bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive ventilation during walking in patients with severe COPD: a randomised cross-over trial
Authors: Dreher M. , Storre J. H. , Windisch W.
Published: March 2007

It was hypothesised that noninvasive positive-pressure ventilation (NPPV) applied during walking prevents exercise-induced hypoxaemia and improves exercise performance in severe chronic obstructive pulmonary disease (COPD) patients already receiving long-term NPPV.

A total of 20 COPD patients (mean±sdage 65.1±8.7 yrs, forced expiratory volume in one second 27±8% predicted and total lung capacity 116±27% pred) reporting dyspnoea, even during mild exertion, underwent two 6-min walking tests with a rollator and supplemental oxygen (2.1±0.9 L·min−1) in a randomised cross-over design: with and without pressure-limited NPPV as used at home (inspiratory:expiratory pressure 2.9±0.44:0.4±0.1 kPa (29±4:4±1 mbar), respiratory frequency 20±2 breaths·min−1).

The arterial oxygen tension significantly increased by 1.39±1.43 kPa (95% confidence interval (CI) 0.71–2.07 kPa) after walking with NPPV, but significantly decreased by 1.43±1.06 kPa (95% CI −1.92 – −0.94 kPa) without NPPV. Dyspnoea, as assessed by the Borg dyspnoea scale, significantly decreased from 6 (interquartile range (IQR) 4.5–10) to 4 (1.5–4.5) and walking distance significantly increased from 209 (IQR 178–279) to 252 (203–314) m when walking was NPPV-aided.

In chronic hypercapnic chronic obstructive pulmonary disease, high-intensity noninvasive positive-pressure ventilation can also be administered during walking with unchanged ventilator settings compared with settings used at rest, thus resulting in improved oxygenation, decreased dyspnoea and increased walking distance. Therefore, noninvasive positive-pressure ventilation during walking could prevent hypoxia-induced complications and could, in future, play a role in palliative care.
Cellular origin of pro-coagulant and (anti)-fibrinolytic factors in bleomycin-injured lungs
Authors: Wygrecka M. , Markart P. , Ruppert C. , Petri K. , Preissner K. T. , Seeger W. , Guenther A.
Published: March 2007

Excessive pro-coagulant and decreased fibrinolytic activities in the alveolar compartment have been repeatedly documented for inflammatory and fibrotic lung diseases. The current authors determined the contribution of different resident lung cells to the altered local production of coagulation- and fibrinolysis-system components in bleomycin-injured mouse lungsviacell-specific and quantitative assessment of mRNA levels of various pro-coagulant and (anti)-fibrinolytic factors.

Laser-assisted microdissection technology was used to sample specific cell populations in combination with subsequent mRNA analysis by real-time quantitative reverse transcriptase-PCR. Additionally, western blot analysis, immunohistochemistry and activity assays were performed.

Following bleomycin challenge, the strongest induction of tissue factor and plasminogen activator inhibitor (PAI)-1 mRNA expression was observed in alveolar macrophages (∼250- and 60-fold induction, respectively). These factors were also upregulated in alveolar type II cells, but to an approximately six-fold lesser extent. In contrast, PAI-2 expression was induced exclusively in alveolar macrophages. A slight increase of urokinase-type plasminogen activator (uPA) expression was also observed in alveolar macrophages (two-fold induction), but uPA activity was reduced due to a disproportionate increase of PAI production.

Alveolar macrophages and, to a lesser extent, alveolar type II cells are the main sources of locally produced pro-coagulant and anti-fibrinolytic factors in bleomycin-injured lungs.
Bacteria and mould components in house dust and children's allergic sensitisation
Authors: Gehring U. , Heinrich J. , Hoek G. , Giovannangelo M. , Nordling E. , Bellander T. , Gerritsen J. , de Jongste J. C. , Smit H. A. , Wichmann H-E. , Wickman M. , Brunekreef B.
Published: March 2007

It has been suggested that early childhood exposure to microbial agents decreases the risk of allergies in children. The current authors studied the association between microbial agents in house dust and allergic sensitisation in children aged 2–4 yrs.

Nested case-control studies were performed within ongoing birth cohort studies in Germany, the Netherlands and Sweden and ∼180 sensitised and 180 nonsensitised children were selected per country. Levels of bacterial endotoxin, β(1,3)-glucans and fungal extracellular polysaccharides (EPS) were measured in dust samples from the children’s mattresses and the living-room floors.

Combined across countries, higher amounts of mattress dust and higher mattress dust loads of endotoxin, β(1,3)-glucans and EPS were associated with a significantly decreased risk of sensitisation to inhalant allergens. After mutual adjustment, only the protective effect of the amount of mattress dust remained significant (odds ratio (95% confidence interval) 0.57(0.39–0.84)).

Higher amounts of mattress dust may decrease the risk of allergic sensitisation to inhalant allergens. The effect might be partly attributable to endotoxin, β(1,3)-glucans and extracellular polysaccharides, but could also reflect (additional) protective effects of (microbial) agents other than the ones measured. It is not possible to distinguish with certainty which component relates to the effect, since their levels are highly correlated.
Mechanism of G1 arrest in the Drosophilaeye imaginal disc
Authors: Escudero Luis M , Freeman Matthew
Published: March 2007

Background

Most differentiating cells are arrested in G1-phase of the cell cycle and this proliferative quiescence appears important to allow differentiation programmes to be executed. An example occurs in the Drosophila eye imaginal disc, where all cells are synchronized and arrested in G1 phase prior to making a fate choice either to initiate the first round of photoreceptor differentiation or to re-enter one terminal mitosis.

Results

We have analysed the mechanism of this temporally regulated G1-phase in order to develop an integrated model of this proliferative regulation. We find that an overlapping set of cell cycle inhibitors combine to form an efficient barrier to cell cycle progression. This barrier depends on both the primary secreted signals that drive retinal development, Dpp and Hh. Each of these has distinct, as well as partially overlapping functions, in ensuring that Cyclin E and dE2F1 are kept in check. Additionally, inhibition of Cyclin A by Roughex is essential, and this regulation is independent of Dpp and Hh.

Conclusion

One implication of these results is to further support the idea that Cyclin A has important functions in S-phase entry as well as in mitosis. The unexpectedly complex network of regulation may reflect the importance of cells being uniformly ready to respond to the inductive signals that coordinate retinal differentiation.
Silencing of beta-carotene hydroxylase increases total carotenoid and beta-carotene levels in potato tubers
Authors: Diretto Gianfranco , Welsch Ralf , Tavazza Raffaela , Mourgues Fabienne , Pizzichini Daniele , Beyer Peter , Giuliano Giovanni
Published: March 2007

Background

Beta-carotene is the main dietary precursor of vitamin A. Potato tubers contain low levels of carotenoids, composed mainly of the xanthophylls lutein (in the beta-epsilon branch) and violaxanthin (in the beta-beta branch). None of these carotenoids have provitamin A activity. We have previously shown that tuber-specific silencing of the first step in the epsilon-beta branch, LCY-e, redirects metabolic flux towards beta-beta carotenoids, increases total carotenoids up to 2.5-fold and beta-carotene up to 14-fold.

Results

In this work, we silenced the non-heme beta-carotene hydroxylases CHY1 and CHY2 in the tuber. Real Time RT-PCR measurements confirmed the tuber-specific silencing of both genes . CHY silenced tubers showed more dramatic changes in carotenoid content than LCY-e silenced tubers, with beta-carotene increasing up to 38-fold and total carotenoids up to 4.5-fold. These changes were accompanied by a decrease in the immediate product of beta-carotene hydroxylation, zeaxanthin, but not of the downstream xanthophylls, viola- and neoxanthin. Changes in endogenous gene expression were extensive and partially overlapping with those of LCY-e silenced tubers: CrtISO, LCY-b and ZEP were induced in both cases, indicating that they may respond to the balance between individual carotenoid species.

Conclusion

Together with epsilon-cyclization of lycopene, beta-carotene hydroxylation is another regulatory step in potato tuber carotenogenesis. The data are consistent with a prevalent role of CHY2, which is highly expressed in tubers, in the control of this step. Combination of different engineering strategies holds good promise for the manipulation of tuber carotenoid content.
A pragmatic randomised controlled trial of hydrotherapy and land exercises on overall well being and quality of life in rheumatoid arthritis
Authors: Eversden Lis , Maggs Fiona , Nightingale Peter , Jobanputra Paresh
Published: March 2007

Background

Hydrotherapy is highly valued by people with rheumatoid arthritis yet few studies have compared the benefits of exercises in heated water against exercises on land. In particular, data on quality of life is rarely reported. This is especially important because patients treated with hydrotherapy often report an enhanced sense of well-being. We report a randomised controlled trial in which we compared the effects of hydrotherapy with exercises on land on overall response to treatment, physical function and quality of life in patients with rheumatoid arthritis.

Methods

One hundred and fifteen patients with RA were randomised to receive a weekly 30-minute session of hydrotherapy or similar exercises on land for 6 weeks. Our primary outcome was a self-rated global impression of change – a measure of treatment effect on a 7-point scale ranging from 1(very much worse) to 7 (very much better) assessed immediately on completion of treatment. Secondary outcomes including EuroQol health related quality of life, EuroQol health status valuation, HAQ, 10 metre walk time and pain scores were collected at baseline, after treatment and 3 months later. Binary outcomes were analysed by Fisher's exact test and continuous variables by Wilcoxon or Mann-Whitney tests.

Results

Baseline characteristics of the two groups were comparable. Significantly more patients treated with hydrotherapy (40/46, 87%) were much better or very much better than the patients treated with land exercise (19/40, 47.5%), p < 0.001 Fisher's exact test. Eleven patients allocated land exercise failed to complete treatment compared with 4 patients allocated hydrotherapy (p = 0.09). Sensitivity analyses confirmed an advantage for hydrotherapy if we assumed non-completers would all not have responded (response rates 70% versus 38%; p < 0.001) or if we assumed that non-completers would have had the same response as completers (response rates 82% versus 55% p = 0.002). Ten metre walk time improved after treatment in both cases (median pre-treatment time for both groups combined 10.9 seconds, post-treatment 9.1 s, and 3 months later 9.6 s). There was however no difference between treatment groups. Similarly there were no significant differences between groups in terms of changes to HAQ, EQ-5D utility score, EQ VAS and pain VAS.

Conclusion

Patients with RA treated with hydrotherapy are more likely to report feeling much better or very much better than those treated with land exercises immediately on completion of the treatment programme. This perceived benefit was not reflected by differences between groups in 10-metre walk times, functional scores, quality of life measures and pain scores.
Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury
Authors: Mehta Ravindra L , Kellum John A , Shah Sudhir V , Molitoris Bruce A , Ronco Claudio , Warnock David G , Levin Adeera ,   the Acute Kidney Injury Network
Published: March 2007

Introduction

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI.

Methods

Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results.

Results

The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed.

Conclusion

We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.
Natural killer dendritic cells are an intermediate of developing dendritic cells
Authors: Chen Li , Calomeni Edward , Wen Jing , Ozato Keiko , Shen Rulong , Gao Jian-Xin
Published: March 2007

NK dendritic cells (DCs; NKDCs) appear to emerge as a distinct DC subset in humans and rodents, which have the functions of NK cells and DCs. However, the developmental relationship of NKDCs (CD11c+NK1.1+) to CD11c+NK1.1– DCs has not been addressed. Herein, we show that NKDCs exist exclusively in the compartment of CD11c+MHC II– cells in the steady state and express variable levels of DC subset markers, such as the IFN-producing killer DC marker B220, in a tissue-dependent manner. They can differentiate into NK1.1– DCs, which is accompanied by the up-regulation of MHC Class II molecules and down-regulation of NK1.1 upon adoptive transfer. However, NK cells (NK+CD11c–) did not differentiate into NK1.1+CD11c+ cells upon adoptive transfer. Bone marrow-derived Ly6C+ monocytes can be a potential progenitor of NKDCs, as some of them can differentiate into CD11c+NK1.1+ as well as CD11c+NK1.1– cells in vivo. The steady-state NKDCs have a great capacity to lyse tumor cells but little capability to present antigens. Our studies suggest that NKDCs are an intermediate of developing DCs. These cells appear to bear the unique surface phenotype of CD11c+NK1.1+MHC II– and possess strong cytotoxic function yet show a poor ability to present antigen in the steady state. These findings suggest that NKDCs may play a critical role in linking innate and adaptive immunity.
Drosophilafollicle cells are patterned by multiple levels of Notch signaling and antagonism between the Notch and JAK/STAT pathways
Authors: Assa-Kunik Efrat , Torres Isabel L. , Schejter Eyal D. , Johnston Daniel St , Shilo Ben-Zion
Published: March 2007

The specification of polar, main-body and stalk follicle cells in the germarium of the Drosophila ovary plays a key role in the formation of the egg chamber and polarisation of its anterior-posterior axis. High levels of Notch pathway activation, resulting from a germline Delta ligand signal, induce polar cells. Here we show that low Notch activation levels,originating from Delta expressed in the polar follicle cells, are required for stalk formation. The metalloprotease Kuzbanian-like, which cleaves and inactivates Delta, reduces the level of Delta signaling between follicle cells, thereby limiting the size of the stalk. We find that Notch activation is required in a continuous fashion to maintain the polar and stalk cell fates. We further demonstrate that mutual antagonism between the Notch and JAK/STAT signaling pathways provides a crucial facet of follicle cell patterning. Notch signaling in polar and main-body follicle cells inhibits JAK/STAT signaling by preventing STAT nuclear translocation, thereby restricting the influence of this pathway to stalk cells. Conversely,signaling by JAK/STAT reduces Notch signaling in the stalk. Thus, variations in the levels of Notch pathway activation, coupled with a continuous balance between the Notch and JAK/STAT pathways, specify the identity of the different follicle cell types and help establish the polarity of the egg chamber.
Spectrophotometric Assay for Complex I of the Respiratory Chain in Tissue Samples and Cultured Fibroblasts
Authors: Janssen Antoon JM , Trijbels Frans JM , Sengers Rob CA , Smeitink Jan AM , van den Heuvel Lambert P , Wintjes Liesbeth TM , Stoltenborg-Hogenkamp Berendien JM , Rodenburg Richard JT
Published: March 2007

Background: A reliable and sensitive complex I assay is an essential tool for the diagnosis of mitochondrial disorders, but current spectrophotometric assays suffer from low sensitivity, low specificity, or both. This deficiency is mainly due to the poor solubility of coenzyme-Q analogs and reaction mixture turbidity caused by the relatively high concentrations of tissue extract that are often required to measure complex I.

Methods: We developed a new spectrophotometric assay to measure complex I in mitochondrial fractions and applied it to muscle and cultured fibroblasts. The method is based on measuring 2,6-dichloroindophenol reduction by electrons accepted from decylubiquinol, reduced after oxidation of NADH by complex I. The assay thus is designed to avoid nonspecific NADH oxidation because electrons produced in these reactions are not accepted by decylubiquinone, resulting in high rotenone sensitivity.

Results: The assay was linear with time and amount of mitochondria. The Km values for NADH and 2,6-dichloroindophenol in muscle mitochondria were 0.04 and 0.017 mmol/L, respectively. The highest complex I activities were measured with 0.07 mmol/L decylubiquinone and 3.5 g/L bovine serum albumin. The latter was an essential component of the reaction mixture, increasing the solubility of decylubiquinone and rotenone. In patients with previously diagnosed complex I deficiencies, the new assay detected the complex I deficiencies in both muscle and fibroblasts.

Conclusions: This spectrophotometric assay is reproducible, sensitive, and specific for complex I activity because of its high rotenone sensitivity, and it can be applied successfully to the diagnosis of complex I deficiencies.
Komma & Co: Zwiegespräch zwischen Grammatik und Performanz
Authors: Bredel Ursula , Primus Beatrice
Published: March 2007

Three voices in this dialogue reconstruct the most common views on the main function of punctuation. Performance Senior hypothesizes that punctuation is motivated by intonation – a very common but nevertheless questionable assumption. The second voice, Grammar, argues that punctuation, especially the comma, should be analyzed as representing syntactic structure. In this model the comma is a universal sign for a clause-internal non-subordinative concatenation, such as coordination or dislocation. In German and other languages there is an additional condition that licenses the comma at a clause-internal sentence boundary. The third voice, Performance Junior, pleads for a performance-based, reader-oriented reconstruction of the whole system of punctuation. Including the full stop, the colon and the semicolon in her investigation, she shows that punctuation marks reflect specific strategies of parsing sentences. This is achieved by a compositional formal and functional analysis of complex marks such as colon and semicolon. The main empirical results of the present contribution and the problems that clause-internal non-subordinative concatenation such as coordination and dislocation pose for syntactic theories force us to reconsider the relation between grammar and performance. In short, small marks make us face big issues. Appropriately for an anniversary issue, we have chosen the dialogue as a genre invented by the Ancient Greeks for purposes of rhetorical entertainment and instruction. It is particularly well suited to render opposed opinions and to encourage the readers to pursue their own train of thought.
Stammkonstanz ohne Stützformen
Authors: Geilfuß-Wolfgang Jochen
Published: March 2007

In German as in several other languages, the written forms of stems are often more constant than their spoken forms. This has traditionally been described in at least two different ways. In one approach, spelling encodes the abstract sound representations of morphemes, therefore ignoring sound variation at successive levels; in another approach, the spelling of the stems is determined by privileged base forms. In this paper, I analyse the constant spelling of stems in inflection as a case of paradigm uniformity, doing without abstract sound representations and privileged base forms.
A Randomized, Controlled Trial of Acetaminophen, Ibuprofen, and Codeine for Acute Pain Relief in Children With Musculoskeletal Trauma
Authors: Clark Eric , Plint Amy C. , Correll Rhonda , Gaboury Isabelle , Passi Brett
Published: March 2007

OBJECTIVE. Our goal was to determine which of 3 analgesics, acetaminophen, ibuprofen, or codeine, given as a single dose, provides the most efficacious analgesia for children presenting to the emergency department with pain from acute musculoskeletal injuries.

PATIENTS AND METHODS. Children 6 to 17 years old with pain from a musculoskeletal injury (to extremities, neck, and back) that occurred in the preceding 48 hours before presentation in the emergency department were randomly assigned to receive orally 15 mg/kg acetaminophen, 10 mg/kg ibuprofen, or 1 mg/kg codeine. Children, parents, and the research assistants were blinded to group assignment. The primary outcome was change in pain from baseline to 60 minutes after treatment with study medication as measured by using a visual analog scale.

RESULTS. A total of 336 patients were randomly assigned, and 300 were included in the analysis of the primary outcome (100 in the acetaminophen group, 100 in the ibuprofen group, and 100 in the codeine group). Study groups were similar in age, gender, final diagnosis, previous analgesic given, and baseline pain score. Patients in the ibuprofen group had a significantly greater improvement in pain score (mean decrease: 24 mm) than those in the codeine (mean decrease: 11 mm) and acetaminophen (mean decrease: 12 mm) groups at 60 minutes. In addition, at 60 minutes more patients in the ibuprofen group achieved adequate analgesia (as defined by a visual analog scale <30 mm) than the other 2 groups. There was no significant difference between patients in the codeine and acetaminophen groups in the change in pain score at any time period or in the number of patients achieving adequate analgesia.

CONCLUSIONS. For the treatment of acute traumatic musculoskeletal injuries, ibuprofen provides the best analgesia among the 3 study medications.
Evaluation of Psychopathological Conditions in Children With Heavy Prenatal Alcohol Exposure
Authors: Fryer Susanna L. , McGee Christie L. , Matt Georg E. , Riley Edward P. , Mattson Sarah N.
Published: March 2007

OBJECTIVE. This study compared the prevalence of psychopathological conditions in children with heavy prenatal alcohol exposure (N = 39) and nonexposed, typically developing peers (N = 30), matched with respect to age, gender, and socioeconomic status.

METHODS. Caregivers were interviewed with either the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version, or the Computerized Diagnostic Interview Schedule for Children, Version IV. Statistical resampling methods were used to create 95% confidence intervals for the difference between the proportions of children with psychopathological conditions in the exposed and control groups.

RESULTS. Group differences were seen in the attention-deficit/hyperactivity disorder, depressive disorders, oppositional defiant disorder, conduct disorder, and specific phobia outcome categories. The group difference in the attention-deficit/hyperactivity disorder category was by far the largest effect observed.

CONCLUSIONS. These results suggest that fetal alcohol exposure should be considered a possible factor in the pathogenesis of childhood psychiatric disorders. These data provide clinically relevant information about the mental health problems that children with fetal alcohol exposure are likely to face.
Bacterial Imprinting of the Neonatal Immune System: Lessons From Maternal Cells?
Authors: Perez Pablo F. , Doré Joël , Leclerc Marion , Levenez Florence , Benyacoub Jalil , Serrant Patrick , Segura-Roggero Iris , Schiffrin Eduardo J. , Donnet-Hughes Anne
Published: March 2007

OBJECTIVE. We examined the presence of a natural bacterial inoculum in breast milk and its intracellular transport from the maternal intestine to the breast through the circulation.

METHODS. Breast milk and peripheral blood were collected aseptically from healthy donors at various times after delivery, and the presence of viable bacteria was determined through plating. Temporal temperature gradient gel electrophoresis was used to examine the bacterial ribosomal DNA content in milk cells, maternal peripheral blood mononuclear cells, and feces and in corresponding infant feces. Blood from nongravid nonlactating women served as control samples. Bacterial translocation to extraintestinal tissues was also evaluated in virgin, pregnant, and lactating mice.

RESULTS. Breast milk contained a low total concentration of microbes of <103 colony-forming units per mL. Temporal temperature gradient gel electrophoresis revealed that maternal blood and milk cells contained the genetic material of a greater biodiversity of enteric bacteria. Some bacterial signatures were common to infant feces and to samples of maternal origin. Bacterial translocation from the gut to mesenteric lymph nodes and mammary gland occurred during late pregnancy and lactation in mice.

CONCLUSIONS. Bacterial translocation is a unique physiologic event, which is increased during pregnancy and lactation in rodents. Human breast milk cells contain a limited number of viable bacteria but a range of bacterial DNA signatures, as also found in maternal peripheral blood mononuclear cells. Those peripheral blood mononuclear cells showed greater biodiversity than did peripheral blood mononuclear cells from control women. Taken together, our results suggest that intestinally derived bacterial components are transported to the lactating breast within mononuclear cells. We speculate that this programs the neonatal immune system to recognize specific bacterial molecular patterns and to respond appropriately to pathogens and commensal organisms.
Vaccine Effectiveness Against Medically Attended, Laboratory-Confirmed Influenza Among Children Aged 6 to 59 Months, 2003–2004
Authors: Shuler Carrie M. , Iwamoto Martha , Bridges Carolyn Buxton , Marin Mona , Neeman Ruth , Gargiullo Paul , Yoder Terrace A. , Keyserling Harry L. , Terebuh Pauline D.
Published: March 2007

OBJECTIVES. Influenza is a leading cause of illness among children. Studies rarely have measured influenza vaccine effectiveness among young children, particularly when antigenic match between vaccine and circulating viruses is suboptimal. We assessed vaccine effectiveness against medically attended, laboratory-confirmed influenza for children who were aged 6 to 59 months during the 2003–2004 influenza season.

METHODS. In a case-control study that was conducted in a single pediatric practice, case patients who were aged 6 to 59 months and had laboratory-confirmed influenza were age matched 1:2 to eligible control subjects. Vaccination status was ascertained as of the date of the case patient’s symptom onset. Conditional logistic regression was used to calculate vaccine effectiveness, adjusting for underlying medical conditions and health care usage.

RESULTS. We identified 290 influenza case patients who were seen for medical care from November 1, 2003, to January 31, 2004. Vaccine effectiveness among fully vaccinated children, compared with unvaccinated children, was 49%. Partially vaccinated children who were aged 6 to 23 months had no significant reduction in influenza (vaccine effectiveness: −70%), but partially vaccinated children who were aged 24 to 59 months had a significant (65%) reduction in influenza, compared with unvaccinated children.

CONCLUSIONS. Full vaccination provided measurable protection against laboratory-confirmed influenza among children who were aged 6 to 59 months during a season with suboptimal vaccine match. No vaccine effectiveness was identified with partial vaccination among children who were aged 6 to 23 months, affirming that children need to be fully vaccinated to obtain protective effects. These results strengthen the evidence of the vaccine’s ability to reduce substantially the burden of disease in this age group.
Citrin Deficiency: A Novel Cause of Failure to Thrive That Responds to a High-Protein, Low-Carbohydrate Diet
Authors: Dimmock David , Kobayashi Keiko , Iijima Mikio , Tabata Ayako , Wong Lee-Jun , Saheki Takeyori , Lee Brendan , Scaglia Fernando
Published: March 2007

The proband was born at 36 weeks, appropriate for gestational age, to nonconsanguineous white parents. There was no evidence of hyperbilirubinemia or intrahepatic cholestasis in the neonatal period, and she had normal newborn screen results. She presented with 3 episodes of life-threatening bleeding and anemia. The diagnostic evaluation for her bleeding diathesis revealed an abnormal clotting profile with no biochemical evidence for hepatocellular damage. She was incidentally noted to have severe growth deceleration that failed to respond to 502 kJ/kg (120 kcal/kg) per day of protein-hydrolyzed formula. An extensive diagnostic workup for failure to thrive, which was otherwise normal, included plasma amino acid analysis that revealed hyperglutaminemia and citrulline levels within the reference range. Testing of a repeat sample revealed isolated hypercitrullinemia. No argininosuccinic acid was detected. Her ammonia level and urine orotic acid were within the reference ranges. Subsequent plasma amino acid analysis exhibited a profile suggestive of neonatal intrahepatic cholestasis caused by citrin deficiency with elevations in citrulline, methionine, and threonine. Western blotting of fibroblasts demonstrated citrin deficiency, and a deletion for exon 3 was found in the patient's coding DNA of the SLC25A13 gene. On the basis of the experience with adults carrying this condition, the patient was given a high-protein, low-carbohydrate diet. The failure to thrive and bleeding diathesis resolved. When compliance with the dietary prescription was relaxed, growth deceleration was again noted, although significant bleeding did not recur. This is the first report of an infant of Northern European descent with citrin deficiency. The later age at presentation with failure to thrive and bleeding diathesis and without obvious evidence of neonatal intrahepatic cholestasis expands the clinical spectrum of citrin deficiency. This case emphasizes the importance of continued dietary control and growth monitoring in children with neonatal intrahepatic cholestasis caused by citrin deficiency and identifies a new metabolic entity responsible for failure to thrive.
Preventive Dental Care for Children in the United States: A National Perspective
Authors: Lewis Charlotte W. , Johnston Brian D. , Linsenmeyar Kristi A. , Williams Alexis , Mouradian Wendy
Published: March 2007

OBJECTIVE. Preventive dental care is a cornerstone of optimal oral health. However, in 1996, only 38% of US children received preventive dental care. We used the National Survey of Children's Health to (1) describe the proportion of US children with ≥1 preventive dental visit within the previous year, (2) identify factors that were associated with preventive dental care use, and (3) test the hypothesis that preventive dental care use by near-poor children is associated with State Child Health Insurance Program policies for covering dental care.

METHODS. The National Survey of Children's Health includes data from 102353 children, weighted to represent 72.7 million children, nationally. Our outcome of interest was ≥1 preventive dental visit in the past year. We conducted multivariate regression analysis to identify factors that were associated significantly with this outcome using Stata survey capabilities.

RESULTS. In 2003, 72% of US children had a reported preventive dental care visit in the previous year. On multivariable analysis, we found that being young, black or multiracial relative to white, lower income, and lacking a personal doctor were variables with a significantly lower likelihood of a preventive dental visit. Children in states with State Child Health Insurance Program dental coverage and broadest income eligibility had a 24% higher likelihood of a preventive dental visit when compared with children in states with limited or no State Child Health Insurance Program coverage for dental services, on adjusted analysis.

CONCLUSIONS. Although the proportion of US children with a preventive dental visit now is higher than previously reported, children who are at highest risk for dental problems still are those who are least likely to receive preventive dental care. When states cover preventive dental care at income eligibility levels ≥200% of the federal poverty level, there is a greater likelihood that near-poor children will receive preventive dental care.
Experience With Bisphosphonates in Osteogenesis Imperfecta
Authors: Glorieux Francis H.
Published: March 2007

Until recently, medical management of osteogenesis imperfecta, a genetic disorder of reduced bone mass and frequent fractures, was elusive, and treatment was focused on maximizing mobility and function. The introduction of bisphosphonates for the treatment of osteogenesis imperfecta 14 years ago changed this paradigm. Cyclic intravenous pamidronate therapy leads to an increase in bone density and a decrease in fracture rate in patients with osteogenesis imperfecta. Pamidronate therapy has a positive impact on functional parameters including improved energy, decreased bone pain, and increased ambulation. Histomorphometric studies have shown that the reduced osteoclast activity results in gains in cortical thickness and trabecular bone volume. Potential negative effects may include prolonged time to heal after osteotomies and a decrease in the rate of bone remodeling. Overall, it seems clear that the benefits of pamidronate therapy outweigh its potential risks in moderate-to-severe osteogenesis imperfecta, and pamidronate therapy has become the standard of care for patients with this condition. Questions remain regarding when treatment should be stopped and the need for pamidronate therapy in patients with mild osteogenesis imperfecta.
Has Blood Pressure Increased in Children in Response to the Obesity Epidemic?
Authors: Chiolero Arnaud , Bovet Pascal , Paradis Gilles , Paccaud Fred
Published: March 2007

The associations between elevated blood pressure and overweight, on one hand, and the increasing prevalence over time of pediatric overweight, on the other hand, suggest that the prevalence of elevated blood pressure could have increased in children over the last few decades. In this article we review the epidemiologic evidence available on the prevalence of elevated blood pressure in children and trends over time. On the basis of the few large population-based surveys available, the prevalence of elevated blood pressure is fairly high in several populations, whereas there is little direct evidence that blood pressure has increased during the past few decades despite the concomitant epidemic of pediatric overweight. However, a definite conclusion cannot be drawn yet because of the paucity of epidemiologic studies that have assessed blood pressure trends in the same populations and the lack of standardized methods used for the measurement of blood pressure and the definition of elevated blood pressure in children. Additional studies should examine if favorable secular trends in other determinants of blood pressure (eg, dietary factors, birth weight, etc) may have attenuated the apparently limited impact of the epidemic of overweight on blood pressure in children.
Incidence, Prognosis, and Risk Factors for Fatigue and Chronic Fatigue Syndrome in Adolescents: A Prospective Community Study
Authors: Rimes Katharine A. , Goodman Robert , Hotopf Matthew , Wessely Simon , Meltzer Howard , Chalder Trudie
Published: March 2007

OBJECTIVE. The objective of this study was to describe the incidence, prevalence, risk factors, and prognosis of fatigue, chronic fatigue, and chronic fatigue syndrome in 11- to 15-year-olds.

METHODS. A random general population sample (n = 842) of British adolescents and their parents were assessed at baseline and 4 to 6 months later. The main outcomes were fatigue, chronic fatigue, and chronic fatigue syndrome, operationally defined.

RESULTS. The incidence over 4 to 6 months was 30.3% for fatigue, 1.1% for chronic fatigue, and 0.5% for chronic fatigue syndrome. The point prevalence was 34.1% and 38.1% for fatigue, 0.4% and 1.1% for chronic fatigue, and 0.1% and 0.5% for chronic fatigue syndrome at time 1 and time 2, respectively. Of participants who were fatigued at time 1, 53% remained fatigued at time 2. The 3 cases of chronic fatigue and 1 case of chronic fatigue syndrome at time 1 had recovered by time 2. Higher risk for development of chronic fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and maternal distress; in multivariate analysis, baseline anxiety or depression remained a significant predictor of chronic fatigue. Increased risk for development of fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and older age; in multivariate analyses, these factors and female gender all were significant predictors of fatigue.

CONCLUSIONS. The incidence rates for chronic fatigue and chronic fatigue syndrome in this adolescent sample were relatively high, but the prognosis for these conditions was good. This prospective study provides evidence for an association between emotional/behavioral problems and subsequent onset of fatigue/chronic fatigue.
Patient and Hospital Correlates of Clinical Outcomes and Resource Utilization in Severe Pediatric Sepsis
Authors: Odetola Folafoluwa O. , Gebremariam Achamyeleh , Freed Gary L.
Published: March 2007

OBJECTIVE. Our goal was to describe patient and hospital characteristics associated with in-hospital mortality, length of stay, and charges for critically ill children with severe sepsis.

METHODS. Our study consisted of a retrospective study of children 0 to 19 years of age hospitalized with severe sepsis using the 2003 Kids' Inpatient Database. We generated national estimates of rates of hospitalization and then compared in-hospital mortality, length of stay, and total charges according to patient and hospital characteristics using multivariable regression methods. Severity of illness was measured by using all-patient refined diagnosis-related group severity of illness classification into minor, moderate, major, and extreme severity.

RESULTS. There were an estimated 21448 hospitalizations for severe pediatric sepsis nationally in 2003. The in-hospital mortality rate was 4.2%. Comorbid illness was present in 34% of hospitalized children. Most (70%) of the extremely ill children were admitted to children's hospitals. Length of stay was longer among patients with higher illness severity and nonsurvivors compared with survivors (13.5 vs 8.5 days). Hospitalizations at urban or children's hospitals were also associated with longer length of stay than nonchildren's or rural hospitals, respectively. Higher charges were associated with higher illness severity, and nonsurvivors had 2.5-fold higher total charges than survivors. Also, higher charges were observed among hospitalizations in urban or children's hospitals. In multivariable regression analysis, multiple comorbid illnesses, multiple organ dysfunction, and greater severity of illness were associated with higher odds of mortality and longer length of stay. Higher hospital charges and longer length of stay were observed among transfer hospitalizations and among hospitalizations to children's hospitals and nonchildren's teaching hospitals compared with hospitals, which had neither children's nor teaching status.

CONCLUSIONS. Mortality from severe pediatric sepsis is associated with patient illness severity, comorbid illness, and multiple organ dysfunction. Many characteristics are associated with resource consumption, including type of hospital, source of admission, and illness severity.
Testing for Drugs of Abuse in Children and Adolescents: Addendum—Testing in Schools and at Home
Authors:   Committee on Substance Abuse and Council on School Health
Published: March 2007

The American Academy of Pediatrics continues to believe that adolescents should not be drug tested without their knowledge and consent. Recent US Supreme Court decisions and market forces have resulted in recommendations for drug testing of adolescents at school and products for parents to use to test adolescents at home. The American Academy of Pediatrics has strong reservations about testing adolescents at school or at home and believes that more research is needed on both safety and efficacy before school-based testing programs are implemented. The American Academy of Pediatrics also believes that more adolescent-specific substance abuse treatment resources are needed to ensure that testing leads to early rehabilitation rather than to punitive measures only.
Epidermal Growth Factor Signaling Mediated by Grb2 Associated Binder1 Is Required for the Spatiotemporally Regulated Proliferation of Olig2-Expressing Progenitors in the Embryonic Spinal Cord
Authors: Hayakawa-Yano Yoshika , Nishida Keigo , Fukami Shinichi , Gotoh Yukiko , Hirano Toshio , Nakagawa Toshiyuki , Shimazaki Takuya , Okano Hideyuki
Published: March 2007

Gab1 (Grb2 associated binder1) has been identified as an adaptor molecule downstream of many growth factors, including epidermal growth factor (EGF), fibroblast growth factor, and platelet-derived growth factor, which have been shown to play crucial roles as mitotic signals for a variety of neural progenitor cells, including stem cells, both in vitro and in vivo. Here, we show that Gab1 deficiency results in a reduction in the number of Olig2-positive (Olig2+) progenitor cells in the developing mouse spinal cord after embryonic day 12.5 (E12.5), when gliogenesis starts in the pMN domain where the EGF receptor (EGFR) is expressed predominantly. Our in vitro analysis further revealed that Gab1 is essential for EGF-dependent proliferation of Olig2+ progenitor cells derived from the E12.5 ventral and E14.5 dorsal but not ventral spinal cord, whereas Gab1 is always required for the activation of Akt1 but not of ERK1/2. Moreover, we found that the action of the Gab1/Akt pathway is context-dependent, since constitutively active Akt1 could rescue the proliferation defect only in the E12.5 spinal cord of the Gab1-deficient mouse in vitro. Finally, we demonstrated that EGFR-deficient mice and Gab1-deficient mice showed a similar reduction in the number of Olig2+ progenitor cells in the developing spinal cord. These findings indicate that EGFR-mediated signaling through Gab1/Akt contributes to the sufficient expansion of Olig2+ progenitor cells in a spatiotemporally regulated manner, which represents the origin of glial cells in the developing spinal cord.

Disclosure of potential conflicts of interest is found at the end of this article.
Duox expression and related H2O2 measurement in mouse thyroid: onset in embryonic development and regulation by TSH in adult
Authors: Milenkovic Milutin , De Deken Xavier , Jin Ling , De Felice Mario , Di Lauro Roberto , Dumont Jacques E , Corvilain Bernard , Miot Francoise
Published: March 2007

In the thyroid, H2O2 is produced at the apical pole of thyrocytes by one or two NADPH oxidases (NOX), Duox1/2 proteins. The onset of Duox expression was analysed by immunohistochemistry in the developing mouse thyroid in parallel with thyroglobulin (Tg) iodination and the expression of other thyroid differentiation markers. Duox proteins were found at embryonic day (E) 15.5 and were mainly localised at the apical pole of thyrocytes. Tg was detected 1 day before (E14.5) and Tg iodination was concomitant with the expression of both Duox and Na+/I− symporter (NIS; E15.5). The role of TSH in regulating Duox expression and H2O2 accumulation was evaluated in thyroids of adult mice with reduced (Tshrhyt/hyt or mice treated with thyroxine) or increased (methimazole or perchlorate treatment) TSH/Tshr activity. In mice with suppressed TSH/Tshr activity, Duox expression was only partially decreased when compared with wild-type, as observed by western blot. In Tshrhyt/hyt strain, Duox was still expressed at the apical pole and H2O2 measurements were normal. On the other hand, chronic TSH stimulation of the gland led to a decrease of H2O2 measurements without affecting Duox expression. The onset of Duox protein expression is compatible with their proposed function in thyroid hormone synthesis and it can be considered as a functional marker of the developing thyroid. However, Duox expression in adult is much less regulated by TSH than NIS and thyroperoxidase. It is not always correlated with the overall thyroid H2O2 accumulation, highlighting the importance of additional regulatory mechanisms which control either the production or H2O2 degradation.
Pregnancy associated plasma protein-A is necessary for expeditious fracture healing in mice
Authors: Miller Bradley S , Bronk James T , Nishiyama Takayuki , Yamagiwa Hiroshi , Srivastava Alok , Bolander Mark E , Conover Cheryl A
Published: March 2007

Pregnancy-associated plasma protein A (PAPP-A), a metalloproteinase that regulates IGF bioavailability in vitro through cleavage of inhibitory IGF-binding protein-4 (IGFBP-4), has been implicated in skeletal development and injury repair responses. However, direct in vivo data are lacking. In this study, we used PAPP-A knock-out (KO) mice to determine the role of PAPP-A in fracture repair. Stabilized mid-shaft fractures were produced in femurs of 3-month-old mice. At 14 days post-fracture, complete bony bridging of the fracture callus was seen radiographically in wild-type but not in PAPP-A KO mice. Histological examination 5 to 28 days post-fracture showed reductions in the amount of intramembranous bone formation, cartilage production, endochondral ossification and remodeling in PAPP-A KO compared with wild-type mice. However, fracture healing appeared similar in both groups at 42 days post-fracture when analyzed by histology. A similar degree of healing strength in wild-type and PAPP-A KO femurs was demonstrated by mechanical testing at 28 and 42 days post-fracture. Untreated cultures of day 5 fracture calluses from wild-type mice showed robust IGFBP-4 protease activity and IGF receptor phosphorylation, whereas fracture calluses from PAPP-A KO mice had no IGFBP-4 protease activity and reduced IGF receptor phosphorylation. These data demonstrate a marked delay in fracture healing in PAPP-A KO compared with wild-type mice, and suggest that PAPP-A is necessary in the early phases of the process for expeditious fracture repair. The ability of PAPP-A to enhance local IGF action may be an important mechanism for optimizing the fracture repair response.