Multitask Versus Multicomponent Training on Cognitive and Motor Functions in Persons With Mild Cognitive Impairment: A Randomized Trial.

This study aims to compare the effects of multitask (MTT; multiple tasks performed simultaneously) and multicomponent training (MCT; various types of exercise performed sequentially) on processing speed, cognitive functions, gait speed, and balance functions in persons with mild cognitive impairment. Forty-two persons with mild cognitive impairment were randomly allocated to MTT (n = 21) or MCT (n = 21). Outcome measures included processing speed, cognitive functions (attention and executive functions), single-task gait speed, dual-task gait speed (DTGS-Arithmetic and DTGS-Verbal), and balance functions. Processing speed (except inhibition), cognitive functions, gait speed, and balance functions improved in the MTT and MCT groups following training, with no significant differences between the groups in processing speed or cognitive functions. The MCT group improved more on single-task gait speed (F = 15.097; p = .000; r = .270) and DTGS (DTGS-Arithmetic; F = 10.594; p = .002; r = .214), while the MTT group improved more on balance functions (F = 4.366; p = .043; r = .101). MTT and MCT strategies can be used to improve cognitive and physical outcomes in persons with mild cognitive impairment.

Experience and Prognosis of Systemic Neonatal Thrombosis at a Level III NICU.

OBJECTIVE: The objective of this article was to evaluate neonates diagnosed systemic thrombosis and their outcomes. METHODS: We retrospectively evaluated data of neonatal systemic thrombosis between January 2011 and December 2016. RESULTS: Among 4376 hospitalized, 30 neonates (0.69%) were diagnosed systemic thrombosis. Their mean birth weight was 2422±1152 g (680 to 4750 g), gestational age was 35±5.4 weeks (25 to 41 wk). There were 25 neonates (83.3%) with venous, 5 patients (16.7%) with arterial thrombosis. The most common sites that thrombi localized were major vessels (n=11) and central nervous system (n=8). Central catheter insertion (76.7%) and prematurity (46.7%) were the most common risk factors. Congenital prothrombotic risk factors included G1691A mutation in factor V Leiden (n=1), mutation in factor XIII (n=1), C677T mutation in methylenetetrahydrofolate reductase (n=6). More than 1 congenital risk factor was identified in 5 patients. The patients were treated with low-molecular weight heparin. The mortality rate was 13.3% (n=4). Two patients required amputation (left foot, left upper extremity). Unilateral renal atrophy (n=1), cerebral palsy (n=2), hemiparesis (n=1) were identified among followed 24 patients. CONCLUSIONS: Critically ill neonates are at risk for thrombosis, and devastating consequences can result. As indwelling catheters and prematurity are important, careful monitorization, early diagnosis and therapy, cautious care of central catheter might reduce the incidence and adverse outcome.

Reference values of anthropometric measurements in healthy late preterm and term infants

Background/aim: Geographical distribution, ethnicity, and other socioeconomic factors may affect anthropometric measurements, and for that reason each society should determine their own measurements accounting for those factors. In this study, we aimed to determine the anthropometric measurements of healthy late preterm and term infants to compare the results with other national and international studies. Materials and methods: This sectional study was carried out among 1197 infants born with a gestational age of ≥35 weeks. Chest circumference, ear length, foot length, palmar length, middle finger length, philtrum distance, inner and outer canthal distances, and palpebral fissure length were measured in the first 24 h of life. Results: All measurements of late preterm infants were smaller than those of term infants (P ˂ 0.05). Compared with male infants, the chest circumference, ear length, foot length, palmar length, philtrum distance, and inner canthal distances of the female infants were lower (P ˂ 0.05). No significant differences were found between male and female infants' middle finger length, outer canthal distance, and palpebral fissure length measurements. Percentile values for all measurements of 35­42-week male and female infants were described. Conclusion: These measurements of male and female infants born between 35 and 42 weeks may be useful for early detection of syndromes by detecting anatomical abnormalities in our population.

Characterization of transcription factor response kinetics in parallel.

BACKGROUND: Transcription factors (TFs) are effectors of cell signaling pathways that regulate gene expression. TF networks are highly interconnected; one signal can lead to changes in many TF levels, and one TF level can be changed by many different signals. TF regulation is central to normal cell function, with altered TF function being implicated in many disease conditions. Thus, measuring TF levels in parallel, and over time, is crucial for understanding the impact of stimuli on regulatory networks and on diseases. RESULTS: Here, we report the parallel analysis of temporal TF level changes due to multiple stimuli in distinct cell types. We have analyzed short-term dynamic changes in the levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), signal transducer and activator of transcription 3 (Stat3), cAMP response element-binding protein (CREB), glucocorticoid receptor (GR), and TATA binding protein (TBP), in breast and liver cancer cells after tumor necrosis factor-alpha (TNF-α) and palmitic acid (PA) exposure. In response to both stimuli, NF-kB and CREB levels were increased, Stat3 decreased, and TBP was constant. GR levels were unchanged in response to TNF-α stimulation and increased in response to PA treatment. CONCLUSIONS: Our results show significant overlap in signaling initiated by TNF-α and by PA, with the exception that the events leading to PA-mediated cytotoxicity likely also include induction of GR signaling. These results further illuminate the dynamics of TF responses to cytokine and fatty acid exposure, while concomitantly demonstrating the utility of parallel TF measurement approaches in the analysis of biological phenomena.

Association of vitamin D receptor gene polymorphisms and bronchopulmonary dysplasia.

BACKGROUND: Vitamin D and its receptor (VDR) have important roles in perinatal lung development. The aim of this study was to investigate the relationship between VDR gene polymorphism and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: VDR Fok I, Bsm I, Apa I, and Taq I polymorphisms were genotyped using restriction fragment length polymorphism in 109 preterm infants (47 with BPD, 62 without BPD). RESULTS: In univariate analysis, Ff (odds ratio (OR) = 3.937, P = 0.022, 95% confidence interval (CI) = 1.22-12.69) and ff (OR = 5.23, P = 0.004, 95% CI = 1.69-16.23) genotypes of Fok I were associated with the increased risk of BPD; whereas tt genotype of Taq 1 was associated with a protective effect against BPD (OR = 0.30, P = 0.04, 95% CI = 0.09-0.94). In multivariate logistic regression analysis, variant Fok 1 genotype increased risk of BPD (OR = 4.11, 95% CI = 1.08-15.68, P = 0.038) independent of patent ductus arteriosus, sepsis, mechanical ventilation, and surfactant treatment. Taq 1, Bsm 1, and Apa 1 polymorphisms did not have any effect. CONCLUSION: After adjusting for multiple confounders, VDR Fok 1 polymorphism was associated with the increased frequency of BPD. Further studies are needed to assess the contribution of VDR signaling to the pathogenesis of BPD and to determine if VDR polymorphisms may be suitable for identifying infants at high risk for BPD.

Does base excess predict kidney injury in neonates with hypoxic-ischemic encephalopathy?

In neonates with hypoxic-ischemic encephalopathy (HIE), we studied the correlation between cord blood base excess (BE) and kidney function. Among 225 infants, 29 % had oliguria. BE levels differed significantly between oliguric and non-oliguric infants (p < 0.01), with a negative correlation to kidney injury (r = -0.544, p < 0.01). BE < -18 had 85 % specificity and 76 % sensitivity in predicting kidney injury (AUC = 0.88). These findings suggest BE as a valuable indicator of impending kidney injury in HIE infants, though underlying mechanisms may vary.

Quantitative, solution-phase profiling of multiple transcription factors in parallel.

Transcription factors are regulatory proteins that bind to specific sites of chromosomal DNA to enact responses to intracellular and extracellular stimuli. Transcription factor signalling networks are branched and interconnected so that any single transcription factor can activate many different genes and one gene can be activated by a combination of different transcription factors. Thus, trying to characterize a cellular response to a stimulus by measuring the level of only one transcription factor potentially ignores important simultaneous events that contribute to the response. Hence, parallel measurements of transcription factors are necessary to capture the breadth of valuable information about cellular responses that would not be obtained by measuring only a single transcription factor. We have sought to develop a new, scalable, flexible, and sensitive approach to analysis of transcription factor levels that complements existing parallel approaches. Here, we describe proof-of-principle analyses of purified human transcription factors and breast cancer nuclear extracts. Our assay can successfully quantify transcription factors in parallel with ~10-fold better sensitivity than current techniques. Sensitivity of the assay can be further increased by 200-fold through the use of PCR for signal amplification.

Latest developments in experimental and computational approaches to characterize protein-lipid interactions.

Understanding the functional roles of all the molecules in cells is an ultimate goal of modern biology. An important facet is to understand the functional contributions from intermolecular interactions, both within a class of molecules (e.g. protein-protein) or between classes (e.g. protein-DNA). While the technologies for analyzing protein-protein and protein-DNA interactions are well established, the field of protein-lipid interactions is still relatively nascent. Here, we review the current status of the experimental and computational approaches for detecting and analyzing protein-lipid interactions. Experimental technologies fall into two principal categories, namely solution-based and array-based methods. Computational methods include large-scale data-driven analyses and predictions/dynamic simulations based on prior knowledge of experimentally identified interactions. Advances in the experimental technologies have led to improved computational analyses and vice versa, thereby furthering our understanding of protein-lipid interactions and their importance in biological systems.

Molecular mechanism by which palmitate inhibits PKR autophosphorylation.

PKR (double-stranded RNA-activated protein kinase) is an important component of the innate immunity, antiviral, and apoptotic pathways. Recently, our group found that palmitate, a saturated fatty acid, is involved in apoptosis by reducing the autophosphorylation of PKR at the Thr451 residue; however, the molecular mechanism by which palmitate reduces PKR autophosphorylation is not known. Thus, we investigated how palmitate affects the phosphorylation of the PKR protein at the molecular and biophysical levels. Biochemical and computational studies show that palmitate binds to PKR, near the ATP-binding site, thereby inhibiting its autophosphorylation at Thr451 and Thr446. Mutation studies suggest that Lys296 and Asp432 in the ATP-binding site on the PKR protein are important for palmitate binding. We further confirmed that palmitate also interacts with other kinases, due to the conserved ATP-binding site. A better understanding of how palmitate interacts with the PKR protein, as well as other kinases, could shed light onto possible mechanisms by which palmitate mediates kinase signaling pathways that could have implications on the efficacy of current drug therapies that target kinases.

Desferrioxamine treatment of iron overload secondary to RH isoimmunization and intrauterine transfusion in a newborn infant.

Intrauterine transfusion is the standard of care in the management of severe Rh isoimmunization. Desferrioxamine has been used for the treatment of iron overload secondary to hemolysis and intrauterine transfusions in Rh isoimmunization cases. Here, we report a preterm infant born at 34 weeks of gestational age who had formerly received intrauterine transfusions for Rhesus hemolytic disease and presented with severe hyperferritinemia and elevated liver enzymes in the first week of life. Desferrioxamine treatment was started due to a ferritin level of 28,800 ng/ml and continued for 13 weeks. Although the treatment was successful, we observed resistant leukopenia which resolved after the cessation of treatment. In conclusion, iron overload secondary to intrauterine transfusions can be treated successfully with desferrioxamine; however, neonatologists must be aware of the possible side effects of this drug which has been used in only a limited number of newborns.

Association between vitamin D level and community-acquired late-onset neonatal sepsis. / Asociación entre la concentración de vitamina D y la sepsis neonatal extrahospitalaria de aparición tardía.

INTRODUCTION: The objective was to determine the relationship between mother and infant vitamin D levels and late onset sepsis. POPULATION AND METHODS: Infants born > 37 weeks of gestational age who were hospitalized with the diagnosis of late-onset sepsis were enrolled to this prospective case control study. VitaminD levels of the infants and their mothers in the study and a control group were compared. RESULTS: Fourty six term patients with late-onset sepsis composed the study group, 46 patients with hyperbilirubinemia as the control group. Vitamin D supplementation during pregnancy was lower in mothers of study group compared to the control group (p = 0.001). Serum 25-hydroxyvitamin D levels of infants and mothers in the study group were significantly lower than the control group (p < 0.001). There was a positive correlation between 25-hydroxyvitamin D levels of mothers and infants in both groups (r: 0.38, p < 0.001). The best cut off value of 25-hydroxyvitamin D, which determines the risk of late-onset sepsis in neonates, was detected as 15.45 ng/ml (sensitivity: 91.3 %, specificity: 71.7 %, area under the curve: 0.824, p < 0.001). CONCLUSIONS: In this study, 25-hydroxyvitamin D levels were found to be lower in term infants with late-onset sepsis and among their mothers compared to the control group. Positive correlation was found between serum 25(OH)D levels of infants and their mothers.

Introducción. El objetivo fue determinar la relación entre la concentración materna e infantil de vitamina D y la sepsis de aparición tardía. Población y métodos. En este estudio se incluyó a los bebés nacidos con >37 semanas de gestación hospitalizados con diagnóstico de sepsis de aparición tardía. Se comparó la concentración de vitamina D de los niños y sus madres del grupo del estudio y del de referencia. Resultados. El grupo del estudio incluyó a 46 pacientes con sepsis de aparición tardía nacidos a término y el grupo de referencia, 46 pacientes con hiperbilirrubinemia. La suplementación con vitamina D durante el embarazo fue menor en las madres del grupo del estudio que en el de referencia (p = 0,001). La concentración sérica de 25-hidroxivitamina D [25(OH)D] de los niños y las madres del grupo del estudio fue significativamente menor que la del grupo de referencia (p < 0,001). Se observó una correlación positiva entre la 25(OH)D en las madres y los niños de ambos grupos (r: 0,38; p < 0,001). El valor de corte para la 25(OH)D, que determina el riesgo de sepsis neonatal de aparición tardía, se estableció en 15,45 ng/ml (sensibilidad: 91,3 %; especificidad: 71,7 %; área bajo la curva: 0,824; p < 0,001). Conclusiones. La concentración de 25(OH)D fue inferior en los bebés nacidos a término con sepsis de aparición tardía y sus madres en comparación con el grupo de referencia. La correlación entre la concentración sérica de 25(OH)D de los niños y sus madres fue positiva.

Emerging affinity-based techniques in proteomics.

Proteomes of interest, such as the human proteome, have such complexity that no single technique is adequate for the complete analysis of the constituents. Depending on the goal (e.g., identification of a novel protein vs measurement of the level of a known protein), the tools required can vary significantly. While existing methods provide valuable information, their limitations drive the development of complementary, innovative methods to achieve greater breadth of coverage, dynamic range or specificity of analysis. We will discuss affinity-based methods and their applications, focusing on their unique advantages. In addition, we will describe emerging methods with potential value to proteomics, as well as the challenges that remain for proteomic studies.

A Novel Homozygous Mutation in the KCNJ11 Gene of a Neonate with Congenital Hyperinsulinism and Successful Management with Sirolimus.

Congenital hyperinsulinism (CHI) is the most common cause of neonatal persistent hypoglycemia caused by mutations in nine known genes. Early diagnosis and treatment are important to prevent brain injury. The clinical presentation and response to pharmacological therapy may vary depending on the underlying pathology. Genetic analysis is important in the diagnosis, treatment, patient follow-up, and prediction of recurrence risk within families. Our patient had severe hypoglycemia and seizure following birth. His diagnostic evaluations including genetic testing confirmed CHI. He was treated with a high-glucose infusion, high-dose diazoxide, nifedipine, and glucagon infusion. A novel homozygous mutation (p.F315I) in the KCNJ11 gene, leading to diazoxide-unresponsive CHI, was identified. Both parents were heterozygous for this mutation. Our patient's clinical course was complicated by severe refractory hypoglycemia; he was successfully managed with sirolimus and surgical intervention was not required. Diazoxide, nifedipine, and glucagon were discontinued gradually following sirolimus therapy. The patient was discharged at 2 months of age on low-dose octreotide and sirolimus. His outpatient clinical follow-up continues with no episodes of hypoglycemia. We present a novel homozygous p.F315I mutation in the KCNJ11 gene leading to diazoxide-unresponsive CHI in a neonate. This case illustrates the challenges associated with the diagnosis and management of CHI, as well as the successful therapy with sirolimus.

Asociación entre la concentración de vitamina D y la sepsis neonatal extrahospitalaria de aparición tardía / Association between vitamin D level and community-acquired late-onset neonatal sepsis

Introducción. El objetivo fue determinar la relación entre la concentración materna e infantil de vitamina D y la sepsis de aparición tardía. Población y métodos. En este estudio se incluyó a los bebés nacidos con ≥ 37 semanas de gestación hospitalizados con diagnóstico de sepsis de aparición tardía. Se comparó la concentración de vitamina D de los niños y sus madres del grupo del estudio y del de referencia. Resultados. El grupo del estudio incluyó a 46 pacientes con sepsis de aparición tardía nacidos a término y el grupo de referencia, 46 pacientes con hiperbilirrubinemia. La suplementación con vitamina D durante el embarazo fue menor en las madres del grupo del estudio que en el de referencia (p = 0,001). La concentración sérica de 25-hidroxivitamina D [25(OH)D] de los niños y las madres del grupo del estudio fue significativamente menor que la del grupo de referencia (p < 0,001). Se observó una correlación positiva entre la 25(OH)D en las madres y los niños de ambos grupos (r: 0,38; p < 0,001). El valor de corte para la 25(OH)D, que determina el riesgo de sepsis neonatal de aparición tardía, se estableció en 15,45 ng/ml (sensibilidad: 91,3 %; especificidad: 71,7 %; área bajo la curva: 0,824; p < 0,001). Conclusiones. La concentración de 25(OH)D fue inferior en los bebés nacidos a término con sepsis de aparición tardía y sus madres en comparación con el grupo de referencia. La correlación entre la concentración sérica de 25(OH)D de los niños y sus madres fue positiva.

Introduction. The objective was to determine the relationship between mother and infant vitamin D levels and late onset sepsis. Population and methods.Infants born ≥37 weeks of gestational age who were hospitalized with the diagnosis of late-onset sepsis were enrolled to this prospective case control study. VitaminD levels of the infants and their mothers in the study and a control group were compared. Results. Fourty six term patients with lateonset sepsis composed the study group, 46 patients with hyperbilirubinemia as the control group. Vitamin D supplementation during pregnancy was lower in mothers of study group compared to the control group (p = 0.001). Serum 25-hydroxyvitamin D levels of infants and mothers in the study group were significantly lower than the control group (p < 0.001). There was a positive correlation between 25-hydroxyvitaminD levels of mothers and infants in both groups (r: 0.38, p < 0.001). The best cut off value of 25-hydroxyvitamin D, which determines the risk of late-onset sepsis in neonates, was detected as 15.45 ng/ml (sensitivity: 91.3 %, specificity: 71.7 %, area under the curve: 0.824, p < 0.001). Conclusions.In this study, 25-hydroxyvitaminD levels were found to be lower in term infants with late-onset sepsis and among their mothers compared to the control group. Positive correlation was found between serum 25(OH)D levels of infants and their mothers. Key words: newborn infant, sepsis,

Treatment of Congenital Complete Atrioventricular Heart Block With Permanent Epicardial Pacemaker in Neonatal Lupus Syndrome.

INTRODUCTION: Neonatal lupus syndrome (NLS) is a passively acquired autoimmune condition due to the transplacental passage of maternal anti-Ro/SSA and anti-La/SSB antibodies in mothers with systemic lupus erythematosus (SLE), and congenital complete heart block (CHB) is its most serious manifestation. Skin and hepatic involvement may occur in later infancy. CASE PRESENTATION: A term infant with fetal bradycardia, detected at the 23rd gestational age, was diagnosed with CHB due to NLS and was successfully treated with a permanent epicardial pacemaker. The patient was reported here due to rarity of the procedure in neonatal period. CONCLUSIONS: Mothers with SLE should be screened and closely followed up during pregnancy for the development of fetal atrioventricular (AV) block.

Factors affecting bilirubin levels during first 48 hours of life in healthy infants.

OBJECTIVE: To investigate the relationship of delivery type, maternal anesthesia, feeding modalities, and first feeding and meconium passage times with early bilirubin levels of healthy infants. METHODS: Cord, 24 hours' and 48 hours' total bilirubin levels were measured in 388 study infants. RESULTS: Infants born with cesarean section were fed later and more often had mixed feeding. First meconium passage was delayed with general anesthesia. Cord, 24 and 48 hours' bilirubin levels were not correlated with first feeding time, meconium passage time, mode of delivery, existence and type of anesthesia, and feeding modalities. Being in high intermediate risk zone at 72 hours of Bhutani's nomogram was only related to first feeding time and high cord bilirubin level. Late preterm infants were more frequently born with cesarean section and offered supplementary formula. Therefore, first meconium passage times and bilirubin levels were similar in the late preterm and term infants. CONCLUSIONS: Type of delivery or anesthesia, late prematurity, feeding modalities, and first meconium passage time were not related to early bilirubin levels in healthy neonates, but delayed first feeding and high cord bilirubin levels were related to be in higher risk zone for later hyperbilirubinemia.