Short- and long-term impact of hyperoxia on the blood and retinal cells' transcriptome in a mouse model of oxygen-induced retinopathy.

BACKGROUND: We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. METHODS: A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays. RESULTS: There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17. CONCLUSION: There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.

Transcriptome analysis reveals dysregulation of genes involved in oxidative phosphorylation in a murine model of retinopathy of prematurity.

BACKGROUND: Retinal gene expression pattern is severely altered after exposition to hyperoxia in mice with oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity. Gene ontology and signaling pathway analyses may add new insights into a better understanding of the pathogenesis of this disease. METHODS: Seven-day-old C57BL/6J mice (n = 60) were exposed to 75% oxygen for 5 days and then recovered in room air. The controls (n = 60) were kept in the normoxic conditions. Retinas were harvested immediately following hyperoxia, during the phase of maximal neovascularization, and at the time of neovascularization regression. The retinal RNA samples were evaluated for gene expression using mouse gene expression microarrays. DAVID annotation tools were used for gene ontology and pathway analyses. RESULTS: The most significantly enriched signaling pathways during the neovascularization phase of OIR were: focal adhesion; ECM-receptor interaction; PI3K-Akt; oxidative phosphorylation; and Alzheimer's, Parkinson's and Huntington's disease signaling pathways. Genes involved in apoptosis, cell proliferation, cell differentiation, and immune responses were associated with neovascularization regression. CONCLUSIONS: Performed analyses revealed the possible involvement of various signaling pathways in OIR pathomechanism, mostly specific to the OIR phase. Dysregulation of genes involved in oxidative phosphorylation may have an impact on neovascularization development.

Prospective plasma proteome changes in preterm infants with different gestational ages.

BACKGROUND: In this study, we aimed to analyze time-resolved plasma proteome changes in preterm neonates stratified by their gestational age to detect malfunctioning pathways that derive from the systemic immaturity of the neonate and to highlight those that are differentially regulated during the early development. METHODS: Preterm newborns were enrolled in three subgroups with different gestational ages: before 26 weeks of gestation (group 1), between 27 and 28 weeks of gestation (group 2), and between 29 and 30 (group 3) weeks of gestation. Plasma protein abundances were assessed at two time points (at preterm delivery and at the 36th week of post-menstrual age) by quantitative proteomics. RESULT: The quantitative analysis of plasma proteome in preterm infants revealed a multitude of time-related differences in protein abundances between the studied groups. We report protein changes in several functional domains, including inflammatory domains, immunomodulatory factors, and coagulation regulators as key features, with important gestational age-dependent hemopexin induction. CONCLUSION: The global trend emerging from our data, which can collectively be interpreted as a progression toward recovery from the perinatal perturbations, highlights the profound impact of gestation duration on the ability to bridge the gap in systemic homeostasis after preterm labor.

Comparison of whole genome expression profile between preterm and full-term newborns.

OBJECTIVES: Evaluate the time dependent expression of genes in preterm neonates and verify the influence of ontogenic maturation and the environmental factors on the gene expression after birth. MATERIAL AND METHODS: The study was carried out on 20 full-term newborns and 62 preterm newborns (mean birth weight = 1002 [g] (SD: 247), mean gestational age = 27.2 weeks (SD: 1.9)). Blood samples were drawn from all the study participants at birth and at the 36th week postmenstrual age from the preterm group to assess whole genome expression in umbilical cord blood and in peripheral blood leukocytes, respectively. (SurePrint G3 Human Gene Expression v3, 8x60K Microarrays (Agilent)). RESULTS: A substantial number of genes was found to be expressed differentially at the time of birth and at 36 PMA in comparison to the term babies with more genes being down-regulated than up-regulated. However, the fold change in the majority of cases was < 2.0. Extremely preterm and very preterm infants were characterized by significantly down-regulated cytokine and chemokine related pathways. The number of down-regulated genes decreased and number of up-regulated genes increased at 36 PMA vs. cord blood. There were no specific gene expression pathway profiles found within the groups of different gestational ages. CONCLUSIONS: Preterm delivery is associated with a different gene expression profile in comparison to term delivery. The gene expression profile changes with the maturity of a newborn measured by the gestational age.

Modification of the Schwartz equations for children increases their accuracy at eGFR > 60 mL/min/1.73 m(2).

AIM: Estimation of eGFR in children with normal kidney function using the Schwartz equations results in underestimating real GFR. MATERIALS AND METHODS: We propose modification of three Schwartz equations - two based on creatinine concentration (eGFRScrBS bedside) and (eGFRScr) and one 3-marker based on creatinine, urea and cystatin C concentrations (eGFRS3M). The iohexol test (reference method) was performed 417 times in 353 children >2 years with mean GFR: 98 ± 31.6 ml/min/1.73m(2). The assessment included also the Filler and Zappitelli equations. The modification was performed using methods: (1) based on equation, eGFRcor = a [eGFR - T] + T, where T = 50, if eGFR > T, and a equals for: eGFRScrBS 1.4043, for eGFRScr 2.0048, for eGFRS3M 1.2951, and (2) based on correction of all coefficients of the original equation. RESULTS: For comparison of all the results and for children with GFR< 60, 60-90, 90-135 and > 135 ml/min/1.73m(2) the correlation coefficient, relative error (RE) and root mean square relative error (RMSRE) was employed and revealed improvement of RE from 25.9 to 6.8 and 3.9% (depending on the correction method) for eGFRScr; from 19 to 8.1 and 3.9% for eGFRScrBS and: from 11.6% to 2.0 and 2.3% for eGFRS3M (respectively). The RMSRE values changed from 30 to 21.3 and 19.8% for eGFRScr, from 25.1 to 21.6 and 19.8% for eGFRScrBS and from 19.1 to 15.8 and 15.3 % for eGFRS3M. CONCLUSIONS: Modifications of Schwartz equations at GFR > 60 ml/min/1.73m(2) significantly improves the accuracy of calculating eGFR. The 3-markers equation is more accurate and should be employed frequently.

[Office and 24-hour ambulatory blood pressure measurements in hypertension assessment in children with chronic kidney disease].

Introduction: Hypertension (HT) is one of the major risk factors of chronic kidney disease (CKD) progression and cardiovascular complications. The aim of the study was to analyze blood pressure (BP) values and assess the usefulness of clinical measurements in BP monitoring in children with chronic kidney disease. Material and methods: The study was conducted in 62 children (40 boys and 22 girls) aged 4,2-18,6 years (median age 12.4 (9.1; 16.0) with CKD stages 1 + 2 (n = 9), 3 (n = 17), 4 (n = 15) and 5. Creatinine concentration was measured and glomerular filtration rate was calculated using the Schwartz formula. Each of the patients underwent clinical BP measurements and 24-hour ambulatory blood pressure monitoring (ABPM). Results: Based on clinical meaurements elevated BP values were found in 25 patients (40.3%): in stages 1 + 2 in 33.3%, in stage 3 in 41.2%, in stage 4 in 46.6% and in stage 5 in 38.1% patients. Hypertension was diagnosed with ABPM in 30 patients (48.4% of the studied population): in stages 1 + 2 - 3 patients (33.3%), in stage 3 - 8 patients (47, 1%), in stage 4 - 7 patients (46.7%) and stage 5 - 12 patients (57.1%). Only 12 patients (19.4%) had hypertension diagnosed in both clinical and ABPM measurements. White coat effect was found in 13 children (21.0%) and masked HT in 18 children (29.0%). In 24-hour BP monitoring the highest values of systolic, diastolic and mean BP values were found in children with masked HT. In children with masked HT higher values of 24-hour systolic (120 vs. 105.5 mmHg, p<0.001) and diastolic (75 vs. 65 mmHg, p<0.001) BP compared with clinical values were detected. Children with masked HT had significantly higher nighttime diastolic BP compared with children with HT (1.43 vs. 0.74 z-score, p<0.001). Conclusions: The large percentage of children with masked hypertension is an indication for frequent ABPM measurements in children with chronic kidney diseses. Office measurements are not sufficient to detect HT in children with CKD. The best diagnostic method to confirm and monitor hypertension in patients with CKD is 24-hour ambulatory blood pressure monitoring.

Relationship between water compartments, body composition assessed by bioelectrical impedance analysis and blood pressure in school children.

BACKGROUND: Electrical bioimpedance analysis (BIA) is becoming more widely used in clinical practice as a method of body composition analysis. In healthy children blood pressure (BP) changes with age, body mass and height. Until now the relation between water compartments and BP in healthy children has not been evaluated. The aim of this study was to evaluate the relationship between body composition as well as water compartments (measured by electrical bioimpedance) and BP. METHODS: The study was performed in 72 children (32 girls and 40 boys) aged: 6-7 and 12-13 years. BIA measurements were taken using Nutriguard Data Input device with Bianostic electrodes and following parameters were calculated: total body water (TBW), lean body mass (LBM), fat mass (FM), intra- and extracellular water (ICW, ECW) and phase angle alpha. BP was measured twice using the oscillometric method. RESULTS: Elevated BP > 95th percentile for gender, age and height were observed in 9 children. A significant correlation between systolic (S)BP and TBW (R = 0.4023, p < 0.001), LBM (R = 0.3600, p = 0.002), FM (R = 0.4725, p < 0.001), ECW (R = 0.4598, p < 0.001) and body mass index (BMI) (R = 0.4089, p < 0.001) was found. Furthermore, diastolic (D)BP significantly correlated with TBW (R = 0.3056, p = 0.011), LBM (R = 0.2783, p = 0.021), FM (R = 0.3956, p < 0.001), ECW (R = 0.3869, p = 0.001) and BMI (R = 0.3550, p = 0.002). In the studied group malnutrition (weight < 3rd percentile) was found in 8 children and 2 had obesity (BMI > 95th percentile). Growth disorders were found in 6 children (5 of them being undernourished). CONCLUSIONS: In the studied children SBP and DBP correlated with water compartments, lean body and fat masses derived from BIA. The problem of unrecognized hypertension and malnutrition in children and adolescents is still underestimated in the Polish population.

Relationship between serum IgA/C3 ratio and severity of histological lesions using the Oxford classification in children with IgA nephropathy.

BACKGROUND: The aim of this study was to evaluate the usefulness of serum immunoglobulin A/complement factor 3 (IgA/C3) ratio for predicting histological severity of kidney lesions in children with IgA nephropathy (IgAN) based on World Health Organization (WHO) and the Oxford classification (OC). METHODS: We studied 89 children with IgAN with a mean age of 11.38 ± 4.1 years (range 2-18 years). Based on available medical records, we retrospectively evaluated clinical data, IgA/C3 ratio, and kidney biopsy findings using the five-grade WHO classification and the OC The mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy/interstitial fibrosis (T) (MEST) score (absent = 0, present = 1) calculated as the sum of M+E+S+T ranging from 0 to 4. RESULTS: Mean IgA/C3 ratio values were significantly higher (P < 0.05) in patients with M1, S1, and T1 compared with M0, S0, and T0, respectively (P < 0.05); there were no differences in the WHO classification. We found a significant positive correlation between the IgA/C3 ratio and proteinuria (r = 0.24) and determined optimal cutoff values of the IgA/C3 ratio, with a corresponding confidence interval for specific MEST scores. CONCLUSIONS: The IgA/C3 ratio in children with IgAN may be a useful marker of the severity of lesions found in kidney biopsy as evaluated using the OC.

Does aberrant architecture of nuclear LINC complex stop muscle cell development?

The linker of nucleoskeleton and cytoskeleton (LINC) complex is a structure that spans the entire nuclear envelope (NE) and integrates the nuclear interior with the cytoskeleton. Lamin A/C together with nesprins that mainly reside along the inner nuclear membrane (INM) and outer nuclear membrane (ONM) are core components of the LINC complex. Integrity of this specific nuclear structure is critical for muscle cell maturation and function. In the present study, we analyzed the ultrastructure of the LINC complex observed in two neonates with severe hypotonia and respiratory distress. Disruption of the LINC complex manifests in a wide separation of the ONM from the INM; the loss of perinuclear space (PNS) and delayed muscle cell maturation were predominating findings. This nuclear phenomenon has never been reported and provides further support for the appearance of a neonatal form of laminopathy.

[Do we successfully treat anemia and calcium-phosphate disorders in children with chronic kidney disease at the beginning of the twenty-first century?]. / Czy na poczatku XXI wieku skutecznie leczymy niedokrwistosc i zaburzenia wapniowo-fosforanowe u dzieci z przewlekla choroba nerek?

UNLABELLED: In children with chronic kidney disease (CKD) anemia and calcium-phosphate disturbances are already present at early stages of the disease and require a comprehensive treatment. The aim of this study was to evaluate the efficacy of the treatment of biochemical disturbances, depending on the severity of CKD in children. MATERIAL AND METHODS: The study included 71 children (44 boys, 27 girls) with CKD stage 1-5. Mean age was 11 ± 5 years, mean height: 135.7 ± 28 cm and mean eGFR 32 ml/min/1.73 m2. The serum hemoglobin, urea, creatinine, cystatin C, calcium, phosphorus and parathyroid hormone (PTH) levels were measured. eGFR was calculated according to Schwartz and Filler formulas, employing creatinine and cystatin C as markers. Patients were divided into groups depending on the stage of CKD [group 1: CKD stage 1+2 (GFR > 60), group 2: CKD stage 3 (GFR = 30-59) Group 3: CKD stage 4 (GFR = 15-29 ml/min/1.73 m2), group 4 - dialyzed children]. RESULTS: The concentration of he- moglobin depending on the stage of CKD (group 1 vs. group 2 vs. group 3 vs group 4) was 12.95 vs. 12.68 vs. 12.47 vs. 11.3 g/dI, respectively. The concentration of total and ionized calcium was significantly lower in children on dialysis compared to patients treated conservatively. With the progression of CKD the concentration of phosphorus (1.39 vs. 1.4 vs. 1.49 vs. 1.82 mmolI) and PTH (21.7 vs 48.6 vs 99.9 vs. 219 pg/ml) significantly increased. Treatment with erythropoietin was used in 48% of children, calcium carbonate in 55% and alphacalcidol in 56% of patients. CONCLUSIONS: Despite the use of regular treatment, with the progression of CKD a progression of anemia, increased serum phosphate and parathyroid hormone and a decrease in calcium levels in studied children was observed. The severity of metabolic disorders in dialyzed children indicates the need for administration of new and more effective drugs, to prevent early enough complications of CKD in the form of mineral bone disease and cardiovascular complications.

Clinical validity of urinary interleukin 18 and interleukin 6 determinations in preterm newborns.

INTRODUCTION: Preterm newborns are at a particular risk of acute kidney injury (AKI) and sepsis. PURPOSE: Assessment of urinary interleukin 18 (ulL-18) and urinary interleukin 6 (ulL-6) concentrations in association with AKI and sepsis respectively in newborns hospitalized in Neonatal Intensive Care Unit (NICU). MATERIAL AND METHODS: An evaluation was carried out of the dependence of ulL-18 on neonatal birth weight (BW) and AKI as well as ulL6 on sepsis. In prospective study, the evaluation included 58 children with BW up to 2000 g. Clinical observations spanned the period between the 1st and 28th day of life. RESULTS: The mean gestational age was 30.3 Hbd, mean BW was 1361.9 g. AKI was diagnosed in 35 (60.3%), sepsis in 22 (39.7%) neonates. For median values of uIL-18 and ulL-18/mgCr, as well as for mean logarithmically transformed values of ulL-18 and ulL-18/mgCr, negative, statistically significant linear correlations were demonstrated for BW. In population, median value of ulL-18 and ulL-18/mgCr decreased respectively by 8.21 pg/ml and 84.8 pg/mgCr per each 100 g increment of BW. A negative, statistically significant linear correlation with an average strength was noted for the dependency of the duration of AKI and BW. No significant differences were observed in uIL-18 and ulL-181 mgCr values between the investigated days of AKI and reference group. There was noted a significant increase of the values of uIL-6 and uIL-6/ mgCr on day 0 of sepsis confirmed by the ROC analysis with AUROC 78% and 74%, respectively. CONCLUSIONS: ulL-18 and ulL-18/mgCr values might be a reliable marker of renal tubules maturation in newborns; ulL-18 is not a reliable marker in diagnosing AKI in neonatal population; ulL-6 and uIL-6/ mgCr concentration values measured on actual days may be regarded an early marker of sepsis; AKI duration in preterm neonates is negatively correlated with BW.

Transcriptome profiling of the newborn mouse brain after hypoxia-reoxygenation: hyperoxic reoxygenation induces inflammatory and energy failure responsive genes.

BACKGROUND: Supplemental oxygen used during resuscitation can be detrimental to the newborn brain. The aim was to determine how different oxygen therapies affect gene transcription in a hypoxia-reoxygenation model. METHODS: C57BL/6 mice (n = 56), postnatal day 7, were randomized either to 120 min of hypoxia 8% O2 followed by 30 min of reoxygenation with 21, 40, 60, or 100% O2, or to normoxia followed by 30 min of 21 or 100% O2. Affymetrix 750k expression array was applied with RT-PCR used for validation. Histopathology and immunohistochemistry 3 d after hypoxia-reoxygenation compared groups reoxygenated with 21 or 100% O2 with normoxic controls (n = 22). RESULTS: In total, ~81% of the gene expression changes were altered in response to reoxygenation with 60 or 100% O2 and constituted many inflammatory-responsive genes (i.e., C5ar2, Stat3, and Ccl12). Oxidative phosphorylation was downregulated after 60 or 100% O2. Iba1(+) cells were significantly increased in the striatum and hippocampal CA1 after both 21 and 100% O2. CONCLUSION: In the present model, hypoxia-reoxygenation induces microglial accumulation in subregions of the brain. The transcriptional changes dominating after applying hyperoxic reoxygenation regimes include upregulating genes related to inflammatory responses and suppressing the oxidative phosphorylation pathway.

Acute kidney injury in a single pediatric intensive care unit in Poland: a retrospective study.

BACKGROUND/AIMS: The recent improvements of management of patients in pediatric intensive care units (PICU) are associated with improved outcome. However, this decrease in mortality is associated with an increased number of children with acute kidney injury (AKI), especially in patients with multiorgan failure. METHODS: The report presents a retrospective analysis of 25 cases of AKI (assessed based on the pRIFLE criteria) in PICU within 7 years. RESULTS: AKI was diagnosed in 1.24% of all hospitalized children. AKI percentage duration (as compared to the total hospitalization time) in the children who died vs. the survivors was 79.55% vs. 46.19%, respectively (p<0.05). The mortality rate of AKI patients was 40% which was 4.4-times higher as compared to the total mortality rate in PICU. The final cumulative survival ratio (FCSR) of patients meeting the oliguria criterion (which was met in 48% of AKI patients) was 37% vs. 49% in non-oliguric children. Averaged urine output values in the first week of hospitalization in the deceased vs. survivors were 1.49 vs. 2.57 ml/kg/h, respectively (p<0.05). CONCLUSIONS: Oliguria should not be considered as a sensitive parameter for AKI diagnosing in children below one year of age. A decreased mean urine output in the first week of PICU hospitalization (less than 1.4 ml/kg/h) should be considered as a poor prognostic factor. In many cases AKI was diagnosed too infrequently and too late.

[Familial case of oral-facial-digital syndrome type 1 (OFD 1)]. / Rodzinny przypadek zespolu ustno-twarzowo-palcowego typu 1 (OFD 1).

UNLABELLED: Ciliopathies are phenotypically and genetically heterogeneous disorders that share ciliary dysfunction as a common pathological mechanism. Ciliary dysfunction results in a broad range of malformations including renal, hepatic and pancreatic cysts, visceral abnormalities, retinal degeneration, anosmia, cerebellar or other brain anomalies, polydactyly, bronchiectasis and infertility. The paper presents a familial case of oral-facial-digital syndrome type 1 in 14 year old girl suspected to polycystic kidney disease. CONCLUSIONS: Molecular testing in daughters of known OFD1 mutation carriers and mothers of affected daughters seems to be reasonable. Not each case of policystic kidney disease which looks like autosomal dominant policystic kiedney disease is actually the above disease. The insight into the pathogenesis of ciliopathies is mandatory for understanding these combined congenital anomaly syndromes of seemingly unrelated symptoms of hepatorenal and pancreatic fibrocystic disease. Close interdisciplinary approach is mandatory in terms of efficient and reliable diagnostic and therapeutic interventions in patients presenting with ciliopathies.

Knowledge and Attitudes of Dialysis Patients Toward Kidney Transplantation: Preliminary Report from a Pilot Study Preceding a Cross-Sectional Nationwide Evaluation.

BACKGROUND: The knowledge and attitudes of dialyzed patients toward the best method of renal replacement treatment (ie, kidney transplantation [KTx]) may be the main factor motivating them to apply and be put on the national kidney transplant waiting list, resulting in a better prognosis. OBJECTIVE: Assessment of the knowledge and attitudes of dialyzed patients toward KTx. METHODS: A pilot study is considered an introductory step before the nationwide project, which will cover dialysis centers in Poland from 2023 to 2024. The authorship 4-part questionnaire, including self-assessment knowledge, attitude dimension, pain and mental evaluation section, was made available to 30 patients with hemodialysis aged 30 to 75 years. RESULTS: The median age of the patients was 59 years. The primary cause of end-stage renal disease (ESRD) was glomerulonephritis (33%). Most of the patients stayed on hemodialysis for 2 years or less (57%); 43% of the patients declared insufficient knowledge in the field of KTx, 41% of the patients were not informed at the nephrology clinic that KTx remains one of the methods of renal replacement therapy, and 65% did not receive information about the possibility of preemptive or early transplantation from a relative donor. Only 34% of the patients considered KTx to be a much better treatment option than dialysis, but only 20% of those were on the national waiting list for KTx. CONCLUSIONS: The pilot study showed insufficient knowledge of patients with ESRD regarding kidney transplantation as a method of renal replacement therapy. There is a need to introduce an effective educational program.

Transcriptome profiling of the newborn mouse lung after hypoxia and reoxygenation: hyperoxic reoxygenation affects mTOR signaling pathway, DNA repair, and JNK-pathway regulation.

BACKGROUND: The use of oxygen in acute treatment of asphyxiated term newborns is associated with increased mortality. It is unclear how hyperoxic reoxygenation after hypoxia affects transcriptional changes in the newborn lung. METHODS: On postnatal day 7, C57BL/6 mice (n = 62) were randomized to 120-min hypoxia (fraction of inspired oxygen (FiO2) 0.08) or normoxia. The hypoxia group was further randomized to reoxygenation for 30 min with FiO2 0.21, 0.40, 0.60, or 1.00, and the normoxia group to FiO2 0.21 or 1.00. Transcriptome profiling was performed on homogenized lung tissue using the Affymetrix 750k expression array, and validation was carried out by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: The hypoxia-reoxygenation model induced hypoxia-inducible factor 1 (HIF-1) targets like Vegfc, Adm, and Aqp1. In total, ~70% of the significantly differentially expressed genes were detected in the two high hyperoxic groups (FiO2 0.60 and 1.00). Reoxygenation with 100% oxygen after hypoxia uniquely upregulated Gadd45g, Dusp1, Peg3, and Tgm2. Pathway analysis identified mammalian target of rapamycin (mTOR) signaling pathway, DNA repair, c-jun N-terminal kinase (JNK)-pathway regulation, and cell cycle after hyperoxic reoxygenation was applied. CONCLUSION: Acute hypoxia induces HIF-1 targets independent of the reoxygenation regime applied. Hyperoxic reoxygenation affects pathways regulating cell growth and survival. DNA-damage-responsive genes are restricted to reoxygenation with 100% oxygen.

New insight into the pathogenesis of retinopathy of prematurity: assessment of whole-genome expression.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the most common preventable causes of blindness and impaired vision among children in developed countries. The aim of the study was to compare whole-genome expression in the first month of life in groups of infants with and without ROP. METHODS: Blood samples were drawn from 111 newborns with a mean gestational age of 27.8 wk on the 5th, 14th, and 28th day of life (DOL). The mRNA samples were evaluated for gene expression with the use of human whole-genome microarrays. The infants were divided into two groups: no ROP (n = 61) and ROP (n = 50). RESULTS: Overall, 794 genes were differentially expressed on the 5th DOL, 1,077 on the 14th DOL, and 3,223 on the 28th DOL. In each of the three time points during the first month of life, more genes were underexpressed than overexpressed in the ROP group. Fold change (FC), which was used in analysis of gene expression data, ranged between 1.0 and 1.5 in the majority of genes differentially expressed. CONCLUSION: Pathway enrichment analysis revealed that genes in four pathways related to inflammatory response were consistently downregulated due to the following variables: ROP and gestational age.

Impact of antenatal glucocorticosteroids on whole-genome expression in preterm babies.

AIM: To study the impact that using antenatal steroid to treat threatened preterm delivery has on whole-genome expression. METHODS: A prospective whole-genome expression study was carried out on 50 newborn infants, delivered before 32 weeks gestation, who had been exposed to antenatal steroids, including 40 who had received a full antenatal steroid course. Seventy infants not exposed to antenatal steroids formed the control group. Microarray analyses were performed five and 28 days after delivery, and the results were validated by real-time PCR. The study was conducted between September 2008 and November 2010. RESULTS: Twenty thousand six hundred and ninety-three genes were studied in the infants' leucocytes. Thirteen were differentially expressed 5 days after delivery, but there were no differences at day 28. Four genes related to cancer or inflammation were up-regulated. Nine genes were down-regulated: six were Y-linked and associated with malignancies, graft-versus-host disease, male infertility and cell differentiation and three were associated with pre-eclampsia, oxidative stress and chloride/bicarbonate exchange. Seven gene pathways were up-regulated at day five and only one at day 28. These were associated with cell growth, cell cycle regulation, metabolism and apoptosis. CONCLUSION: Antenatal steroid therapy affects a limited number of genes and gene pathways in leucocytes in preterm babies at day five of life. The effect is short-lived, but long-term effects cannot be ruled out.

Coronary artery abnormalities in Kawasaki disease.

INTRODUCTION: Kawasaki disease is the number one cause of acquired heart disease among children in developed countries. AIM: The aim of the study was a retrospective analysis of the factors that may influence the persistence of coronary artery abnormalities in patients with Kawasaki disease. MATERIALS AND METHODS: Analyzing the medical records of patients hospitalized in the University Children's Hospital of Krakow in the years 2005-2011 we collected the data of 28 patients diagnosed with Kawasaki disease. The group was divided into two subgroups, depending on the duration of the persistence of changes in the coronary arteries - A (n = 17) for up to 6 months, B (n = 11) - for more than 6 months. Both groups were analyzed for the presence of factors that may influence the course of the disease. RESULTS: There were more boys in group A (11 boys (65%), 6 girls (35%)), whereas in group B the distribution was more uniform (6 boys (55%), 5 girls (45%)). The age of onset in group A was 37.9 months (SD 30.8), in group B 39.5 months (SD 16.7). 17.6% of patients in group A and 36.4% in group B were treated with glucocorticoids. CONCLUSIONS: In the group of patients in which coronary artery abnormalities disappeared more quickly, male and slightly older children dominated. The only difference observed between the 2 groups related to the frequency of the use of glucocorticoids, they were used more often in children, in whom coronary artery abnormalities persisted longer.

[Early markers of acute kidney injury in newborns]. / Wczesne markery ostrego uszkodzenia nerek w okresie noworodkowym.

The incidence of acute kidney injury (AKI) at neonatal intensive care units (NICU) is estimated as 6-24%. Traditional AKI markers i.e. serum creatinine (SCr) concentration, fractional sodium exertion, urine sodium concentration and renal failure index--are low sensitivity and low specificity markers but beside remain very late ones. Serum creatinine concentration arises 48 hours after renal tissue damage. The paper presents contemporary knowledge concerning concentration reference ranges of some early AKI biomarkers (NGAL, hKIM1, OPN, IL18)--either in term or preterm newborns. The most current reports about chosen AKI biomarkers in newborns with uncomplicated clinical course and in children with AKI within the course of sepsis or after cardiopulmonary bypass surgery--were discussed. Disposing of the reliable clinical data referring to early AKI biomarkers constitutes a valuable aid for clinicians who having got to know about the actual risk possess the time for proper clinical interventions.