bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing of the IKKε gene by siRNA inhibits invasiveness and growth of breast cancer cells
Authors: Qin Bin , Cheng Kun 
Published: October 2010

Abstract
Introduction
IκB kinase ε (IKKε) is a member of the IKK family that plays an important role in the activation of NF-κB. Overexpressed in more than 30% of breast cancers, IKKε has been recently identified as a potential breast cancer oncogene. The purpose of the present study is to examine the therapeutic potential of IKKε siRNA on human breast cancer cells.

Methods
Eight siRNAs targeting different regions of the IKKε mRNA were designed, and the silencing effect was screened by quantitative real-time RT-PCR. The biological effects of synthetic siRNAs on human breast cancer cells were investigated by examining the cell proliferation, migration, invasion, focus formation, anchorage-independent growth (via soft agar assay), cell cycle arrest, apoptosis (via annexing binding), NF-κB basal level, and NF-κB-related gene expressions upon the IKKε silencing.

Results
Silencing of IKKε in human breast cancer cells resulted in a decrease of focus formation potential and clonogenicity as well as in vitro cell migration/invasion capabilities. Moreover, knockdown of IKKε suppressed cell proliferation. Cell cycle assay showed that the anti-proliferation effect of IKKε siRNA was mediated by arresting cells in the G0/G1 phase, which was caused by downregulation of cyclin D1. Furthermore, we demonstrated that silencing of IKKε inhibited the NF-κB basal activity as well as the Bcl-2 expression. Significant apoptosis was not observed in breast cancer cells upon the silencing of IKKε. The present study provided the first evidence that silencing IKKε using synthetic siRNA can inhibit the invasiveness properties and proliferation of breast cancer cells.

Conclusions
Our results suggested that silencing IKKε using synthetic siRNA may offer a novel therapeutic strategy for breast cancer.
Severe burn injury in europe: a systematic review of the incidence, etiology, morbidity, and mortality
Authors: Brusselaers Nele , Monstrey Stan , Vogelaers Dirk , Hoste Eric , Blot Stijn 
Published: October 2010

Abstract
Introduction
Burn injury is a serious pathology, potentially leading to severe morbidity and significant mortality, but it also has a considerable health-economic impact. The aim of this study was to describe the European hospitalized population with severe burn injury, including the incidence, etiology, risk factors, mortality, and causes of death.

Methods
The systematic literature search (1985 to 2009) involved PubMed, the Web of Science, and the search engine Google. The reference lists and the Science Citation Index were used for hand searching (snowballing). Only studies dealing with epidemiologic issues (for example, incidence and outcome) as their major topic, on hospitalized populations with severe burn injury (in secondary and tertiary care) in Europe were included. Language restrictions were set on English, French, and Dutch.

Results
The search led to 76 eligible studies, including more than 186,500 patients in total. The annual incidence of severe burns was 0.2 to 2.9/10,000 inhabitants with a decreasing trend in time. Almost 50% of patients were younger than 16 years, and ~60% were male patients. Flames, scalds, and contact burns were the most prevalent causes in the total population, but in children, scalds clearly dominated. Mortality was usually between 1.4% and 18% and is decreasing in time. Major risk factors for death were older age and a higher total percentage of burned surface area, as well as chronic diseases. (Multi) organ failure and sepsis were the most frequently reported causes of death. The main causes of early death (<48 hours) were burn shock and inhalation injury.

Conclusions
Despite the lack of a large-scale European registration of burn injury, more epidemiologic information is available about the hospitalized population with severe burn injury than is generally presumed. National and international registration systems nevertheless remain necessary to allow better targeting of prevention campaigns and further improvement of cost-effectiveness in total burn care.
The Association Between Developmental Coordination Disorder and Other Developmental Traits
Authors: Lingam Raghu , Golding Jean , Jongmans Marian J. , Hunt Linda P. , Ellis Matthew , Emond Alan 
Published: October 2010

OBJECTIVE:To explore associations between developmental coordination disorder (DCD) and attention, language, social skills, and academic ability in a population-based cohort.METHODS:We analyzed data (N = 6902) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Probable DCD was defined as children below the 15th centile of the ALSPAC Coordination Test aged 7 years with functional impairment in activities of daily living or handwriting, excluding children with neurologic difficulties or an IQ of &lt;70. Four developmental domains were assessed by using standardized tests between the ages of 7.5 and 9 years: attention; language skills (expressive language, comprehension, short-term memory); social skills (nonverbal skills and social communication); and academic ability (reading and spelling). The worst 5% of each trait was used to define impairment. We used multiple logistic regression models to assess the association between probable DCD and each trait. Our final model controlled for IQ, socioeconomic factors, and other developmental traits not in the domain assessed.RESULTS:A total of 346 (5.0%) children met criteria for probable DCD. Probable DCD was associated with difficulties in attention (odds ratio [OR]: 1.94 [95% confidence interval (CI): 1.17–3.24]), nonword repetition (OR: 1.83 [95% CI: 1.26–2.66]), social communication (OR: 1.87 [95% CI: 1.15–3.04]), reading (OR: 3.35 [95% CI: 2.36–4.77]), and spelling (OR: 2.81 [95% CI: 2.03–3.90]).CONCLUSIONS:Children with probable DCD had an increased risk of difficulties in attention, social skills, reading, and spelling. These additional difficulties need to be screened for during assessment and considered when formulating interventions.
Costs and Consequences of Universal Sibling Screening for Vesicoureteral Reflux: Decision Analysis
Authors: Routh Jonathan C. , Grant Frederick D. , Kokorowski Paul , Lee Richard S. , Fahey Frederic H. , Treves S. Ted , Nelson Caleb P. 
Published: October 2010

OBJECTIVE:Our objective was to evaluate screening for vesicoureteral reflux (VUR) among siblings of patients with VUR, in terms of cost, radiation exposure, and number of febrile urinary tract infections (fUTIs) averted.METHODS:We constructed a Markov model to evaluate 2 competing management options, that is, universal screening (cystographic evaluation of all siblings without symptoms) and usual care (cystographic evaluation of siblings only after fUTIs). Published data were used to inform all model inputs. Costs were estimated by using a societal perspective.RESULTS:Universal screening yielded 2980 fUTIs, whereas usual care yielded 6330. Therefore, universal screening for VUR in a cohort of 100 000 siblings 1 year of age without symptoms resulted in the prevention of 1 initial fUTI per 3360 siblings, at an excess cost of $55 600 per averted fUTI, in comparison with usual care. These estimates were heavily dependent on screening age and the effectiveness of antibiotic prophylaxis; prevention of a single fUTI would require screening of 166 siblings 5 years of age and 694 siblings 10 years of age. Similarly, if prophylaxis was ineffective in preventing fUTIs, then up to 10 000 siblings would need to be screened for prevention of a single fUTI.CONCLUSIONS:Prevention of a single fUTI would require screening of 30 to 430 siblings 1 year of age without symptoms, at an estimated excess cost of $56 000 to $820 000 per averted fUTI. These estimates are heavily dependent on screening age and the effectiveness of antibiotic prophylaxis.
Physiologic and Clinical Benefits of Noninvasive Ventilation in Infants With Pierre Robin Sequence
Authors: Leboulanger Nicolas , Picard Arnaud , Soupre Véronique , Aubertin Guillaume , Denoyelle Françoise , Galliani Eva , Roger Gilles , Garabedian Eréa-Noël , Fauroux Brigitte 
Published: October 2010

OBJECTIVE:
The objective of the study was to determine the clinical and physiologic benefits of noninvasive respiratory support (NRS) (continuous positive airway pressure or noninvasive positive pressure ventilation) for infants with a Pierre Robin sequence (PRS).

METHODS:
Breathing patterns, respiratory efforts, and gas exchange were analyzed for 7 infants with a PRS during spontaneous breathing and during NRS. Clinical outcomes with duration of NRS and need for a tracheotomy and/or nutritional support was evaluated.

RESULTS:
Compared with spontaneous breathing, breathing patterns, respiratory efforts, and transcutaneous carbon dioxide pressures improved during NRS; the mean respiratory rate decreased from 55 ± 9 to 37 ± 7 breaths per minute (P = .063), the mean inspiratory time/total duty cycle decreased from 59 ± 9% to 40 ± 7% (P = .018), the mean esophageal pressure swing decreased from 29 ± 13 to 9 ± 4 cm H2O (P = .017), the diaphragmatic pressure-time product decreased from 844 ± 308 to 245 ± 126 cm H2O-second per minute (P = .018), and the mean transcutaneous carbon dioxide pressure during sleep decreased from 57 ± 7 to 31 ± 7 mm Hg (P = .043). All of the patients could be discharged successfully from the hospital with NRS. The mean duration of NRS was 16.7 ± 12.2 months. Six patients could be weaned from nutritional support, and none required a tracheotomy.

CONCLUSIONS:
NRS is able to improve breathing patterns and respiratory outcomes for infants with severe upper airway obstruction attributable to a PRS, which supports its use as a first-line treatment.
Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study: 2-Year Outcomes
Authors: Asztalos Elizabeth V. , Murphy Kellie E. , Hannah Mary E. , Willan Andrew R. , Matthews Stephen G. , Ohlsson Arne , Kelly Edmond N. , Saigal Saroj , Ross Susan , Delisle Marie-France , Amankwah Kofi , Guselle Patricia , Gafni Amiram , Lee Shoo K. , Armson B. Anthony , Sananes Renee , Tomat Laura ,   for the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study Collaborative Group
Published: October 2010

OBJECTIVE:
The aim of this study was to determine the effects of repeated courses of prenatal corticosteroid therapy versus placebo on death or neurologic impairment among the children enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, at 18 to 24 months of age.

METHODS:
A total of 2305 infants were eligible for follow-up evaluation; 2104 infants (1069 in the prenatal corticosteroid therapy group and 1035 in the placebo group) were monitored. The primary outcome was death or neurologic impairment, defined as either cerebral palsy or cognitive delay, at 18 to 24 months of age. The secondary outcomes were measurements of growth (height, weight, and head circumference).

RESULTS:
Children exposed to multiple courses of prenatal corticosteroid therapy had similar rates of death or neurologic impairment, compared with children exposed to placebo (148 children [13.8%] vs 142 children [13.7%]; odds ratio: 1.001[95% confidence interval: 0.75–1.30]; P = .95). They had a mean weight of 11.94 kg, compared with 12.14 kg in the placebo group (P = .04), a mean height of 85.51 cm, compared with 85.46 cm (P = .87), and a mean head circumference of 48.18 cm, compared with 48.25 cm (P = .45).

CONCLUSIONS:
Multiple courses of prenatal corticosteroid therapy, given every 14 days, did not increase or decrease the risk of death or neurologic impairment at 18 to 24 months of age, compared with a single course of prenatal corticosteroid therapy. Continued follow-up monitoring of these children is necessary to assess neurobehavioral function, school performance, and possible susceptibility to disease.
Maternal or Paternal Suicide and Offspring's Psychiatric and Suicide-Attempt Hospitalization Risk
Authors: Kuramoto S. Janet , Stuart Elizabeth A. , Runeson Bo , Lichtenstein Paul , Långström Niklas , Wilcox Holly C. 
Published: October 2010

OBJECTIVE:We examined whether the risk for psychiatric morbidity requiring inpatient care was higher for offspring who experienced parental suicide, compared with offspring of fatal accident decedents, and whether the association varied according to the deceased parent's gender.METHODS:Children and adolescents (0–17 years of age) who experienced maternal (N = 5600) or paternal (N = 17 847) suicide in 1973–2003 in Sweden were identified by using national, longitudinal, population-based registries. Cox regression modeling was used to compare psychiatric hospitalization risks among offspring of suicide decedents and propensity score–matched offspring of accident decedents.RESULTS:Offspring of maternal suicide decedents had increased risk of suicide-attempt hospitalization, after controlling for psychiatric hospitalization for decedents and surviving parents, compared with offspring of maternal accidental decedents. Offspring of paternal suicide decedents had similar risk of suicide-attempt hospitalization, compared with offspring of accident decedents, but had increased risk of hospitalization attributable to depressive and anxiety disorders. The magnitude of risks for offspring suicide-attempt hospitalization was greater for those who experienced maternal versus paternal suicide, compared with their respective control offspring (interaction P = .05; offspring of maternal decedents, adjusted hazard ratio: 1.80 [95% confidence interval: 1.19–2.74]; offspring of paternal decedents, adjusted hazard ratio: 1.14 [95% confidence interval: 0.96–1.35]).CONCLUSIONS:Maternal suicide is associated with increased risk of suicide-attempt hospitalization for offspring, beyond the risk associated with maternal accidental death. However, paternal suicide is not associated with suicide-attempt hospitalization. Future studies should examine factors that might differ between offspring who experience maternal versus paternal suicide, including genetic or early environmental determinants.
Neonatal Nurse Practitioners: Distribution, Roles and Scope of Practice
Authors: Freed Gary L. , Dunham Kelly M. , Lamarand Kara E. , Loveland-Cherry Carol , Martyn Kristy K. ,   the American Board of Pediatrics Research Advisory Committee
Published: October 2010

OBJECTIVE:
We sought to determine the distribution and scope of practice of the neonatal nurse practitioner (NNP) workforce across the United States.

METHODS:
To determine distribution, we used counts of certified NNPs from the National Certification Corp (Chicago, IL). We calculated state NNP/child population ratios as the number of NNPs divided by the state population 0 to 17 years of age. We calculated NNP/NICU bed ratios as the number of NNPs divided by the total number of NICU beds per state. To characterize roles and scope of practice, we conducted a mail survey of a random national sample of 300 NNPs in states that license nurse practitioners to practice independently and 350 NNPs in states that require physician involvement.

RESULTS:
The greatest concentrations of NNPs per capita were in the Midwest, South, and Mid-Atlantic region. Thirty-one states had &lt;100 total NNPs. The survey response rate was 77.1%. More than one-half of NNP respondents (54% [n = 211]) reported that they spent the majority of their time in a community hospital, whereas more than one-third (37% [n = 144]) were in an academic health center. Only 2% (n = 7) reported that they engaged in independent practice.

CONCLUSIONS:
As with many health care professionals, the supply of NNPs may not be distributed according to need. With increasing concern regarding the availability of NNPs, comprehensive studies that examine the demand for NNPs and the roles of other clinicians in the NICU should provide a greater understanding of appropriate NICU workforce capacity and needs.
Family Nurse Practitioners: Roles and Scope of Practice in the Care of Pediatric Patients
Authors: Freed Gary L. , Dunham Kelly M. , Loveland-Cherry Carol , Martyn Kristy K. ,   the American Board of Pediatrics Research Advisory Committee
Published: October 2010

OBJECTIVE:
The goal was to characterize the pediatric role and scope of practice of family nurse practitioners (FNPs).

METHODS:
A mail survey of a random national sample of 1000 FNPs, stratified according to states that license nurse practitioners to practice independently, was performed. Frequencies were calculated and bivariate analyses were performed to determine the level of association between practice characteristics and practice state, practice location (urban versus rural), and type of care provided (primary versus specialty).

RESULTS:
The overall response rate was 75.9%. Sixty-six percent of respondents (n = 416) reported that they currently provided care to children, and 18% (n = 110) reported that they had never provided care to children. Fifty-four percent of FNPs who provided care to children (n = 222) reported that children represented ≤25% of their current patient populations. Few FNPs (9% [n = 39]) reported that children represented &gt;75% of their total patient populations.

CONCLUSIONS:
Among FNPs who provide care to children, pediatric patients represent only a small fraction of their patient populations. FNPs are unlikely to have a significant impact on the availability of either primary or subspecialty care for children in the near future.
OCT1 Expression in Adipocytes Could Contribute to Increased Metformin Action in Obese Subjects
Authors: Moreno-Navarrete José María , Ortega Francisco J. , Rodríguez-Hermosa José-Ignacio , Sabater Mònica , Pardo Gerard , Ricart Wifredo , Fernández-Real José Manuel 
Published: October 2010

OBJECTIVE
Metformin has been well characterized in vitro as a substrate of liver-expressed organic cation transporters (OCTs). We investigated the gene expression and protein levels of OCT-1 and OCT-2 in adipose tissue and during adipogenesis and evaluated their possible role in metformin action on adipocytes.

RESEARCH DESIGN AND METHODS
OCT1 and OCT2 gene expressions were analyzed in 118 adipose tissue samples (57 visceral and 61 subcutaneous depots) and during human preadipocyte differentiation. To test the possible role of OCT1 mediating the response of adipocytes to metformin, cotreatments with cimetidine (OCT blocker, 0.5 and 5 mmol/l) and metformin were made on human preadipocytes and subcutaneous adipose tissue (SAT).

RESULTS
OCT1 gene was expressed in both subcutaneous and visceral adipose tissue. In both fat depots, OCT1 gene expression and protein levels were significantly increased in obese subjects. OCT1 gene expression in isolated preadipocytes significantly increased during differentiation in parallel to adipogenic genes. Metformin (5 mmol/l) decreased the expression of lipogenic genes and lipid droplets accumulation while increasing AMP-activated protein kinase (AMPK) activation, preventing differentiation of human preadipocytes. Cotreatment with cimetidine restored adipogenesis. Furthermore, metformin decreased IL-6 and MCP-1 gene expression in comparison with differentiated adipocytes. Metformin (0.1 and 1 mmol/l) decreased adipogenic and inflammatory genes in SAT. OCT2 gene expression was not detected in adipose tissue and was very small in isolated preadipocytes, disappearing during adipogenesis.

CONCLUSIONS
OCT1 gene expression and protein levels are detectable in adipose tissue. Increased OCT1 gene expression in adipose tissue of obese subjects might contribute to increased metformin action in these subjects.
Optimization of 5-rod Car Suspension for Elastokinematic and Dynamic Characteristics
Authors: Knapczyk Józef , Maniowski Michał 
Published: October 2010

Optimization of 5-rod Car Suspension for Elastokinematic and Dynamic CharacteristicsThe paper presents optimization of 5-rod (5-link) suspension mechanism used in passenger cars for independent guiding of the wheels. Selected stiffness coefficients defined for five elastomeric bushings installed in joints of the suspension rods are considered as design variables. Two models with lumped parameters (i.e. elastokinematic and dynamic) of wheel-suspension-car body system are formulated to describe relationships between the design variables and the performance indexes including car active safety and ride comfort, respectively. The multi-criteria goal function is minimized using a deterministic algorithm. The suspension with optimized bushings rates fulfils desired elastokinematic criteria together with a defined dynamic criterion, describing the so-called rolling comfort. An event of car passing over short road bump is considered as dynamic conditions. The numerical example deals with an actual middle-class passenger car with 5-rod suspension at the front driven axle. Estimation of the models parameters and their verification were carried out on the basis of indoor and outdoor experiments. The proposed optimization procedure can be used to improve the suspension design or development cycle.
Surgical treatment of vulvar vestibulitis: a review
Authors: Tommola Päivi , Unkila‐Kallio Leila , Paavonen Jorma 
Published: October 2010

AbstractVulvar vestibulitis syndrome, a subset of vulvodynia, is a complex pain syndrome. It causes severe dyspareunia and affects mainly young women. The etiology is unknown and no uniformly effective treatment exists. Surgery has been considered as ‘the last resort’ in the management of patients not responding to conservative treatment modalities. For this review, all studies of surgical treatment of vulvar vestibulitis were evaluated. We describe the evolution of vestibulectomy techniques through the years. Our aim was also to find out whether any surgical technique is better than others providing better patient satisfaction and lower complication rates. We conclude that surgical technique as such plays a relatively small role. Surgery seems to be effective. However, lack of randomized trials and insufficient data on complication rates must be emphasized.
Decreased 1,25‐dihydroxy vitamin D levels in women with intrahepatic cholestasis of pregnancy
Authors: Wikström Shemer Elisabeth , Marschall Hanns‐Ulrich 
Published: October 2010

AbstractObjective. The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) involves impaired bile acid and estrogen/progesterone metabolism and excretion based on genetic and environmental factors. The role of vitamin D is undefined. Design. Observational study. Setting. Department of Obstetrics and Gynecology, Danderyd Hospital, Stockholm, Sweden. Population. Swedish. Method. We measured serum 1,25‐dihydroxy vitamin D3 (1,25‐D3) and parathormone in 22 women with ICP at presentation, in comparison with 11 healthy women at delivery. Results. ICP women had significantly (p = 0.0041) lower levels of 1,25‐D3 in serum (76.4 ± 23.1 vs. 112.0 ± 40 ng/L, mean ± SD), unrelated to serum bile acids. 1,25‐D3 levels were inversely correlated (p < 0.05) to meconium staining of amniotic fluid. Parathormone levels did not differ between ICP and healthy women. Conclusion. Lower 1,25‐D3 levels in ICP are inversely correlated by meconium staining, a major indicator of fetal distress. Our finding may have pathogenetic and clinical implications since vitamin D regulates steroid metabolism and 1,25‐D3 deficiency may impair fetal outcome.