SARS-CoV-2 Antibody Kinetics in Unvaccinated Hospitalized Children With COVID-19.

BACKGROUND: Antibody levels decline a few months post-acute COVID-19, but humoral memory persists in adults. Age and disease severity may affect antibody responses. This study aims to evaluate the presence and durability of antibody responses in children with COVID-19. METHODS: A prospective, single-center study, involving unvaccinated children 0-16 years of age who were hospitalized with COVID-19 between October 2020 and December 2021, was conducted. Serological testing for anti-Spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG and neutralizing antibodies was performed at diagnosis and at 1-, 3-, 6- and 12-months post-infection. RESULTS: A total of 65 immunocompetent children were enrolled [mean age (±SD): 6.7 (±6.4) years; males: 56.9%]. At 3 months, 40/44 (91%) children were seropositive; seropositivity persisted in 22/26 (85%) children at 6 months and in 10/12 (83%) children at 12 months. There was no evidence that age was modifying the prediction of variance of SARS-CoV-2 IgG levels. In contrast, SARS-CoV-2 IgG levels varied with time and disease severity. The association with time was non-linear, so that with increasing time there was a significant reduction in SARS-CoV-2 IgG levels [coef, 0.044 (95% confidence interval {CI}: 0.061-0.028), P < 0.001]. For each increment of time, the higher disease severity group was associated with 0.9 lower SARS-CoV-2 IgG levels. Everyone varied from the average effect of time with an SD of 0.01, suggesting that individuals may have different trajectories across time. CONCLUSION: Disease severity, but not age, influences antibody titers among children hospitalized with COVID-19. SARS-CoV-2 infection induces durable seroconversion in these children with detectable IgG levels at 1 year after infection.

Plasma Brain Natriuretic Peptide Levels in Children with Chronic Kidney Disease and Renal Transplant Recipients: A Single Center Study.

Pediatric chronic kidney disease (CKD) patients, as well as kidney transplant patients, are at an increased risk of developing cardiovascular disease. BNP measurement, as a biomarker of cardiovascular risk, has been recommended to this high-risk population. Plasma BNP levels were measured in 56 CKD children in either pre-dialysis stage, hemodialysis (HD) or renal transplant recipients (RTRs) and in 76 sex- and age-matched healthy controls. BNP levels were investigated in HD children, before and after the completion of their HD session. BNP levels in total CKD population, in pre-dialysis stage patients and on HD were significantly higher, compared to the respective controls. HD children had higher BNP levels compared to CKD patients in the pre-dialysis stage. Moreover, post-HD BNP concentration was slightly higher than pre-HD, with the difference being marginally statistically significant. BNP was positively correlated with eGFR, creatinine, cystatin-C and parathormone and negatively with albumin and 25-hydroxyvitamin D. A positive correlation between BNP concentration and the ratio of E/A in pulse-wave Doppler echocardiography was also observed. In conclusion, CKD pediatric patients, mainly those undergoing HD, have high plasma BNP levels which do not decrease after the HD session. This is indicative of a greater risk for future cardiovascular disease.

Bcl-2 and caspase-9 serum levels in children and adolescents with idiopathic epilepsy and active seizures.

BACKGROUND: In the present study we investigated the levels of proapoptotic caspase-9 and antiapoptotic Bcl-2 proteins in the sera of children and adolescents with idiopathic epilepsy and tried to relate the findings to the patients' clinical parameters. METHODS: This retrospective study consisted of 118 children and adolescents with idiopathic epilepsy, categorized according to type and number of seizures, duration of the disease and the control of seizures and 30 age- and sex-matched controls. The relapse of seizures was taken into consideration. RESULTS: Mean serum level between Bcl-2 and caspase-9 was significantly higher only in Bcl-2 patients, compared to controls (P≤0.0001) and (P=0.987) respectively. Significant difference in Bcl-2 level was found among the different types of focal seizures. Caspase-9 level was statistically different in patients with two or more seizures per month compared to those with one seizure per month (P=0.048). No correlation was found between Bcl-2 and caspase-9 levels and age, gender, seizure frequency, total number of seizures and the duration of epilepsy. No significant difference was found in patients with and without drug treatment. CONCLUSIONS: Bcl-2 displays an association with apoptosis and highlights the potential of being a surrogate biomarker for active seizures and epilepsy. There is a significant difference in Bcl-2 serum level among the different types of focal seizures. Proapoptotic caspase-9 cannot act as a marker of active seizures and epilepsy. Caspase-9 serum level is increased acutely in controlled cases after a single relapse.

Overexpression of the GR Riborepressor LncRNA GAS5 Results in Poor Treatment Response and Early Relapse in Childhood B-ALL.

Glucocorticoids (GCs) remain the cornerstone of childhood acute lymphoblastic leukemia (chALL) therapy, exerting their cytotoxic effects through binding and activating of the glucocorticoid receptor (GR). GAS5 lncRNA acts as a potent riborepressor of GR transcriptional activity, and thus targeting GAS5 in GC-treated chALL could provide further insights into GC resistance and support personalized treatment decisions. Herein, to study the clinical utility of GAS5 in chALL prognosis and chemotherapy response, GAS5 expression was quantified by RT-qPCR in bone marrow samples of chB-ALL patients at diagnosis (n = 164) and at end-of-induction (n = 109), treated with ALL-BFM protocol. Patients' relapse and death were used as clinical end-points for survival analysis. Bootstrap analysis was performed for internal validation, and decision curve analysis assessed the clinical net benefit for chALL prognosis. Our findings demonstrated the elevated GAS5 levels in blasts of chALL patients compared to controls and the significantly higher risk for short-term relapse and poor treatment outcome of patients overexpressing GAS5, independently of their clinicopathological data. The unfavorable prognostic value of GAS5 overexpression was strongly validated in the high-risk/stem-cell transplantation subgroup. Finally, multivariate models incorporating GAS5 levels resulted in superior risk stratification and clinical benefit for chALL prognostication, supporting personalized prognosis and precision medicine decisions in chALL.

Cathelicidin levels in nasal secretions are associated with the severity of acute bronchiolitis.

OBJECTIVE: To investigate the association of serum vitamin D and nasal secretion antimicrobial peptides (AMPs) levels with the severity of acute bronchiolitis. STUDY DESIGN: We conducted a prospective single pediatric tertiary care center cohort study of inpatients aged 0-18 months with a first episode of acute bronchiolitis from November 1st 2014 to April 30th 2017. Disease severity was determined by the length of hospitalization and supplemental hospital data. Qualitative measurements included serum 25(OH)D and nasal secretion LL-37 and ß-defensin-2 levels. Correlations were examined with the Mann-Whitney and Kruskal-Wallis criteria for qualitative and the correlation coefficient Spearman's rho for quantitative factors. Multiple linear and logarithmic regression were performed to adjust for confounding factors. RESULTS: The study population consisted of 153 infants and toddlers with median age 3.1 months (interquartile range:1.6-4.9). No association was found between serum 25(OH)D and AMPs nasal secretions levels. Serum 25(OH)D and nasal secretion ß-defensin-2 levels were not associated with the severity of bronchiolitis. In contrast, LL-37 levels were inversely associated with the length of hospitalization (rho = -0.340, p = .001), the need for medication use (p = .001), as well as the duration of oxygen supplementation (rho = -0.339, p = .001), and intravenous fluid administration (rho = -0.323, p = .001). This association remained significant after adjustment for potential confounders. CONCLUSION: A significant association between LL-37 nasal secretions levels with the severity of acute bronchiolitis was found in hospitalized infants and toddlers. The role of LL-37 in the pathogenesis of bronchiolitis merits further investigation.

Perinatal lipocalin-2 profile at the extremes of fetal growth.

BACKGROUND: Lipocalin-2 (LCN-2) has been identified as an osteoblast-secreted hormone regulating immunity, inflammation and metabolic homeostasis and has emerged as a diagnostic and prognostic biomarker for acute kidney injury in neonates. We investigated the impact of fetal growth on antepartum maternal serum, cord serum and breast milk LCN-2 concentrations and the associations of the latter with perinatal parameters. METHODS: Maternal serum, cord serum and breast milk LCN-2 concentrations were measured by ELISA in samples from 80 mothers who delivered 40 appropriate (AGA), 20 large for gestational age (LGA) and 20 intrauterine growth restricted (IUGR) neonates, classified by customized weight centiles. LCN-2 concentrations were associated with birth weight, customized centile, gender, maternal age and delivery mode. RESULTS: Antepartum maternal serum LCN-2 concentrations were significantly higher in women delivering AGA infants compared to the other two groups. Cord blood LCN-2 concentrations were significantly higher compared to maternal ones; furthermore, they were significantly elevated in the IUGR group compared to the LGA one (p = .019). Lowest concentrations were detected in breast milk, which did not differ between the three growth groups. A negative correlation was documented between cord blood LCN-2 concentrations and customized centiles (r: -0.304, p = .007). CONCLUSIONS: The higher cord serum LCN-2 concentrations, compared to maternal ones, may point to its fetal origin and potential role in intrauterine growth. The negative correlation of cord LCN-2 concentrations with customized centiles, possibly implies reduced nephron endowment/subclinical kidney damage in IUGR neonates. The extremely low LCN-2 breast milk concentrations could imply that the secretion of LCN-2 from maternal circulation to breast milk is not influenced by factors leading to intrauterine growth pathology.

Cardiovascular Risk Factors and Subclinical Atherosclerosis in Greek Adolescents with Polycystic Ovary Syndrome: Its Relationship with Body Mass Index.

Polycystic ovary syndrome (PCOS) is the most common endocrine condition affecting 6-18% of adolescents and is strongly associated with obesity and cardiovascular risk factors, enhancing the risk of atherosclerosis. Thirty-two adolescents with newly diagnosed PCOS were evaluated for lipid profile disorders, insulin resistance, inflammation, non-alcoholic fatty liver disease (NAFLD), and subclinical atherosclerosis through measurements of carotid intima-media thickness (cIMT). The relationships of the above markers with increased body mass index and abdominal obesity were investigated. Twenty-three adolescents (72%) were overweight (OW) or obese (OB). The OW/OB group had significantly higher insulin, HOMA-IR, high-sensitive C-reactive protein (hsCRP), visceral adiposity index (VAI), and lipid accumulation product (LAP) levels; and lower glucose-per-insulin ratios and HDL-C levels compared to the healthy weight group. The cIMT and small dense low-density lipoprotein cholesterol (sdLDL-C) levels did not differ between the two groups. Similarly, cIMT and sdLDL-C levels did not differ between PCOS-adolescents and healthy controls. CIMT was positively correlated with systolic blood pressure and waist circumference per height ratio. In conclusion, OW/OB PCOS-adolescents have a cluster of adverse factors predisposing them to atherosclerotic cardiovascular disease. Therefore, early cardiovascular risk assessment, as well as timely and targeted interventions, are necessary for prevention.

The Effect of Long-Term Atorvastatin Therapy on Carotid Intima-Media Thickness of Children With Dyslipidemia.

Carotid intima-media thickness (cIMT) has been proposed as an early marker of subclinical atherosclerosis in high risk children. Children with heterozygous familial hypercholesterolemia have greater cIMT than matched healthy controls or their unaffected siblings. Statin therapy may delay the progression of cIMT, although long-term studies in children are scarce. We evaluated the effect of atorvastatin treatment on cIMT in children with dyslipidemia. We studied 81 children/adolescents, 27 with severe dyslipidemia (low-density lipoprotein cholesterol [LDL-C] ≥190 mg/dL) and 54 sex- and age-matched healthy controls; LDL-C ≤ 130 mg/dL and lipoprotein (a), Lp(a), ≤30 mg/dL. In the children with dyslipidemia, cIMT was measured twice, before and on treatment (18.2 ± 7.7 months). Anthropometric data, a full lipid profile, liver, kidney, and thyroid function were evaluated. Males with dyslipidemia had a greater cIMT than male controls after adjustment for other factors (P = .049). In addition, a nonstatistically significant decrease in cIMT was observed after treatment (P = .261). Treatment with atorvastatin resulted in a significantly improved lipid profile. Females with dyslipidemia had a significantly thinner cIMT than males. Children with normal and high Lp(a) levels had similar cIMT values. In conclusion, treatment with atorvastatin had a beneficial effect on the lipid profile and cIMT progression in children with severe dyslipidemia.

Inhibitors of osteoblastogenesis in early human milk and maternal serum: evidence for protective properties of mother's milk on bone.

Objective: Lactation is associated with a dramatic increase of maternal bone turnover, leading to a reversible bone loss. Early life nutrition may influence later osteoporosis risk. Proteins synthesized by the group of wingless (Wnt) genes are key mediators of osteoblastogenesis and bone formation. We aimed to investigate maternal milk and serum concentrations of the inhibitors of the Wnt signaling pathway, Dickkopf-1 (DKK-1) and sclerostin.Material and methods: In 80 women, maternal milk and serum concentrations of DKK-1 and sclerostin were determined by ELISA on the 3rd-4th day postpartum. Concentrations were associated with various maternal, gestational and neonatal characteristics.Results: DKK-1 and sclerostin were detectable in early milk [mean ± SD: 817.17 ± 259.61 pg/mL, median (range) 258.04 (2452.40-53.17) pg/mL, respectively] at significantly lower concentrations than in maternal serum [mean ± SD: 3375.36 ± 416.75 pg/mL, median (range) 16 200.54 (58 832.00-3012.60) pg/mL, respectively], (p < .000). Maternal milk sclerostin concentrations positively correlated with respective serum ones (r = 0.599, p = .000). Maternal serum and milk sclerostin concentrations positively correlated with maternal body mass index (r = 0.37, p = .001 and r =0.38, p = .000, respectively), while maternal serum sclerostin concentrations were higher in primiparas (p = .002).Conclusion: DKK-1 and sclerostin are present in early human milk at significantly lower concentrations, compared with maternal serum, probably contributing to the short- and long-term benefits of mother's milk for bone health. Moreover, the large amounts of both substances in maternal serum may represent disruption of the Wnt cascade, contributing to the well-known lactation-associated bone loss, which seems to be greater in primiparas and obese mothers.

Cord blood fatty acid-binding protein-4 levels are upregulated at both ends of the birthweight spectrum.

AIM: Fatty acid-binding protein-4 (FABP4) is an adipokine associated with obesity and signs of the metabolic syndrome. We aimed to investigate at birth in term neonates with normal and abnormal intrauterine growth concentrations of FABP4 and associate them with various perinatal parameters. METHODS: Serum cord blood FABP4 levels were prospectively determined by ELISA in 80 singleton term appropriate-for-gestational-age (AGA), intrauterine growth-restricted (IUGR) and large-for-gestational-age (LGA) neonates. RESULTS: Compared to the AGA group, cord blood FABP4 levels were increased in the IUGR and LGA groups. Additionally, they were higher in early-term than full-term neonates. A significant U-shaped correlation was recorded between serum FABP4 levels and birthweight. A significant negative correlation between cord blood FABP4 and gestational age in the whole study population was noted. CONCLUSION: Cord blood FABP4 levels were significantly higher at the extremes of foetal growth at term and negatively correlated with gestational age, being increased in early-term versus full-term neonates. Further longitudinal studies with larger sample sizes are required to elucidate FABP4 implication in foetal growth and its association with future adverse cardiometabolic outcomes in the offspring.

Perinatal sclerostin concentrations in abnormal fetal growth: the impact of gestational diabetes.

OBJECTIVE: To prospectively evaluate maternal and cord blood concentrations of sclerostin - an osteocyte-secreted factor, inhibiting osteoblast differentiation and bone formation and associated with adverse metabolism - in pregnancies with normal and abnormal fetal growth. METHODS: Plasma sclerostin concentrations were determined by ELISA in 80 maternal and 80 cord blood samples from asymmetric intrauterine-growth-restricted (IUGR, n = 30), large-for-gestational-age (LGA, n = 30), and appropriate-for-gestational-age (AGA, n = 20) singleton full-term pregnancies. Fourteen out of 30 mothers with LGA offspring presented with gestational diabetes mellitus (GDM). RESULTS: Maternal and fetal sclerostin concentrations did not differ among LGA, IUGR, and AGA groups. Fetal concentrations were higher than maternal. In LGA group, maternal concentrations were elevated in cases of GDM (b = 13.009, 95%CI 1.425-24.593, p = .029). In a combined group and the IUGR group, maternal concentrations were elevated in older mothers (b = 0.788, 95%CI 0.190-1.385, p = .010, and b = 0.740, 95%CI 0.042-1.438, p = .039, respectively). CONCLUSIONS: Maternal and fetal sclerostin concentrations may not be differentially regulated in pregnancies complicated by abnormal fetal growth. Circulating maternal levels are higher in cases of GDM, probably implying reduced bone formation. Sclerostin up-regulation with aging may be one of the molecular pathways responsible for the observed age-related decline in bone synthesis, leading to accelerated bone loss in humans.

Preadipocyte factor-1 in maternal, umbilical cord serum and breast milk: The impact of fetal growth.

BACKGROUND/OBJECTIVE: To study the concentrations of preadipocyte factor-1 (Pref-1) -an inhibitor of adipocyte differentiation, implicated in adipose tissue metabolism, late metabolic disorders and fetal growth- in maternal and umbilical cord serum, as well as maternal milk and correlate above concentrations with intrauterine growth and other perinatal parameters. MATERIAL AND METHODS: Pref-1 concentrations were determined by ELISA in antepartum maternal and umbilical cord serum, as well as day 3 to 4 postpartum breast milk, deriving from 80 women, who delivered 40 appropriate (AGA), 20 large for gestational age (LGA) and 20 intrauterine growth restricted (IUGR) neonates, classified by the use of customized birth-weight standards adjusted for significant determinants of fetal growth. RESULTS: Umbilical cord serum Pref-1 concentrations were significantly higher than antepartum maternal ones (p < 0.001), while breast milk concentrations were the lowest (p < 0.001 concerning umbilical serum, p < 0.001 concerning maternal serum). Umbilical cord serum Pref-1 concentrations were significantly lower in the LGA group than in the AGA one (p = 0.044). Breast milk and maternal serum Pref-1 concentrations did not differ between the three intrauterine growth groups. Maternal serum and breast milk Pref-1 concentrations did not correlate with maternal age, body mass index before and after gestation, birth weight, body length, and customized centile. A positive weak correlation was recorded between maternal serum and milk Pref-1 concentrations (r = 0.238, p = 0.034). CONCLUSIONS: Pref-1 concentrations in umbilical cord serum are higher than in antepartum maternal serum, probably pointing to its fetal origin and role in intrauterine growth. Breast milk concentrations, being extremely low, and possibly implying infant protection from metabolic disorders, positively correlate with maternal serum ones, conceivably suggesting a transfer of the substance from the circulation to the breast. Umbilical cord serum Pref-1 concentrations were lower in LGA fetuses/neonates, as compared to respective AGA ones.

BCL2L12 improves risk stratification and prediction of BFM-chemotherapy response in childhood acute lymphoblastic leukemia.

Background Risk-adjusted treatment has led to outstanding improvements of the remission and survival rates of childhood acute lymphoblastic leukemia (ALL). Nevertheless, overtreatment-related toxicity and resistance to therapy have not been fully prevented. In the present study, we evaluated for the first time the clinical impact of the apoptosis-related BCL2L12 gene in prognosis and risk stratification of BFM-treated childhood ALL. Methods Bone marrow specimens were obtained from childhood ALL patients upon disease diagnosis and the end-of-induction (EoI; day 33) of the BFM protocol, as well as from control children. Following total RNA extraction and reverse transcription, BCL2L12 expression levels were determined by qPCR. Patients' cytogenetics, immunophenotyping and minimal residual disease (MRD) evaluation were performed according to the international guidelines. Results BCL2L12 expression was significantly increased in childhood ALL and correlated with higher BCL2/BAX expression ratio and favorable disease markers. More importantly, BCL2L12 expression was associated with disease remission, while the reduced BCL2L12 expression was able to predict patients' poor response to BFM therapy, in terms of M2-M3 response and MRD≥0.1% on day 15. The survival analysis confirmed the significantly higher risk of the BFM-treated patients underexpressing BCL2L12 at disease diagnosis for early relapse and worse survival. Lastly, evaluation of BCL2L12 expression clearly strengthened the prognostic value of the established disease prognostic markers, leading to superior prediction of patients' outcome and improved specificity of BFM risk stratification. Conclusions The expression levels of the apoptosis-related BCL2L12 predict response to treatment and survival outcome of childhood ALL patients receiving BFM chemotherapy.

Clinical utility of miR-143/miR-182 levels in prognosis and risk stratification specificity of BFM-treated childhood acute lymphoblastic leukemia.

Although childhood acute lymphoblastic leukemia (ALL) is characterized by high remission rates, there are still patients who experience poor response to therapy or toxic effects due to intensive treatment. In the present study, we examined the expression profile of miR-143 and miR-182 in childhood ALL and evaluated their clinical significance for patients receiving Berlin-Frankfurt-Münster (BFM) protocol. Bone marrow specimens from 125 childhood ALL patients upon diagnosis and the end-of-induction (EoI; day 33), as well as from 64 healthy control children undergone RNA extraction, polyadenylation, and reverse transcription. Expression levels of miRNAs were quantified by qPCR analysis. Patients' cytogenetic, immunohistotype and MRD evaluation was performed according to international guidelines. Median follow-up time was 86.0 months (95% CI 74.0-98.0), while patients' mean DFS and OS intervals were 112.0 months (95% CI 104.2-119.8) and 109.2 months (95% CI 101.2-117.3), respectively. Bone marrow levels of miR-143/miR-182 were significantly decreased in childhood ALL patients at diagnosis and increased in more than 90% of patients at the EoI. Patients' survival analysis highlighted that children overexpressing miR-143/miR-182 at the EoI presented significantly higher risk for short-term relapse (log-rank test: p = 0.021; Cox regression: HR = 4.911, p = 0.038) and death (log-rank test: p = 0.028; Cox regression: HR = 4.590, p = 0.046). Finally, the evaluation of the miR-143/miR-182 EoI levels along with the established disease prognostic markers resulted to improved prediction of BFM-treated patients' survival outcome and response to therapy and additionally to superior BFM risk stratification specificity. Concluding, miR-143 and miR-182 could serve as novel prognostic molecular markers for pediatric ALL treated with BFM chemotherapy.

Influence of hypercholesterolemia on serum antibodies against oxidized LDL in children and adolescents.

BACKGROUND: The oxidation of low-density lipoprotein (LDL; oxLDL) appears to play a key role in the early development of atherosclerosis. Increased serum antibodies against the oxLDL (anti-oxLDL antibodies) have been found in adults with atherosclerotic disease, as well as in healthy adults. The clinical significance and its precise role (atherogenic or atheroprotective), however, have not yet been clarified. This aim of this study was therefore to evaluate anti-oxLDL antibodies in healthy children and adolescents with and without hypercholesterolemia. METHODS: The study involved 312 subjects, aged 4-18 years, 141 with LDL cholesterol (LDL-C) ≥130 mg/dL and 171 with acceptable LDL-C (<110 mg/dL). Total anti-oxLDL antibodies, total cholesterol, LDL-C and high-density lipoprotein cholesterol, triglycerides, apolipoproteins A1 and B, lipoprotein (a) and high-sensitivity C-reactive protein were measured in fasting serum. The anti-oxLDL antibodies were measured on enzyme-linked immunosorbent assay. RESULTS: Anti-oxLDL antibodies were similar in the hypercholesterolemia and non-hypercholesterolemia groups. Girls had significantly higher anti-oxLDL antibodies compared with boys. There was no significant correlation of antibodies with age or body mass index. Increased apolipoprotein B was an important factor for lower anti-oxLDL antibodies, while all other parameters had no significant association with anti-oxLDL antibodies. CONCLUSION: In children and adolescents with hypercholesterolemia, total anti-oxLDL antibodies cannot serve as a marker for risk for atherosclerosis or for future cardiovascular disease.

Potential prognostic biomarkers of cardiovascular disease in fetal macrosomia: the impact of gestational diabetes.

OBJECTIVE: Fetal macrosomia is associated with cardiac hypertrophy and increased cardiovascular risk. Cardiac biomarkers may play diagnostic/prognostic role in cardiovascular disease. We tested whether cardiac biomarkers are differentially expressed in cord blood samples of full-term singleton large-for-gestational-age (LGA), as compared to appropriate-for-gestational-age (AGA) pregnancies. METHODS: Cardiotrophin-1 (CT-1), Titin, pentraxin (PTX-3) and soluble CD36 (sCD36) concentrations were determined in 80 cord blood samples from a) LGA pregnancies due to maternal diabetes (n = 8), overweight/obese (n = 11), excessive weight gain (n = 7), without specific pathology (n = 14), b) AGA normal pregnancies (controls, n = 40). Neonates were classified as LGA or AGA based on customized birth weight (BW) standards. RESULTS: CT-1 and Titin concentrations were higher in LGA than AGA pregnancies (p < .001 and p = .023, respectively). A subgroup analysis (in the LGA group) showed increased CT-1 concentrations only in diabetic pregnancies. PTX-3 and sCD36 concentrations were similar in LGA and AGA fetuses. In the LGA group, PTX-3 concentrations positively correlated with birth-weight (r = .416, p = .008) and respective sCD36 concentrations (r = .443, p = .004). CONCLUSION: Higher Titin concentrations in LGAs possibly represent a candidate molecular mechanism underlying the association between fetal macrosomia and cardiomyocyte/diastolic dysfunction. CT-1 is up-regulated only in LGAs exposed to maternal diabetes. PTX-3 and sCD36 are probably not affected by excessive fetal growth.

Differential expression of cord blood neurotrophins in gestational diabetes: the impact of fetal growth abnormalities.

OBJECTIVE: Gestational diabetes mellitus (GDM) may induce fetal macrosomia or growth restriction and is associated with later offspring neurodevelopmental disorders. We aimed to determine whether neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-4 (NT-4) are differentially expressed in cord blood samples at birth in large-for-gestational-age (LGA), intrauterine-growth-restricted (IUGR) and appropriate-for-gestational-age (AGA) offspring of diabetic mothers, as compared to AGA controls from non-diabetic mothers. METHODS: BDNF, NGF and NT-4 concentrations were prospectively determined in 80 cord blood samples from LGA (n = 15), IUGR (n = 12) and AGA (n = 33) diabetic, as well as from AGA normal (controls, n = 20) singleton full-term pregnancies. RESULTS: Fetal BDNF concentrations considerably decreased in GDM, as compared with normal pregnancies [(b = -2.836, 95%CI -5.067 to (-0.604), p = 0.013)] and were higher in females (b = 2.298, 95%CI 0.357-4.238, p = 0.021). Cord blood NGF concentrations were lower in IUGR than AGA infants (p = 0.038). CONCLUSIONS: BDNF is down-regulated in the fetus exposed to GDM, independently of the fetal growth pattern, probably representing a candidate mechanism underlying the association between maternal diabetes and later psychopathology. IUGR fetuses born to diabetic mothers present with NGF deficiency, which may contribute to their long-term neurodevelopmental sequelae. Gender-dependent differences in fetal BDNF may partly explain the higher prevalence of adverse neurodevelopmental outcomes following brain insults in male infants.

miR-125b predicts childhood acute lymphoblastic leukaemia poor response to BFM chemotherapy treatment.

BACKGROUND: Despite the favourable survival rates of childhood acute lymphoblastic leukaemia (ALL), a significant number of patients present resistance to antileukaemic agents and dismal prognosis. In this study, we analysed miR-125b expression in childhood ALL and evaluated its clinical utility for patients treated with Berlin-Frankfurt-Münster (BFM) protocol. METHODS: The study included 272 bone marrow specimens obtained on diagnosis and on BFM day 33 from 125 patients and 64 healthy children. Following extraction, RNA was polyadenylated and reverse transcribed. miR-125b levels were quantified by quantitative PCR. Cytogenetics, immunohistotype and MRD were analysed according to international guidelines. RESULTS: Downregulated miR-125b levels were detected in childhood ALL patients and correlated with adverse prognosis. Following BFM induction, miR-125b levels were significantly increased, however, elevated day 33/diagnosis miR-125b ratio was associated with unfavourable disease features. Loss of miR-125b during diagnosis and higher day 33/diagnosis ratio were correlated with stronger risk for disease short-term relapse and patients' worse survival. Moreover, multivariate regression models highlighted the independent prognostic value of miR-125b for childhood ALL. Finally, the combination of miR-125b with clinically used disease markers clearly enhanced the prediction of patients' resistance to BFM chemotherapy. CONCLUSIONS: miR-125b significantly improves the prognosis of childhood ALL patients' outcome under BFM treatment.

Plasma Urotensin II levels in children and adolescents with chronic kidney disease: a single-centre study.

BACKGROUND: Increased plasma Urotensin II (UII) levels have been found in adults with renal diseases. Studies in children are scarce. The objective of the study is to estimate plasma UII levels in subjects with chronic kidney disease (CKD) stages 3 to 5 and renal transplant recipients (RTR). In addition, the correlation of UII with anthropometric features and biochemical parameters was assessed. METHODS: Fifty-four subjects, aged 3 to 20 years old, 23 with CKD, 13 with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) and 18 RTR were enrolled. A detailed clinical evaluation was performed. Biochemical parameters of renal and liver function were measured. Plasma UII levels were measured in all patients and in 117 healthy controls, using a high sensitive enzyme immunoassay (EIA) kit. All data were analyzed using STATA™ (Version 10.1). RESULTS: Median UII and mean log-transformed UII levels were significantly higher in CKD and RTR patients compared to healthy subjects (p < 0.001). HD patients had higher but not statistically significant UII and log-UII levels than controls. UII levels increased significantly at the end of the HD session and were higher than controls and in line to those of other patients. The geometric scores of UII in HD (before dialysis), CKD and RTR patients increased respectively by 42, 136 and 164% in comparison with controls. Metabolic acidosis was associated with statistical significant change in log-UII levels (p = 0.001). Patients with metabolic acidosis had an increase in UII concentration by 76% compared to those without acidosis. CONCLUSIONS: Children and adolescents with CKD, particularly those who are not on HD and RTR, have significantly higher levels of UII than healthy subjects. UII levels increase significantly at the end of the HD session. The presence of metabolic acidosis affects significantly plasma UII levels.