Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies.

BACKGROUND: Data on the long-term impact of SARS-CoV-2 infection in children and young people (CYP) are conflicting. We assessed evidence on long-term post-COVID symptoms in CYP examining prevalence, risk factors, type and duration. METHODS: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 and 31/07/2021. Eligible studies reported CYP ≤19 years with confirmed or probable SARS-CoV-2 with any symptoms persisting beyond acute illness. Random effects meta-analyses estimated pooled risk difference in symptom prevalence (controlled studies only) and pooled prevalence (uncontrolled studies also included). Meta-regression examined study characteristics hypothesised to be associated with symptom prevalence. Prospectively registered: CRD42021233153. FINDINGS: Twenty two of 3357 unique studies were eligible, including 23,141 CYP. Median duration of follow-up was 125 days (IQR 99-231). Pooled risk difference in post-COVID cases compared to controls (5 studies) were significantly higher for cognitive difficulties (3% (95% CI 1, 4)), headache (5% (1, 8)), loss of smell (8%, (2, 15)), sore throat (2% (1, 2)) and sore eyes (2% (1, 3)) but not abdominal pain, cough, fatigue, myalgia, insomnia, diarrhoea, fever, dizziness or dyspnoea. Pooled prevalence of symptoms in post-COVID participants in 17 studies ranged from 15% (diarrhoea) to 47% (fatigue). Age was associated with higher prevalence of all symptoms except cough. Higher study quality was associated with lower prevalence of all symptoms, except loss of smell and cognitive symptoms. INTERPRETATION: The frequency of the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. This systematic review and meta-analysis highlights the critical importance of a control group in studies on CYP post SARS-CoV-2 infection.

Hypertrophic osteopathy in South Australian koalas (Phascolarctos cinereus) with concurrent pulmonary actinomycosis.

Pulmonary actinomycosis is described in 17 South Australian koalas necropsied between 2016 and 2019. From these cases, four koalas had secondary hypertrophic osteopathy. Plain radiographical and computed tomography images demonstrated periosteal reaction on multiple appendicular skeletal bones in all cases, including scapula, humerus, ulna, radius, ilium, femur, tibia, fibula, metacarpus, metatarsus and phalanx. Grossly, periosteal surfaces of the metaphyses and diaphyses of long bones were thickened and roughened; microscopically, this was characterised by bi-layered proliferation of well-differentiated trabecular bony spicules oriented perpendicular to the cortex (pseudocortices) and separated by vascular connective tissue, typical for hypertrophic osteopathy. Well characterised in domestic species and rarely reported in marsupials, this is the first radiographical and pathological characterisation of hypertrophic osteopathy in koalas, associated with pulmonary actinomycosis in all cases.

Symmetric dimethylarginine values in koalas (Phascolarctos cinereus) based on oxalate nephrosis status.

Oxalate nephrosis is a prevalent renal disease in koalas (Phascolarctos cinereus) of the Mount Lofty Ranges population in South Australia. The symmetric dimethylarginine (SDMA) assay is widely used in companion animals to diagnose renal disease, particularly in the early stages. This study aimed to determine: (1) reference intervals for SDMA in koalas and (2) SDMA values of koalas with oxalate nephrosis. Blood samples were collected from 41 Mount Lofty Ranges koalas euthanased on welfare grounds. Koalas were necropsied and, based on renal histopathology, were classified as unaffected (n = 22) or affected (n = 19) by oxalate nephrosis. Serum or plasma samples were analysed for creatinine, urea and SDMA and urine samples for urine specific gravity (USG). The reference interval for SDMA in unaffected koalas was 2.4-22.9 µg/dL. In koalas with oxalate nephrosis, SDMA was elevated in 74% of cases above the upper limit of the confidence interval. SDMA was elevated in three affected koalas with normal creatinine values. A positive correlation was found between SDMA and creatinine (R = 0.775, P < 0.001) and SDMA and urea (R = 0.580, P < 0.001) and a negative correlation between SDMA and USG (R = -0.495, P = 0.027). In conclusion, SDMA correlates well with other commonly used tests of renal function in koalas and should be included as part of the standard diagnostic process to increase the accuracy of oxalate nephrosis diagnosis in koalas.

Nitrogen removal from coke making wastewater through a pre-denitrification activated sludge process.

Under the Industrial Emissions Directive (IED), coke production wastewater must be treated to produce an effluent characterised by a total nitrogen (TN) <50 mg/L. An anoxic-aerobic activated sludge pilot-plant (1 m3) fed with coke production wastewater was used to investigate the optimal operational requirements to achieve such an effluent. The loading rates applied to the pilot-plant varied between 0.198-0.418 kg COD/m3.day and 0.029-0.081 kg TN/m3.day, respectively. The ammonia (NH4+-N) removals were maintained at 96%, after alkalinity addition. Under all conditions, phenol and SCN- remained stable at 96% and 100%, respectively with both being utilised as carbon sources during denitrification. The obtained results showed that influent soluble chemical oxygen demand (sCOD) to TN ratio of should be maintained at >5.7 to produce an effluent TN <50 mg/L. Furthermore, nitrite accumulation was observed under all conditions indicating a disturbance to the denitrification pathway. Overall, the anoxic-aerobic activated sludge process was shown to be a robust and reliable technology to treat coke making wastewater and achieve the IED requirements. Nevertheless, the influent to the anoxic tank should be monitored to ensure a sCOD:TN ratio >5.7 or, alternately, the addition of an external carbon source should be considered.

Induction of neutralizing antibody response against koala retrovirus (KoRV) and reduction in viral load in koalas following vaccination with recombinant KoRV envelope protein.

Koala retrovirus (KoRV) infects the majority of Australia's koalas (Phascolarctos cinereus) and has been linked to several life-threatening diseases such as lymphoma and leukemia, as well as Chlamydia and thus poses a threat to the continued survival of this species. While quarantine and antiretroviral drug treatment are possible control measures, they are impractical, leaving vaccination as the only realistic option. In this study, we examined the effect of a recombinant envelope protein-based anti-KoRV vaccine in two groups of South Australian koalas: KoRV infected or KoRV free. We report a successful vaccination response in the koalas with no vaccine-associated side effects. The vaccine induced a significant humoral immune response as well as the production of neutralizing antibodies in both groups of koalas. We also identified B-cell epitopes that were differentially recognized in KoRV-infected versus KoRV-free koalas following vaccination. Importantly, we also showed that vaccination had a therapeutic effect on koalas infected exogenously with KoRV by reducing their circulating viral load. Together, this study highlights the possibility of successfully developing a vaccine against KoRV infection in koalas.

A survey of staffing levels in paediatric diabetes services throughout the UK.

AIMS: To assess staffing levels of healthcare professionals involved in the care of children and young people with diabetes in the UK. METHODS: A web-based questionnaire was distributed to lead consultant paediatricians from all paediatric diabetes services in the UK between October and December 2014. Data on staffing levels and other aspects of diabetes services were collected and differences between the four nations of the UK and across the 10 English diabetes networks were explored. RESULTS: Some 175 services (93%) caring for 29 711 children and young people aged ≤ 24 years with diabetes participated in the survey. Northern Ireland and Wales had the lowest ratio of total staff to patient population. Nursing caseloads per one whole-time equivalent (WTE) nurse ranged from 71 patients in England to 110 patients in Northern Ireland with only 52% of the UK services meeting the Royal College of Nursing recommended nurse-to-patient ratio of > 1 : 70. Scotland and Northern Ireland had the highest ratio of consultants and fully trained doctors per 1000 patients (3.5 WTE). Overall, 17% of consultants had a Certificate of Completion of Training in Endocrinology and Diabetes. Some 44% of dietitians were able to adjust insulin dose. Only 43% of services provided 24-h access to advice from the diabetes team and 82% of services had access to a psychologist. Staffing levels adjusted for volume were not directly related to glycaemic performance of services in England and Wales. CONCLUSIONS: Wide variations in staffing levels existed across the four nations of the UK and important gaps were present in key areas.

Clinic variation in glycaemic control for children with Type 1 diabetes in England and Wales: a population-based, multilevel analysis.

AIM: To understand the scope for improving children's glycaemic outcomes by reducing variation between clinics and examine the role of insulin regimen and clinic characteristics. METHODS: Cross-sectional analysis of 2012-2013 National Paediatric Diabetes Audit data from 21 773 children aged < 19 years with Type 1 diabetes cared for at 176 clinics organized into 11 regional diabetes networks in England and Wales. Variation in HbA1c was explored by multilevel models with a random effect for clinic. The impact of clinic context was quantified by computing the per cent of total variation in HbA1c which occurs between clinics (intraclass correlation coefficient; ICC). RESULTS: Overall, 69 of the 176 diabetes clinics (39%) had a glycaemic performance that differed significantly from the national average after adjusting for patient case-mix with respect to age, gender, diabetes duration, deprivation and ethnicity. However, differences between clinics accounted for 4.7% of the total variation in HbA1c . Inclusion of within-clinic HbA1c standard deviation led to a substantial reduction in ICC to 2.4%. Insulin regimen, clinic volume and diabetes networks had a small or moderate impact on ICC. CONCLUSIONS: Differences between diabetes clinics accounted for only a small portion of the total variation in glycaemic control because most of the variation was within clinics. This implies that national glycaemic improvements might best be achieved not only by targeting poor centres but also by shifting the whole distribution of clinics to higher levels of quality.

Young people with Type 1 diabetes of non-white ethnicity and lower socio-economic status have poorer glycaemic control in England and Wales.

BACKGROUND: The impact of ethnicity and socio-economic status (SES) on glycaemic control during childhood Type 1 diabetes is poorly understood in England and Wales. METHODS: We studied 18 478 children with Type 1 diabetes (< 19 years) attending diabetes clinics and included in the 2012-2013 National Paediatric Diabetes Audit. Self-identified ethnicity was categorized as white, Asian, black, mixed, other and 'not-stated' (did not to divulge ethnicity). A small area measure of SES was estimated from the Index of Multiple Deprivation. Multiple linear regression was used to assess associations between ethnicity, SES and glycaemic control (mean HbA1c levels) accounting for age, gender and diabetes duration. The impact of insulin pump use on the ethnicity/SES-HbA1c associations was tested in 13 962 children. RESULTS: All children from minority ethnic groups had higher mean HbA1c compared with white children, with largest differences observed in black and mixed ethnicities [8 mmol/mol (2.9%), 95% CI 5-11 and 7 mmol/mol (2.8%), 95% CI 5-9, respectively]. Lower SES was associated with higher mean HbA1c with a dose effect. The lowest SES group had a mean HbA1c that was 7 mmol/mol (2.8%) (95% CI 6-8) higher compared with the highest SES group, adjusted for ethnicity. Estimates for ethnicity were attenuated, but significant on adjustment for SES. Fewer non-white (white 20.3 vs. black 5.5%) and deprived (least deprived 21.1 vs. most deprived 13.2%) children were on insulin pump therapy. Ethnicity and SES remained significant predictors of HbA1c after accounting for insulin pump use. CONCLUSION: The association between ethnicity and glycaemic control persists after adjustment for deprivation and pump use. An alternative approach to intensive insulin therapy might benefit these vulnerable children.

Ecological conditions of ponds situated on blast furnace slag deposits located in South Gare Site of Special Scientific Interest (SSSI), Teesside, UK.

Slag, a by-product from the iron and steel industry, has a range of applications within construction and is used in wastewater treatment. Historically considered a waste material, little consideration was given to the environmental impacts of its disposal. South Gare (a Site of Special Scientific Interest) located at the mouth of the Tees estuary, UK, formed on slag deposits used to create a sea wall and make the land behind permanent. Over time, ponds formed in depressions with the water chemistry, being significantly impacted by the slag deposits. Calcium levels reached 504 mg/L, nitrate 49.0 mg/L and sulphate 1,698 mg/L. These levels were also reflected in the composition of the sediment. pH (5.10-9.90) and electrical conductivity (2,710-3,598 µS/cm) were variable but often notably high. Pb, Cu and Cd were not present within the water, whilst Zn ranged from 0.027 to 0.37 mg/L. Heavy metal levels were higher in surface sediments. Zinc was most dominant (174.3-1,310.2 mg/L) followed by Pb (9.9-431 mg/L), Cu (8.4-41.8 mg/L) and Cd (0.4-1.1 mg/L). A sediment core provided a historical overview of the ponds. The ponds were unfavourable for aquatic biodiversity and unsuitable for drinking water abstraction.

Performance of permeable media rotating reactors used for pretreatment of wastewaters.

The impact of organic loading rate (OLR) on carbonaceous materials and ammonia removal was assessed in bench scale rotating media biofilm reactors treating real wastewater. Media composition influences biofilm structure and therefore performance. Here, plastic mesh, reticulated coarse foam and fine foam media were operated concurrently at OLRs of 15, 35 and 60 g sCOD m(-2)d(-1) in three bench scale shaft mounted advanced reactor technology (SMART) reactors. The sCOD removal rate increased with loading from 6 to 25 g sCOD m(-2)d(-1) (P < 0.001). At 35 g BOD5m(-2)d(-1), more than double the arbitrary OLR limit of normal nitrifying conditions (15 g BOD5m(-2)d(-1)); the removal efficiency of NH(4)-N was 82 ± 5, 27 ± 19 and 39 ± 8% for the mesh, coarse foam and fine foam media, respectively. Increasing the OLR to 35 gm(-2)d(-1) decreased NH(4)-N removal efficiency to 38 ± 6, 21 ± 4 and 21 ± 6%, respectively. The mesh media achieved the highest stable NH(4)(+)-N removal rate of 6.5 ± 1.6 gm(-2)d(-1) at a sCOD loading of 35 g sCOD m(-2)d(-1). Viable bacterial numbers decreased with increasing OLR from 2 × 10(10)-4 × 10(9) cells per ml of biofilm from the low to high loading, suggesting an accumulation of inert non-viable biomass with higher OLR. Increasing the OLR in permeable media is of practical benefit for high rate carbonaceous materials and ammonia removal in the pretreatment of wastewater.

Sentinel node biopsy in papillary thyroid cancer--what is the potential?

PURPOSE: Sentinel node biopsy (SNB) may identify lymph node metastases in patients with papillary thyroid cancer (PTC), enabling selective application of central node dissection (CND). The aim of this study was to assess the feasibility of implementing SNB in patients undergoing thyroidectomy for a cytologically indeterminate/suspicious/malignant thyroid nodule and to determine the potential improvement in clinical outcomes and the costs associated with the SNB technique. METHODS: The treatment strategies and clinical and pathological outcomes of two retrospective cohorts of patients who underwent preoperative thyroid FNA over a 5-year period in two different centres were studied. The potential for implementing the SNB technique and the benefits and costs associated with implementation were estimated. RESULTS: In centre 1, in 819 adult patients who had thyroid fine-needle aspiration cytology, the final cytology was indeterminate, suspicious and diagnostic of malignancy in 113, 29 and 28 patients, respectively. One hundred eight patients were 'suitable' for SNB. Twenty-three of these patients had PTC, six of whom underwent CND. Of these six patients, node metastasis was absent in five--the cohort in whom prophylactic CND may have been avoided consequent to a negative 'sentinel node' biopsy. Morbidity attributable to CND may have been avoided in up to four patients over a 5-year period. Costs associated with implementation of SNB outweighed any potential savings. Analysis of 491 patients in centre 2 confirmed that the benefit of SNB in PTC was similarly limited; morbidity attributable to CND may have been avoided in up to seven patients over a 5-year period. CONCLUSIONS: Even under ideal conditions (assuming 100 % node identification rate and 0 % false negative rate), the potential short- to medium-term benefit of sentinel node biopsy in patients with thyroid cancer in centres implementing a policy of selective or routine prophylactic CND is low.

Fate and behaviour of copper and zinc in secondary biological wastewater treatment processes: I. Evaluation of biomass adsorption capacity.

The current sources of copper and zinc in municipal wastewaters have been considered, and the changes in the concentrations and quantities of these two elements entering sewage treatment works over the last three decades have been calculated. The concentrations and quantities of the heavy metals cadmium, chromium, copper, mercury, nickel, lead and zinc, entering UK sewage treatment works, have been reduced by between 50% and 90% during this period. However, the reductions in copper and zinc appear to be at the lower end of these ranges and thus remain a cause for concern, particularly their concentrations in sewage effluents and their potential environmental impacts on receiving waters. Bench studies have been undertaken to predict removals by three types of biological wastewater treatment plants: trickling filters, conventional activated sludge and membrane bioreactors, to determine if any of these processes are more efficacious for the removal of these metals. These results suggest that, despite membrane bioreactor biomass achieving the lowest effluent suspended solids concentration and having the lowest effluent chemical oxygen demand, which is accepted as a surrogate measure of organic chemical chelating ability of the aqueous phase, they produce the highest effluent values for the two metals in this study (copper and zinc). Removals of zinc and copper in biological wastewater treatment processes are probably primarily determined by those factors influencing metal solubility in the biomass matrix.

Fate and behaviour of copper and zinc in secondary biological wastewater treatment processes: II. Removal at varying sludge age.

The mechanisms for the removal of heavy metals during secondary biological treatment of wastewater, with particular emphasis on the activated sludge process, are considered. It is concluded that the predominant mechanism is the entrapment and co-settlement of insoluble metal species in the mixed liquor (biomass). Secondary extracellular polymeric materials, particularly extracellular polysaccharides and other capsule-forming materials, may also play a role. In general, removal of both copper and zinc was superior at the higher sludge ages employed in this study, 4.3 and 8 days, and can in part be attributed to the superior removals of both biochemical oxygen demand and effluent suspended solids achieved at these sludge ages compared with the lowest sludge age studied, 3.6 days. For both copper and zinc there is an increase in soluble metal across the activated sludge process. However, significant removal of both metals occurs as a consequence of the removal of substantial amounts of insoluble metal. The presence of returned sludge liquors, high in settleable solids, to the mixed liquor appears to moderately enhance the percentage removal of copper and zinc. Membranes used in place of secondary sedimentation also enhance removal of both metals by reducing effluent suspended solids. It is concluded that there is potential for maximizing metal removal by optimization of secondary biological treatment in a sustainable manner, without recourse to energy-intensive or chemically-dependent tertiary treatment technologies.

Is there a causal relationship between the hypoxia-ischaemia associated with cardiorespiratory arrest and subdural haematomas? An observational study.

The aim of this study was to determine the frequency of subdural haematomas (SDHs) occurring in infants presenting following atraumatic cardiorespiratory collapse. This study was a review of retrospective case notes, brain imaging and post-mortem examinations carried out in the paediatric intensive care unit (PICU) and emergency department (ED) in a tertiary paediatric centre in the UK. The study included infants and children less than 4 years old dying in the ED or admitted to the PICU after atraumatic cardiorespiratory arrest. We identified macroscopic SDHs on brain imaging or post-mortem examination. Of those children who experienced a cardiorespiratory arrest from a non-traumatic cause and met inclusion criteria, 33 presented and died in the ED and 17 were admitted to the PICU. These children had a post-mortem examination, brain imaging or both. None of these infants had a significant SDH. One child had a small clot adherent to the dura found on post-mortem and two had microscopic intradural haemorrhage, but it is unclear in each case whether this was artefact, as each had otherwise normal brains. Subdural haematoma arising in infants or young children in the context of catastrophic cardiorespiratory compromise from a non-traumatic cause was not observed.

Oral versus i.v. antibiotics for community-acquired pneumonia in children: a cost-minimisation analysis.

Community-acquired pneumonia represents a high financial burden to healthcare providers. This manuscript seeks to estimate and compare the costs of treating children hospitalised with community-acquired pneumonia, with oral and intravenous antibiotics, thus determining which treatment is cost minimising. A cost-minimisation analysis was undertaken alongside a randomised controlled non-blinded equivalence trial. 232 children (from eight paediatric centres in England) diagnosed with pneumonia, who required admission to hospital, were randomised to receive oral amoxicillin or i.v. benzyl penicillin. The analysis considered the cost to the health service, patients and society, from pre-admission until the child was fully recovered. Oral amoxicillin and i.v. benzyl penicillin have equivalent efficacy. Children treated with i.v. antibiotics were found to have significantly longer in-patient stays (3.12 versus 1.93 days; p<0.001). i.v. treatment was found to be more expensive than oral treatment ( pound1,256 versus pound769; difference pound488; 95% CI: pound233- pound750), such that treatment of community-acquired pneumonia with oral amoxicillin would result in savings of between pound473 and pound518 per child (euro545 and euro596 per child) admitted. The findings demonstrate that oral amoxicillin is a cost-effective treatment for the majority of children admitted to hospital with pneumonia.

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression.

The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary 'Western' lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity.

An evidence-based guideline for children presenting with acute breathing difficulty.

OBJECTIVE: The aim of this study was to develop an evidence-based guideline for use primarily by junior clinicians to assist with the management of children presenting to the hospital with an acute breathing difficulty. METHODS: An overview of the literature provided a framework of clinical questions for the management of a child with an acute breathing difficulty on which to base a systematic literature review. Relevant articles were appraised by the research fellow and graded according to their quality. A national panel of 50 clinicians was provided, by post, with the clinical questions, research papers, appraisals and the grades of recommendations generated. They were asked to check the grades allocated to the recommendations and the accuracy of the language used. They were also provided with all the clinical questions for which there was insufficient evidence to reach a conclusion but for which a consensus recommendation was required. A Delphi method was used to formalise the consensus process. For all recommendations, panel members were asked to rate their level of agreement on a 1-9-point Likert scale. The results of the first round were fed back, and appropriate alterations to the recommendations made or additional recommendations included. The process of rating was repeated, and the final guideline was developed based on the consensus reached. RESULTS: Following two iterative rounds, the guideline was completed as a full technical document, with a series of key recommendations and an algorithm. It was based on 10 grade A (evidence from systematic review or meta-analyses), 5 grade B, 17 grade C and 31 grade D (consensus or expert opinion) recommendations. CONCLUSION: We have developed an evidence-based guideline that has subsequently been successfully implemented in the paediatric emergency departments and disseminated nationally. Results showing the effect of the guideline upon practice will be published separately.

Effect of maternal nutrient restriction from early to midgestation on cardiac function and metabolism after adolescent-onset obesity.

Maternal nutrient restriction (NR) from early to midgestation has marked effects on endocrine sensitivity and organ function of the resulting offspring. We hypothesized that early NR may reset the expression profile of genes central to myocardial energy metabolism, influencing ectopic lipid deposition and cardiac function in the obese adult offspring. NR offspring were exposed to an "obesogenic" environment, and their cardiac function and molecular indexes of myocardial energy metabolism were assessed to explore the hypothesis that an obese individual's risk of heart disease may be modified after maternal NR. Pregnant sheep were fed 100% (control) or 50% (NR) energy requirement from days 30 to 80 of gestation and 100% energy requirement thereafter. At weaning, offspring were exposed to an obesogenic environment or remained lean. At approximately 1 yr of age, the hemodynamic response of these offspring to hypotension, together with left ventricular expression profiles of fatty acid-binding protein 3 (FABP3), peroxisome proliferator-activated receptor-gamma (PPARgamma) and its coactivator (PGC)-1alpha, acetyl-CoA carboxylase (ACC), AMP-activated protein kinase (AMPK)-alpha(2), and voltage-dependent anion channel 1 (VDAC1), was determined. Obesity produced left ventricular hypertrophy in all animals, with increased ectopic (myocardial) lipid in NR offspring. Obesity per se significantly reduced myocardial transcript expression of PGC-1alpha, AMPKalpha(2), VDAC1, and ACC and increased expression of PPARgamma and FABP3. However, although NR animals were similarly obese, their transcript expression of ACC, PPARgamma, and FABP3 was similar to that of lean animals, indicating altered cardiac energy metabolism. Indeed, blunted tachycardia and an amplified inotropic response to hypotension characterized cardiac function in obese NR offspring. The results suggest that maternal NR during early organogenesis can precipitate an altered myocardial response to hypotension and increased myocardial lipid deposition in the adult offspring after adolescent-onset obesity, potentially rendering these individuals more at risk of early heart failure as they age.