bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Cerebral Palsy in 8-Year-Old Children in Three Areas of the United States in 2002: A Multisite Collaboration
Authors: Yeargin-Allsopp Marshalyn , Van Naarden Braun Kim , Doernberg Nancy S. , Benedict Ruth E. , Kirby Russell S. , Durkin Maureen S.
Published: February 2008

OBJECTIVE. The goal was to estimate the prevalence of cerebral palsy and cerebral palsy subtypes among children in 3 areas of the United States by using a population-based surveillance system.

METHODS. Using methods developed by the Centers for Disease Control and Prevention Metropolitan Atlanta Developmental Disabilities Surveillance Program, investigators from the Autism and Developmental Disabilities Monitoring Network conducted surveillance of cerebral palsy among 8-year-old children living in northern Alabama, metropolitan Atlanta, and southeastern Wisconsin in 2002 (N = 114897). Cross-sectional data were collected through retrospective record review from multiple sources. Cases were linked to birth certificate and census files to obtain additional information. Period prevalence estimates were calculated per 1000 children 8 years of age.

RESULTS. The average prevalence of cerebral palsy across the 3 sites was 3.6 cases per 1000, with notably similar site-specific prevalence estimates (3.3 cases per 1000 in Wisconsin, 3.7 cases per 1000 in Alabama, and 3.8 cases per 1000 in Georgia). At all sites, prevalence was higher in boys than girls (overall boy/girl ratio: 1.4:1). Also, at all sites, the prevalence of cerebral palsy was highest in black non-Hispanic children and lowest in Hispanic children. At all sites, the prevalence among children living in low- and middle-income neighborhoods was higher than that among children living in high-income neighborhoods. Spastic cerebral palsy was the most common subtype (77% of all cases), with bilateral spastic cerebral palsy dominating the spastic group (70%).

CONCLUSION. These findings contribute new knowledge to the epidemiology of cerebral palsy in the United States. The similarities in prevalence rates and patterns of cerebral palsy reported for 8-year-old children at 3 geographically distinct sites provide evidence of the reliability of the surveillance methods used by the Autism and Developmental Disabilities Monitoring Network.
Neurodevelopmental Outcomes After Staged Palliation for Hypoplastic Left Heart Syndrome
Authors: Tabbutt Sarah , Nord Alex S. , Jarvik Gail P. , Bernbaum Judy , Wernovsky Gil , Gerdes Marsha , Zackai Elaine , Clancy Robert R. , Nicolson Susan C. , Spray Thomas L. , Gaynor J. William
Published: February 2008

OBJECTIVE. The goal was to determine the relative effects of underlying genetic factors and current management strategies on neurodevelopmental disabilities among one-year old survivors of palliation for hypoplastic left heart syndrome.

METHODS. Children who underwent staged reconstruction for hypoplastic left heart syndrome and variants were assessed at 1 year of age by using a neuromuscular examination and the Bayley Scales of Infant Development II, which provide the Mental Development Index and the Psychomotor Development Index. The effects of perioperative, operative, and genetic variables on developmental scores were evaluated.

RESULTS. The median birth weight was 3.3 kg (range: 2.1–4.5 kg). Eight-three patients (94%) underwent multiple operations with cardiopulmonary bypass during the first year of life (median: 2 operations). Seven patients (8%) required extracorporeal membrane oxygenation. Twenty-five patients (28%) had a confirmed or suspected genetic syndrome. At 1 year of age, the neuromuscular examination results were abnormal or suspect for 57 patients (65%). The median Mental Development Index score was 90, and 10 patients (11%) had scores of <70 (2 SDs below the general population mean). The median Psychomotor Development Index score was 73, and 42 patients (48%) had scores of <70. In multivariate analyses, younger gestational age, the presence of a genetic syndrome, and the need for preoperative intubation had significant negative effects on neurodevelopmental outcomes. No association was found with operative factors, including duration of deep hypothermic circulatory arrest.

CONCLUSIONS. At 1 year of age, there was a significant incidence of neurodevelopmental disabilities in children with hypoplastic left heart syndrome and variants; motor scores were particularly concerning. Many children had suspected or confirmed genetic syndromes, which negatively affected neurodevelopmental outcomes. Surgical variables did not affect neurologic outcomes.
Pertussis Hospitalizations Among Infants in the United States, 1993 to 2004
Authors: Cortese Margaret M. , Baughman Andrew L. , Zhang Rongping , Srivastava Pamela U. , Wallace Gregory S.
Published: February 2008

OBJECTIVE. We sought to describe the rates of pertussis hospitalization among infants by using databases that do not rely on passive reporting and compare with results obtained from the passive national surveillance system.

METHODS. The incidence of infant pertussis hospitalization in 1993 to 2004 was determined by using 2 national hospitalization discharge databases (Nationwide Inpatient Sample and Kids’ Inpatient Database) and the National Notifiable Disease Surveillance System/Supplemental Pertussis Surveillance System. Rates were determined for separate age groups among infants <1 year of age. Pertussis complications and procedures were examined by using the Kids’ Inpatient Database.

RESULTS. In 1993 to 2004, the pertussis hospitalization rates for infants ≤2 months of age were generally stable, by the discharge databases. The incidence of infant pertussis hospitalization obtained from the Nationwide Inpatient Sample and Kids’ Inpatient Database was ∼2 times greater than that obtained from the passive reporting system. Infants 1 to 2 months of age had the highest incidence (239 hospitalizations per 100000 live births in the 2003 Kids’ Inpatient Database). An annual average of 2678 hospitalizations occurred in 2000 and 2003; 86% occurred in infants ≤3 months of age. Among those with ages provided, 95% of infants who required mechanical ventilation and all of those who died were ≤3 months of age.

CONCLUSIONS. Pertussis hospitalization incidence rates among the youngest infants were generally stable in 1993 to 2004 and were highest for infants 1 to 2 months of age. The impact of the new adolescent and adult tetanus-diphtheria-acellular pertussis vaccines on infant pertussis should be monitored through such discharge databases. Additional vaccination strategies should be evaluated to protect infants as early in life as possible.
Bone Mineral Density Deficits in Survivors of Childhood Cancer: Long-term Follow-up Guidelines and Review of the Literature
Authors: Wasilewski-Masker Karen , Kaste Sue C. , Hudson Melissa M. , Esiashvili Natia , Mattano Leonard A. , Meacham Lillian R.
Published: February 2008

The development of curative therapy for most pediatric malignancies has produced a growing population of childhood cancer survivors who are at increased risk for a variety of health problems resulting from their cancer or its treatment. Because of the fact that many treatment-related sequelae may not become clinically apparent until the survivor attains maturity or begins to age, the ability of primary care providers to anticipate late effects of treatment is essential for providing timely interventions that prevent or correct these sequelae and their adverse effects on quality of life. Altered bone metabolism during treatment for childhood cancer may interfere with attainment of peak bone mass, potentially predisposing to premature onset of and more severe complications related to osteopenia and osteoporosis. Bone mineral deficits have been reported after treatment for a variety of pediatric malignancies and represent morbidity that can be reduced or prevented through lifestyle changes and attention to other common cancer-related sequelae such as hypogonadism. The Children's Oncology Group long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers provide risk-based surveillance recommendations that are based on expert opinion and review of the scientific literature for potential late effects of pediatric cancer therapy including osteopenia. This review summarizes the existing literature that has defined characteristics of cancer survivors at risk for bone mineral deficits and contributed to the surveillance and counseling recommendations outlined in the Children's Oncology group long-term follow-up guidelines.
Motivations of Mothers to Enroll Their Newborn Infants in General Clinical Research on Well-Infant Care and Development
Authors: Maayan-Metzger Ayala , Kedem-Friedrich Peri , Kuint Jacob
Published: February 2008

OBJECTIVE. The purpose of this work was to identify possible motivations for mothers to consent to having their newborn infants participate in medical research on well-infant care and to compare between mothers of term infants and mothers of stable preterm infants.

METHODS. Two-hundred mothers answered a questionnaire regarding their consent to have their newborns participate in 5 simulated studies at different risk levels and their willingness to provide a telephone number for future contact. Demographic data, attitudes about medicine, medical research, and evaluation of research conditions served as predictors of the degree of consent.

RESULTS. Degree of consent was affected mainly by perceived risk, because the research did not offer a direct personal benefit; that is, 80% consented to a psychological study as opposed to 25% who consented to a vaccine study. The strength of the predicting variables differentiated according to the suggested study. No significant difference was found between the mothers of term infants (n = 127) and the mothers of preterm infants (n = 73), either in the degree of consent to the 5 suggested studies or in the predicting variables, except for the measure of actual behavior (ie, revealing a telephone number). Only 23% of the mothers of term infants in comparison with 48% of the mothers of preterm infants were willing to reveal their telephone numbers.

CONCLUSIONS. There is some willingness to consent when the infant is healthy and the research is not directed at solving a specific problem of the infant. The degree of consent decreases in accordance with the increase in risk. The altruistic motive is the main predictor for research that is perceived as very risky. The benefit of learning about their infant's development served as a motivating force for less risky studies. We deduce that pointing out personal benefits to balance the usual conveyed information on risks or burdens of the research can increase the willingness to consent.
Early Determinants of Fractures in Rett Syndrome
Authors: Downs Jennepher , Bebbington Ami , Woodhead Helen , Jacoby Peter , Jian Le , Jefferson Amanda , Leonard Helen
Published: February 2008

OBJECTIVES. The goals were to compare the fracture incidence in Rett syndrome with that in the general population and to investigate the impact of genotype, epilepsy, and early motor skills on subsequent fracture incidence in girls and young women with Rett syndrome.

METHODS. The Australian Rett syndrome study, a population-based study operating since 1993, investigated Australian subjects with Rett syndrome born since 1976. The 234 (81.2%) of 288 verified cases in the Australian Rett syndrome database in 2004 whose families had completed follow-up questionnaires and provided information about fracture history were included in the analyses. The main outcomes were fracture incidence in the Rett syndrome population and fracture risk according to genotype, presence of epilepsy, and early motor profile.

RESULTS. Fracture incidence in this cohort was 43.3 episodes per 1000 person-years, nearly 4 times greater than the population rate. Risk was increased specifically in cases with p.R270X mutations and in cases with p.R168X mutations. Having epilepsy also increased fracture risk, even after adjustment for genotype.

CONCLUSIONS. Girls and young women with Rett syndrome are at increased risk of fracture. Those with mutations found previously to be more severe and those with epilepsy have an increased propensity toward fractures. Improved understanding of the risk factors for fracture could contribute to better targeting of interventions to decrease fracture incidence in this vulnerable population.
Prospective Assessment of the Effect of Needle Length and Injection Site on the Risk of Local Reactions to the Fifth Diphtheria-Tetanus-Acellular Pertussis Vaccination
Authors: Jackson Lisa A. , Starkovich Patty , Dunstan Maya , Yu Onchee , Nelson Jennifer , Dunn John , Rees Thom , Zavitkovsky Ann , Maus Diane , Froeschle James E. , Decker Michael
Published: February 2008

OBJECTIVE. Local reactions are relatively common after the fifth diphtheria-tetanus-acellular pertussis vaccination, but factors associated with an increased risk of those reactions are not well defined. The objective of this study was to assess the relationship between needle length and injection site on the risk of local reactions to the fifth diphtheria-tetanus-acellular pertussis vaccination administered in the context of usual clinical care.

METHODS. In this prospective assessment, parents reported signs and symptoms of adverse events for 7 days after vaccination. The relative risk of adverse events in relation to needle length (16 or 25 mm) and injection site (arm or thigh) was estimated in multivariate analyses that adjusted for age, gender, and BMI.

RESULTS. Of the 1315 study participants, 89% were vaccinated in the arm, and 67% were vaccinated with a 25-mm needle. Among children vaccinated in the arm, use of the shorter 16-mm needle was associated with a significantly higher risk of any redness, ≥5 cm of redness, persistent redness on day 2, and pain compared with vaccination with a 25-mm needle. Similar trends among the smaller group of children vaccinated in the thigh were also suggested but were not statistically significant. In analyses that were restricted to children vaccinated with a 25-mm needle, vaccination in the thigh versus arm was associated with a substantially lower risk of ≥5 cm of redness and a significantly lower risk of swelling and any itching but not with any difference in the risk of pain, irritability, or change in activity.

CONCLUSIONS. These findings suggest that a 25-mm needle should be used for the fifth diphtheria-tetanus-acellular pertussis vaccination regardless of injection site and that vaccination in the thigh is an option that may be considered by parents and providers who would like to decrease the risk of local reactions characterized by redness and swelling.
Intrauterine Risk Factors for Precocious Atherosclerosis
Authors: Skilton Michael R.
Published: February 2008

Evidence from noninvasive ultrasound studies of the neonatal aorta and fetal and early childhood postmortem studies indicates that impaired fetal growth, in utero exposure to maternal hypercholesterolemia, and diabetic macrosomia may all be important risk factors for vascular changes consistent with the earliest physical signs of atherosclerosis. Although the exact mechanisms that underlie these associations remain unclear, animal models have suggested that the use of antioxidant, lipid-lowering, and other innovative therapies may counteract the impact of these intrauterine risk factors for cardiovascular disease. This review summarizes the current evidence for intrauterine factors that have a direct impact on atherosclerosis and provides potential treatment and prevention strategies.
Plasma Biomarkers of Oxidative Stress: Relationship to Lung Disease and Inhaled Nitric Oxide Therapy in Premature Infants
Authors: Ballard Philip L. , Truog William E. , Merrill Jeffrey D. , Gow Andrew , Posencheg Michael , Golombek Sergio G. , Parton Lance A. , Luan Xianqun , Cnaan Avital , Ballard Roberta A.
Published: February 2008

OBJECTIVES. Inhaled nitric oxide treatment for ventilated premature infants improves survival without bronchopulmonary dysplasia. However, there has been no information regarding possible effects of this therapy on oxidative stress. We hypothesized that inhaled nitric oxide therapy would not influence concentrations of plasma biomarkers of oxidative stress.

PATIENTS AND METHODS. As part of the Nitric Oxide Chronic Lung Disease Trial, we collected blood samples at specified intervals from a subpopulation of 100 infants of <1250 g birth weight who received inhaled nitric oxide (20 ppm, weaned to 2 ppm) or placebo gas for 24 days. Plasma was assayed for total protein and for 3-nitrotyrosine and carbonylation by using immunoassays.

RESULTS. The demographic characteristics and primary outcome for the infants were representative of the entire group of infants who were in the Nitric Oxide Chronic Lung Disease Trial. For all infants at baseline, before receiving study gas, the concentration of total protein was inversely correlated with the respiratory severity score, and plasma carbonyl was positively correlated with severity score, supporting an association between oxidative stress and severity of lung disease. Infants who survived without bronchopulmonary dysplasia had 30% lower protein carbonylation concentrations at study entry than those who had an adverse outcome. At each of 3 time points (1–10 days) during exposure to study gas, there were no significant differences between control and treated infants for concentrations of plasma protein, 3-nitrotyrosine, and carbonylation.

CONCLUSIONS. Inhaled nitric oxide treatment for premature infants who are at risk for bronchopulmonary dysplasia does not alter plasma biomarkers of oxidative stress, which supports the safety of this therapy.
Toward Transparent Clinical Policies
Authors:   Steering Committee on Quality Improvement and Management
Published: February 2008

Clinical policies of professional societies such as the American Academy of Pediatrics are valued highly, not only by clinicians who provide direct health care to children but also by many others who rely on the professional expertise of these organizations, including parents, employers, insurers, and legislators. The utility of a policy depends, in large part, on the degree to which its purpose and basis are clear to policy users, an attribute known as the policy's transparency. This statement describes the critical importance and special value of transparency in clinical policies, guidelines, and recommendations; helps identify obstacles to achieving transparency; and suggests several approaches to overcome these obstacles.
Increasing the mean grain size in copper films and features
Authors: Vanstreels K. , Brongersma S.H. , Tokei Zs. , Carbonell L. , De Ceuninck W. , D’Haen J. , D’Olieslaeger M.
Published: February 2008

A new grain-growth mode is observed in thick sputtered copper films. This new grain-growth mode, also referred to in this work as super secondary grain growth (SSGG) leads to highly concentric grain growth with grain diameters of many tens of micrometers, and drives the system toward a {100} texture. The appearance, growth dynamics, final grain size, and self-annealing time of this new grain-growth mode strongly depends on the applied bias voltage during deposition of these sputtered films, the film thickness, the post-deposition annealing temperature, and the properties of the copper diffusion barrier layers used in this work. Moreover, a clear rivalry between this new growth mode and the regularly observed secondary grain-growth mode in sputtered copper films was found. The microstructure and texture evolution in these films is explained in terms of surface/interface energy and strain-energy density minimizing driving forces, where the latter seems to be an important driving force for the observed new growth mode. By combining these sputtered copper films with electrochemically deposited (ECD) copper films of different thickness, the SSGG growth mode could also be introduced in ECD copper, but this led to a reduced final SSGG grain size for thicker ECD films. The knowledge about the thin-film level is used to also implement this new growth mode in small copper features by slightly modifying the standard deposition process. It is shown that the SSGG growth mode can be introduced in narrow structures, but optimizations are still necessary to further increase the mean grain size in features.
Effect of WC content on glass formation, thermal stability, and phase evolution of a TiNbCuNiAl alloy synthesized by mechanical alloying
Authors: Li Y.Y. , Yang C. , Chen W.P. , Li X.Q.
Published: February 2008

Amorphous Ti66Nb13Cu8Ni6.8Al6.2 alloy powders with different tungsten carbide (WC) contents were synthesized by mechanical alloying. Outstanding differences in particle size, thermal stability, glass-forming ability, and phase evolution are found for the synthesized Ti-based glassy powders with different WC contents. This is attributed to the fact that the WC was partially alloyed into the glassy matrix and the matrix element Ti was also partially alloyed into the WC particles. The obtained glassy powders exhibit a wide supercooled liquid region above 64 K. Meanwhile, the main crystalline phase is the ductile β-Ti with a high volume fraction in the crystallized alloy powders. These two aspects offer the possibility of easily preparing a plasticity-enhanced bulk composite in the supercooled liquid region by powder metallurgy, which couples the nanosized WC particles with in situ precipitated ductile β-Ti phase.
Metastable face-centered cubic lead zirconate titanate (PZT) and lead lanthanum zirconate titanate (PLZT) nanocrystals synthesized by auto-ignition of metal–polymer gel
Authors: Roy Subir , Bysakh Sandip , Subrahmanyam Jandhyala
Published: February 2008

Nanocrystalline lead zirconate titanate (PZT) and lead lanthanum zirconate titanate (PLZT) have been synthesized in powder form by a single-step auto-ignition of metal–polymer gel precursor. The nanocrystalline powders were characterized using analytical transmission electron microscopy (TEM) equipped with an energy-dispersive x-ray spectrometer (EDXS) for composition analysis. For both PZT and PLZT, nanoparticles of sizes as low as 1–5 nm along with larger nanoparticles of sizes up to 30 nm are observed in the TEM. The selected-area diffraction (SAD) patterns from the nanoparticles revealed a face-centered cubic (fcc) crystal structure for both PZT and PLZT with a lattice parameter of ∼0.51 nm. The formation of PZT and PLZT nanoparticles of sizes below 5 nm with metastable fcc crystal structure has been observed for the first time. It is concluded that, as the crystal size decreases, the system assumes crystal structures of higher symmetry initially through small changes in lattice parameters and, in extreme cases, through chemical disorder for ultrafine nanoparticles.
Comments on “Extracting the plastic properties of metal materials from microindentation tests: Experimental comparison of recently published methods” by B. Guelorget, et al. [J. Mater. Res. 22, 1512 (2007)]: The correct methods of analyzing experimental data and reverse analysis of indentation tests
Authors: Ogasawara Nagahisa , Zhao Manhong , Chiba Norimasa , Chen Xi
Published: February 2008

Based on microindentation experiments of three different metals, Guelorget et al. [J. Mater. Res. 22, 1512 (2007)] have compared the performance of five different indentation methods on extracting material plastic properties—among them, three papers were proposed by Cao and Lu [Acta Mater.52, 4023 (2004); J. Mater. Res.20, 1194 (2005); J. Mech. Phys. Solids53, 49 (2005)] and two papers were published by our group [Ogasawara et al., Scripta Mater.54, 65 (2006); Zhao et al. Acta Mater.54, 23 (2006)]. They argued that the performances of our techniques in [Ogasawara et al., Scripta Mater.54, 65 (2006); Zhao et al. Acta Mater.54, 23 (2006)] were quite poor. Here we show that Guelorget et al. [J. Mater. Res. 22, 1512 (2007)] have made quite a few mistakes and problematic steps when they handled the experiment data and performed reverse analysis. Indeed, the material plastic properties extracted from the correct procedures based on our papers [Ogasawara et al., Scripta Mater.54, 65 (2006); Zhao et al. Acta Mater.54, 23 (2006)] are much better and more stable than that reported in Guelorget et al. [J. Mater. Res. 22, 1512 (2007)]. Several general issues related to interpreting microindentation data and reverse analysis are also discussed, which may serve as important guidelines for similar studies in the future.
Transplantation of Embryonic Stem Cells Improves Nerve Repair and Functional Recovery After Severe Sciatic Nerve Axotomy in Rats
Authors: Cui Lin , Jiang Jun , Wei Ling , Zhou Xin , Fraser Jamie L. , Snider B. Joy , Yu Shan Ping
Published: February 2008

Extensive research has focused on transplantation of pluripotent stem cells for the treatment of central nervous system disorders, the therapeutic potential of stem cell therapy for injured peripheral nerves is largely unknown. We used a rat sciatic nerve transection model to test the ability of implanted embryonic stem (ES) cell-derived neural progenitor cells (ES-NPCs) in promoting repair of a severely injured peripheral nerve. Mouse ES cells were neurally induced in vitro; enhanced expression and/or secretion of growth factors were detected in differentiating ES cells. One hour after removal of a 1-cm segment of the left sciatic nerve, ES-NPCs were implanted into the gap between the nerve stumps with the surrounding epineurium as a natural conduit. The transplantation resulted in substantial axonal regrowth and nerve repair, which were not seen in culture medium controls. One to 3 months after axotomy, co-immunostaining with the mouse neural cell membrane specific antibody M2/M6 and the Schwann cell marker S100 suggested that transplanted ES-NPCs had survived and differentiated into myelinating cells. Regenerated axons were myelinated and showed a uniform connection between proximal and distal stumps. Nerve stumps had near normal diameter with longitudinally oriented, densely packed Schwann cell-like phenotype. Fluoro-Gold retrogradely labeled neurons were found in the spinal cord (T12–13) and DRG (L4-L6), suggesting reconnection of axons across the transection. Electrophysiological recordings showed functional activity recovered across the injury gap. These data suggest that transplanted neurally induced ES cells differentiate into myelin-forming cells and provide a potential therapy for severely injured peripheral nerves.

Disclosure of potential conflicts of interest is found at the end of this article.
Statin and Stromal Cell-Derived Factor-1 Additively Promote Angiogenesis by Enhancement of Progenitor Cells Incorporation into New Vessels
Authors: Shao Hongwei , Tan Yaohong , Eton Darwin , Yang Zhe , Uberti M. Georgina , Li Sen , Schulick Andrew , Yu Hong
Published: February 2008

Angiogenesis requires the mobilization of progenitor cells from the bone marrow and homing of progenitor cells to ischemic tissue. Statins facilitate the former, and the chemokine stromal cell-derived factor-1 (SDF-1) enhances the latter. Their combined influence on angiogenesis was studied in vivo in the ischemic hindlimb C57BL/6 mouse model. The ischemic to non-ischemic perfusion ratio increased from 0.29 ± 0.02 immediately after femoral excision to 0.51 ± 0.10 three weeks after the surgery in the mice treated with either fluvastatin or SDF-1 alone, which is significantly better than the control (0.38 ± 0.05, p < .05, n = 6). The combined use of fluvastatin and SDF-1 further improved the reperfusion ratio (0.62 ± 0.08, p < .05). More cell proliferation, less apoptosis, enhanced bone marrow-derived endothelial progenitor cell (EPC) incorporation and higher capillary density were observed in ischemic tissue treated with both statin and SDF-1. In vitro mono-treatment with either fluvastatin (100 nM) or SDF-1 (100 ng/ml) facilitated EPC proliferation and migration, inhibited EPC apoptosis, enhanced expression of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), and increased Akt phosphorylation and nitric oxide production. These effects were significantly augmented by the two agents together and ablated by inhibitors of either Akt or nitric oxide synthase (NOS). In conclusion, statin and SDF-1 additively enhance progenitor cell migration and proliferation and down-regulate EPC apoptosis, resulting in improved reperfusion via activation of the Akt/NOS pathway and up-regulation of MMP-2 and MMP-9 expression.

Disclosure of potential conflicts of interest is found at the end of this article.
Melanocortin crosstalk with adipose functions: ACTH directly induces insulin resistance, promotes a pro-inflammatory adipokine profile and stimulates UCP-1 in adipocytes
Authors: Iwen K Alexander H , Senyaman Oezge , Schwartz Arne , Drenckhan Maren , Meier Britta , Hadaschik Dirk , Klein Johannes
Published: February 2008

The melanocortin (MC) system is a pivotal component of the hypothalamo-pituitary–adrenal (HPA) stress axis and plays an important role in the pathogenesis of obesity and the metabolic syndrome. Adipose dysfunction is implicated in the pathogenesis of these disorders. We investigated direct ACTH effects on adipose functions in immortalised murine white and brown adipocytes. MC receptor types 2 and 5 were expressed at the mRNA and protein levels and were strongly up-regulated during differentiation. Chronic ACTH stimulation did not affect adipogenesis. Insulin-induced glucose uptake in white adipocytes was acutely and transiently reduced by 45% upon ACTH treatment. Visfatin and adiponectin gene expression was reduced by about 50% in response to ACTH, while interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were acutely up-regulated by 2100 and 60% respectively. Moreover, IL-6 secretion was increased by 1450% within 4 h of ACTH treatment. In brown adipocytes, stimulation with ACTH caused a 690% increase in uncoupling protein (UCP)-1 mRNA levels within 8 h, followed by a 470% increase in UCP-1 protein concentrations after 24 h. Consistently, p38 mitogen-activated protein kinase (MAPK) phosphorylation was acutely increased by 1800% in response to ACTH stimulation, and selective inhibition of p38 MAPK abolished the ACTH-mediated UCP-1 protein increase. Taken together, ACTH acutely promotes an insulin-resistant, pro-inflammatory state and transiently enhances energy combustion. In conditions characterised by a dysregulation of the HPA stress axis such as the metabolic syndrome, direct MC interaction with adipocytes may contribute to dysregulated energy balance, insulin resistance and cardiometabolic complications.
Thyroid hormone stimulation of extracellular signal-regulated kinase and cell proliferation in human osteoblast-like cells is initiated at integrin αVβ3
Authors: Scarlett A , Parsons M P , Hanson P L , Sidhu K K , Milligan T P , Burrin J M
Published: February 2008

The aim of the present study was to examine whether triiodo-l-thyronine (T3) or l-thyroxine (T4) rapidly activated the mitogen-activated protein kinase (MAPK) intracellular signalling cascade in osteoblast-like cells and investigate whether this activation was initiated at the integrin αVβ3 cell surface receptor. Using PCR and western blotting, the expression of integrin αVβ3 mRNA and protein was demonstrated in the human osteoblast-like cell lines MG-63 and SaOS-2. The treatment of MG-63 cells with T3 (10 nM) or T4 (100 nM) for 10 min stimulated extracellular signal-regulated kinase activity (ERK, a component of the MAPK pathway) as determined by fluorescent immunocytochemistry and an immunocomplex activity assay (T3 by 10.7-fold, P<0.01 and T4 by 10.4-fold, P<0.01 compared with control). T3 (10 nM) and T4 (100 nM) also significantly stimulated thymidine incorporation into MG-63 cells by 2.3±0.7-fold (P<0.01) and 2.1±0.1-fold (P<0.05) respectively. To establish whether transient ERK activation via the integrin αVβ3 cell surface receptor mediated these effects, MG-63 cells were pretreated for 30 min with the specific MAPK kinase inhibitor, U0126 (1 μM), or an anti-integrin αVβ3-blocking antibody. Both pretreatments significantly inhibited T3- and T4-stimulated ERK activation and abolished T3-stimulated thymidine incorporation (P<0.01). T4-stimulated incorporation was significantly inhibited from 2.1- to 1.3-fold above control (P<0.05). Thus, our results suggest that T3 and T4 rapidly stimulate ERK activation in MG-63 cells via integrin αVβ3 and that one functional effect of this ERK activation is increased DNA synthesis.
Single-chain human gonadotropin analogs induce follicle development in sheep
Authors: Lemke Elyse P , Adams Betty M , Jablonka-Shariff Albina , Boime Irving , Adams Thomas E
Published: February 2008

The biopotency of single-chain analogs of human hFSH, human chorionic gonadotropin (hCG), and a dually active gonadotropin construct (FcCGβα) was examined. Sheep (bwt=61.4±1.1 kg; n=6 ewes/treatment) received a single injection (5 IU/kg, i.v.) of the hFSH analog (Fcα), the hCG analog (CGβα), FcCGβα, or Fcα and CGβα. Control animals received conditioned media. Ovulation was induced 3 days after analog administration using hCG (1000 IU, i.v.). Basal serum concentrations of estradiol (E2) were maintained in control animals. Neither Fcα nor CGβα alone induced significant E2 production during the pre-hCG period. Conversely, serum concentrations of E2 were increased (P<0.05) 2 days after administration of FcCGβα or Fcα+ CGβα. Although P4 concentrations were maintained at basal levels in control animals, significant increase was noted in all other treatment groups during the post-hCG period. Final ovarian weight was significantly increased (P<0.05) in animals receiving Fcα, Fcα+ CGβα, or FcCGβα, but not CGβα alone. Most of the ovarian enlargement was attributed to the formation of corpora lutea. Collectively, these observations demonstrate that the single-chain analogs of the human gonadotropins are active in sheep. The construct with singular FSH activity supports follicle development but not E2 production. Conversely, the construct that incorporates β-domains from both CG and FSH has dual activity. The long-lived nature of the single-chain constructs suggests that these recombinant gonadotropins may be effective alternatives to pituitary- or placenta-derived gonadotropins in out-of-season breeding and/or superovulation protocols.
Insulin secretion in islets from mice with a double knockout for the dense core vesicle proteins islet antigen-2 (IA-2) and IA-2β
Authors: Henquin Jean-Claude , Nenquin Myriam , Szollosi Andras , Kubosaki Atsutaka , Louis Notkins Abner
Published: February 2008

Islet antigen-2 (IA-2 or ICA 512) and IA-2β (or phogrin) are major autoantigens in type 1 diabetes. They are located in dense core secretory vesicles including insulin granules, but their role in β-cell function is unclear. Targeted disruption of either IA-2 or IA-2β, or both, impaired glucose tolerance, an effect attributed to diminution of insulin secretion. In this study, we therefore characterized the dynamic changes in cytosolic Ca2+([Ca2+]c) and insulin secretion in islets from IA-2/IA-2β double knockout (KO) mice. High glucose (15 mM) induced biphasic insulin secretion in IA-2/IA-2β KO islets, with a similar first phase and smaller second phase compared with controls. Since the insulin content of IA-2/IA-2β KO islets was ∼45% less than that of controls, fractional insulin secretion (relative to content) was thus increased during first phase and unaffected during second phase. This peculiar response occurred in spite of a slightly smaller rise in [Ca2+]c, could not be attributed to an alteration of glucose metabolism (NADPH fluorescence) and also was observed with tolbutamide. The dual control of insulin secretion via the KATP channel-dependent triggering pathway and KATP channel-independent amplifying pathway was unaltered in IA-2/IA-2β KO islets, and so were the potentiations by acetylcholine or cAMP (forskolin). Intriguingly, amino acids, in particular the cationic arginine and lysine, induced larger fractional insulin secretion in IA-2/IA-2β KO than control islets. In conclusion, IA-2 and IA-2β are dispensable for exocytosis of insulin granules, but are probably more important for cargo loading and/or stability of dense core vesicles.
Regulation of mammary parenchymal growth by the fat pad in prepubertal dairy heifers: role of inflammation-related proteins
Authors: Thorn Stephanie R , Purup Stig , Vestergaard Mogens , Sejrsen Kris , Meyer Matthew J , Van Amburgh Micheal E , Boisclair Yves R
Published: February 2008

In prepubertal heifers, the mammary parenchyma consists of epithelial and myoepithelial cells growing within a mammary fat pad (MFP). The MFP produces IGF-I that stimulates epithelial cell proliferation. In other species, adipose tissue expansion induces inflammation-related proteins (IRP), such as tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-1β transforming growth factor β, monocyte chemoattractant protein 1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1). The MFP production of IRP may influence mammary development because they impair not only insulin but also IGF-I actions. Moreover, the MFP expansion seen with development and increased nutrition coincides with reduced parenchymal growth. Our first objective was to identify IRP capable of altering proliferation of bovine mammary epithelial cells. TNFα, but neither IL-6, IL-1β MCP-1 nor PAI-1, inhibited basal and IGF-I-stimulated proliferation in MAC-T cells and primary cells isolated from heifers. Our second objective was to determine whether MFP expression of IRP changed in a manner consistent with inhibition of parenchymal growth. MFP expression was measured from 100 to 350 kg body weight (experiment 1) or at 240 kg body weight (experiment 2) in dairy heifers offered restricted or high planes of nutrition. In experiment 1, neither nutrition nor development altered MFP expression of TNFα. Nutrition increased MCP-1 and PAI-1 but only before MFP expansion and after cessation of allometric parenchymal growth. In experiment 2, nutrition increased TNFα and PAI-1, but not MCP-1. Thus, MFP expansion increases IRP production in cattle, but this is unlikely to contribute to reduced parenchymal growth observed with development or increased nutrition.
CYP27A1 expression in gilthead sea bream (Sparus auratus, L.): effects of calcitriol and parathyroid hormone-related protein
Authors: Bevelander Gideon S , Pinto Elsa S L C , Canario Adelino V M , Spanings Tom , Flik Gert
Published: February 2008

Little is known about vitamin D metabolism in fishes. Several reports have shown hydroxylase activities in various organs to produce vitamin D metabolites, but the enzymes involved have not been isolated or characterized. We isolated and characterized a renal mitochondrial hydroxylase, CYP27A1, that governs vitamin D metabolism in gilthead sea bream, Sparus auratus. The enzyme is highly expressed in kidney and to a far lesser extent in liver. When treated with 25-hydroxy vitamin D or calcitriol, the kidney responded differentially and time dependently with CYP27A1 mRNA expression levels. This response substantiates a role for CYP27A1 in fish vitamin D metabolism. This notion is strengthened by upregulation of CYP27A1 in sea bream treated with parathyroid hormone-related protein (PTHrP), and suggests an original role for PTHrP in calcitriol-regulated processes n fish similar to the role of PTH in mammalian vitamin D-dependent processes.
Health Selection Among New Immigrants
Authors: Akresh Ilana Redstone , Frank Reanne
Published: February 2008

Objectives. We sought to quantify the extent of health selection (i.e., the degree to which potential immigrants migrate, or fail to migrate, on the basis of their health status) among contemporary US immigrant groups and evaluate the degree that selection explains variation in self-rated health among US legal permanent residents.

Methods. Data came from the New Immigrant Survey 2003 cohort. We estimated the extent of positive and negative health selection through a unique series of questions asking immigrants in the United States to evaluate their health and compare it to that of citizens in their country of origin.

Results. The extent of positive health selection differed significantly across immigrant groups and was related to compositional differences in the socioeconomic profiles of immigrant streams.

Conclusions. The salience of socioeconomic status and English-language ability in explaining health differentials across immigrant groups reinforces the importance of further research on the role of these factors in contributing to the health of immigrants above and beyond the need for additional attention to the health selection process.
HIV and Sexually Transmitted Infection Risk Behaviors and Beliefs Among Black West Indian Immigrants and US-Born Blacks
Authors: Hoffman Susie , Beckford Jarrett Sharlene T. , Kelvin Elizabeth A. , Wallace Scyatta A. , Augenbraun Michael , Hogben Matthew , Liddon Nicole , McCormack William M. , Rubin Steve , Wilson Tracey E.
Published: February 2008

Objectives. We compared Black West Indian immigrants' and US-born Blacks' sexual and drug-use risk behaviors and their beliefs related to using condoms and informing partners of sexually transmitted infections (STIs) to identify possible differences in risk.

Methods. We drew data from the baseline assessment of a clinic-based intervention designed to increase partner STI notification.

Results. Black West Indian men were less likely than were US-born Black men to report nonregular partners. There were no differences in condom use. US-born Black women were more likely than were Black West Indian women to be extremely confident that they could convince their regular partners to use condoms (odds ratio [OR] = 2.40; 95% confidence interval [CI] = 1.21, 4.76), whereas there were no differences between Black West Indian and US-born Black men on this measure (interaction P = .06). US-born Black women were more likely than were Black West Indian women to be extremely confident in their ability to discuss STI screening with their regular partners (OR = 1.89; 95% CI = 1.03, 3.47).

Conclusions. Black West Indian women's lower levels of confidence that they can discuss STI screening with their regular partners and convince these partners to use condoms may increase their infection risk. Gender-sensitive interventions are warranted for Black West Indian immigrants, especially women.
Estimating the Return of Persons Living With HIV/AIDS to New Orleans: Methods for Conducting Disease Surveillance in the Wake of a Natural Disaster
Authors: Robinson William T. , Wendell Debbie , Gruber DeAnn , Foxhood Joseph , Scalco M. Beth , Zapata Amy
Published: February 2008

Hurricane Katrina disrupted HIV/AIDS surveillance by invalidating the New Orleans, La, surveillance and population data on persons living with HIV/AIDS. We describes 2 methods—population return and HIV surveillance data—to estimate the return of the infected population to New Orleans. It is estimated that 58% to 64% of 7068 persons living with HIV/AIDS returned by summer 2006. Although developed for HIV planning, these methods could be used with other disease surveillance programs.
Scope of Rapid HIV Testing in Private Nonprofit Urban Community Health Settings in the United States
Authors: Bogart Laura M. , Howerton Devery , Lange James , Becker Kirsten , Setodji Claude Messan , Asch Steven M.
Published: February 2008

Objectives. We examined patterns of rapid HIV testing in a multistage national random sample of private, nonprofit, urban community clinics and community-based organizations to determine the extent of rapid HIV test availability outside the public health system.

Methods. We randomly sampled 12 primary metropolitan statistical areas in 4 regions; 746 sites were randomly sampled across areas and telephoned. Staff at 575 of the sites (78%) were reached, of which 375 were eligible and subsequently interviewed from 2005 to 2006.

Results. Seventeen percent of the sites offered rapid HIV tests (22% of clinics, 10% of community-based organizations). In multivariate models, rapid test availability was more likely among community clinics in the South (vs West), clinics in high HIV/AIDS prevalence areas, clinics with on-site laboratories and multiple locations, and clinics that performed other diagnostic tests.

Conclusions. Rapid HIV tests were provided infrequently in private, nonprofit, urban community settings. Policies that encourage greater diffusion of rapid testing are needed, especially in community-based organizations and venues with fewer resources and less access to laboratories.
Analysis of Media Agenda Setting During and After Hurricane Katrina: Implications for Emergency Preparedness, Disaster Response, and Disaster Policy
Authors: Barnes Michael D. , Hanson Carl L. , Novilla Len M. B. , Meacham Aaron T. , McIntyre Emily , Erickson Brittany C.
Published: February 2008

Media agenda setting refers to the deliberate coverage of topics or events with the goal of influencing public opinion and public policy. We conducted a quantitative content analysis of 4 prominent newspapers to examine how the media gathered and distributed news to shape public policy priorities during Hurricane Katrina.

The media framed most Hurricane Katrina stories by emphasizing government response and less often addressing individuals’ and communities’ level of preparedness or responsibility. Hence, more articles covered response and recovery than mitigation and preparation. The newspapers studied focused significantly more on government response than on key public health roles in disaster management.

We discuss specific implications for public health professionals, policymakers, and mass media so that, in the future, coordination can be enhanced among these entities before, during, and after disasters occur.
Highly Active Antiretroviral Therapy Use and HIV Transmission Risk Behaviors Among Individuals Who Are HIV Infected and Were Recently Released From Jail
Authors: Clements-Nolle Kristen , Marx Rani , Pendo Michael , Loughran Eileen , Estes Milton , Katz Mitchell
Published: February 2008

We evaluated highly active anti-retroviral therapy (HAART) use and risk behaviors among 177 inmates who were HIV infected and were released and reincarcerated in San Francisco, Calif, jails over a 12-month period. During the month preceding reincarceration, HIV transmission risk behaviors were common among respondents, and 59% of those with a history of antiretroviral use were not taking HAART. HAART discontinuation was independently associated with homelessness, marijuana use, injection drug use, and not receiving community medical care. Postrelease interventions for inmates who are HIV infected are needed.
Relations Between Health Indicators and Residential Proximity to Coal Mining in West Virginia
Authors: Hendryx Michael , Ahern Melissa M.
Published: February 2008

We used data from a survey of 16493 West Virginians merged with county-level coal production and other covariates to investigate the relations between health indicators and residential proximity to coal mining. Results of hierarchical analyses indicated that high levels of coal production were associated with worse adjusted health status and with higher rates of cardiopulmonary disease, chronic obstructive pulmonary disease, hypertension, lung disease, and kidney disease. Research is recommended to ascertain the mechanisms, magnitude, and consequences of a community coal-mining exposure effect.