bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin-releasing properties of the frog skin peptide pseudin-2 and its [Lys18]-substituted analogue
Authors: Abdel-Wahab Yasser H.A. , Power Gavin J. , Ng Ming T. , Flatt Peter R. , Conlon J. Michael 
Published: December 2007

Abstract
Pseudin-2 is a cationic α-helical peptide that was first isolated from the skin of the paradoxical frog Pseudis paradoxa on the basis of its antimicrobial activity. We have investigated the insulin-releasing properties and cytotoxicity of the peptide, together with selected analogues with increased cationicity and hydrophobicity. At concentrations in the range 10-9–10-6 m, pseudin-2, and its [Lys18], [Phe8], and [d-Lys3,d-Lys10,d-Lys14] derivatives, stimulated insulin release from the BRIN-BD11 clonal β-cell line without increasing release of lactate dehydrogenase. The [Lys18] analogue was the most potent (46% increase in insulin release at 10-9 m) and the most effective (215% increase in insulin release at 10-6 m). The more cationic [Lys3,Lys10,Lys14] and [Lys3,Lys10,Lys14,Lys21] analogues lacked insulinotropic action and the more hydrophobic [Phe16] analogue was cytotoxic at concentrations ≥10-7 m. Pseudin-2 and [Lys18]-pseudin-2 had no effect on intracellular calcium concentrations and stimulated insulin release in the absence of external calcium. [Lys18]-pseudin-2 (10-8 m) stimulated insulin release in the presence of diazoxide and verapamil. Our results demonstrate that pseudin-2 stimulates insulin secretion from BRIN-BD11 cells by a mechanism involving Ca2+-independent pathways and identify [Lys18]-pseudin-2 as a peptide that may have potential for development as a therapeutically valuable insulinotropic agent for the treatment of type 2 diabetes.
Effects of gastric inhibitory polypeptide (GIP) and related analogues on glucagon release at normo- and hyperglycaemia in Wistar rats and isolated islets
Authors: Cassidy Roslyn S. , Irwin Nigel , Flatt Peter R. 
Published: December 2007

Abstract
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine K-cells in response to nutrient absorption. This study has utilised numerous well-characterised dipeptidyl peptidase IV-resistant GIP analogues to evaluate the glucagonotropic actions of GIP in Wistar rats and isolated rat islets. Intraperitoneal administration of GIP analogues (25 nmol/kg body weight) in combination with glucose had no effect on circulating glucagon concentrations compared to controls in Wistar rats. However, plasma glucose concentrations were significantly (p<0.05 to p<0.001) lowered by the GIP-receptor agonists, N-AcGIP, GIP(Lys37)PAL and N-AcGIP(Lys37)PAL. The GIP antagonist, (Pro3)GIP, caused a significant (p<0.05) reduction in glucagon levels following concurrent administration with saline in Wistar rats. In isolated rat islets native GIP induced a significant (p<0.01) enhancement of glucagon release at basal glucose concentrations, which was completely annulled by (Pro3)GIP. Furthermore, glucagon release in the presence of GLP-1, GIP(Lys37)PAL, N-AcGIP(Lys37)PAL and (Pro3)GIP was significantly (p<0.05 to p<0.001) decreased compared to native GIP in isolated rat islets. These data indicate a modest effect of GIP on glucagon secretion from isolated rat islets, which was not observed in vivo. However, the GIP agonists N-AcGIP, GIP(Lys37)PAL and N-AcGIP(Lys37)PAL had no effect on glucagon release demonstrating an improved therapeutic potential for the treatment of type 2 diabetes.
Cathepsin V, but not cathepsins L, B and K, may release angiostatin-like fragments from plasminogen
Authors: Puzer Luciano , Barros Nilana M.T. , Paschoalin Thaysa , Hirata Izaura Y. , Tanaka Aparecida S. , Oliveira Marcelo C. , Brömme Dieter , Carmona Adriana K. 
Published: December 2007

Abstract
Cathepsin V is a lysosomal cysteine peptidase highly expressed in corneal epithelium; however, its function in the eye is still unknown. Here, we describe the capability of cathepsin V to hydrolyze plasminogen, which is also expressed in human cornea at levels high enough to produce physiologically relevant amounts of angiostatin-related molecules. The co-localization of these two proteins suggests an important role for the enzyme in the maintenance of corneal avascularity, essential for optimal visual performance. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of plasminogen digestion by cathepsin V revealed the generation of three major products of 60, 50 and 40 kDa, which were electrotransferred to polyvinylidene difluoride membranes and excised for characterization. NH2-terminal amino acid sequencing of these fragments revealed the sequences EKKVYL, TEQLAP and LLPNVE, respectively. These data are compatible with cleavage sites at plasminogen F94–E95, S358–T359 and V468–L469 peptide bonds generating fragments of the five-kringle domains. In contrast, we did not detect any plasminogen degradation by cathepsins B, K and L. Using a Matrigel assay, we confirmed the angiogenesis inhibition activity on endothelial cells caused by plasminogen processing by cathepsin V. Our results suggest a novel physiological role for cathepsin V related to the control of neovascularization in cornea.
Functional tyrosine residue in the active center of human dipeptidyl peptidase III
Authors: Salopek-Sondi Branka , Vukelić Bojana , Špoljarić Jasminka , Šimaga Šumski , Vujaklija Dušica , Makarević Janja , Jajčanin Nina , Abramić Marija 
Published: December 2007

Abstract
Human dipeptidyl peptidase III (DPP III) is a member of the metallopeptidase family M49 with an implied role in the pain-modulatory system and endogenous defense against oxidative stress. Here, we report the heterologous expression of human DPP III and the site-directed mutagenesis results which demonstrate a functional role for Tyr318 at the active site of this enzyme. The substitution of Tyr318 to Phe decreased k
cat by two orders of magnitude without altering the binding affinity of substrate, or of a competitive hydroxamate inhibitor designed to interact with S1 and S2 subsites. The results indicate that the conserved tyrosine could be involved in transition state stabilization during the catalytic action of M49 peptidases.
Controlling Feeding Practices: Cause or Consequence of Early Child Weight?
Authors: Farrow Claire Victoria , Blissett Jacqueline 
Published: December 2007

INTRODUCTION. The exertion of control during child feeding has been associated with both underweight and overweight during childhood. What is as-yet unclear is whether controlling child feeding practices causally affect child weight or whether the use of control may be a reactive response to concerns about high or low child weight. The aims of this study were to explore the direction of causality in these relationships during infancy.
METHODS. Sixty-two women gave informed consent to take part in this longitudinal study that spanned from birth to 2 years of child age. Mothers completed the Child Feeding Questionnaire at 1 year, and their children were weighed at 1 and 2 years of age. Child weight scores were converted into standardized z scores that accounted for child age and gender.
RESULTS. Controlling for child weight at 1 year, the use of pressure to eat and restriction at 1 year significantly predicted lower child weight at 2 years.
CONCLUSIONS. Controlling feeding practices in infancy have an impact on children's weight at 2 years. The use of restrictive child feeding practices during infancy predicts lower child weight at age 2 years, which may reinforce mothers' use of this strategy in the longer term despite its potential association with disinhibition and greater child weight in later childhood.
A Comparison of Alternative Risk-Assessment Strategies for Predicting Significant Neonatal Hyperbilirubinemia in Term and Near-Term Infants
Authors: Keren Ron , Luan Xianqun , Friedman Susan , Saddlemire Stephanie , Cnaan Avital , Bhutani Vinod K. 
Published: December 2007

OBJECTIVE. The purpose of this work was to compare the predictive accuracy of alternative risk-assessment strategies used to screen for the risk of significant neonatal hyperbilirubinemia.
PATIENTS AND METHODS. We conducted a prospective cohort study of 823 term and near-term newborns admitted to the well-infant nursery at the Hospital of the University of Pennsylvania. Maternal, infant, and delivery risk factors for significant hyperbilirubinemia were obtained from chart review, structured interviews with parents, and nurse assessments before discharge. Transcutaneous bilirubin measurement was performed daily until discharge and once by a visiting home nurse between 3 and 8 days of life. We used the c statistic to compare the predictive accuracy of 3 risk-assessment strategies for estimating the risk of significant neonatal hyperbilirubinemia, defined as a bilirubin level that at any time after birth exceeded or was within 1 mg/dL (17 μmol/L) of the hour-specific phototherapy treatment threshold recommended by the American Academy of Pediatrics in 2004. The compared strategies included those that use (1) a predischarge bilirubin level (obtained before 52 hours) expressed as a risk zone on an hour-specific bilirubin nomogram, (2) clinical risk factors other than the predischarge bilirubin level, and (3) a combination of the predischarge bilirubin risk zone and additional clinical risk factors.
RESULTS. Forty-eight patients (6%) developed significant neonatal hyperbilirubinemia. The predischarge (&lt;52 hours) bilirubin level expressed as a risk zone on the bilirubin nomogram and a prediction model that combined multiple other clinical risk factors had similar accuracy for predicting significant hyperbilirubinemia. The only clinical risk factor that could be added to the predischarge risk zone to improve overall predictive accuracy was gestational age. The predischarge bilirubin risk zone and gestational age could be used to stratify patients into a large group (n = 523 [70%]) of infants with a very low (0.2%) risk of developing significant hyperbilirubinemia, a small group of infants (n = 127 [17%]) with a low (4%) risk of developing significant hyperbilirubinemia, and an even smaller group of infants (n = 100 [13%]) with a high (42%) risk of developing significant hyperbilirubinemia.
CONCLUSIONS. An infant's risk of developing significant hyperbilirubinemia can be simply and accurately assessed by using just the infant's predischarge bilirubin level and gestational age.
Timing of Solid Food Introduction in Relation to Eczema, Asthma, Allergic Rhinitis, and Food and Inhalant Sensitization at the Age of 6 Years: Results From the Prospective Birth Cohort Study LISA
Authors: Zutavern Anne , Brockow Inken , Schaaf Beate , von Berg Andrea , Diez Ulrike , Borte Michael , Kraemer Ursula , Herbarth Olf , Behrendt Heidrun , Wichmann H-Erich , Heinrich Joachim ,   LISA Study Group
Published: December 2007

OBJECTIVE. Current prophylactic feeding guidelines recommend a delayed introduction of solids for the prevention of atopic diseases. This study investigates whether a delayed introduction of solids (past 4 or 6 months) is protective against the development of eczema, asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years.METHODS. Data from 2073 children in the ongoing LISA birth cohort study were analyzed at 6 years of age. Multivariate logistic regression analyses were performed for all children and for children without skin or allergic symptoms within the first 6 months of life to take into account reverse causality.RESULTS. A delayed introduction of solids (past 4 or 6 months) was not associated with decreased odds for asthma, allergic rhinitis, or sensitization against food or inhalant allergens at 6 years of age. On the contrary, food sensitization was more frequent in children who were introduced to solids later. The relationship between the timing of solid food introduction and eczema was not clear. There was no protective effect of a late introduction of solids or a less diverse diet within the first 4 months of life. However, in children without early skin or allergic symptoms were considered, eczema was significantly more frequent in children who received a more diverse diet within the first 4 months.CONCLUSIONS. This study found no evidence supporting a delayed introduction of solids beyond 4 or 6 months for the prevention of asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. For eczema, the results were conflicting, and a protective effect of a delayed introduction of solids cannot be excluded. Positive associations between late introduction of solids and food sensitization have to be interpreted with caution. A true protective effect of a delayed introduction of solids on food sensitization seems unlikely.
Estimating the Effectiveness of Screening for Scoliosis: A Case-Control Study
Authors: Bunge Eveline M. , Juttmann Rikard E. , van Biezen Frans C. , Creemers Huub , Hazebroek-Kampschreur Alice A. J. M. , Luttmer Bert C. F. , Wiegersma P. Auke , de Koning Harry J. ,   for the Netherlands Evaluation Study on Screening for Scoliosis (NESCIO) Group
Published: December 2007

OBJECTIVE. The aim of this study was to test the hypothesis that screening for scoliosis is effective in reducing the need for surgical treatment.
METHODS. The study was a case-control study. A total of 125 consecutive patients who were treated surgically for idiopathic scoliosis between January 2001 and October 2004 and who were born on or after January 1, 1984, were invited; 108 agreed to participate. A total of 216 control subjects were selected randomly and anonymously, matched with respect to age and gender. For 279 adolescents, exact screening exposure and outcomes could be analyzed. Case subjects were recruited from 4 university and 6 nonuniversity Dutch hospitals; control subjects were recruited from all 37 municipal health services in the Netherlands.
RESULTS. Screen-detected patients received diagnoses at a significantly younger age than did otherwise-detected patients (10.8 ± 2.6 vs 13.4 ± 1.7 years). In total, 32.8% of the surgically treated patients had been screened between 11 and 14 years of age, compared with 43.4% of the control subjects. The odds ratio for being exposed to screening was 0.64. In total, 28% of the patients were diagnosed as having scoliosis before 11 years of age.
CONCLUSIONS. Our results showed no evidence that screening for scoliosis reduced the need for surgery. Abolishing screening seems justified, especially because the effectiveness of early treatment with bracing is still strongly debated. A randomized, controlled trial on the effectiveness of treating patients with idiopathic scoliosis with bracing is urgently needed.
A Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine Extended Release in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
Authors: Biederman Joseph , Melmed Raun D. , Patel Anil , McBurnett Keith , Konow Jennifer , Lyne Andrew , Scherer Noreen ,   for the SPD503 Study Group
Published: December 2007

OBJECTIVE. With this study we assessed the efficacy and safety of an extended-release formulation of guanfacine compared with placebo for the treatment of children and adolescents with attention-deficit/hyperactivity disorder.METHODS. In this multicenter, double-blind, placebo-controlled, fixed-dosage escalation study, patients aged 6 to 17 years were randomly assigned to 1 of 3 treatment groups of guanfacine extended release (2, 3, or 4 mg/day) or placebo for 8 weeks. The primary outcome measurement was the Attention-Deficit/Hyperactivity Disorder Rating Scale IV total score. Secondary measurements included Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale–Revised: Short Form, and Conners' Teacher Rating Scale–Revised: Short Form.RESULTS. A total of 345 patients were randomly assigned to placebo (n = 86) or guanfacine extended release 2 mg (n = 87), 3 mg (n = 86), or 4 mg (n = 86) treatment groups. Least-squares mean changes from baseline to the end point in Attention-Deficit/Hyperactivity Disorder Rating Scale IV total scores were significant in all groups of children taking guanfacine extended release: −16.18 in the 2-mg group, −16.43 in the 3-mg group, and −18.87 in the 4-mg group, compared with −8.48 in the placebo group. All groups of children taking guanfacine extended release showed significant improvement on hyperactivity/impulsivity and inattentiveness subscales of the Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale–Revised: Short Form, and Conners' Teacher Rating Scale–Revised: Short Form assessments compared with placebo. The most commonly reported treatment-emergent adverse events were headache, somnolence, fatigue, upper abdominal pain, and sedation. Small to modest changes in blood pressure, pulse rate, and electrocardiogram parameters were observed but were not clinically meaningful.CONCLUSIONS. Guanfacine extended release met the primary and secondary efficacy end points. It was well tolerated and effective compared with placebo.
Household Food Insecurity: Associations With At-Risk Infant and Toddler Development
Authors: Rose-Jacobs Ruth , Black Maureen M. , Casey Patrick H. , Cook John T. , Cutts Diana B. , Chilton Mariana , Heeren Timothy , Levenson Suzette M. , Meyers Alan F. , Frank Deborah A. 
Published: December 2007

OBJECTIVES. In this study, we evaluated the relationship between household food security status and developmental risk in young children, after controlling for potential confounding variables.METHODS. The Children's Sentinel Nutritional Assessment Program interviewed (in English, Spanish, or Somali) 2010 caregivers from low-income households with children 4 to 36 months of age, at 5 pediatric clinic/emergency department sites (in Arkansas, Massachusetts, Maryland, Minnesota, and Pennsylvania). Interviews included demographic questions, the US Food Security Scale, and the Parents' Evaluations of Developmental Status. The target child from each household was weighed, and weight-for-age z score was calculated.RESULTS. Overall, 21% of the children lived in food-insecure households and 14% were developmentally “at risk” in the Parents' Evaluations of Developmental Status assessment. In logistic analyses controlling for interview site, child variables (gender, age, low birth weight, weight-for-age z score, and history of previous hospitalizations), and caregiver variables (age, US birth, education, employment, and depressive symptoms), caregivers in food-insecure households were two thirds more likely than caregivers in food-secure households to report that their children were at developmental risk.CONCLUSIONS. Controlling for established correlates of child development, 4- to 36-month-old children from low-income households with food insecurity are more likely than those from low-income households with food security to be at developmental risk. Public policies that ameliorate household food insecurity also may improve early child development and later school readiness.
Relationships of Cardiovascular Phenotypes With Healthy Weight, at Risk of Overweight, and Overweight in US Youths
Authors: Zhu Haidong , Yan Weili , Ge Dongliang , Treiber Frank A. , Harshfield Gregory A. , Kapuku Gaston , Snieder Harold , Dong Yanbin 
Published: December 2007

OBJECTIVE. This study aimed to evaluate comprehensively the cardiovascular phenotypes of cardiovascular disease-free youths at risk of overweight, in comparison with healthy weight and overweight.
METHODS. Casual and ambulatory blood pressure measurements, noninvasive hemodynamic profiles, pulse wave velocity, left ventricular structure and function, and overnight sodium excretion were examined in a cohort of US black and white youths (n = 972; mean age: 17.6 ± 3.3 years).
RESULTS. The occurrence of at risk of overweight was ∼17% in either black youths or white youths. In white youths, there was a ∼2-mmHg increase in casual systolic blood pressure for each increasing step in the 3 BMI categories (healthy weight, 109.5 ± 0.5 mmHg; at risk of overweight, 111.5 ± 0.6 mmHg; overweight, 113.5 ± 1.1 mmHg). Ambulatory systolic blood pressure showed a similar increase with the increase in BMI. A blunted nocturnal decline in ambulatory diastolic blood pressure with the categorical BMI increase was observed in black youths. In both racial groups, cardiac output and stroke volume were significantly enhanced sequentially from healthy weight to at risk of overweight to overweight. In black youths, both casual and ambulatory heart rate increased significantly with the increase in BMI. Moreover, there was a linear increase of left ventricular mass index from the healthy-weight group to the at risk of overweight group, with the overweight group having the highest value. In white youths, carotid-dorsalis pedis pulse wave velocity increased significantly as the BMI increased. Regardless of race, overnight sodium excretion showed a significant increase from healthy-weight subjects to overweight subjects, with at risk of overweight subjects having intermediate values.
CONCLUSIONS. Youths at risk of overweight, compared with healthy-weight youths, seem to have increased cardiovascular risks. Our data suggest that the status of at risk of overweight already has clinical implications in youths.
Simulation of In-Hospital Pediatric Medical Emergencies and Cardiopulmonary Arrests: Highlighting the Importance of the First 5 Minutes
Authors: Hunt Elizabeth A. , Walker Allen R. , Shaffner Donald H. , Miller Marlene R. , Pronovost Peter J. 
Published: December 2007

OBJECTIVES. Outcomes of in-hospital pediatric cardiopulmonary arrest are dismal. Recent data suggest that the quality of basic and advanced life support delivered to adults is low and contributes to poor outcomes, but few data regarding pediatric events have been reported. The objectives of this study were to (1) measure the median elapsed time to initiate important resuscitation maneuvers in simulated pediatric medical emergencies (ie, “mock codes”) and (2) identify the types and frequency of errors committed during pediatric mock codes.METHODS. A prospective, observational study was conducted of 34 consecutive hospital-based mock codes. A mannequin or computerized simulator was used to enact unannounced, simulated crisis situations involving children with respiratory distress or insufficiency, respiratory arrest, hemodynamic instability, and/or cardiopulmonary arrest. Assessment included time elapsed to initiation of specific resuscitation maneuvers and deviation from American Heart Association guidelines.RESULTS. Among the 34 mock codes, the median time to assessment of airway and breathing was 1.3 minutes, to administration of oxygen was 2.0 minutes, to assessment of circulation was 4.0 minutes, to arrival of any physician was 3.0 minutes, and to arrival of first member of code team was 6.0 minutes. Among cardiopulmonary arrest scenarios, elapsed time to initiation of compressions was 1.5 minutes and to request for defibrillator was 4.3 minutes. In 75% of mock codes, the team deviated from American Heart Association pediatric basic life support protocols, and in 100% of mock codes there was a communication error.CONCLUSIONS. Alarming delays and deviations occur in the major components of pediatric resuscitation. Future educational and organizational interventions should focus on improving the quality of care delivered during the first 5 minutes of resuscitation. Simulation of pediatric crises can identify targets for educational intervention to improve pediatric cardiopulmonary resuscitation and, ideally, outcomes.