bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cord blood interleukin‐6 as a predictor of early‐onset neonatal sepsis
Authors: Cernada María , Badía Natalia , Modesto Vicente , Alonso Ricardo , Mejías Asunción , Golombek Sergio , Vento Máximo 
Published: December 2011

AbstractAim:  To compare diagnostic accuracy in cord blood of interleukin‐6 (IL‐6) with C‐reactive protein (CRP) as predictors of early‐onset neonatal sepsis (EOS) in newborns with prenatal risk factors for infection.Methods:  During 12 months, cord blood IL‐6 and CRP were measured immediately after birth in neonates with prenatal risk factors of infection. The odds of developing sepsis based on IL‐6 and CRP values were calculated using likelihood ratios (LR), and their accuracy as predictors was compared by binary logistic regression. Multivariable logistic regression analyses were performed to identify independent risk factors for sepsis.Results:  Ten of 128 neonates (7.8%) were diagnosed with EOS confirmed with positive blood culture in five cases (3.9%). Cord blood IL‐6 was a greater predictor of sepsis than CRP [ROC for IL‐6 (0.88) vs. CRP (0.70)]. IL‐6‐positive and IL‐6‐negative LR [7.14 vs. −0.11] were superior to those calculated for CRP [2.86 vs. −0.51]. Chorioamnionitis and Apgar at 1 min were identified as independent risk factors for EOS.Conclusions:  Cord blood IL‐6 showed superior LR than CRP; therefore, it is a better predictor to initiate treatment in neonates with prenatal infectious risk factors immediately after birth.
Fluctuations of anti‐Xa concentrations during maintenance enoxaparin therapy for neonatal thrombosis
Authors: Lulic‐Botica Mirjana , Rajpurkar Madhvi , Sabo Cindy , Tutag‐Lehr Victoria , Natarajan Girija 
Published: December 2011

AbstractAim:  To evaluate fluctuations in anti‐Xa concentrations in infants treated with enoxaparin for thrombosis and describe clinical outcomes.Methods:  A retrospective chart review was performed on infants treated with enoxaparin in the Neonatal Intensive Care Unit, and data on enoxaparin doses, anti‐Xa concentrations, clinical characteristics and outcomes were abstracted.Results:  Our cohort (n = 26) had a median gestation of 36 (range, 23–41) weeks, birthweight of 2522 (510–3912) grams and 5‐min Apgar score of 8(4–9). Fifteen (57.7%) infants were males. Thromboses was diagnosed at a median age of 22 (range, 1–97) days; enoxaparin was initiated at 27.5 (range, 4–98) days at a mean (SD) dose of 1.4 (0.3) mg/kg every 12 h. Therapeutic anti‐Xa concentrations (0.5–1 U/mL) were achieved at a mean (SD) dose of 2.1 (0.6) mg/kg at 12.5 (12.2) days of treatment. Of the 143 anti‐Xa concentrations, 39 (27%) were within the therapeutic range. During maintenance therapy following initial therapeutic anti‐Xa concentration, 40% concentrations were therapeutic. Minor bleeding was noted in four infants and intracranial bleed in one infant; four infants died. During treatment, thrombocytopenia, renal and hepatic impairment during treatment were noted in 7, 2 and 4 infants, respectively. Clot resolution was observed in 21 (81%) infants.Conclusions:  Anti‐Xa concentrations fluctuate during maintenance enoxaparin therapy, with therapeutic levels being achieved only sporadically in young infants. Despite this, enoxaparin appears efficacious in thrombosis resolution. Further studies on the impact of stringent control of concentrations on outcomes in this population are warranted.
Health outcomes among Swedish children: the role of social capital in the family, school and neighbourhood
Authors: Eriksson Ulrika , Hochwälder Jacek , Carlsund Åsa , Sellström Eva 
Published: December 2011

AbstractAim:  The aim of the study was to explore the extent to which Swedish children’s perceptions of social capital in the family, school and neighbourhood predicted health complaints and well‐being.Methods:  The study used data from the Swedish Health Behaviour in School‐aged Children survey. The sample consisted of 3926 children aged 11–15 years. Correlations and hierarchical multiple linear regression were performed.Results:  Higher degrees of family, school and neighbourhood social capital corresponded to lower levels of health complaints and higher levels of well‐being. Social capital in these three spheres had a cumulative effect on children’s health and well‐being.Conclusions:  Social capital in the family, school and neighbourhood matters for children’s health and well‐being and the contributions from each context seem to be additive. Besides the family context, investments for improving child health should primarily be in the school, focusing on social relations and on creating safe and cohesive school environments. Neighbourhood social capital is also of importance and so must be taken into consideration when planning child health promotion interventions.
Estimation of body surface area in various childhood ages – validation of the Mosteller formula
Authors: El Edelbi Ranaa , Lindemalm Synnöve , Eksborg Staffan 
Published: December 2011

AbstractAim:  The aim of the present study was to validate the Mosteller formula for the estimation of body surface area (BSA) in various childhood ages. Many physiological processes including drug metabolism correlate with values for BSA. In addition, dosing of many drugs, especially drugs with low therapeutic index, for example, anti‐neoplastics, are based on estimated values of BSA.Methods:  Published data from measured BSA in 268 children and infants (median age: 8 month; range: 0–18 years) were compared with BSA values estimated by the Mosteller formula. Correlation between estimated and measured BSA values was performed by the Spearman rank correlation. Bias and precision were evaluated as outlined by Sheiner and Beal. Measured and estimated BSA values were compared by the Eksborg’s plot.Results:  Measured values of BSA and BSA values estimated by the Mosteller formula were closely correlated (rs = 0.973; p < 0.0001). The formula of Mosteller had with a precision of 9.38% and underestimated BSA by 4.06%. The quotients Estimated/Measured BSA were within the range 0.9–1.1 in 71.3% of the observations, but deviation up to 35% occurred.Conclusion:  The Mosteller formula underestimates BSA in the paediatric population and must be used with precautions because of low precision, most pronounced in neonates and infants.
The reliability of the disabled children's quality‐of‐life questionnaire in Swedish children with diabetes
Authors: Chaplin JE , Hallman M , Nilsson NO , Lindblad B 
Published: December 2011

AbstractAim:  To determine the reliability of the disabled children’s quality‐of‐life measure (DISABKIDS) chronic generic questionnaire and diabetes module in children. The questionnaire is being evaluated for repeated routine health‐related quality‐of‐life (HrQoL) assessment and in association with the Swedish national paediatric diabetes registry (Swediabkids), which is a tool for regular clinical use.Methods:  Children and parents completed the questionnaire during a routine visit to the diabetes clinic. In total, 120 families completed the test and retest. Split‐half reliability correlation and intraclass correlation (ICC) coefficients were calculated. Bland & Altman plots were calculated on the generic HRQoL domain.Results:  Both child and parent versions showed good internal consistency. Test–retest ICC coefficients for the generic HrQoL module were 0.913 for the children and 0.820 for the parent version. All generic domains independently showed good reliability. The diabetes module had a score of 0.855 for children and 0.823 for parents. Split‐half correlation for generic and diabetes modules was 0.930 and 0.848 for children, 0.953 and 0.903 for parents. Bland and Altman plots showed substantial agreement between the two administrations for both children and parents.Conclusion:  The DISABKIDS questionnaire is a reliable instrument for the repeated measurements of HrQoL in children with diabetes.
Markers of systemic inflammation in children with hyperuricemia
Authors: Wasilewska Anna , Tenderenda Edyta , Taranta‐Janusz Katarzyna , Tobolczyk Jolanta , Stypułkowska Justyna 
Published: December 2011

AbstractAim:  The purpose of the study was to investigate serum concentrations of the monocyte chemoattractant protein‐1 (MCP‐1) and high‐sensitivity CRP (hs‐CRP) in children with hyperuricemia and to evaluate its association with obesity.Patients and Methods:  The study involved 52 hyperuricemic patients with mean age of 15.53 ± 1.7 years. Twenty‐seven healthy individuals with normal serum uric acid (SUA) level were selected as the control group (C). Serum MCP‐1 and hs‐CRP were measured by enzyme‐linked immunosorbent assay (ELISA) and immunonephelometry, respectively.Results:  Hyperuricemic patients showed increased sMCP‐1 (median: 69.58 pg/mL) and hs‐CRP (median: 0.53 mg/L) vs. controls (48.39 pg/mL, 0.24 mg/L; respectively) (p < 0.01). The obese children also presented significantly higher levels of sMCP‐1 and hs‐CRP (median, 81.69 and 1.18 mg/L, respectively) in comparison with nonobese (median, 59.62 and 0.41 mg/L, respectively; p < 0.01). Only hs‐CRP correlated positively with body mass index Z‐score (r = 0.33, p < 0.05). Receiver operator characteristic analyses checking the sensitivity and specificity of examined markers for hyperuricemia revealed the higher area under the curve (AUC) for sMCP‐1; however, the difference between AUC for sMCP‐1 and for hs‐CRP was not significant (p > 0.05).Conclusion:  Serum MCP‐1 and hs‐CRP are elevated in hyperuricemic patients, but the role of obesity in inflammation markers needs further investigation.
Interaction of HRP‐2 isoforms with HDGF. Chromatin binding of a specific heteromer
Authors: Thakar Ketan , Votteler Ina , Kelkar Dipti , Shidore Teja , Gupta Shivangi , Kelm Sørge , Dietz Frank 
Published: December 2011

Hepatoma‐derived growth‐factor‐related protein 2 (HRP‐2) belongs to a family with five additional members: hepatoma‐derived growth factor (HDGF); lens epithelium‐derived growth factor; and the HDGF‐related proteins ‐1, ‐3 and ‐4. Very little is known regarding the function of HRP‐2 in particular. This study shows for the first time heteromer formation of different members of the HRP family; HDGF and HRP‐2. In addition, we discovered a previously unknown splice variant of HRP‐2 mRNA encoding for a protein with a 53‐amino acid deletion in its hath region. This HRP‐2 isoform c interacts preferentially with a processed form of HDGF probably because of the loss of an α helix of HRP‐2. Furthermore, in contrast to other isoforms of HRP‐2, isoform c binds to chromatin similar to its most closely related family member lens epithelium‐derived growth factor with potential consequences regarding its function in HIV integration. Interestingly, only the new HRP‐2 isoform c and a processed form of HDGF are displaced from condensed mitotic metaphase chromatin. In conclusion, these observations provide a new perspective for understanding the biological functions of HDGF and related proteins.Structured digital abstract
HRP2 a and Hdgf physically interact by bimolecular fluorescence complementation (View interaction)
HRP2 a and Hdgf colocalize by fluorescence microscopy (View interaction)
HRP2 b physically interacts with Hdgf by pull down (View Interaction: 1, 2)
Hdgf and HRP2 c physically interact by bimolecular fluorescence complementation (View interaction)
Hdgf and HRP2 b colocalize by fluorescence microscopy (View interaction)
HRP2 a physically interacts with Hdgf by pull down (View Interaction: 1, 2)
Hdgf and HRP2 b physically interact by bimolecular fluorescence complementation (View interaction)
HRP2 c physically interacts with Hdgf by pull down (View Interaction: 1, 2)
Hdgf and HRP2 c colocalize by fluorescence microscopy (View interaction)
Mapping out the multistage fibrillation of glucagon
Authors: Ghodke Shirin , Nielsen Søren B. , Christiansen Gunna , Hjuler Hans A. , Flink James , Otzen Daniel 
Published: December 2011

The 29‐residue peptide hormone glucagon forms many different morphological types of amyloid‐like fibrils, depending on solvent conditions. Here, we combine time‐series far‐UV CD with singular value decomposition analysis to reveal six different conformational states populated during fibrillation at 25 °C and pH 2.5. The existence of these states is supported by complementary fluorescence and electron microscopy data. This highlights a multitude of structural transitions of glucagon from unordered structure to β sheets, β turns and further tertiary‐level changes. We attribute the observed unusual far‐UV CD spectra to tertiary‐level structural changes during the formation and maturation of fibrils. The fibrillation model for the whole process involves the formation of three oligomeric species and two different morphologies of fibrils in the same solution. The visualization of annular pore‐like species in the early stages of glucagon fibrillation and the prevalence of such species in the amyloidogenesis of several proteins indicates that they may be a common feature of the fibrillation process. This study gives significant insights into the stepwise conversion of soluble glucagon to its fibrillar state and identifies the importance of fibril twisting for its thermodynamic stabilization.Structured digital abstract
Glucagon and Glucagon bind by circular dichroism (View interaction)
Glucagon and Glucagon bind by transmission electron microscopy (View interaction)
Glucagon and Glucagon bind by fluorescence technology (View interaction)
Conservation of structure and mechanism within the transaldolase enzyme family
Authors: Samland Anne K. , Baier Shiromi , Schürmann Melanie , Inoue Tomoyuki , Huf Sabine , Schneider Gunter , Sprenger Georg A. , Sandalova Tatyana 
Published: December 2011

Transaldolase (Tal) is involved in the central carbon metabolism, i.e. the non‐oxidative pentose phosphate pathway, and is therefore a ubiquitous enzyme. However, Tals show a low degree in sequence identity and vary in length within the enzyme family which previously led to the definition of five subfamilies. We wondered how this variation is conserved in structure and function. To answer this question we characterised and compared the Tals from Bacillus subtilis, Corynebacterium glutamicum and Escherichia coli, each belonging to a different subfamily, with respect to their biochemical properties and structures. The overall structure of the Tal domain, a (β/α)8‐barrel fold, is well conserved between the different subfamilies but the enzymes show different degrees of oligomerisation (monomer, dimer and decamer). The substrate specificity of the three enzymes investigated is quite similar which is reflected in the conservation of the active site, the phosphate binding site as well as the position of a catalytically important water molecule. All decameric enzymes characterised so far appear to be heat stable no matter whether they originate from a mesophilic or thermophilic organism. Hence, the thermostability might be due to the structural properties, i.e. tight packing, of these enzymes.DatabaseThe crystal structures have been deposited in the Protein Data Bank with accession code 3R8R for BsTal and 3R5E for CgTal.Structured digital abstract
BsTal and BsTal bind by x‐ray crystallography (View interaction)
BsTal and BsTal bind by x‐ray crystallography (View interaction)
Chronic Vitamin C Deficiency does not Accelerate Oxidative Stress in Ageing Brains of Guinea Pigs
Authors: Tveden‐Nyborg Pernille , Hasselholt Stine , Miyashita Namiyo , Moos Torben , Poulsen Henrik E. , Lykkesfeldt Jens 
Published: December 2011

AbstractIncreased oxidative stress in the brain has consistently been implied in ageing and in several degenerative brain disorders. Acting as a pivotal antioxidant in the brain, vitamin C is preferentially retained during deficiency and may play an essential role in neuroprotection during ageing. Thus, a lack of vitamin C could be associated with an increase in redox imbalance in the ageing brain. The present study compared oxidative stress of ageing to that of a long‐term non‐scorbutic vitamin C deficiency in guinea pigs. Adults (3–9 months old) were compared to old (36–42 months old) animals during a 6‐month dietary intervention by assessing vitamin C transport and redox homoeostasis in the brain. In contrast to our hypothesis, chronic vitamin C deficiency did not affect the measured markers of oxidative stress in the brains of adult and aged animals. However, aged animals generally showed increased lipid oxidation (p < 0.001), decreased glutathione (p < 0.05), increased p53 mRNA expression (p < 0.01) and somewhat elevated DNA oxidation (p = 0.08) compared to adult counterparts irrespective of dietary vitamin C intake. Increased mRNA expression of sod1 (p < 0.05) and svct2 (p = 0.05) was observed in aged animals together with increased superoxide dismutase activity (p < 0.01) and cerebrospinal fluid vitamin C status (p < 0.001) suggesting a compensatory effort that did not counterbalance the effects of ageing. Essentially, no effects of age were observed in the liver demonstrating the brain's unique susceptibility to redox imbalance. Consistent with previous findings, we show that ageing per se constitutes a considerable oxidative insult in the brain. However, our data also suggest that a long‐term poor vitamin C status does not accelerate this process.
Benzo[α]pyrene‐Induced Anti‐Depressive‐like Behaviour in Adult Female Mice: Role of Monoaminergic Systems
Authors: Bouayed Jaouad , Bohn Torsten , Tybl Elisabeth , Kiemer Alexandra K. , Soulimani Rachid 
Published: December 2011

AbstractBenzo[α]pyrene (B[α]P) is a ubiquitous environmental pollutant exhibiting adverse effects on cognitive function and behaviour. In this study, depressive or antidepressive effects of B[α]P were investigated. Here, we report that a subacute B[α]P oral exposure (0.02–0.2 mg/kg) increases mobility behaviour in female adult mice in the tail suspension test, but not in the forced swimming test, without altering locomotion, suggesting that the tail suspension test was a more sensitive indicator of B[α]P‐induced neurobehavioural disturbance. This might be because of differences in neurochemical substrates and pathways, mediating the performance in these behavioural models of depression. The effect of B[α]P on female adult mice in the tail suspension test was similar to that obtained with subacute treatment of the antidepressant reference drug imipramine (10 mg/kg). Therefore, B[α]P at 0.02 mg/kg and 0.2 mg/kg induces an antidepressant‐like effect in mice, suggesting a neurobehavioural disturbance after oral exposure to this environmental compound. Furthermore, oral exposure to B[α]P at 0.02 mg/kg significantly increased gene expression levels of the brain receptors 5‐hydroxytryptamine (serotonin) 1A (5HT1A) and alpha‐1D adrenergic (ADRA1D). In summary, the presented findings suggest that subacute oral exposure to B[α]P results in behavioural changes in female adult mice, possibly caused by alterations in the serotoninergic and adrenergic systems.
CB1 receptor antagonists: new discoveries leading to new perspectives
Authors: Kirilly E. , Gonda X. , Bagdy G. 
Published: December 2011

AbstractCB1 receptor antagonists were among the most promising drug targets in the last decade. They have been explored and found to be effective as therapeutic agents for obesity and related cardiometabolic problems; however, use of rimonabant, the first marketed CB1 receptor antagonist, has been suspended because of its anxiogenic and depressogenic side effects. Because some other antiobesity drugs, like dexfenfluramine or sibutramine, were also suspended, the unmet need for drugs that reduce body weight became enormous. One approach that emerged was the use of CB1 receptor antagonists that poorly cross the blood brain barrier, the second, the development of neutral antagonists instead of inverse agonists, and the third, use of personalized medicine, namely the selection of the patient population without psychiatric side effects. In this review, we dissect the peripheral and central mechanisms involved in the effects of CB1 receptor antagonists and argue that central mechanisms are more or less involved in most cardiometabolic therapeutic effects and thus, among patients with unsatisfactory therapeutic response to compounds with peripheral action, centrally acting antagonists may be needed. An analysis of pharmacogenetic factors may help to identify persons who are at no or low risk for psychiatric adverse effects. Here, we present the models and identify molecular mechanisms and receptors involved in the effects of stress‐, anxiety‐ and depression‐related neurocircuitries sensitive to CB1 receptor antagonists, like the serotonergic, noradrenergic and dopaminergic systems, which are not only regulated by CB1 receptors, but also regulate the synthesis of the endocannabinoid 2‐arachidonoyl‐glycerol.
Study of the TmoS/TmoT two‐component system: towards the functional characterization of the family of TodS/TodT like systems
Authors: Silva‐Jiménez Hortencia , García‐Fontana Cristina , Cadirci Bilge Hilal , Ramos‐González María Isabel , Ramos Juan Luis , Krell Tino 
Published: December 2011

SummaryThe two‐component system TmoS/TmoT controls the expression of the toluene‐4‐monooxygenase pathway in Pseudomonas mendocina RK1 via modulation of PtmoX activity. The TmoS/TmoT system belongs to the family of TodS/TodT like proteins. The sensor kinase TmoS is a 108 kDa protein composed of seven different domains. Using isothermal titration calorimetry we show that purified TmoS binds a wide range of aromatic compounds with high affinities. Tightest ligand binding was observed for toluene (KD = 150 nM), which corresponds to the highest affinity measured between an effector and a sensor kinase. Other compounds with affinities in the nanomolar range include benzene, the 3 xylene isomers, styrene, nitrobenzene or p‐chlorotoluene. We demonstrate that only part of the ligands that bind to TmoS increase protein autophosphorylation in vitro and consequently pathway expression in vivo. These compounds are referred to as agonists. Other TmoS ligands, termed antagonists, failed to increase TmoS autophosphorylation, which resulted in their incapacity to stimulate gene expression in vivo. We also show that TmoS saturated with different agonists differs in their autokinase activities. The effector screening of gene expression showed that promoter activity of PtmoX and PtodX (controlled by the TodS/TodT system) is mediated by the same set of 22 compounds. The common structural feature of these compounds is the presence of a single aromatic ring. Among these ligands, toluene was the most potent inducer of both promoter activities. Information on the TmoS/TmoT and TodS/TodT system combined with a sequence analysis of family members permits to identify distinct features that define this protein family.