bluuebunny/crossref_metadata_2025 huggingface dataset:
Degradation of the LDL receptors by PCSK9 is not mediated by a secreted protein acted upon by PCSK9 extracellularly
Authors: Holla Øystein L , Cameron Jamie , Berge Knut Erik , Ranheim Trine , Leren Trond P
Published: March 2007

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) post-transcriptionally degrades the low density lipoprotein receptors (LDLR). However, it is unknown whether PCSK9 acts directly on the LDLR or if PCSK9 activates another protein that in turn causes degradation of the LDLR.

Results

We have transiently transfected HepG2 cells with wild-type and mutant D374Y-PCSK9 plasmids to study the effect of the conditioned medium on the LDLR of untransfected HepG2 cells. The ability of the conditioned medium to reduce the internalization of LDL was abolished by removal of recombinant PCSK9 from the conditioned medium by affinity chromatography. Thus, PCSK9 is the only factor in the conditioned medium able to mediate degradation of the LDLR. Moreover, fractionation of the conditioned medium by gel filtration showed that the ability of the fractions to reduce the internalization of LDL, closely paralleled the amount of D374Y-PCSK9 in the fractions. Incubation of a secreted, truncated LDLR without cytoplasmic and transmembrane domains, as well as membrane fractions from HepG2 cells, with conditioned medium containing PCSK9, did not reduce the amount of LDLR as determined by western blot analysis. Thus, the LDLR is not degraded by PCSK9 on the cell surface. The LDLR of HepG2 cells incubated with conditioned medium was protected from PCSK9-mediated degradation by the addition of nocodazole or ammonium chloride, but was not protected when the conditioned medium was made hypertonic. These findings indicate that the intracellular degradation of the LDLR involves intracellular transport along microtubules, an acidic intracellular compartment and that it occurs even when endocytosis through clathrin-coated pits has been blocked.

Conclusion

Degradation of the LDLR by PCSK9 is not mediated by a secreted protein acted upon by PCSK9 extracellularly. Also the PCSK9-mediated degradation of the LDLR does not take place on the cell surface. Rather, the PCSK9-mediated degradation of the LDLR appears to take place intracellularly and occurs even when endocytosis through clathrin-coated pits is blocked by hypertonic medium.
Distinctive expression patterns of 185/333 genes in the purple sea urchin, Strongylocentrotus purpuratus: an unexpectedly diverse family of transcripts in response to LPS, β-1,3-glucan, and dsRNA
Authors: Terwilliger David P , Buckley Katherine M , Brockton Virginia , Ritter Nicole J , Smith L Courtney
Published: March 2007

Background

A diverse set of transcripts called185/333is strongly expressed in sea urchins responding to immune challenge. Optimal alignments of full-length185/333cDNAs requires the insertion of large gaps that define 25 blocks of sequence calledelements. The presence or absence of individual elements also defines a specificelement patternfor each message. Individual sea urchins were challenged with pathogen associated molecular patterns (PAMPs) (lipopolysaccharide, β-1,3-glucan, or double stranded RNA), and changes in the185/333message repertoire were followed over time.

Results

Each animal expressed a diverse set of185/333messages prior to challenge and a 0.96 kb message was the predominant size after challenge. Sequence analysis of the cloned messages indicated that the major element pattern expressed in immunoquiescent sea urchins was eitherC1orE2.1. In contrast, most animals responding to lipopolysaccharide, β-1,3-glucan or injury, predominantly expressed messages of theE2pattern. In addition to the major patterns, extensive element pattern diversity was observed among the different animals before and after challenge. Nucleotide sequence diversity of the transcripts increased in response to β-1,3-glucan, double stranded RNA and injury, whereas diversity decreased in response to LPS.

Conclusion

These results illustrate that sea urchins appear to be able to differentiate among different PAMPs by inducing the transcription of different sets of185/333genes. Furthermore, animals may share a suite of185/333genes that are expressed in response to common pathogens, while also maintaining a large number of unique genes within the population.
Cost-effectiveness of collaborative care including PST and an antidepressant treatment algorithm for the treatment of major depressive disorder in primary care; a randomised clinical trial
Authors: IJff Marjoliek A , Huijbregts Klaas ML , van Marwijk Harm WJ , Beekman Aartjan TF , Hakkaart-van Roijen Leona , Rutten Frans F , Unützer Jürgen , van der Feltz-Cornelis Christina M
Published: March 2007

Background

Depressive disorder is currently one of the most burdensome disorders worldwide. Evidence-based treatments for depressive disorder are already available, but these are used insufficiently, and with less positive results than possible. Earlier research in the USA has shown good results in the treatment of depressive disorder based on a collaborative care approach with Problem Solving Treatment and an antidepressant treatment algorithm, and research in the UK has also shown good results with Problem Solving Treatment. These treatment strategies may also work very well in the Netherlands too, even though health care systems differ between countries.

Methods/design

This study is a two-armed randomised clinical trial, with randomization on patient-level. The aim of the trial is to evaluate the treatment of depressive disorder in primary care in the Netherlands by means of an adapted collaborative care framework, including contracting and adherence-improving strategies, combined with Problem Solving Treatment and antidepressant medication according to a treatment algorithm. Forty general practices will be randomised to either the intervention group or the control group. Included will be patients who are diagnosed with moderate to severe depression, based on DSM-IV criteria, and stratified according to comorbid chronic physical illness. Patients in the intervention group will receive treatment based on the collaborative care approach, and patients in the control group will receive care as usual. Baseline measurements and follow up measures (3, 6, 9 and 12 months) are assessed using questionnaires and an interview. The primary outcome measure is severity of depressive symptoms, according to the PHQ9. Secondary outcome measures are remission as measured with the PHQ9 and the IDS-SR, and cost-effectiveness measured with the TiC-P, the EQ-5D and the SF-36.

Discussion

In this study, an American model to enhance care for patients with a depressive disorder, the collaborative care model, will be evaluated for effectiveness in the primary care setting. If effective across the Atlantic and across different health care systems, it is also likely to be an effective strategy to implement in the treatment of major depressive disorder in the Netherlands.
Exercise on Prescription: trial protocol and evaluation of outcomes
Authors: Sørensen Jes B , Kragstrup Jakob , Kjær Kirsten , Puggaard Lis
Published: March 2007

Background

In many countries exercise prescriptions are used in an attempt to initiate a physically active lifestyle in sedentary populations. Previous studies have primarily evaluated low intensive exercise prescription interventions and found moderately positive effects on physical activity and aerobic fitness. In a highly intensive Danish exercise prescription scheme called 'Exercise on Prescription' (EoP) the general practitioners can prescribe EoP to sedentary patients with lifestyle diseases. The aim of this randomized trial is to assess the short- and long-term effects of the EoP scheme. Thus, the aim of this paper is to describe the randomized controlled trial designed for evaluating effectiveness of EoP, and to present results from validations of outcome measures.

Methods/Design

EoP involves a 16-week supervised training intervention and five counselling sessions (health profiles). All patients referred to EoP were eligible for the trial and were offered participation during the baseline health profile. Comparisons between the EoP group and the control group were made at baseline, and after four and ten months. Physiological measures used were maximal oxygen uptake (VO2max), glycosylated haemoglobin (HbA1c), bodyweight, and BMI. Patient-reported measures used were physical activity, health-related quality of life, amount and intensity of exercise, compliance with national guidelines for physical activity, and physical fitness. The validation of the cycle ergometer test found a strong correlation between maximal work capacity and VO2max, and acceptable test-retest reliability at group level. Calibration of the HbA1c apparatus was stable over ten weeks with minimal use, and test-retest reliability was good. High agreement percents were found for test-retest reliability for the self-administered questionnaire.

Discussion

The trial is designed to provide information about the effectiveness of the EoP scheme. The trial is part of a health technology assessment of EoP, which besides the effectiveness covers the patient perspective, the organization, and the health economy. All three methods validated were found useful for the EoP trial.
Breast metastasis from a renal cell cancer
Authors: Alzaraa Ahmed , Vodovnik Aleksandar , Montgomery Hugh , Saeed Mohammed , Sharma Narinder
Published: March 2007

Background

Metastases to the breast from extramammary tumours are uncommon, and metastatic renal cell carcinoma to the breast is extremely rare. We report a metastasis to the breast from a renal primary with the radiological and histopathological features.

Case presentation

An 81-year-old lady was seen in the breast clinic for a right breast mass after sustaining a fall. Clinical examination and investigations revealed a metastatic cancer from a renal primary. She received surgical treatment only and is under regular follow-up in the oncology clinic.

Conclusion

The treatment strategy for metastatic breast diseases is based on a proper assessment of such cases by surgeons, radiologists and histopathologists.
Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain
Authors: Toscano Christopher D , Prabhu Vinaykumar V , Langenbach Robert , Becker Kevin G , Bosetti Francesca
Published: March 2007

Background

Cyclooxygenase (COX)-1 and COX-2 produce prostanoids from arachidonic acid and are thought to have important yet distinct roles in normal brain function. Deletion of COX-1 or COX-2 results in profound differences both in brain levels of prostaglandin E2 and in activation of the transcription factor nuclear factor-κB, suggesting that COX-1 and COX-2 play distinct roles in brain arachidonic acid metabolism and regulation of gene expression. To further elucidate the role of COX isoforms in the regulation of the brain transcriptome, microarray analysis of gene expression in the cerebral cortex and hippocampus of mice deficient in COX-1 (COX-1-/-) or COX-2 (COX-2-/-) was performed.

Results

A majority (>93%) of the differentially expressed genes in both the cortex and hippocampus were altered in one COX isoform knockout mouse but not the other. The major gene function affected in all genotype comparisons was 'transcriptional regulation'. Distinct biologic and metabolic pathways that were altered in COX-/- mice included β oxidation, methionine metabolism, janus kinase signaling, and GABAergic neurotransmission.

Conclusion

Our findings suggest that COX-1 and COX-2 differentially modulate brain gene expression. Because certain anti-inflammatory and analgesic treatments are based on inhibition of COX activity, the specific alterations observed in this study further our understanding of the relationship of COX-1 and COX-2 with signaling pathways in brain and of the therapeutic and toxicologic consequences of COX inhibition.
Analysis of proteomic profiles and functional properties of human peripheral blood myeloid dendritic cells, monocyte-derived dendritic cells and the dendritic cell-like KG-1 cells reveals distinct characteristics
Authors: Horlock Claire , Shakib Farouk , Mahdavi Jafar , Jones Nick S , Sewell Herb F , Ghaemmaghami Amir M
Published: March 2007

Background

Dendritic cells (DCs) are specialized antigen presenting cells that play a pivotal role in bridging innate and adaptive immune responses. Given the scarcity of peripheral blood myeloid dendritic cells (mDCs) investigators have used different model systems for studying DC biology. Monocyte-derived dendritic cells (moDCs) and KG-1 cells are routinely used as mDC models, but a thorough comparison of these cells has not yet been carried out, particularly in relation to their proteomes. We therefore sought to run a comparative study of the proteomes and functional properties of these cells.

Results

Despite general similarities between mDCs and the model systems, moDCs and KG-1 cells, our findings identified some significant differences in the proteomes of these cells, and the findings were confirmed by ELISA detection of a selection of proteins. This was particularly noticeable with proteins involved in cell growth and maintenance (for example, fibrinogen γ chain (FGG) and ubiquinol cytochrome c) and cell-cell interaction and integrity (for example, fascin and actin). We then examined the surface phenotype, cytokine profile, endocytic and T-cell-activation ability of these cells in support of the proteomic data, and obtained confirmatory evidence for differences in the maturation status and functional attributes between mDCs and the two DC models.

Conclusion

We have identified important proteomic and functional differences between mDCs and two DC model systems. These differences could have major functional implications, particularly in relation to DC-T cell interactions, the so-called immunological synapse, and, therefore, need to be considered when interpreting data obtained from model DC systems.
Progesterone Receptor Isoforms and Proliferation in the Rat Mammary Gland during Development
Authors: Kariagina Anastasia , Aupperlee Mark D. , Haslam Sandra Z.
Published: March 2007

Progesterone (P), acting through progesterone receptor (PR) isoforms A and B, plays an important role in normal mammary gland development and is implicated in the etiology of breast cancer. Because of significant similarities between human and rat mammary gland development and hormonal responsiveness of mammary cancers, we investigated P action in the rat mammary gland. By immunohistochemical methods we determined PRA and PRB expression at puberty, sexual maturity, pregnancy, and lactation and after postlactational involution and their functional roles in the regulation of proliferation. PRA expression was restricted to luminal epithelial cells, whereas PRB was expressed in both luminal and myoepithelial cells, indicating a novel role of PRB in myoepithelial cell regulation. The majority of PRA-positive (PRA+) cells coexpressed PRB. In the pubertal and adult virgin mammary gland, PRA+PRB+ cells also expressed nuclear cyclin D1 but did not contain the proliferation marker bromodeoxyuridine. Based on a lack of phosphorylated retinoblastoma protein expression and the expression patterns of the cyclin-dependent kinase inhibitors p21 and p27 in these cells, we conclude that PRA+PRB+ cells appear to be cell cycle arrested and do not proliferate. PRA+ cells were decreased in the adult gland and during and after pregnancy. The percentage of PRB+ cells was relatively constant throughout development, and in a significant proportion of cells, only PRB was detected. During development, and especially during pregnancy, a high percentage of PRB+ cells were positive for bromodeoxyuridine. From this observation, we conclude that these cells proliferate and that P acting through PRB may directly stimulate proliferation.
The role of larval fat cells in adultDrosophila melanogaster
Authors: Aguila Jerell R. , Suszko Justin , Gibbs Allen G. , Hoshizaki Deborah K.
Published: March 2007

In the life history of holometabolous insects, distinct developmental stages are tightly linked to feeding and non-feeding periods. The larval stage is characterized by extensive feeding, which supports the rapid growth of the animal and allows accumulation of energy stores, primarily in the larval fat body. In Drosophila melanogaster access to these stores during pupal development is possible because the larval fat body is preserved in the pupa as individual fat cells. These larval fat cells are refractive to autophagic cell death that removes most of the larval cells during metamorphosis. The larval fat cells are thought to persist into the adult stage and thus might also have a nutritional role in the young adult. We used cell markers to demonstrate that the fat cells in the young adult are in fact dissociated larval fat body cells, and we present evidence that these cells are eventually removed in the adult by a caspase cascade that leads to cell death. By genetically manipulating the lifespan of the larval fat cells, we demonstrate that these cells are nutritionally important during the early, non-feeding stage of adulthood. We experimentally blocked cell death of larval fat cells using the GAL4/UAS system and found that in newly eclosed adults starvation resistance increased from 58 h to 72 h. Starvation survival was highly correlated with the number of remaining larval fat cells. We discuss the implications of these results in terms of the overall nutritional status of the larva as an important factor in adult survival in environmental stresses such as starvation.
Characterization of very-low density lipoprotein particle diameter dynamics in relation to egg production in a passerine bird
Authors: Salvante Katrina G. , Lin Gina , Walzem Rosemary L. , Williams Tony D.
Published: March 2007

During avian egg production, oestrogen mediates marked increases in hepatic lipid production and changes in the diameter of assembled very-low density lipoprotein (VLDL). A nearly complete shift from generic VLDL (∼70 nm in diameter), which transports lipids to peripheral tissues, to yolk-targeted VLDL (VLDLy) (∼30 nm), which supplies the yolk with energy-rich lipid, has been observed in the plasma of laying domestic fowl. We validated an established dynamic laser scattering technique for a passerine songbird Taeniopygia guttata, the zebra finch, to characterize the dynamics of VLDL particle diameter distribution in relation to egg production. We predicted that non-gallinaceous avian species that have not been selected for maximum egg production would exhibit less dramatic shifts in lipid metabolism during egg production. As predicted, there was considerable overlap between the VLDL particle diameter distributions of laying and non-laying zebra finches. But unexpectedly, non-laying zebra finches had VLDL diameter distributions that peaked at small particles and had relatively few large VLDL particles. As a result, laying zebra finches, in comparison, had diameter distributions that were shifted towards larger VLDL particles. Nevertheless,laying zebra finches, like laying chickens, had larger proportions of particles within proposed VLDLy particle diameter ranges than non-laying zebra finches (e.g. sVLDLy: 50% vs 37%). Furthermore, zebra finches and chickens had similar modal (29.7 nm in both species) and median (32.7 nm vs 29.6 nm) VLDL particle diameters during egg production. Therefore,although zebra finches and chickens exhibited opposing directional shifts in VLDL particle diameter distribution during egg production, the modifications to VLDL particle structure in both species resulted in the realization of a common goal, i.e. to produce and maintain a large proportion of small VLDL particles of specific diameters that are capable of being incorporated into newly forming egg yolks.)
How important are skeletal muscle mechanics in setting limits on jumping performance?
Authors: James Rob S. , Navas Carlos A. , Herrel Anthony
Published: March 2007

Jumping is an important locomotor behaviour used by many animals. The power required to perform a jump is supplied by skeletal muscle. The mechanical properties of skeletal muscle, including the power it can produce, are determined by its composition, which in turn reflects trade-offs between the differing tasks performed by the muscle. Recent studies suggest that muscles used for jumping are relatively fast compared with other limb muscles. As animals get bigger absolute jump performance tends to increase, but recent evidence suggests that adult jump performance may be relatively independent of body size. As body size increases the relative shortening velocity of muscle decreases, whereas normalised power output remains relatively constant. However, the relative shortening velocity of the fastest muscle fibre types appears to remain relatively constant over a large body size range of species. It appears likely that in many species during jumping, other factors are compensating for, or allowing for, uncoupling of jumping performance from size-related changes in the mechanical properties of muscle. In some species smaller absolute body size is compensated for by rapid development of locomotor morphology to attain high locomotor performance early in life. Smaller animal species also appear to rely more heavily on elastic storage mechanisms to amplify the power output available from skeletal muscle. Adaptations involving increased relative hindlimb length and relative mass of jumping muscles, and beneficial alteration of the origin and/or insertion of jumping muscles, have all been found to improve animal jump performance. However, further integrative studies are needed to provide conclusive evidence of which morphological and physiological adaptations are the most important in enhancing jump performance.
Changing salinity induces alterations in hemolymph ion concentrations and Na+ and Cl– transport kinetics of the anal papillae in the larval mosquito,Aedes aegypti
Authors: Donini Andrew , Gaidhu Mandeep P. , Strasberg Dana R. , O'Donnell Michael J.
Published: March 2007

Mosquito larvae are found in diverse aquatic habitats ranging from freshwater to hypersaline water and must often deal with rapid changes in habitat salinity. We transferred larvae of Aedes aegypti from freshwater to 30% seawater, or vice versa, and measured the time course of changes in their hemolymph ion concentrations, using ion-selective microelectrodes. We also reported the Michaelis–Menten kinetics of Na+ and Cl– transport by the anal papillae for the first time using the scanning ion-selective electrode technique (SIET). Hemolymph concentrations of Na+, Cl– and H+ increased within 6 h, when larvae were transferred from freshwater to seawater and decreased within 6 h, when transferred from seawater to freshwater. Kinetic parameters for Na+ and Cl– transport by the anal papillae were altered after only 5 h following transfer between freshwater (FW) and 30% seawater (30%SW). The Jmax (maximum transport rate) for both ions decreased when larvae were transferred to 30%SW, whereas the Kt (a measure of transporter affinity) increased for Na+ transport but was unaltered for Cl– transport, suggesting that Na+ and Cl– uptake are independent. Data reveal significant changes in ion transport by the anal papillae of mosquito larvae when they are faced with changes in external salinity such that Na+and Cl– uptake decrease in higher salinity. The alterations in Na+ and Cl– uptake may be a consequence of changes in hemolymph ion levels when larvae encounter altered salinity. The rapid changes in ion transport described here compliment the previously observed long term alterations in the morphology and ultrastructure of the anal papillae.
The role of resilience on psychological adjustment and physical health in patients with diabetes
Authors: Yi Joyce P. , Vitaliano Peter P. , Smith Ronald E. , Yi Jean C. , Weinger Katie
Published: March 2007

Objective. This study used a longitudinal design to investigate the buffering role of resilience on worsening HbA1c and self‐care behaviours in the face of rising diabetes‐related distress.

Method. A total of 111 patients with diabetes completed surveys and had their glycosylated haemoglobin (HbA1c) assessed at baseline and at 1‐year follow‐up. Resilience was defined by a factor score of self‐esteem, self‐efficacy, self‐mastery and optimism. Diabetes‐related distress and self‐care behaviours were also assessed.

Results. Baseline resilience, diabetes‐related distress and their interaction predicted physical health (HbA1c) at 1 year. Patients with low, moderate and high resilience were identified. Those with low or moderate resilience levels showed a strong association between rising distress and worsening HbA1c across time (r = .57, .56, respectively). However, those with high resilience scores did not show the same associations (r = .08). Low resilience was also associated with fewer self‐care behaviours when faced with increasing distress (r = −.55). These correlation coefficients remained significant after controlling for starting‐points.

Conclusion. In patients with diabetes, resilience resources predicted future HbA1c and buffered worsening HbA1c and self‐care behaviours in the face of rising distress levels.
Postterm Delivery and Risk for Epilepsy in Childhood
Authors: Ehrenstein Vera , Pedersen Lars , Holsteen Vibeke , Larsen Helle , Rothman Kenneth J. , Sørensen Henrik T.
Published: March 2007

OBJECTIVE. Postterm delivery is a risk factor for perinatal complications, some of which increase risk for neurologic morbidity. We aimed to examine the association between postterm delivery and risk for epilepsy in childhood.

METHODS. We conducted a cohort study of singleton children who were born in 3 Danish counties from 1980 to 2001. Birth registry data were linked with hospital records to identify cases of epilepsy in the first 12 years of life. We included children who were born at ≥39 gestational weeks and computed crude, age-specific, and birth weight standardized incidence rates of epilepsy. We estimated adjusted incidence rate ratios according to mode of delivery by Poisson regression.

RESULTS. Among the 277435 nonpreterm births, 32557 were at ≥42 weeks, including 3396 at ≥43 weeks. Nearly one fourth of the 2805 epilepsy cases occurred in the first year of life. In that period, birth weight standardized incidence rate ratios for epilepsy were 1.3 for birth at 42 weeks and 2.0 for birth at ≥43 weeks, compared with birth at 39 to 41 weeks. Among children who were delivered by cesarean section, incidence rate ratios adjusted for birth weight, presentation, malformations, and county were 1.4 for birth at 42 completed weeks and 4.9 for birth at ≥43 weeks, compared with term vaginal births. There was a similar tendency among children who were delivered with the assistance of instruments. We found no evidence for the association between postterm delivery and risk for epilepsy beyond the first year of life.

CONCLUSIONS. Prolonged gestation is a risk factor for early epilepsy; the added increase in risk for instrument-assisted and cesarean deliveries could be attributable to factors that are related to both birth complications and epilepsy.
Lead Exposure, IQ, and Behavior in Urban 5- to 7-Year-Olds: Does Lead Affect Behavior Only by Lowering IQ?
Authors: Chen Aimin , Cai Bo , Dietrich Kim N. , Radcliffe Jerilynn , Rogan Walter J.
Published: March 2007

BACKGROUND. Lead exposure in childhood lowers IQ scores, but its effect on children's behavior is less clear. Because IQ, per se, affects behavior, measuring the direct effect of lead requires measuring and then adjusting for IQ. In addition, either peak blood lead concentration, usually at 2 years old, or the lower blood lead level measured at school age may be the most relevant. Few studies have all of this information.

OBJECTIVES. The purpose of this work was to differentiate the direct effect of lead on behavior and the indirect effect through IQ and to examine the strength of the association for peak and concurrent blood lead concentration.

METHODS. Data come from a clinical trial of the chelating drug succimer to prevent cognitive impairment in 780 urban 12- to 33-month-olds with blood lead concentrations of 20 to 44 μg/dL. The children were followed from ages 2 to 7 years. The trial data were analyzed as a prospective observational study.

RESULTS. Blood lead concentration at 2 years old was not associated with Conners' Parent Rating Scale-Revised scores at 5 years of age or Behavioral Assessment Systems for Children scores at 7 years of age. Blood lead level at 7 years of age had direct effects on the Behavioral Assessment Systems for Children behavioral symptoms index, externalizing, and school problems at age 7.

CONCLUSIONS. Concurrent blood lead concentration was associated with externalizing and school problems scales at 7 years of age, and the effect was not entirely mediated through the effect of lead on IQ.
Measles-Mumps-Rubella and Varicella Vaccine Responses in Extremely Preterm Infants
Authors: D'Angio Carl T. , Boohene Paulina A. , Mowrer Anne , Audet Susette , Menegus Marilyn A. , Schmid D. Scott , Beeler Judy A.
Published: March 2007

OBJECTIVE. Extremely preterm infants mount lower antibody responses than term infants to several vaccines. The objective of this study was to measure the immunogenicity of measles-mumps-rubella and varicella vaccines in preterm and term children.

METHODS. Immune status before immunization and immune response after immunization with measles-mumps-rubella and varicella vaccines at 15 months of age were compared in 32 infants, 16 of whom were preterm (<29 weeks' gestation) and 16 of whom were term (≥37 weeks' gestation) at birth. Blood was drawn before vaccination and 3 to 6 weeks thereafter. Measles antibody was measured by plaque reduction neutralization assay. Mumps and rubella immunoglobulin G were measured in available sera by enzyme-linked fluorescent immunoassay. Varicella immunoglobulin G was measured in available sera by glycoprotein enzyme-linked immunosorbent assay. Values that were above or below the assay limits were assigned values double or half those limits, respectively. The primary outcome was the geometric mean antibody titer.

RESULTS. Preterm children had lower mumps and rubella geometric mean titers than did term children before vaccine, and nearly all children were seronegative for each of the 4 vaccine antigens before immunization. Measles, mumps, rubella, and varicella geometric mean titers were similar between groups after vaccine. All children were seropositive for measles after vaccine, whereas 13 of 14 preterm and 11 of 13 term children were seropositive for mumps, 13 of 14 preterm and 13 of 13 term children were seropositive for rubella, and 11 of 16 preterm and 9 of 15 term children were seropositive for varicella.

CONCLUSIONS. Preterm children mounted antibody responses that were similar to those of term children after measles-mumps-rubella and varicella vaccines at 15 months of age.
Parent Use of Touchscreen Computer Kiosks for Child Health Promotion in Community Settings
Authors: Thompson Darcy A. , Lozano Paula , Christakis Dimitri A.
Published: March 2007

OBJECTIVES. The goals were to evaluate the use of touchscreen computer kiosks, containing only child health–promoting information, in urban, low-income, community settings and to characterize the users of these kiosks.

METHODS. Three user-driven touchscreen computer kiosks were placed in low-income urban locations in Seattle, Washington, from March 2005 to October 2005. The locations included a public library, a Department of Motor Vehicles office, and a McDonald's restaurant. Users selected age-appropriate modules with prevention information and screening tools. Users entered the age of the child and were presented with age-appropriate modules. On exiting, users were asked to rate their experience and to provide basic demographic data.

RESULTS. In total, there were 1846 kiosk sessions. Almost one half occurred at McDonald's. Seventy-eight percent of users identified themselves as first-time users. Users sought information for children of all ages. Sixty-one percent of first-time users explored 1 module. First-time users were most interested in television/media use (16%), smoke exposure (14%), attention-deficit/hyperactivity disorder screening (12%), and asthma assessment (11%). At-risk children were identified in 52% of sessions. Eighty-seven percent of first-time users who completed the asthma assessment had children whose asthma was uncontrolled. Twenty-eight percent of users responded to ≥1 question on the exit survey. Of those, 48% had less than a high school education, and 26% had never used the Internet. Approximately one half found the kiosk easy to use (57%) and the information easy to understand (55%); 66% said there was at least some new information. Fifty-five percent planned to try some of the things they had learned, and 49% intended to talk to their child's doctor about what they had learned.

CONCLUSIONS. User-driven computer kiosks were used in community settings to obtain child health information. Users found the kiosks easy to use. Additional study on improving use and understanding the impact is needed.
Comparison of Proliferative and Multilineage Differentiation Potential of Human Mesenchymal Stem Cells Derived from Umbilical Cord and Bone Marrow
Authors: Baksh Dolores , Yao Raphael , Tuan Rocky S.
Published: March 2007

Human umbilical cord perivascular cells (HUCPVCs) have been shown to have a high proliferative potential and the capacity to differentiate into an osteogenic phenotype. HUCPVCs have thus been considered a possible extra-embryonic mesenchymal stem cell (MSC) source for cell-based therapies. To assess this potential, we compared HUCPVCs to the “gold standard” bone marrow mesenchymal stromal cells (BMSCs) with respect to their proliferation, differentiation, and transfection capacities. HUCPVCs showed a higher proliferative potential than BMSCs and were capable of osteogenic, chondrogenic, and adipogenic differentiation. Interestingly, osteogenic differentiation of HUCPVCs proceeded more rapidly than BMSCs. Additionally, HUCPVCs expressed higher levels of CD146, a putative MSC marker, relative to BMSCs. HUCPVCs showed comparable transfection efficiency as BMSCs using a nucleofection method but were more amenable to transfection with liposomal methods (FuGENE). Gene array analysis showed that HUCPVCs also expressed Wnt signaling pathway genes that have been implicated in the regulation of MSCs. The similar characteristics between HUCPVCs and MSCs support the applicability of HUCPVCs for cell-based therapies.

Disclosure of potential conflicts of interest is found at the end of this article.
Oxidative stress increases placental and endothelial cell activin A secretion
Authors: Mandang Stephen , Manuelpillai Ursula , Wallace Euan M
Published: March 2007

Circulating levels of activin A are significantly increased in women with preeclampsia when compared with those with a normal pregnancy. The mechanisms underlying these increased levels are unknown. We undertook these studies to explore whether oxidative stress might be the mechanism. We exposed trophoblast explants, human umbilical vein endothelial cells (HUVECs) and peripheral blood monocytes to oxidative stress in vitro using xanthine/xanthine oxidase (X/XO), measuring activin A and isoprostane in conditioned media and mRNA for activin βA in explants and HUVECs. We also measured isoprostane and activin A in serum from 21 women with preeclampsia and from 20 women with a normal pregnancy. Treatment with X/XO significantly increased 8-isoprostane production from placental explants, HUVECs and monocytes, indicative of oxidative stress, and significantly increased activin A output from placental explants (139.1 ± 27.4 per mg wet weight vs 322.9 ± 89.7 pg/ml per mg wet weight, P = 0.02) and from HUVECs (1.2 ± 0.2 vs 3.2 ± 1.8 ng/ml, P = 0.04). There was no effect on activin A output from monocytes. X/XO significantly increased βA mRNA in placental explants but not in HUVECs. Maternal plasma levels of 8-isoprostane and activin A were significantly higher in women with preeclampsia when compared with controls (333.8 ± 70 vs 176.3 ± 26.2 pg/ml, P = 0.04 and 49.5 ± 7 vs 13.1 ± 1.2 ng/ml, P < 0.001 respectively). In the women with preeclampsia, but not in those with a normal pregnancy, circulating levels of 8-isoprostane and activin A were significantly and positively correlated (r2 = 0.72; P < 0.001). These data suggest that oxidative stress may be one of the mechanisms underlying increased circulating activin A in preeclampsia.
Effects of genistein, resveratrol, and quercetin on steroidogenesis and proliferation of MA-10 mouse Leydig tumor cells
Authors: Chen Yu-Chyu , Nagpal Madan L , Stocco Douglas M , Lin Tu
Published: March 2007

This study was performed to compare the effects of three well-known phytoestrogens such as genistein, resveratrol, and quercetin on steroidogenesis in MA-10 mouse tumor Leydig cells. Addition of genistein or resveratrol to MA-10 cells resulted in decreases in the cAMP-stimulated progesterone secretion, but quercetin had an opposite response. Steroidogenic acute regulatory (StAR) mRNA expression and StAR promoter activity in transiently transfected MA-10 cells were significantly reduced by genistein or resveratrol, but increased by quercetin. Genistein was found to inhibit MA-10 cell proliferation, while resveratrol and quercetin had no effect. Quercetin-induced increase in cAMP-stimulated progesterone secretion was reversed by ICI 182,780, an estrogen receptor (ER) antagonist. However, ICI 182,780 had no effect on cAMP plus quercetin-stimulated StAR promoter activity. To examine whether non-ER factors are associated with quercetin-stimulated progesterone production, we treated MA-10 cells with EGTA to deprive them of extracellular Ca2+. We found that EGTA inhibited quercetin-plus cAMP-stimulated progesterone secretion and StAR promoter activity. Blocking of Ca2+ influx through L- or T-type voltage-gated Ca2+ channels with verapamil or mibefradil respectively, attenuated quercetin-stimulated progesterone secretion, while they had no effect on quercetin-plus cAMP-stimulated StAR promoter activity. Blocking of intracellular Ca2+ efflux by sodium orthovanadate, a Ca2+-pump inhibitor, blocked quercetin- plus cAMP-stimulated progesterone secretion and StAR promoter activity in MA-10 cells. Finally, EGTA or vanadate reduced quercetin and cAMP-increased in StAR mRNA expression in MA-10 cells, while ICI 182,780 had no effect. Taken together, these results indicate that phytoestrogens have differential effects on steroidogenesis in MA-10 cells.
Effect of height on delayed collapse of cuttings in stiff clay
Authors: Ellis E. A. , O'Brien A. S.
Published: March 2007

The ‘delayed collapse’ of cuttings in stiff high-plasticity clay is known to be significantly affected by long-term recovery of pore pressures and progressive failure resulting from brittle material behaviour. Limit equilibrium methods are not well equipped to model these effects, but the increasing use of numerical modelling offers new potential to improve understanding of these failure mechanisms. A series of numerical analyses incorporating brittle material behaviour has been undertaken, specifically considering deep-seated first-time failure of cuttings in weathered London Clay. Because of progressive failure, the average mobilised strength is between the peak bulk strength and the residual strength. In current practice, parameter selection is often based on Chandler and Skempton's back-analysis of several deep-seated failures in the ‘brown’ weathered London Clay. This paper considers variation of the critical (minimum) height for delayed deep-seated failure in cuttings in weathered London Clay with slope angle, and variation of mobilised strength with cutting height.
Subgingival Chlorhexidine Varnish Administration as an Adjunct to Same‐Day Full‐Mouth Root Planing. II. Microbiological Observations
Authors: Cosyn Jan , Sabzevar Mehran Moradi
Published: March 2007

Background: Recently, the clinical additive value of a highly concentrated chlorhexidine (CHX) varnish, when applied subgingivally as an adjunct to scaling and root planing, was described. The objective of the present study was to investigate the microbiological impact of a treatment strategy for chronic periodontitis based on a combination of same‐day full‐mouth root planing and subgingival CHX varnish administration.

Methods: A randomized, controlled, single‐blind, parallel trial was conducted on 33 non‐smoking chronic periodontitis patients. The control group received oral hygiene instructions and same‐day full‐mouth root planing. The test group received the same instructions and treatment; however, all pockets also were disinfected using a supersaturated CHX varnish. Subgingival plaque samples were collected from the deepest site per quadrant in each patient at baseline and after 1, 3, and 6 months. Pooled sample analysis was performed using a multiplex polymerase chain reaction–based method for the identification of Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythensis (Tf), Treponema denticola (Td), and Prevotella intermedia (Pi).

Results: In terms of detection frequency and bacterial levels, significant, mainly temporary, reductions from baseline were found in both groups. When a comparison was made between the control and the test group, significant differences in the detection frequency of Tf (P = 0.024) and Td (P = 0.024), which favored the test group, were found at 1 month. A similar phenomenon was seen for Td (P = 0.031) based on bacterial levels. An important trend toward lower Tf levels in the test group also was found at 1 month (P = 0.052). Compared to baseline levels, microbiological benefits in the test group seemed to be maintained, at least in part, over a 6‐month period. In contrast, all microbial levels had relapsed in the control group at study termination.

Conclusion: The microbiological results of the present study promote the subgingival administration of a highly concentrated CHX varnish as an adjunct to same‐day full‐mouth root planing.
Treatment of Glenohumeral Arthritis with a Hemiarthroplasty
Authors: Wirth Michael A. , Tapscott R. Stacy , Southworth Carleton , Rockwood Charles A.
Published: March 2007

BACKGROUND:

Glenohumeral hemiarthroplasty is well established as a method to treat glenohumeral arthritis. This study was designed to report longer-term results and to provide a decision model to assist surgeons in achieving successful outcomes. Our selection strategy for hemiarthroplasty included shoulders with (1) a concentric glenoid with eburnated bone, (2) a nonconcentric glenoid that could be converted to a smooth concentric surface, and (3) a humeral head centered within the glenoid after soft-tissue balancing.

METHODS:

Fifty-seven consecutive patients (sixty-four shoulders) who had osteoarthritis of the glenohumeral joint, without advanced disease in the glenoid, were treated with hemiarthroplasty. In each instance, a modular prosthesis was implanted. Clinical assessment was performed preoperatively and at one-year intervals postoperatively for at least five years with use of patient self-assessment instruments, including the American Shoulder and Elbow Surgeons questionnaire, the Simple Shoulder Test, and a visual analog pain scale. A detailed radiographic analysis was performed to determine the presence of glenohumeral subluxation, periprosthetic radiolucency, and glenoid bone loss.

RESULTS:

Forty-three patients (fifty shoulders) were followed for a minimum of five years (mean, 7.5 years). Of the remaining fourteen patients (fourteen shoulders), ten were lost to follow-up, three had died, and one was excluded. For the Simple Shoulder Test, and for every visual analog scale measure, the results at the final follow-up evaluation were significantly better than the preoperative results (p < 0.0001 for each). The mean Simple Shoulder Test score at the time of the final follow-up was 9.4 positive responses compared with 9.7 positive responses at the two-year evaluation (p = 0.32), and the mean visual analog scale score for pain was 18.6 points compared with 14.9 points at two years (p = 0.45). Radiographic analysis showed the majority of stems had either no lucency or lucencies only near the tip of the stem. Glenoid bone loss and subluxation improved postoperatively, and the results were maintained at the final follow-up evaluation.

CONCLUSIONS:

Shoulder hemiarthroplasty provides sustained good-to-excellent pain relief and functional improvement at five to ten years postoperatively in carefully selected patients with osteoarthritis.
Early Results of a New Method of Treatment for Idiopathic Congenital Vertical Talus
Authors: Dobbs Matthew B. , Purcell Derek B. , Nunley Ryan , Morcuende Jose A.
Published: March 2007

BACKGROUND:

The treatment of idiopathic congenital vertical talus has traditionally consisted of manipulation and application of casts followed by extensive soft-tissue releases. However, this treatment is often followed by severe stiffness of the foot and other complications. The purpose of this study was to evaluate a new method of manipulation and cast immobilization, based on principles used by Ponseti for the treatment of clubfoot deformity, followed by pinning of the talonavicular joint and percutaneous tenotomy of the Achilles tendon in patients with idiopathic congenital vertical talus.

METHODS:

The cases of eleven consecutive patients who had a total of nineteen feet with an idiopathic congenital vertical talus deformity were retrospectively reviewed at a minimum of two years following treatment with serial manipulations and casts followed by limited surgery consisting of percutaneous Achilles tenotomy (all nineteen feet), fractional lengthening of the anterior tibial tendon (two) or the peroneal brevis tendon (one), and percutaneous pin fixation of the talonavicular joint (twelve). The principles of manipulation and application of the plaster casts were similar to those used by Ponseti to correct a clubfoot deformity, but the forces were applied in the opposite direction. Patients were evaluated clinically and radiographically at the time of presentation, immediately postoperatively, and at the time of the latest follow-up. Radiographic measurements obtained at these times were compared. In addition, the radiographic data at the final evaluation were compared with normal values for an individual of the same age as the patient.

RESULTS:

Initial correction was obtained both clinically and radiographically in all nineteen feet. A mean of five casts was required for correction. No patient underwent extensive surgical releases. At the final evaluation, the mean ankle dorsiflexion was 25° and the mean plantar flexion was 33°. Dorsal subluxation of the navicular recurred in three patients, none of whom had had pin fixation of the talonavicular joint. At the time of the latest follow-up, there was a significant improvement (p < 0.0001) in all of the measured radiographic parameters compared with the pretreatment values, and all of the measured angles were within normal values for the patient's age.

CONCLUSIONS:

Serial manipulation and cast immobilization followed by talonavicular pin fixation and percutaneous tenotomy of the Achilles tendon provides excellent results, in terms of the clinical appearance of the foot, foot function, and deformity correction as measured radiographically at a minimum two years, in patients with idiopathic congenital vertical talus.