Effectiveness of zinc protoporphyrin/heme ratio and ferritin for assessing iron status in preterm infants.

BACKGROUND: Since iron is crucial for many tissue processes, we, therefore, aimed to assess ferritin and the zinc protoporphyrin to heme ratio (ZnPP/H) as indicators of iron status in preterm newborns, particularly during certain inflammatory episodes. METHODS: From 170 preterm babies, paired ferritin and ZnPP/H measurements were collected twice (on the first postnatal day and six weeks later). To compare these measures and assess the impact of anemia, sepsis, and packed red blood cell transfusion (PRBT), three different scenarios were considered. RESULTS: Compared to the non-anemic group, the anemic patients' serum ferritin level was considerably lower (p = 0.044), whereas the anemic patients' ZPP/H ratio was significantly greater (p < 0.001). In neonates with sepsis, ferritin levels were considerably greater in both anemic and non-anemic septic neonates compared to neonates without sepsis (p < 0.001 for each). Regarding ZPP/H ratio, no appreciable variations were found between the two groups. In addition, serum ferritin significantly increased following each PRBT (p < 0.001 for each). As a result of each PRBT, the ZPP/H ratio considerably decreased (p < 0.001). CONCLUSION: As a measure of iron status during particular inflammatory processes like infection and PRBT, ZnPP/H may be more accurate.

Prophylactic Evidence of MSCs-Derived Exosomes in Doxorubicin/Trastuzumab-Induced Cardiotoxicity: Beyond Mechanistic Target of NRG-1/Erb Signaling Pathway.

Trastuzumab (Trz) is a humanized monoclonal antibody targeting epidermal growth factor receptor 2 (HER2; ErbB2). The combined administration of Trz and doxorubicin (DOX) has shown potent anti-cancer efficacy; however, this regimen may be accompanied by severe cardiac toxicity. Mesenchymal stem cells (MSCs)-derived exosomes are nanosized vesicles that play a crucial role in cell-cell communication and have shown efficacy in the treatment of various diseases. In this study, we aim to investigate the cardioprotective effects of MSCs-derived exosomes in a DOX/Trz- mediated cardiotoxicity model, and the possible mechanisms underlying these effects are elucidated. Forty-nine male rats were randomly assigned into four groups: Group I (control); Group II (Dox/Trz); Group III (protective group); and Group IV (curative group). Cardiac hemodynamic parameters, serum markers of cardiac injury, oxidative stress indices, and cardiac histopathology were investigated. Further, transcript profile of specific cardiac tissue injury markers, apoptotic markers, and fibrotic markers were analyzed using qRT-PCR, while the protein expressions of pAkt/Akt, pERK/ERK, pJNK/JNK, pJNK/JNK, and pSTAT3/STAT3 were evaluated by ELISA. Additionally, cardiac mirR-21 and miR-26a were assessed. A combined administration of DOX/Trz disrupted redox and Ca2+ homeostasis in cardiac tissue induced myocardial fibrosis and myofibril loss and triggered cardiac DNA damage and apoptosis. This cardiotoxicity was accompanied by decreased NRG-1 mRNA expression, HER2 protein expression, and suppressed AKT and ERK phosphorylation, while triggering JNK phosphorylation. Histological and ultra-structural examination of cardiac specimens revealed features typical of cardiac tissue injury. Moreover, a significant decline in cardiac function was observed through biochemical testing of serum cardiac markers and echocardiography. In contrast, the intraperitoneal administration of MSCs-derived exosomes alleviated cardiac injury in both protective and curative protocols; however, superior effects were observed in the protective protocol. The results of the current study indicate the ability of MSCs-derived exosomes to protect from and attenuate DOX/Trz-induced cardiotoxicity. The NRG-1/HER2, MAPK, PI3K/AKT, PJNK/JNK, and PSTAT/STAT signaling pathways play roles in mediating these effects.

Risk Factors of Intractable Epilepsy in Children with Cerebral Palsy.

OBJECTIVES: We aimed to investigate the risk factors predicting the development of intractable epilepsy in children with cerebral palsy (CP), with an emphasis on perinatal characteristics, seizure semiology, imaging, and EEG findings. MATERIALS & METHODS: Following a descriptive, retrospective, case-control design, 106 children with CP and epilepsy from 2015 to 2020 were studied (46 children with CP and intractable epilepsy and 60 with CP and controlled epilepsy). Data were retrieved from medical records of participants (i.e., demographics, clinical characteristics, perinatal history, etiology of seizure and CP, seizure semiology, intellectual functions, therapeutic options, brain imaging, and EEG findings). RESULTS: We established a model of the most important risk factors that can predict intractable epilepsy in children with CP. The model included the additive effect of a poor Apgar score at 5 minutes, the presence of neonatal seizures, focal epilepsy, and focal slowing on the EEG background (Area under the receiver operating characteristic of 0.810). CONCLUSION: The findings can be used to identify intractable epilepsy in children who suffer from CP with further support by offering early therapeutic interventions intended to reduce the burden of refractory seizures.

The Impact of Antiepileptic Drugs on Thyroid Function in Children with Epilepsy: New Versus Old.

OBJECTIVES: To investigate the effects of traditional antiepileptic drugs (AEDs) versus newer AEDs on the thyroid hormone profile of children with epilepsy. MATERIALS & METHODS: A total of 80 children with epilepsy were included in this study and were divided into two groups. Group 1 included 40 children with epilepsy on traditional AEDs, and group 2 included 40 children with epilepsy on newer AEDs. Forty healthy children were also included as the control group (group 3). We analyzed the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH). RESULTS: In epileptic children treated with traditional drugs, there was a significant reduction in the serum level of FT4 and a significant increase in TSH concentration, compared to the control group (P<0.001). Conversely, epileptic children treated with newer AEDs showed no significant changes in the serum concentrations of FT3, FT4, and TSH, compared to the control group. CONCLUSION: Traditional AEDs have more significant effects on thyroid hormone profile, compared to newer AEDs.

Serum Neuron-specific Enolase and S100 Calcium-binding Protein B in Pediatric Diabetic Ketoacidosis

Objective: Neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) are markers of different neurological disorders. The aim was to investigate the relationship between NSE and S100B serum concentrations and the severity of diabetic ketoacidosis (DKA) in diabetic children. Methods: Eighty children with DKA, 40 with type 1 diabetes mellitus (T1DM) without DKA and 40 healthy controls were enrolled. Severity of DKA was assessed according to blood pH and bicarbonate concentration. Serum NSE and S100B were measured in all participants. In the DKA group serum NSE and S100B were measured at three time points, at admission and at 12 hours and 24 hours after starting treatment. Results: Children with DKA showed significantly higher serum levels of NSE at all time points compared to children with T1DM without DKA and controls (p<0.01), while serum S100B concentrations did not differ between the three cohorts. Children with T1DM but without DKA also had significantly higher serum levels of NSE (p<0.01) compared to healthy controls. Patients with low Glasgow Coma Scale score (GCSS) and those with moderate and severe DKA had significantly higher levels of NSE at all time points (p<0.01 for each) compared to patients with normal GCSS and those with mild DKA. No significant differences were found in serum S100B levels according to the severity of DKA and GCS (p>0.05). Younger age, lower GCSS, higher glucose and HbA1c, lower pH and lower serum bicarbonate were the risk factors associated with elevated NSE. Conclusion: Serum NSE is elevated in all patients with type 1 DM and, in patients with DKA, correlates with severity of DKA. However, serum S100B concentration did not differ between T1DM with or without DKA and healthy controls.

Impact of Vitamin D Supplementation on Attention-Deficit Hyperactivity Disorder in Children.

BACKGROUND: The role of nutrients and dietary factors in attention-deficit hyperactivity disorder (ADHD) remains unclear. OBJECTIVES: The primary objective was to evaluate the serum vitamin D level in children with a diagnosis of ADHD. The secondary objective was to detect the effect of vitamin D supplementation on cognitive function in those with vitamin D deficiency. METHODS: A total of 50 children with ADHD and 40 healthy controls were included in the study. We measured the serum level of vitamin D. Patients with vitamin D deficiency were subdivided into 2 groups: one with vitamin D supplementation and the other without vitamin D supplementation. Further assessment and follow-up of children with ADHD was done. The Wisconsin Card Sorting Test, Conners' Parent Rating Scale, and Wechsler Intelligence Scale for Children were performed at baseline and follow-up in all cohorts with an ADHD diagnosis. RESULTS: The diagnosis of vitamin D deficiency was significantly greater in children with ADHD compared with the control group ( P < 0.05). Children with ADHD had significantly ( P = 0.0009) lower values of serum vitamin D (17.23 ± 8.98) than the control group(31.47 ± 14.42). The group receiving vitamin D supplementation demonstrated improvement in cognitive function in the conceptual level, inattention, opposition, hyperactivity, and impulsivity domains. CONCLUSION: Vitamin D supplementation in children with ADHD may improve cognitive function.

Pre- and postcaptopril renal scintigraphy as a screening test for renovascular hypertension in children.

We studied the ability of pre- and postcaptopril renal scintigraphy to predict renovascular disease (RVD) in children. Retrospective review of medical notes and radiology reports of all hypertensive children who had had both pre- and postcaptopril renal scintigraphy with [(99m)Tc] dimercaptosuccinic acid (DMSA) and/or [(99m)Tc] mercaptoacetyltriglycine (MAG3) and digital subtraction angiography (DSA). 81 children aged 1-18 (median 10) years were studied with 62% (51) having a diagnosis of RVD. Main renal artery disease, intrarenal disease, and both main and intrarenal artery disease were present in 25, 14, and 12 patients respectively. The isotope study accurately diagnosed RVD, confirmed by DSA, in 47% (24 of 51) children, with eight false positive studies. The sensitivity, specificity, and positive and negative predictive values of the isotope study to predict RVD were 48%, 73%, 76%, and 51%, respectively. Pre- and postcaptopril renal scintigraphy was unable to predict RVD in children.