire focusing on food consumption/preparation behaviours and environmental risk factors. Analyses were conducted using multiple logistic regression. Consuming raw meat, rare meat, or unpasteurised cow or goat milk products was associated with increased odds of seropositivity (unadjusted Odds Ratios: 2.192, 1.613, and 1.718 , respectively). In separate models by sex, consuming raw meat, or consuming unpasteurised cow or goat milk products, was associated with increased odds of seropositivity among women; washing hands after touching meat with decreased odds of seropositivity among women (adjusted OR (AOR): 0.462); and cleaning cat litterbox with increased odds of seropositivity among men (AOR: 5.241). This is the first study to assess associations between behavioural and environmental risk factors and T. gondii seropositivity in a US population with high seroprevalence for T. gondii. Our study emphasises the importance of proper food safety behaviours to avoid the risk of infection.
The COVID-19 pandemic has created an unprecedented global crisis, necessitating drastic changes to living conditions, social life, personal freedom and economic activity. No study has yet examined the presence of psychiatric symptoms in the UK population under similar conditions.
Aims
We investigated the prevalence of COVID-19-related anxiety, generalised anxiety, depression and trauma symptoms in the UK population during an early phase of the pandemic, and estimated associations with variables likely to influence these symptoms.
Method
Between 23 and 28 March 2020, a quota sample of 2025 UK adults aged 18 years and older, stratified by age, gender and household income, was recruited by online survey company Qualtrics. Participants completed standardised measures of depression, generalised anxiety and trauma symptoms relating to the pandemic. Bivariate and multivariate associations were calculated for demographic and health-related variables.
Results
Higher levels of anxiety, depression and trauma symptoms were reported compared with previous population studies, but not dramatically so. Anxiety or depression and trauma symptoms were predicted by young age, presence of children in the home, and high estimates of personal risk. Anxiety and depression were also predicted by low income, loss of income and pre-existing health conditions in self and others. Specific anxiety about COVID-19 was greater in older participants.
Conclusions
This study showed a modest increase in the prevalence of mental health problems in the early stages of the pandemic, and these problems were predicted by several specific COVID-related variables. Further similar surveys, particularly of those with children at home, are required as the pandemic progresses.
Despite a putative role for estrogen in depression, studies on the association between depression and estrogen receptor (ER) polymorphisms are surprisingly lacking.
Objectives
To determine the association between ER polymorphisms and late-life depression in 6809 men and women and to investigate factors which could modify this association.
Method
Community-dwelling elderly aged 65 years and older were recruited in France as part of the Three City Study. Depression was assessed using the Centre for Epidemiological Studies Depression Scale and the Mini-International Neuropsychiatric Interview, according to DSM-IV criteria. The association between five polymorphisms of the ER-α and ER-β with depression was determined using multi-adjusted logistic regression models.
Results
Men with the AA genotype of the ER-β rs4986938 polymorphism had an increased risk of depression, while in women, carriers of the A allele for the ER-β rs1256049 had an increased risk. Subsequent analysis indicated that the increased risk in women occurred only in those not using hormone treatment. In women the CC and GG genotypes of the ER-α PvuII and XbaI, respectively were associated with a decreased risk of depression. A significant interaction between the ER-α PvuII and ER-β rs4986938 polymorphisms suggests they may act together to modify the depression risk.
Conclusions
Sex-specific associations between ER polymorphisms and depression have been identified, with HT appearing to be beneficial for genetically vulnerable women. These findings of distinct genetic susceptibility to late-life depression may be important for designing novel hormone-based therapies that would have optimal effectiveness in sub-groups of depressed women and men.
Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6–23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (–1·93 (95 % CI –1·88, –1·97)) v. placebo (–1·88 (95 % CI –1·83, –1·92)), and the opposite occurred among initially anaemic children (final mean LAZ –1·90 (95 % CI –1·86, –1·94) in MNP v. –1·92 (95 % CI –1·88, –1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.
Iron oxides resulting from the corrosion of large quantities of steel that are planned to be installed throughout a deep geological disposal facility (GDF) are expected to be one of the key surfaces of interest for controlling radionuclide behaviour under disposal conditions. Over the lengthy timescales associated with a GDF, the system is expected to become anoxic so that reduced Fe(II) phases will dominate. Batch experiments have therefore been completed in order to investigate how a model reduced Fe-oxide surface (wüstite, Fe1–xO) alters as a function of exposure to aqueous solutions with compositions representative of conditions expected within a GDF. Additional experiments were performed to constrain the effect that highly alkaline solutions (up to pH 13) have on the adsorption behaviour of the uranyl (UO22+) ion onto the surfaces of both wüstite and portlandite [Ca(OH)2; representative of the expected cementitious phases]. Surface co-ordination chemistry and speciation were determined by ex situ X-ray absorption spectroscopy measurements (both X-ray absorption near-edge structure analysis (XANES) and extended X-ray absorption fine structure analysis (EXAFS)). Diffraction, elemental analysis and XANES showed that the bulk solid composition and Fe oxidation state remained relatively unaltered over the time frame of these experiments (120 h), although under alkaline conditions possible surface hydroxylation is observed, due presumably to the formation of surface hydroxyl complexes. The surface morphology, however, is altered significantly with a large degree of roughening and an observed decrease in the average particle size. Reduction of U(VI) to U(IV) occurs during adsorption in almost all cases and this is interpreted to indicate that wüstite may be an effective reductant of U during surface adsorption. This work also shows that increasing the carbonate concentration in reactant solutions dramatically decreases the adsorption coefficients for U on both wüstite and portlandite, consistent with U speciation and surface reactivity determined in other studies. Finally, the EXAFS results include new details about exactly how U bonds to this metal oxide surface.
Excavations at several locations in Verteba Cave have uncovered a large amount of human skeletal remains in association with faunal bones and Tripolye material culture. We aim to establish radiocarbon (14C) dates for eight sites and to evaluate whether these deposits are singular events, or slow accumulations over time. 14C measurements, along with stable carbon and nitrogen isotope data from human and faunal remains, were collected from 18 specimens. Stable isotope values were used to evaluate human and animal diet, and whether freshwater reservoir effects offset measured dates. We found diets of the sampled species had limited to no influence from freshwater resources. Human diet appears to be dominated by terrestrial plants and herbivores. Four new sites were identified as Eneolithic. Comparisons of dates from top and bottom strata for two sites (7 and 20) reveal coeval dates, and we suggest that these deposits represent discrete events rather than slow continuous use. Lastly, we identified dates from the Mesolithic (8490±45 BP, 8765±30 BP), Iron Age (2505±20 BP), Slavic state era (1315±25 BP), and Medieval Period (585±15 BP), demonstrating periodic use of the cave by humans prior to and after the Eneolithic.
To date, Ireland has been a leading light in the provision of youth mental health services. However, cognisant of the efforts of governmental and non-governmental agencies working in youth mental health, there is much to be done. Barriers into care as well as discontinuity of care across the spectrum of services remain key challenges. This editorial provides guidance for the next stage of development in youth mental care and support that will require significant national engagement and resource investment.
Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.
Deficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes.
Methods
The sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes.
Results
Whole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP.
Conclusions
Abnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.
Trypanosoma cruzi, causative agent of Chagas disease, co-infects its triatomine vector with its sister species Trypanosoma rangeli, which shares 60% of its antigens with T. cruzi. Additionally, T. rangeli has been observed to be pathogenic in some of its vector species. Although T. cruzi–T. rangeli co-infections are common, their effect on the vector has rarely been investigated. Therefore, we measured the fitness (survival and reproduction) of triatomine species Rhodnius prolixus infected with just T. cruzi, just T. rangeli, or both T. cruzi and T. rangeli. We found that survival (as estimated by survival probability and hazard ratios) was significantly different between treatments, with the T. cruzi treatment group having lower survival than the co-infected treatment. Reproduction and total fitness estimates in the T. cruzi and T. rangeli treatments were significantly lower than in the co-infected and control groups. The T. cruzi and T. rangeli treatment group fitness estimates were not significantly different from each other. Additionally, co-infected insects appeared to tolerate higher doses of parasites than insects with single-species infections. Our results suggest that T. cruzi–T. rangeli co-infection could ameliorate negative effects of single infections of either parasite on R. prolixus and potentially help it to tolerate higher parasite doses.
Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat diet in utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.