Ebola virus-induced eye sequelae: a murine model for evaluating glycoprotein-targeting therapeutics.

BACKGROUND: Ebola virus disease (EVD) survivors experience ocular sequelae including retinal lesions, cataracts, and vision loss. While monoclonal antibodies targeting the Ebola virus glycoprotein (EBOV-GP) have shown promise in improving prognosis, their effectiveness in mitigating ocular sequelae remains uncertain. METHODS: We developed and characterized a BSL-2-compatible immunocompetent mouse model to evaluate therapeutics targeting EBOV-GP by inoculating neonatal mice with vesicular stomatitis virus expressing EBOV-GP (VSV-EBOV). To examine the impact of anti-EBOV-GP antibody treatment on acute retinitis and ocular sequelae, VSV-EBOV-infected mice were treated with polyclonal antibodies or monoclonal antibody preparations with antibody-dependent cellular cytotoxicity (ADCC-mAb) or neutralizing activity (NEUT-mAb). FINDINGS: Treatment with all anti-EBOV-GP antibodies tested dramatically reduced viremia and improved survival. Further, all treatments reduced the incidence of cataracts. However, NEUT-mAb alone or in combination with ADCC-mAb reduced viral load in the eyes, downregulated the ocular immune and inflammatory responses, and minimized retinal damage more effectively. INTERPRETATION: Anti-EBOV-GP antibodies can improve survival among EVD patients, but improved therapeutics are needed to reduce life altering sequelae. This animal model offers a new platform to examine the acute and long-term effect of the virus in the eye and the relative impact of therapeutic candidates targeting EBOV-GP. Results indicate that even antibodies that improve systemic viral clearance and survival can differ in their capacity to reduce acute ocular inflammation, and long-term retinal pathology and corneal degeneration. FUNDING: This study was partly supported by Postgraduate Research Fellowship Awards from ORISE through an interagency agreement between the US DOE and the US FDA.

Longitudinal associations between cardiovascular biomarkers and metabolic syndrome during puberty: the PUBMEP study.

Puberty has been described as a life stage of considerable metabolic risk specially for those with obesity. The low-grade systemic inflammatory status associated with obesity could be one of the connections with metabolic syndrome (MetS). Thus, we aimed to assess the relationship between inflammatory and cardiovascular biomarkers and the development of MetS during puberty. Seventy-five children from the PUBMEP study (33 females), aged 4-18 years, were included. Cardiovascular and inflammatory biomarkers were measured in the prepubertal and pubertal stage, including high-sensitivity C-reactive protein (CRP), leptin, tumor necrosis factor-alpha (TNFα), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP-1), total plasminogen activator inhibitor-1 (tPAI), resistin, adiponectin, myeloperoxidase (MPO), and soluble intercellular adhesion molecule-1 (sICAM-1). MetS was diagnosed at each measurement point. Mixed-effects and logistic regressions were performed. Those children with MetS in puberty presented higher prepubertal values of several cardiometabolic biomarkers in comparison to those without MetS (z-score body mass index (zBMI), waist circumference, insulin, HOMA-IR, leptin, and tPAI (p < 0.05)). For prepubertal children with obesity, the odds of developing MetS in puberty were significantly higher in those having high zBMI (OR = 4.27; CI: 1.39-22.59) or high concentrations of tPAI (OR = 1.19; CI: 1.06-1.43). CONCLUSION: Those with obesity with higher prepubertal tPAI plasma levels had 19% higher odds of having MetS at puberty highlighting the existence of association between MetS, obesity, and inflammation already in puberty. Thus, assessing cardiometabolic and inflammatory status in children with obesity already at prepuberty is key to avoiding future comorbidities. WHAT IS KNOWN: • Inflammation, metabolic syndrome, and obesity may have their onset in childhood. • Puberty is a life stage characterized for an increased cardiovascular risk. WHAT IS NEW: • Prepuberty state could be an early indicator of future cardiometabolic risk. • Children with obesity and high total plasminogen have higher odds of future metabolic syndrome.

Methods recently used for the assessment of physical activity in children and adolescents.

PURPOSE OF REVIEW: The aim of this review is to summarize recent evidences and advances on the implementation and the use of new tools to assessing physical activity (PA) in children. RECENT FINDINGS: Technological advances provide, increasingly, new objective methods for the evaluation of PA in children. In addition to accelerometry, there are other objective methods for assessing PA in children such as new wearable monitoring and activity bracelets, smartphone and recording software applications, Global Positioning System or Inertial Sensors Devices. SUMMARY: Doubly labeled water and calorimetry are reference methods to assessing PA but with limitations of use. Accelerometry is an accurate method for measuring sedentary behavior and PA levels in children. In fact, it is a real alternative reference method for the validation of methods and tools of assessing PA. However, there is still no consensus about the most appropriate approach to analyze the duration and intensity of PA in children. Therefore, the implementation of other alternative objective methods, as well as complementation with PA questionnaires, can provide a more precise evaluation of different patterns and behaviors related with sedentarism and PA.

Fitness Levels and Gender Are Related With the Response of Plasma Adipokines and Inflammatory Cytokines in Prepubertal Children.

Background and Aim: Changes in adipokines have been related with the development of metabolic syndrome, frequently associated with obesity, and other risk factors. Fitness seems to promote a healthy cardiovascular status and could be a protector factor, just from childhood. Therefore, the present study aimed to evaluate the relationship between fitness levels with plasma adipokines and inflammatory biomarkers in prepubertal children. Methods: One hundred and thirty-seven healthy normal-weight prepubertal children were recruited from local schools and divided after performing the fitness tests, into two groups according to fitness level-low cardiovascular fitness group (LF) and equal or higher cardiovascular fitness group (HF). Anthropometric variables, blood pressure (BP) and plasma insulin, and leptin, resistin, adiponectin, tumor necrosis factor-alpha, hepatic growth factor, interleukin (IL)-8, monocyte chemoattractant protein-1, nerve growth factor (NGF), and plasminogen activator inhibitor-1 (PAI-1) were measured fasting in both groups to be compared. Univariate analysis of variance, comparative analysis, binary logistic regression, stepwise linear regression, and principal component analysis were conducted to evaluate the association between fitness, BMI, gender, and the biochemical parameters. Results: Girls and boys with HF presented lower waist circumference Z-score, BMI Z-score, systolic BP (only boys) as well as lower levels of leptin and NGF compared with their respective LF group. Regarding the association between variables, fitness showed an inverse relationship with BMI Z-score, leptin, PAI-1, HOMA-IR, resistin, IL-8, and NGF. Conclusion: An adequate level of fitness seems to protect against risk factors related to low-grade inflammation and altered adipokines that are related to the onset of obesity just from the prepubertal stage.

The Metabolic Impact of Two Different Parenteral Nutrition Lipid Emulsions in Children after Hematopoietic Stem Cell Transplantation: A Lipidomics Investigation.

Hematopoietic stem cell transplantation (HSCT) involves the infusion of either bone marrow or blood cells preceded by toxic chemotherapy. However, there is little knowledge about the clinical benefits of parenteral nutrition (PN) in patients receiving high-dose chemotherapy during HSCT. We investigated the lipidomic profile of plasma and the targeted fatty acid profiles of plasma and erythrocytes in children after HSCT using PN with either a fish oil-based lipid emulsion or a classic soybean oil emulsion. An untargeted liquid chromatography high-resolution mass spectrometry platform connected with a novel in silico annotation algorithm was utilized to determine the most relevant chemical subclasses affected. In addition, we explored the interrelation between the lipidomics profile in plasma, the targeted fatty acid profile in plasma and erythrocytes, several biomarkers of inflammation, and antioxidant defense using an innovative data integration analysis based on Latent Components. We observed that the fish oil-based lipid emulsion had an impact in several lipid subclasses, mainly glycerophosphocholines (PC), glycerophosphoserines (PS), glycerophosphoethanolamines (PE), oxidized PE (O-PE), 1-alkyl,2-acyl PS, lysophosphatidylethanolamines (LPE), oxidized PS (O-PS) and dicarboxylic acids. In contrast, the classic soybean oil emulsion did not. Several connections across the different blocks of data were found and aid in interpreting the impact of the lipid emulsions on metabolic health.

Impact of Physical Activity Intensity Levels on the Cardiometabolic Risk Status of Children: The Genobox Study.

Childhood obesity has been related to metabolic syndrome and low-grade chronic inflammation. This study aimed to evaluate the impact of physical activity intensities and practice on inflammation, endothelial damage, and cardiometabolic risk factors in children. There were 513 participants, aged 6-14 years, recruited for the study. Physical activity was measured by accelerometry, and the children were classified into four groups according to quartiles of moderate to vigorous physical activity (MVPA) practice as very low active, low active, moderate active, and high active. Anthropometric measures, blood pressure, and plasma metabolic and proinflammatory parameters were analyzed. Very low active group presented a worse lipid profile and higher insulin, leptin, adiponectin, resistin, matrix metallopeptidase-9, and tissue plasminogen activator inhibitor-1, while lower levels of tumor necrosis factor-alpha, Type 1 macrophages, and interleukin 8 than high-active children. Regression analyses showed that a higher MVPA practice was associated with lower levels of triacylglycerols (ß: -0.118; p = .008), resistin (ß: -0.151; p = .005), tPAI (ß: -0.105; p = .046), and P-selectin (ß: -0.160; p = .006), independently of sex, age, and body mass index (BMI). In contrast, a higher BMI was associated with higher levels of insulin (ß: 0.370; p < .001), Homeostasis Model Assessment (ß: 0.352; p < .001), triacylglycerols (ß: 0.209; p < .001), leptin (ß: 0.654; p < .001), tumor necrosis factor-alpha (ß: 0.182; p < .001), Type 1macrophages (ß: 0.181; p < .001), and tissue plasminogen activator inhibitor (ß: 0.240; p < .001), independently of sex, age, and MVPA. A better anthropometric, metabolic, and inflammatory profile was detected in the most active children; however, these differences were partly due to BMI. These results suggest that a higher MVPA practice and a lower BMI in children may lead to a better cardiometabolic status.

Association of Diet, Physical Activity Guidelines and Cardiometabolic Risk Markers in Children.

The aim was to identify different dietary and physical activity (PA) patterns in 5- to 14-year-old children with a high prevalence of overweight and obesity using cluster analysis based on their adherence to the Spanish Society of Community Nutrition dietary guidelines and levels of PA, and to determine their associations with age, sex, body composition, and cardiometabolic risk markers. In 549 children, hierarchical cluster analysis was used to identify subgroups with similar adherence to dietary recommendations and level of PA. Three clusters were identified: Cluster 1, with the lowest level of vigorous PA and adherence to dietary recommendations; Cluster 2, with the lowest levels of moderate and vigorous PA and the highest adherence to dietary recommendations; and Cluster 3, with the highest level of PA, especially vigorous PA and a medium level adherence to dietary recommendations. Cluster 3 had lower total body fat and higher lean body mass percentages than Cluster 2. Cluster 2 had lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol levels than Cluster 1. The results from our study suggest that it is important to consider adherence to PA recommendations together with adherence to dietary guidelines to understand patterns of obesogenic habits in pediatric populations with high prevalence of overweight and obesity.

Impaired Antioxidant Defence Status Is Associated With Metabolic-Inflammatory Risk Factors in Preterm Children With Extrauterine Growth Restriction: The BIORICA Cohort Study.

Introduction: An impaired antioxidant status has been described during foetal growth restriction (FGR). Similarly, the antioxidant defence system can be compromised in preterm children with extrauterine growth restriction (EUGR). The aim of this prospective study was to evaluate the antioxidant status in prepubertal children with a history of prematurity without FGR, with and without EUGR, compared to a healthy group. Methods: In total, 211 children were recruited and classified into three groups: 38 with a history of prematurity and EUGR; 50 with a history of prematurity and adequate extrauterine growth (AEUG); and 123 control children born at term. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were assessed in lysed erythrocytes with spectrophotometric methods. Plasma levels of the antioxidants α-tocopherol, retinol and ß-carotene were determined through solvent extraction and ultra-high-pressure liquid chromatography coupled to mass spectrometry. Results: Children with the antecedent of EUGR and prematurity had lower CAT activity than the other two groups and lower GPx activity than the control children. Lower SOD, GPx and GR activities were observed in the AEUG group compared to the controls. However, higher concentrations of α-tocopherol and ß-carotene were found in the EUGR group compared to the other groups; retinol levels were also higher in EUGR than in AEUG children. In EUGR and AEUG children, enzymatic antioxidant activities and plasma antioxidants were associated with metabolic syndrome components and pro-inflammatory biomarkers. Conclusions: This study reveals, for the first time, that the EUGR condition and prematurity appear to be linked to an impairment of the antioxidant defence status, which might condition an increased risk of adverse metabolic outcomes later in life.

Prematurity With Extrauterine Growth Restriction Increases the Risk of Higher Levels of Glucose, Low-Grade of Inflammation and Hypertension in Prepubertal Children.

Introduction: An adipose tissue programming mechanism could be implicated in the extrauterine growth restriction (EUGR) of very preterm infants with morbidity in the cardiometabolic status later in life, as has been reported in intrauterine growth restriction. The aim of this study was to assess whether children with a history of prematurity and EUGR, but also with an adequate growth, showed alterations in the metabolic and inflammatory status. Methods: This was a case-control study. A total of 88 prepubertal children with prematurity antecedents were selected: 38 with EUGR and 50 with an adequate growth pattern (PREM group). They were compared with 123 healthy children born at term. Anthropometry, metabolic parameters, blood pressure (BP), C-reactive protein, hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, tumour necrosis factor-alpha (TNF-α) and plasminogen activator inhibitor type-1 were analysed at the prepubertal age. Results: EUGR children exhibited higher BP levels and a higher prevalence of hypertension (46%) compared with both PREM (10%) and control (2.5%) groups. Moreover, there was a positive relationship between BP levels and values for glucose, insulin and HOMA-IR only in children with a EUGR history. The EUGR group showed higher concentrations of most of the cytokines analysed, markedly higher TNF-α, HGF and MCP-1 levels compared with the other two groups. Conclusion: EUGR status leads to cardiometabolic changes and a low-grade inflammatory status in children with a history of prematurity, and that could be related with cardiovascular risk later in life.

The protein S100A4 as a novel marker of insulin resistance in prepubertal and pubertal children with obesity.

BACKGROUND: S100A4 is a metastasis-associated protein also reported as a promising marker for dysfunctional white adipose tissue (WAT) and insulin resistance (IR) in adult and adolescent populations. OBJECTIVE: We aimed to evaluate the association between the protein S100A4 and obesity and IR in children and during pubertal development. DESIGN AND METHODS: The study design consisted of three cross-sectional populations of 249, 11 and 19 prepubertal children respectively (named study population 1, 2 and 3), and a longitudinal population of 53 girls undergoing sexual maturation (study population 4). All subjects were classified into experimental groups according to their sex, obesity and IR status. All study populations counted on anthropometry, glucose, and lipid metabolism, inflammation and cardiovascular biomarkers as well as S100A4 plasma levels measured. The study population 1 was intended as the discovery population in which to elucidate the relationship between Obesity-IR and S100A4 plasma levels in prepubertal children. The cross-sectional populations 2 and 3 further counted on WAT gene expression data for investigating the molecular basis of this association. Instead, the longitudinal study population 4 presented blood whole-genome DNA methylation data at each temporal record, allowing deepening into the Obesity-IR-S1004 relationship during puberty as well as deciphering plausible epigenetic mechanisms altering S100A4 plasma levels. RESULTS: S100A4 plasma levels were strongly associated with several metabolic and anthropometric outcomes, namely IR, in prepubertal non-diabetic obese children. We also found highly significant positive associations during the course of puberty between the increase in S100A4 levels and the increase in HOMA-IR (P = 0.0003, FDR = 0.005) and insulin levels (P = 0.0003, FDR = 0.005). Methylation in two-enhancer related CpG sites of the S100A4 region (cg07245635 and cg10447638) was associated with IR biomarkers at the prepubertal stage and with longitudinal changes in these measurements. We further reported an association between visceral WAT (vWAT) S100A4 expression and HOMA-IR, insulin levels and BMI Z-Score, but not with circulating S100A4. CONCLUSIONS: We report for the first time the association of S100A4 with IR and WAT dysfunction in prepubertal populations as well as how the change in plasma S100A4 levels accompanies longitudinal trajectories of IR in children during pubertal development. Moreover, we propose epigenetic changes in two methylation sites and an altered S100A4 vWAT expression as plausible molecular mechanisms underlying this disturbance in obesity.

Effects of Nutritional Education Interventions on Metabolic Risk in Children and Adolescents: A Systematic Review of Controlled Trials.

Childhood obesity is a global public health issue and is linked to metabolic syndrome, which increases the risk of comorbidities such as type 2 diabetes, cardiovascular diseases and cancer. Social, economic and cultural factors influence changes in nutrition and lifestyle characterized by poorer diets and reduced physical activity. This systematic review summarizes the evidence for nutritional education interventions to improve metabolic risks in children and adolescents. Systematic searches of the databases Medline (via PubMed) and Scopus were conducted following PRISMA guidelines. The risk of bias for each study was assessed following the methodology of the Cochrane Collaboration. Ten case-controlled and randomized controlled studies testing nutritional educational interventions targeting children and adolescents from the general population were eligible for inclusion. The sample size was 3915 and the age range was 7-20 years. The duration of intervention ranged from 12 weeks to 20 years. All the studies that provided data on abdominal obesity reported differences in favour of the intervention. However, data on the effects on the remaining components of metabolic syndrome remain inconclusive. These results support the role of nutritional education interventions as a strategy to reduce central adiposity and its possible unhealthy consequences in children and adolescents.

Mechanisms of Action of Probiotics.

Probiotics are living microorganisms that confer health benefits to the host when administered in adequate amounts; however, dead bacteria and their components can also exhibit probiotic properties. Bifidobacterium and strains of lactic acid bacteria are the most widely used bacteria that exhibit probiotic properties and are included in many functional foods and dietary supplements. Probiotics have been shown to prevent and ameliorate the course of digestive disorders such as acute, nosocomial, and antibiotic-associated diarrhea; allergic disorders such as atopic dermatitis (eczema) and allergic rhinitis in infants; and Clostridium difficile-associated diarrhea and some inflammatory bowel disorders in adults. In addition, probiotics may be of interest as coadjuvants in the treatment of metabolic disorders, including obesity, metabolic syndrome, nonalcoholic fatty liver disease, and type 2 diabetes. However, the mechanisms of action of probiotics, which are diverse, heterogeneous, and strain specific, have received little attention. Thus, the aim of the present work was to review the main mechanisms of action of probiotics, including colonization and normalization of perturbed intestinal microbial communities in children and adults; competitive exclusion of pathogens and bacteriocin production; modulation of fecal enzymatic activities associated with the metabolization of biliary salts and inactivation of carcinogens and other xenobiotics; production of short-chain and branched-chain fatty acids, which, in turn, have wide effects not only in the intestine but also in peripheral tissues via interactions with short-chain fatty acid receptors, modulating mainly tissue insulin sensitivity; cell adhesion and mucin production; modulation of the immune system, which results mainly in the differentiation of T-regulatory cells and upregulation of anti-inflammatory cytokines and growth factors, i.e., interleukin-10 and transforming growth factor; and interaction with the brain-gut axis by regulation of endocrine and neurologic functions. Further research to elucidate the precise molecular mechanisms of action of probiotics is warranted.

Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs.

Considerable progress has been made in testing stem cell-derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-grade iPSC-RPE patches revealed specific features that distinguished transplantable from nontransplantable patches. Compared to RPE cells in suspension, our biodegradable scaffold approach improved integration and functionality of RPE patches in rats and in a porcine laser-induced RPE injury model that mimics AMD-like eye conditions. Our results suggest that the in vitro and in vivo preclinical functional validation of iPSC-RPE patches developed here might ultimately be useful for evaluation and optimization of autologous iPSC-based therapies.

Molecular Characterization of New FBXL4 Mutations in Patients With mtDNA Depletion Syndrome.

Encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome 13 (MTDPS13) is a rare genetic disorder caused by defects in F-box leucine-rich repeat protein 4 (FBXL4). Although FBXL4 is essential for the bioenergetic homeostasis of the cell, the precise role of the protein remains unknown. In this study, we report two cases of unrelated patients presenting in the neonatal period with hyperlactacidemia and generalized hypotonia. Severe mtDNA depletion was detected in muscle biopsy in both patients. Genetic analysis showed one patient as having in compound heterozygosis a splice site variant c.858+5G>C and a missense variant c.1510T>C (p.Cys504Arg) in FBXL4. The second patient harbored a frameshift novel variant c.851delC (p.Pro284LeufsTer7) in homozygosis. To validate the pathogenicity of these variants, molecular and biochemical analyses were performed using skin-derived fibroblasts. We observed that the mtDNA depletion was less severe in fibroblasts than in muscle. Interestingly, the cells harboring a nonsense variant in homozygosis showed normal mtDNA copy number. Both patient fibroblasts, however, demonstrated reduced mitochondrial transcript quantity leading to diminished steady state levels of respiratory complex subunits, decreased respiratory complex IV (CIV) activity, and finally, low mitochondrial ATP levels. Both patients also revealed citrate synthase deficiency. Genetic complementation assays established that the deficient phenotype was rescued by the canonical version of FBXL4, confirming the pathological nature of the variants. Further analysis of fibroblasts allowed to establish that increased mitochondrial mass, mitochondrial fragmentation, and augmented autophagy are associated with FBXL4 deficiency in cells, but are probably secondary to a primary metabolic defect affecting oxidative phosphorylation.

Spider Communities and Biological Control in Native Habitats Surrounding Greenhouses.

The promotion of native vegetation as a habitat for natural enemies, which could increase their abundance and fitness, is especially useful in highly simplified settings such as Mediterranean greenhouse landscapes. Spiders as generalist predators may also be involved in intra-guild predation. However, the niche complementarity provided by spiders as a group means that increased spider diversity may facilitate complementary control actions. In this study, the interactions between spiders, the two major horticultural pests, Bemisia tabaci and Frankliniella occidentalis, and their naturally occurring predators and parasitoids were evaluated in a mix of 21 newly planted shrubs selected for habitat management in a highly disturbed horticultural system. The effects of all factors were evaluated using redundancy analysis (RDA) and the generalized additive model (GAM) to assess the statistical significance of abundance of spiders and pests. The GAM showed that the abundance of both pests had a significant effect on hunter spider's abundance, whereas the abundance of B. tabaci, but not F. occidentalis, affected web-weavers' abundance. Ordination analysis showed that spider abundance closely correlated with that of B. tabaci but not with that of F. occidentalis, suggesting that complementarity occurs, and thereby probability of biocontrol, with respect to the targeted pest B. tabaci, although the temporal patterns of the spiders differed from those of F. occidentalis. Conservation strategies involving the establishment of these native plants around greenhouses could be an effective way to reduce pest populations outdoors.

Health Related Quality of Life, Disability, and Pain in Alpha Mannosidosis: Long-Term Data of Enzyme Replacement Therapy With Velmanase Alfa (Human Recombinant Alpha Mannosidase)

Abstract Alpha-mannosidosis, a rare lysosomal storage disorder caused by deficiency of the lysosomal enzyme alpha-mannosidase, results in accumulation of mannose-rich glycoproteins in the tissues and sequelae leading to intellectual disability, ataxia, impaired hearing and speech, recurrent infections, skeletal abnormalities, muscular pain, and weakness. This study aimed to investigate disability, pain, and overall health using the Childhood Health Assessment Questionnaire (CHAQ) and the EuroQol 5 Dimension-5 Level Questionnaire (EQ-5D-5L) in patients with alpha-mannosidosis participating in rhLAMAN-10, a phase III open-label, clinical trial of velmanase alfa, a recombinanthumanlysosomalalpha-mannosidase. Long-termprognosesformost patients withuntreatedalpha-mannosidosisarepoor due to progressive neuromuscular, skeletal, and intellectual deterioration, leading to increased dependence in mobility and activities of daily living and increased caregiver and health-care burden. Long-term CHAQ and EQ-5D-5L data highlight improvement trends in health-related quality of life and a reduction in disability and pain in patients receiving up to 48 months of velmanase alfa treatment.

Cardiac Biomarkers of Low Cardiac Output Syndrome in the Postoperative Period After Congenital Heart Disease Surgery in Children.

INTRODUCTION AND OBJECTIVES: To assess the predictive value of atrial natriuretic peptide, ß-type natriuretic peptide, copeptin, mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I) as indicators of low cardiac output syndrome in children with congenital heart disease undergoing cardiopulmonary bypass (CPB). METHODS: After corrective surgery for congenital heart disease under CPB, 117 children (aged 10 days to 180 months) were enrolled in a prospective observational pilot study during a 2-year period. The patients were classified according to whether they developed low cardiac output syndrome. Biomarker levels were measured at 2, 12, 24, and 48 hours post-CPB. The clinical data and outcome variables were analyzed by a multiple logistic regression model. RESULTS: Thirty-three (29%) patients developed low cardiac output syndrome (group 1) and the remaining 84 (71%) patients were included in group 2. cTn-I levels >14 ng/mL at 2hours after CPB (OR, 4.05; 95%CI, 1.29-12.64; P=.016) and MR-proADM levels>1.5 nmol/L at 24hours following CPB (OR, 15.54; 95%CI, 4.41-54.71; P<.001) were independent predictors of low cardiac output syndrome. CONCLUSIONS: Our results suggest that cTn-I at 2hours post-CPB is, by itself, an evident independent early predictor of low cardiac output syndrome. This predictive capacity is, moreover, reinforced when cTn-I is combined with MR-proADM levels at 24hours following CPB. These 2 cardiac biomarkers would aid in therapeutic decision-making in clinical practice and would also enable clinicians to modify the type of support to be used in the pediatric intensive care unit.

Oxidative stress and inflamatory plasma biomarkers in respiratory syncytial virus bronchiolitis.

INTRODUCTION: Oxidative stress (OS) plays a crucial role in the pathogenesis of inflammatory lung diseases. OBJECTIVES: (i) We determined whether acute bronchiolitis (AB) caused by respiratory syncytial virus (RSV) induced OS; (ii) assessed whether OS biomarkers correlated with the severity of RSV-AB; and (iii) studied whether the levels of interleukins are associated with OS biomarkers. METHODS: We performed an observational study by comparing healthy infants (Group 1) with RSV-AB infants, classified as Group 2 (pulse oximetry (SpO2 ) >93%), and Group 3 (SpO2 ≤ 92%), which needed oxygen therapy. Blood samples were collected to determine the levels of lipid peroxidation (LPO) products (LPO), total glutathione (TG), oxidised glutathione (GSSG), reduced glutathione (GSH), glutathione peroxidase (GPx), interleukins (ILs) IL-10, IL-6, IL-8, interferon-gamma (IFNγ), tumour necrosis factor-alpha (TNFα) and macrophage inflammatory proteins (MIP α and MIP ß). RESULTS: Forty-six RSV-AB infants (47% needed oxygen therapy) and 27 healthy infants were included. The GSH/GSSG ratio was lower in RSV-AB infants than in Group 1 (P<0.001). GSSG and GPx were significantly higher in Group 3. GSSG predicted the need for oxygen therapy with an optimal cut-off point of 15 µM/g for haemoglobin. The GSH/GSSG ratio negatively correlated with IL-6 (P: 0.014), IL-8 (P: 0.014) and IL-10 (P: 0.033). Group 3 exhibited a direct correlation between GPx and IL-10 levels (P: 0.024) and between LPO and MIP ß (P: 0.003). CONCLUSIONS: RSV induced OS in AB. An increase in GSSG correlated with the disease severity in the infants. OS may contribute to the pathogenesis of RSV-AB.

Factores socioculturales determinantes de los hábitos alimentarios de niños de una escuela- jardín en Perú: / Sociocultural factors determinants of eating habits of kindergarten schoolchildren in Peru:

RESUMEN Con el objetivo de explorar los factores socioculturales que determinan los hábitos alimentarios de niños menores de cinco años de una escuela inicial de Chachapoyas en Perú, realizamos un estudio cualitativo mediante entrevistas semiestructuradas a 18 padres y madres. Los factores determinantes de los hábitos alimenticios fueron: la disponibilidad y facilidad de preparación de los alimentos; horario y trabajo desempeñado por los padres; ingesta de café en niños como práctica común; falta de recursos e incertidumbre económica para la planificación alimenticia, y la falta de conocimientos nutricionales. Asimismo, se identificaron creencias que pueden explicar algunos hábitos alimenticios, como los efectos beneficiosos de la comida en familia, la lactancia materna y otros alimentos, o el papel de la alimentación para el buen desarrollo intelectual y físico de los niños. Los resultados aportan evidencia sobre el modo en que los padres afrontan y entienden la alimentación de sus hijos, determinando, a su vez, la calidad de la misma.

ABSTRACT To examine the sociocultural factors that determine the eating habits of children aged less than 5 years who attend kindergarten school in Chachapoyas in Peru, we carried out a qualitative study by means of semi-structured interviews of 18 fathers and mothers. The key factors related to eating habits were as follows: availability and easiness to prepare foods, schedule and work done by parents, intake of coffee in children as a common practice, lack of resources and economic uncertainty for food planning, and the lack of nutritional knowledge. Similarly, beliefs that might explain some eating habits, such as the beneficial effects of eating food as a family, maternal breastfeeding, and others, or the role of nutrition for the appropriate intellectual and physical development of children were identified. Our results provide evidence about the ways parents tackle and understand their children's nutrition while, in turn, determining its quality.