bluuebunny/crossref_metadata_2025 huggingface dataset:
Breaking the hierarchy - a new cluster selection mechanism for hierarchical clustering methods
Authors: Zahoránszky László A , Katona Gyula Y , Hári Péter , Málnási-Csizmadia András , Zweig Katharina A , Zahoránszky-Köhalmi Gergely
Published: October 2009

Background

Hierarchical clustering methods like Ward's method have been used since decades to understand biological and chemical data sets. In order to get a partition of the data set, it is necessary to choose an optimal level of the hierarchy by a so-called level selection algorithm. In 2005, a new kind of hierarchical clustering method was introduced by Palla et al. that differs in two ways from Ward's method: it can be used on data on which no full similarity matrix is defined and it can produce overlapping clusters, i.e., allow for multiple membership of items in clusters. These features are optimal for biological and chemical data sets but until now no level selection algorithm has been published for this method.

Results

In this article we provide a general selection scheme, the level independent clustering selection method, called LInCS. With it, clusters can be selected from any level in quadratic time with respect to the number of clusters. Since hierarchically clustered data is not necessarily associated with a similarity measure, the selection is based on a graph theoretic notion of cohesive clusters. We present results of our method on two data sets, a set of drug like molecules and set of protein-protein interaction (PPI) data. In both cases the method provides a clustering with very good sensitivity and specificity values according to a given reference clustering. Moreover, we can show for the PPI data set that our graph theoretic cohesiveness measure indeed chooses biologically homogeneous clusters and disregards inhomogeneous ones in most cases. We finally discuss how the method can be generalized to other hierarchical clustering methods to allow for a level independent cluster selection.

Conclusion

Using our new cluster selection method together with the method by Palla et al. provides a new interesting clustering mechanism that allows to compute overlapping clusters, which is especially valuable for biological and chemical data sets.
Statin prophylaxis and inflammatory mediators following cardiopulmonary bypass: a systematic review
Authors: Morgan Catherine , Zappitelli Michael , Gill Peter
Published: October 2009

Introduction

Induction of an inflammatory response is thought to have a significant role in the complications that follow cardiopulmonary bypass (CPB). The statin drugs are increasingly being recognized as having potent anti-inflammatory effects and hence have potential to influence an important mechanism of injury in CPB, although there is no current confirmation that this is indeed the case. Our objective was to systematically review if pre-operative prophylactic statin therapy, compared with placebo or standard of care, can decrease the inflammatory response in people undergoing heart surgery with CPB.

Methods

We performed a systematic and comprehensive literature search for all randomized controlled trials (RCTs) of open heart surgery with CPB in adults or children who received prophylactic statin treatment prior to CPB, with reported outcomes which included markers of inflammation. Two authors independently identified eligible studies, extracted data, and assessed study quality using standardized instruments. Weighted mean difference (WMD) was the primary summary statistic with data pooled using a random effects model. Descriptive analysis was used when data could not be pooled.

Results

Eight RCTs were included in the review, with the number of trials for each inflammatory outcome being even more limited. Pooled data demonstrated benefit with the use of statin to attenuate the post-CPB increase in interleukins 6 and 8 (IL-6, IL-8), peak high sensitivity C-reactive protein (hsCRP), and tumor necrosis factor-alpha (TNF-α) post-CPB (WMD [95% confidence interval (CI)] -23.5 pg/ml [-36.6 to -10.5]; -23.4 pg/ml [-35.8 to -11.0]; -15.3 mg/L [CI -26.9 to -3.7]; -2.10 pg/ml [-3.83 to -0.37] respectively). Very limited RCT evidence suggests that prophylactic statin therapy may also decrease adhesion molecules following CPB including neutrophil CD11b and soluble P (sP)-selectin.

Conclusions

Although the RCT evidence may suggest a reduction in post-CPB inflammation by statin therapy, the evidence is not definitive due to significant limitations. Several of the trials were not methodologically rigorous and statin intervention was highly variable in this small number of studies. This systematic review demonstrates that there is a significant gap that exists in the current literature in regards to the potential anti-inflammatory effect of statin therapy prior to CPB.
Feasibility Trial of Letrozole in Combination With Bevacizumab in Patients With Metastatic Breast Cancer
Authors: Traina Tiffany A. , Rugo Hope S. , Caravelli James F. , Patil Sujata , Yeh Benjamin , Melisko Michele E. , Park John W. , Geneus Stephanie , Paulson Matthew , Grothusen Jill , Seidman Andrew D. , Fornier Monica , Lake Diana , Dang Chau , Robson Mark , Theodoulou Maria , Flombaum Carlos D. , Norton Larry , Hudis Clifford A. , Dickler Maura N.
Published: October 2009

Purpose

Preclinical models suggest that the use of anti–vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor–positive metastatic breast cancer (MBC).

Methods

Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease.

Results

Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease ≥ 24 weeks was noted in 67%. Median PFS was 17.1 months.

Conclusion

Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).
American Society of Clinical Oncology 2009 Clinical Evidence Review on Radiofrequency Ablation of Hepatic Metastases From Colorectal Cancer
Authors: Wong Sandra L. , Mangu Pamela B. , Choti Michael A. , Crocenzi Todd S. , Dodd Gerald D. , Dorfman Gary S. , Eng Cathy , Fong Yuman , Giusti Andrew F. , Lu David , Marsland Thomas A. , Michelson Rob , Poston Graeme J. , Schrag Deborah , Seidenfeld Jerome , Benson Al B.
Published: October 2009

Purpose

To review the evidence about the efficacy and utility of radiofrequency ablation (RFA) for hepatic metastases from colorectal cancer (CRHM).

Methods

The American Society of Clinical Oncology (ASCO) convened a panel to conduct and analyze a comprehensive systematic review of the RFA literature from Medline and the Cochrane Collaboration Library.

Results

Because data were considered insufficient to form the basis of a practice guideline, ASCO has instead published a clinical evidence review. The evidence is from single-arm, retrospective, and prospective trials. No randomized controlled trials have been included. The following three clinical issues were considered by the panel: the efficacy of surgical hepatic resection versus RFA for resectable tumors; the utility of RFA for unresectable tumors; and RFA approaches (open, laparoscopic, or percutaneous). Evidence suggests that hepatic resection improves overall survival (OS), particularly for patients with resectable tumors without extrahepatic disease. Careful patient and tumor selection is discussed at length in the literature. RFA investigators report a wide variability in the 5-year survival rate (14% to 55%) and local tumor recurrence rate (3.6% to 60%). The reported mortality rate was low (0% to 2%), and the major complications rate was commonly reported to be between 6% and 9%. RFA is currently performed with all three approaches.

Conclusion

There is a compelling need for more research to determine the efficacy and utility of RFA to increase local recurrence-free, progression-free, and disease-free survival as well as OS for patients with CRHM. Clinical trials have established that hepatic resection can improve OS for patients with resectable CRHM.
Adaptation and failure of pancreatic β cells in murine models with different degrees of metabolic syndrome
Authors: Medina-Gomez Gema , Yetukuri Laxman , Velagapudi Vidya , Campbell Mark , Blount Margaret , Jimenez-Linan Mercedes , Ros Manuel , Orešič Matej , Vidal-Puig Antonio
Published: October 2009

The events that contribute to the expansion of β-cell mass and enhanced β-cell function in insulin-resistant states have not been elucidated fully. Recently, we showed that β-cell adaptation failed dramatically in adult, insulin-resistant POKO mice, which contrasts with the appropriate expansion of β cells in their ob/ob littermates. Thus, we hypothesised that characterisation of the islets in these mouse models at an early age should provide a unique opportunity to: (1) identify mechanisms involved in sensing insulin resistance at the level of the β cells, (2) identify molecular effectors that contribute to increasing β-cell mass and function, and (3) distinguish primary events from secondary events that are more likely to be present at more advanced stages of diabetes. Our results define the POKO mouse as a model of early lipotoxicity. At 4 weeks of age, it manifests with inappropriate β-cell function and defects in proliferation markers. Other well-recognised pathogenic effectors that were observed previously in 16-week-old mice, such as increased reactive oxygen species (ROS), macrophage infiltration and endoplasmic reticulum (ER) stress, are also present in both young POKO and young ob/ob mice, indicating the lack of predictive power with regards to the severity of β-cell failure. Of interest, the relatively preserved lipidomic profile in islets from young POKO mice contrasted with the large changes in lipid composition and the differences in the chain length of triacylglycerols in the serum, liver, muscle and adipose tissue in adult POKO mice. Later lipotoxic insults in adult β cells contribute to the failure of the POKO β cell. Our results indicate that the rapid development of insulin resistance and β-cell failure in POKO mice makes this model a useful tool to study early molecular events leading to insulin resistance and β-cell failure. Furthermore, comparisons with ob/ob mice might reveal important adaptive mechanisms in β cells with either therapeutic or diagnostic potential.
Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells
Authors: Kim Woo-Kyun , Meliton Vicente , Tetradis Sotirios , Weinmaster Gerry , Hahn Theodore J , Carlson Marc , Nelson Stanley F , Parhami Farhad
Published: October 2009

We previously reported that specific oxysterols stimulate osteogenic differentiation of pluripotent bone marrow stromal cells (MSCs) through activation of hedgehog (Hh) signaling and may serve as potential future therapies for intervention in osteopenia and osteoporosis. In this study we report that the osteogenic oxysterol 20(S)-hydroxycholesterol (20S) induces the expression of genes associated with Notch signaling. Using M2-10B4 (M2) MSCs, we found that 20S significantly induced HES-1, HEY-1, and HEY-2 mRNA expression compared with untreated cells, with maximal induction after 48 hours, whereas the nonosteogenic oxysterols did not. Similar observations were made when M2 cells were treated with sonic hedgehog (Shh), and the specific Hh pathway inhibitor cyclopamine blocked 20S-induced Notch target gene expression. 20S did not induce Notch target genes in Smo−/− mouse embryonic fibroblasts, further confirming the role of Hh signaling in 20S-induced expression of Notch target genes. Despite the inability of liver X-receptor (LXR) synthetic ligand TO901317 to induce Notch target genes in M2 cells, LXR knockdown studies using siRNA showed inhibition of 20S-induced HEY-1 but not HES-1 expression, suggesting the partial role of LXR signaling in MSC responses to 20S. Moreover, 20S-induced Notch target gene expression was independent of canonical Notch signaling because neither 20S nor Shh induced CBF1 luciferase reporter activity or NICD protein accumulation in the nucleus, which are hallmarks of canonical Notch signaling activation. Finally, HES-1 and HEY-1 siRNA transfection significantly inhibited 20S-induced osteogenic genes, suggesting that the pro-osteogenic effects of 20S are regulated in part by HES-1 and HEY-1. © 2010 American Society for Bone and Mineral Research
Persistent secondary hyperparathyroidism and vertebral fractures in kidney transplantation: Role of calcium-sensing receptor polymorphisms and vitamin D deficiency
Authors: Giannini Sandro , Sella Stefania , Silva Netto Fatima , Cattelan Catia , Dalle Carbonare Luca , Lazzarin Roberta , Marchini Francesco , Rigotti Paolo , Marcocci Claudio , Cetani Filomena , Pardi Elena , D'Angelo Angela , Realdi Giuseppe , Bonfante Luciana
Published: October 2009

Bone morbidity remains a major problem even after successful renal transplantation. We investigated the role of calcium-sensing receptor (CaSR) polymorphisms and 25-hydroxyvitamin D levels on the persistence of secondary hyperparathyroidism (SHPT) and their relationships with vertebral fractures (VFx) in 125 renal allograft recipients transplanted 44 ± 23 months before. All patients underwent evaluation of the main biochemical parameters of calcium metabolism as well as vertebral and femoral bone density. In 87 patients, CaSR polymorphisms (A986S, R990G, and Q1011E) also were assessed. X-ray images of the lateral spine were obtained in 102 subjects to perform vertebral morphometry. High parathyroid hormone (PTH) and 25-hydroxyvitamin D lower than 80 nmol/L were found in 54% and 97% of patients, respectively, with 40% of these showing vitamin D levels lower than 30 nmol/L. VFx were detected in 57% of the subjects. After multiple adjustments, 25-hydroxyvitamin D, age, and hemodialysis duration, but not CaSR polymorphisms, were found to be significant predictors of high PTH, whereas age and time since transplant were positively related with lower 25-hydroxyvitamin D values. PTH and time since transplant were significantly associated with VFx. Patients with two or more VFx showed serum PTH levels 50% higher than patients without fractures. We therefore conclude that persistent SHPT is a very common feature after renal transplantation and that, unlike CaSR polymorphisms, low 25-hydroxyvitamin D is involved in its pathogenesis. High PTH levels, in turn, are associated with an increased VFx risk, which confirms the need for strategies aimed at lowering serum PTH in this setting as well. © 2010 American Society for Bone and Mineral Research.
The pivotal role of the alternative NF-κB pathway in maintenance of basal bone homeostasis and osteoclastogenesis
Authors: Soysa Niroshani S , Alles Neil , Weih Debra , Lovas Agnes , Mian Anower Hussain , Shimokawa Hitoyata , Yasuda Hisataka , Weih Falk , Jimi Eijiro , Ohya Keiichi , Aoki Kazuhiro
Published: October 2009

The alternative NF-κB pathway consists predominantly of NF-κB-inducing kinase (NIK), IκB kinase α (IKKα), p100/p52, and RelB. The hallmark of the alternative NF-κB signaling is the processing of p100 into p52 through NIK, thus allowing the binding of p52 and RelB. The physiologic relevance of alternative NF-κB activation in bone biology, however, is not well understood. To elucidate the role of the alternative pathway in bone homeostasis, we first analyzed alymphoplasic (aly/aly) mice, which have a defective NIK and are unable to process p100, resulting in the absence of p52. We observed increased bone mineral density (BMD) and bone volume, indicating an osteopetrotic phenotype. These mice also have a significant defect in RANKL-induced osteoclastogenesis in vitro and in vivo. NF-κB DNA-binding assays revealed reduced activity of RelA, RelB, and p50 and no binding activity of p52 in aly/aly osteoclast nuclear extracts after RANKL stimulation. To determine the role of p100 itself without the influence of a concomitant lack of p52, we used p100−/− mice, which specifically lack the p100 inhibitor but still express p52. p100−/− mice have an osteopenic phenotype owing to the increased osteoclast and decreased osteoblast numbers that was rescued by the deletion of one allele of the relB gene. Deletion of both allele of relB resulted in a significantly increased bone mass owing to decreased osteoclast activity and increased osteoblast numbers compared with wild-type (WT) controls, revealing a hitherto unknown role for RelB in bone formation. Our data suggest a pivotal role of the alternative NF-κB pathway, especially of the inhibitory role of p100, in both basal and stimulated osteoclastogenesis and the importance of RelB in both bone formation and resorption. © 2010 American Society for Bone and Mineral Research
Shape variations and anisotropic growth of multiply twinned nanoparticles
Authors: Hofmeister Herbert
Published: October 2009

Cyclic multiple twins as nanoobjects that display nearly regular polyhedron shape variety together with strongly anisotropic shape variations due to growth processes are reviewed with regard to their unique shape evolution based on the specific formation modes as well as on the particular structure of twin-related subunits. The review includes (i) the shape variations due to growth by stacking of tetrahedral subunits, (ii) the role of growth conditions in the shape evolution of multiply twinned nanoparticles, and (iii) the modes of twin-based anisotropic growth including branching growth and unidirectional growth. The particular structures are introduced making use of electron microscopy structural characterization of multiply twinned metal nanoparticles as well as some non-metal examples, and instructive models of the various configurations.
Structural and chemical characterization of nanostructured III – V compound semiconductors by analytical TEM
Authors: Schneider Reinhard
Published: October 2009

The paper reports structural and microchemical investigations of low-dimensional semiconducting materials by combined imaging and spectroscopical techniques of transmission electron microscopy (TEM). The materials systems under investigation comprise graded (Al,Ga)As layers, (In,Ga)As quantum wires in V-grooved (001)InP, and (In,Ga)As quantum dots in GaAs. In order to elucidate structural peculiarities of these objects conventional and high-resolution TEM (CTEM/HRTEM) were performed, whereas information about the chemical composition and element distribution was obtained through electron energy loss spectroscopy (EELS), energy-filtered TEM (EFTEM), and energy-dispersive X-ray spectroscopy (EDXS). Particularly, the application possibilities of EFTEM are here demonstrated for revealing the local element content at high lateral resolution in a semi-quantitative manner.
Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies
Authors: Qvigstad E , Voldner N , Godang K , Henriksen T , Bollerslev J
Published: October 2009

Objective

To monitor β-cell function and insulin sensitivity longitudinally in a large cohort of pregnant women to elucidate mechanisms that influence glycemic control in pregnancy.

Design and methods

Five hundred and fifty-three pregnant Scandinavian women underwent 75 g oral glucose tolerance test (OGTT) at weeks 14–16 and 30–32. Insulin sensitivity (Matsuda index) and β-cell function (ratio of AUCinsulin to AUCglucose, AUCins/glc) were calculated from 520 complete tests, and subsequently β-cell function was adjusted for insulin sensitivity, rendering an oral disposition index (DIo).

Results

Eleven women (2.1%) had gestational diabetes mellitus (GDM1) at weeks 14–16, and 49 (9.4%) at weeks 30–32 (GDM2), which is higher than that previously reported in this region. In the subdivision of OGTT, more overweight (body mass index>25) was found in glucose-intolerant groups (glucose-tolerant women (normal glucose tolerance, NGT) 38 versus GDM2 women 58 and GDM1 women 82%, P<0.005). In early pregnancy, insulin sensitivity was lowest in GDM1, intermediate in GDM2, and highest in NGT. In late pregnancy, insulin sensitivity decreased in all groups, most in gestational diabetes. β-cell function demonstrated minor shifts during pregnancy, but when adjusted for decreasing insulin sensitivity, DIo levels fell by 40% (P<0.001). DIo was significantly attenuated relative to glucose intolerance (GDM1 25% and GDM2 53%) during pregnancy. In overweight women, DIo levels were lower throughout pregnancy (P<0.001 versus normal weight women), this reduction was significant (P<0.01) in both NGT (21–25%) and GDM2 subjects (26–49%).

Conclusion

β-cell function adjusted for insulin sensitivity (DIo) deteriorated during pregnancy in both glucose-tolerant and glucose-intolerant women. The failure to compensate the decrease in insulin sensitivity was accentuated in overweight women.
Adiponectin: serum levels, promoter polymorphism, and associations with birth size and cardiometabolic outcome in young adults born large for gestational age
Authors: Bueno Ana Carolina , Espiñeira Aniette R , Fernandes-Rosa Fábio L , de Souza Roberto Molina , de Castro Margaret , Moreira Ayrton Custódio , Bettiol Heloísa , Barbieri Marco Antonio , Antonini Sonir R
Published: October 2009

Objective

To assess whether the −11391G>A polymorphism in the regulatory region of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth, adiponectinemia, and cardiometabolic risk in adult life.

Design

Case–control study nested within a prospective cohort of 2063 community subjects born in 1978/1979 and followed since birth to date.

Methods

ADIPOQ −11391G>A genotype–phenotype associations were evaluated in 116 subjects born large for gestational age (LGA) and 392 gender-matched controls at birth (birth size), at 8–10 years (catch-down growth), and at 23–25 years of age (cardiometabolic profile).

Results

The −11391A variant allele frequency was higher in LGA subjects (P=0.04). AA genotype was associated with augmented probability of being born LGA (odds ratio=4.14; 95% confidence interval: 1.16–16.7; P=0.03). This polymorphism was associated neither with body composition nor with postnatal growth pattern. At the age of 23–25 years, the −11391A variant allele was associated with higher serum adiponectin levels (GG: 10.7±6.2 versus GA: 12.2±6.5 versus AA: 14.2±6.8 μg/ml; P<0.01). Subjects born LGA presented higher body mass index (BMI; P=0.01), abdominal circumference (P=0.04), blood pressure (P=0.04), and homeostasis assessment model for insulin resistance (P=0.01) than adequate for gestational age. Symmetry at birth did not influence these variables. The occurrence of catch-down of weight was associated with lower BMI and abdominal circumference (P<0.001) at 23–25 years.

Conclusions

The −11391A ADIPOQ gene variant was associated with increased chance of being born LGA and with higher adiponectin levels in early adult life.
Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome
Authors: Diamanti-Kandarakis Evanthia , Christakou Charikleia D , Kandaraki Eleni , Economou Frangiskos N
Published: October 2009

Polycystic ovary syndrome (PCOS) is now recognized to be the most common endocrinopathy in women of reproductive age with a prevalence of 6.6–6.8%. PCOS, a syndrome of unknown etiology, was initially regarded as a reproductive disorder. However, in the last 15 years the role of insulin resistance (IR) has been identified as a significant contributor to the pathogenesis of PCOS, and the metabolic and cardiovascular sequelae of the syndrome have been increasingly appreciated. The coexistence and interaction of reproductive and cardiometabolic abnormalities in the context of PCOS have created a need for a modified therapeutic management of affected women.

Insulin sensitizers, particularly metformin, have been introduced as a pharmaceutical option targeting not only IR, but several other aspects of the syndrome, including reproductive abnormalities. The landscape of the multifaceted actions of metformin evolves to broaden the therapeutic implications of this old drug in a new fashion for patients with PCOS. Most recently, the spectrum of metformin's targets has been expanded, and molecular studies have explored the tissue-specific mechanisms of metformin in the liver, the muscle, the endothelium, and the ovary. The use of metformin in pregnant women with PCOS comprises another scarcely explored, but promising area of research. This review attempts to cover the spectrum of metformin's cellular actions in different tissues and to summarize the current literature regarding the potential medical value of this medication in PCOS. Even if many of these actions are individually modest, they seem to be collectively sufficient to confer therapeutic benefits not only in cardiometabolic aspects but also in reproductive aspects of PCOS.
Serum 25(OH)D3 vitamin status of elderly Finnish women is suboptimal even after summer sunshine but is not associated with bone density or turnover
Authors: Pekkarinen Tuula , Turpeinen Ursula , Hämäläinen Esa , Löyttyniemi Eliisa , Alfthan Henrik , Välimäki Matti J
Published: October 2009

Objective

Concentrations of 50 and 75 nmol/l are proposed as serum 25-hydroxyvitamin D (25(OH)D) target for older people from the view of bone health. We evaluated vitamin D status of elderly Finnish women in light of these definitions, its relationship to bone mineral density (BMD) and turnover, and improvement by summer sunshine.

Design

Population-based study.

Methods

A total of 1604 ambulatory women aged 62–79 years were studied; 66% used vitamin D supplements. Serum 25(OH)D3was measured with HPLC before and after summer, and heel BMD in spring. In subgroups, serum parathyroid hormone (PTH) and type I procollagen aminoterminal propeptide (PINP) were analyzed.

Results

In spring, 60.3% of the women had 25(OH)D3≤50 nmol/l, and the target of 75 nmol/l was reached by 9.1%. For supplement users, the respective numbers were 52.1 and 11.9%. Serum 25(OH)D3did not determine BMD or bone turnover measured by serum PINP. Summer sunshine increased serum 25(OH)D3by 17.4% (P<0.0001), but in autumn 84% of the subjects remained under the target of 75 nmol/l. In supplement users, PTH remained stable but decreased in others during summer (P=0.025).

Conclusions

Vitamin D status of elderly Finnish women is suboptimal if 25(OH)D3levels of 50 or 75 nmol/l are used as a threshold. It is moderately increased by supplement intake and summer sunshine. However, 25(OH)D3concentrations did not influence bone density in terms of serum PINP and bone turnover rate.
Participation of DNA Polymerase ζ in Replication of Undamaged DNA in Saccharomyces cerevisiae
Authors: Northam Matthew R , Robinson Heather A , Kochenova Olga V , Shcherbakova Polina V
Published: October 2009

Translesion synthesis DNA polymerases contribute to DNA damage tolerance by mediating replication of damaged templates. Due to the low fidelity of these enzymes, lesion bypass is often mutagenic. We have previously shown that, in Saccharomyces cerevisiae, the contribution of the error-prone DNA polymerase ζ (Polζ) to replication and mutagenesis is greatly enhanced if the normal replisome is defective due to mutations in replication genes. Here we present evidence that this defective-replisome-induced mutagenesis (DRIM) results from the participation of Polζ in the copying of undamaged DNA rather than from mutagenic lesion bypass. First, DRIM is not elevated in strains that have a high level of endogenous DNA lesions due to defects in nucleotide excision repair or base excision repair pathways. Second, DRIM remains unchanged when the level of endogenous oxidative DNA damage is decreased by using anaerobic growth conditions. Third, analysis of the spectrum of mutations occurring during DRIM reveals the characteristic error signature seen during replication of undamaged DNA by Polζ in vitro. These results extend earlier findings in Escherichia coli indicating that Y-family DNA polymerases can contribute to the copying of undamaged DNA. We also show that exposure of wild-type yeast cells to the replication inhibitor hydroxyurea causes a Polζ-dependent increase in mutagenesis. This suggests that DRIM represents a response to replication impediment per se rather than to specific defects in the replisome components.
Genetic Testing of the Hypothesis That Hybrid Male Lethality Results From a Failure in Dosage Compensation
Authors: Barbash Daniel A
Published: October 2009

Several recent studies have suggested that F1 hybrid male lethality in crosses between Drosophila melanogaster and D. simulans is due to a failure in dosage compensation, caused by incompatibilities between D. simulans dosage compensation proteins and the D. melanogaster X chromosome. Contrary to the predictions of this hypothesis, mutations in four essential D. melanogaster dosage compensation genes are shown here to moderately increase rather than decrease hybrid male viability.
DNA Packaging by λ-Like Bacteriophages: Mutations Broadening the Packaging Specificity of Terminase, the λ-Packaging Enzyme
Authors: Feiss Michael , Reynolds Erin , Schrock Morgan , Sippy Jean
Published: October 2009

The DNA-packaging specificities of phages λ and 21 depend on the specific DNA interactions of the small terminase subunits, which have support helix-turn-recognition helix-wing DNA-binding motifs. λ-Terminase with the recognition helix of 21 preferentially packages 21 DNA. This chimeric terminase's ability to package λDNA is reduced ∼20-fold. Phage λ with the chimeric terminase is unable to form plaques, but pseudorevertants are readily obtained. Some pseudorevertants have trans-acting suppressors that change codons of the recognition helix. Some of these codons appear to remove an unfavorable base-pair contact; others appear to create a novel nonspecific DNA contact. Helper-packaging experiments show that these mutant terminases have lost the ability to discriminate between λ and 21 during DNA packaging. Two cis-acting suppressors affect cosB, the small subunit's DNA-binding site. Each changes a cosBλ-specific base pair to a cosB21-specific base pair. These cosB suppressors cause enhanced DNA packaging by 21-specific terminase and reduce packaging by λ-terminase. Both the cognate support helix and turn are required for strong packaging discrimination. The wing does not contribute to cosB specificity. Evolution of packaging specificity is discussed, including a model in which λ- and 21-packaging specificities diverged from a common ancestor phage with broad packaging specificity.
Snf1p Regulates Gcn5p Transcriptional Activity by Antagonizing Spt3p
Authors: Liu Yang , Xu Xinjing , Kuo Min-Hao
Published: October 2009

The budding yeast Gcn5p is a prototypic histone acetyltransferase controlling transcription of diverse genes. Here we show that Gcn5p is itself regulated by Snf1p and Spt3p. Snf1p likely controls Gcn5p via direct interaction. Mutating four residues in the Gcn5p catalytic domain, T203, S204, T211, and Y212 (TSTY), phenocopies snf1 null cells, including Gcn5p hypophosphorylation, hypoacetylation at the HIS3 promoter, and transcriptional defects of the HIS3 gene. However, overexpressing Snf1p suppresses the above phenotypes associated with the phosphodeficient TSTY mutant, suggesting that it is the interaction with Snf1p important for Gcn5p to activate HIS3. A likely mechanism by which Snf1p potentiates Gcn5p function is to antagonize Spt3p, because the HIS3 expression defects caused by snf1 knockout, or by the TSTY gcn5 mutations, can be suppressed by deleting SPT3. In vitro, Spt3p binds Gcn5p, but the interaction is drastically enhanced by the TSTY mutations, indicating that a stabilized Spt3p–Gcn5p interaction may be an underlying cause for the aforementioned HIS3 transcriptional defects. These results suggest that Gcn5p is a target regulated by the competing actions of Snf1p and Spt3p.
The Brains of Very Preterm Newborns in Clinically Stable Condition May Be Hyperoxygenated
Authors: Sorensen Line Caroe , Greisen Gorm
Published: October 2009

OBJECTIVE: The objective was to compare cerebral oxygenation in preterm newborns with that in healthy term newborns.

METHODS: Forty-six preterm newborns with gestational ages of <33 weeks and 25 healthy term newborns were included. The cerebral tissue oxygenation index (c-TOI) was measured by using near-infrared spectroscopy in clinical steady state on the first day of life (median age: 19.2 hours). The mean gestational ages and birth weights in the 2 groups were 29.1 ± 2.6 weeks versus 39.7 ± 1.3 weeks and 1307 ± 437 g versus 3484 ± 346 g, respectively. Three preterm infants needed mechanical ventilation and 11 received inotropic drugs. Later, 3 preterm infants developed intraventricular hemorrhage and 2 infants died. All term infants were healthy newborns recruited in the maternity ward.

RESULTS: There was a significant difference in c-TOI (preterm: 78.6% [95% confidence interval: 76.9%–80.3%]; term: 74.7% [95% confidence interval: 72.3%–77.1%]). Preterm newborns had significantly lower fractional tissue oxygen extraction, which suggests lower oxygen extraction in this group. There was no significant correlation between head size and c-TOI. The mean peripheral oxygen saturation was 95% in both groups. The median blood Pco2 for the preterm infants was 6.1 kPa (range: 3.4–7.3 kPa).

CONCLUSIONS: Cerebral oxygenation on the first day of life was higher in a group of relatively healthy, very preterm infants in stable condition, compared with healthy term newborns. Slightly elevated blood Pco2 could be the explanation. Prematurity itself does not seem to dispose preterm infants to global cerebral hypoxia.
Asthma Morbidity Among Children Evaluated by Asthma Case Detection
Authors: Gerald Joe K. , Sun Yanhui , Grad Roni , Gerald Lynn B.
Published: October 2009

OBJECTIVE: Population-based asthma detection is a potential strategy to reduce asthma morbidity in children; however, the burden of respiratory symptoms and health care use among children identified by case detection is not well known.

METHODS: Data come from a school-based asthma case detection validation study of 3539 children. Respiratory symptoms, emergency department (ED) visits, and hospitalizations were assessed by questionnaire for children whose case detection result and physician study diagnosis agreed.

RESULTS: Physician evaluation of 530 case detection results yielded 420 cases of agreement (168 children with previously diagnosed asthma, 39 with undiagnosed asthma, and 213 without asthma). Children with previously diagnosed asthma were more likely to be male (P < .0001). No differences in severity were observed in children with previously and undiagnosed asthma (P = .31). Children with undiagnosed asthma reported less frequent daytime and nighttime symptoms than children with previously diagnosed asthma but more than those without asthma (P < .0001). The proportion of children with at least 1 respiratory-related ED visit in the past year was 32%, 3%, and 3% for those with previously diagnosed, undiagnosed, and no asthma, respectively (P < .0001). The proportion with at least 1 respiratory-related hospitalization was 8%, 0%, and 0%, respectively (P < .0001). There were no differences in nonrespiratory ED visits (P = .93).

CONCLUSIONS: Despite similar physician-rated severity, children with undiagnosed asthma reported significantly less frequent respiratory symptoms and health care use than children with previously diagnosed asthma. These findings suggest that the potential health gains from case detection may be smaller than expected.
Can Association Between Preterm Birth and Autism be Explained by Maternal or Neonatal Morbidity?
Authors: Buchmayer Susanne , Johansson Stefan , Johansson Anna , Hultman Christina M. , Sparén Pär , Cnattingius Sven
Published: October 2009

OBJECTIVE: We examined whether an association between preterm birth and risk of autistic disorders could be explained by pregnancy complications or neonatal morbidity.

METHODS: This Swedish, population-based, case-control study included 1216 case subjects with autistic disorders who were born between 1987 and 2002 and 6080 control subjects who were matched with respect to gender, birth year, and birth hospital. We assessed associations between gestational age and autistic disorders and adjusted for maternal, birth, and neonatal characteristics. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: Compared with infants born at term, the unadjusted ORs for autistic disorders among very and moderately preterm infants were 2.05 [95% CI: 1.26–3.34] and 1.55 [95% CI: 1.22–1.96], respectively. When we controlled for maternal, pregnancy, and birth characteristics, ORs were reduced to 1.48 [95% CI: 0.77–2.84] and 1.33 [95% CI: 0.98–1.81], respectively. When we also controlled for neonatal complications, ORs were 0.98 [95% CI: 0.45–2.16] and 1.25 [95% CI: 0.90–1.75], respectively. Reductions in risks of autistic disorders related to preterm birth were primarily attributable to preeclampsia, small-for-gestational age birth, congenital malformations, low Apgar scores at 5 minutes, and intracranial bleeding, cerebral edema, or seizures in the neonatal period. Neonatal hypoglycemia, respiratory distress, and neonatal jaundice were associated with increased risk of autistic disorders for term but not preterm infants.

CONCLUSION: The increased risk of autistic disorders related to preterm birth is mediated primarily by prenatal and neonatal complications that occur more commonly among preterm infants.
Heel-Lancing in Newborns: Behavioral and Spectral Analysis Assessment of Pain Control Methods
Authors: Weissman Amir , Aranovitch Michal , Blazer Shraga , Zimmer Etan Z.
Published: October 2009

OBJECTIVE: Pain experience can alter clinical outcome, brain development, and subsequent behavior in newborns, primarily in preterm infants. The aims of this study were (1) to evaluate several simple, commonly used methods for pain control in newborns and (2) to evaluate the concordance between behavioral and autonomic cardiac reactivity to pain in term neonates during heel-lancing.

METHODS: A prospective study was conducted of 180 term newborn infants who were undergoing heel-lancing for routine neonatal screening of phenylketonuria and hypothyroidism. Newborns were assigned to 6 groups: (1) control (no pain relief intervention); (2) nonnutritive sucking; (3) holding by mother; (4) oral glucose solution; (5) oral formula feeding; or (6) breastfeeding. Outcome measures included the Neonatal Facial Coding System score; cry duration; and autonomic variables obtained from spectral analysis of heart rate variability before, during, and after heel-lancing.

RESULTS: Infants with no pain control showed the highest pain manifestation compared with newborns to whom pain control was provided. Infants who breastfed or received an oral formula showed the lowest increase in heart rate (21 and 23 beats per minute, respectively, vs 36; P < .01), lowest neonatal facial score (2.3 and 2.9, respectively, vs 7.1; P < .001), lowest cry duration (5 and 13 seconds, respectively, vs 49; P < .001), and lowest decrease in parasympathetic tone (−2 and −2.4, respectively, vs 1.2; P < .02) compared with the other groups.

CONCLUSIONS: Any method of pain control is better than none. Feeding and breastfeeding during heel-lancing were found to be the most effective methods of pain relief.
Secondhand Tobacco Smoke Exposure Among Children and Adolescents: United States, 2003–2006
Authors: Marano Cinzia , Schober Susan E. , Brody Debra J. , Zhang Cindy
Published: October 2009

OBJECTIVE: The implementation of policies that prohibit tobacco smoking in public places has resulted in a significant reduction in secondhand smoke (SHS) exposure in the US population; however, such policies do not extend to private homes, where children continue to be exposed. Our objective was to assess SHS exposure among US children and adolescents by using serum cotinine measures to compare those who were exposed to SHS in the home and those without home exposure.

METHODS: We analyzed serum cotinine data from the 2003–2006 National Health and Nutrition Examination Survey for 5518 children (3–11 years) and nonsmoking adolescents (12–19 years). We calculated geometric mean serum cotinine levels by sociodemographic and household characteristics according to self-reported home SHS exposure. Multiple regression analysis was conducted to evaluate independent predictors of serum cotinine levels.

RESULTS: Geometric mean serum cotinine levels were 1.05 ng/mL among those with home SHS exposure and 0.05 ng/mL among those without home exposure. Among children who were exposed to SHS at home, serum cotinine levels were inversely associated with age and were similar for non-Hispanic black and non-Hispanic white children. Conversely, among children without SHS exposure at home, serum cotinine levels were higher among non-Hispanic black compared with non-Hispanic white children, and there was no relationship with age. Mexican American children had the lowest level of SHS exposure.

CONCLUSIONS: Serum cotinine levels were an order of magnitude higher among children with reported SHS exposure at home compared with those with no exposure in the home.
Effectiveness of Belt Positioning Booster Seats: An Updated Assessment
Authors: Arbogast Kristy B. , Jermakian Jessica S. , Kallan Michael J. , Durbin Dennis R.
Published: October 2009

OBJECTIVE: The objective of this study was to provide an updated estimate of the effectiveness of belt-positioning booster (BPB) seats compared with seat belts alone in reducing the risk for injury for children aged 4 to 8 years.

METHODS: Data were collected from a longitudinal study of children who were involved in crashes in 16 states and the District of Columbia from December 1, 1998, to November 30, 2007, with data collected via insurance claims records and a validated telephone survey. The study sample included children who were aged 4 to 8 years, seated in the rear rows of the vehicle, and restrained by either a seat belt or a BPB seat. Multivariable logistic regression was used to determine the odds of injury for those in BPB seats versus those in seat belts. Effects of crash direction and booster seat type were also explored.

RESULTS: Complete interview data were obtained on 7151 children in 6591 crashes representing an estimated 120646 children in 116503 crashes in the study population. The adjusted relative risk for injury to children in BPB seats compared with those in seat belts was 0.55.

CONCLUSIONS: This study reconfirms previous reports that BPB seats reduce the risk for injury in children aged 4 through 8 years. On the basis of these analyses, parents, pediatricians, and health educators should continue to recommend as best practice the use of BPB seats once a child outgrows a harness-based child restraint until he or she is at least 8 years of age.
Influence of cement constitution and temperature on chloride binding in cement paste
Authors: Jensen O. Mejlhede , Korzen M. S. H. , Jakobsen H. J. , Skibsted J.
Published: October 2009

This paper describes effects of cement constitution and temperature on chloride binding in cement paste, which is an important subject in relation to lifetime modelling of reinforced concrete structures. The influence of cement constitution on chloride binding is investigated by substituting cement with pure cement clinker. Both theoretical considerations and experimental data for chloride binding in cement pastes are presented. A physicochemical based model to describe the influence of temperature on physical binding of chloride is presented. Solid-state 27Al and 29Si magic-angle spinning nuclear magnetic resonance spectroscopy has been used for quantification of the anhydrous and hydrated aluminate and silicate phases in the chloride-exposed cement pastes. The 27Al isotropic chemical shift and nuclear quadrupole coupling is reported for a synthetic sample of Friedel's salt, Ca2Al(OH)6Cl·2H2O.
The role of sodium during the hydration of alkali-activated slag
Authors: Wang Shao-Dong
Published: October 2009

This paper presents the results of an investigation into the role of sodium cations during the hydration of alkali-activated slag (AAS). This subject was studied by a combination of powder X-ray diffraction, high-resolution solid-state nuclear magnetic resonance spectroscopy and atomic absorption spectrum analysis. It was found that: there is no evidence that sodium cations take part in cation interchange or play a catalytic role in the early stages of hydration; no sodium cations of a detectable quantity are chemically incorporated into the structure of C-S-H solid solution; and no hydrates of zeolitic type or other crystalline phases containing sodium are formed in the AAS pastes studied. It has been concluded that most sodium in AAS pastes is present in pore solution and may be partly sorbed by C-S-H, and that sodium cations may only have the effect of balancing and maintaining OH− anions during the AAS hydration. The structural incorporation of sodium cations in C-S-H is deemed very limited.
Critical examination of drying damage to cement pastes
Authors: Zhang L. , Glasser F. P.
Published: October 2009

Several methods of drying cement paste prior to determining its physical properties, for example pore size distributions, are critically studied. Phase-pure preparations of ettringite and calcium monosulfoaluminate are used as sensitive indicators of damage. Oven drying at 105°C and drying over strong desiccants, for example MgClO4, is damaging. D-drying for 2–3 h is recommended as a robust but relatively non-damaging treatment. D-drying reduces the water content of ettringite to ∼30 H2O per formula unit, but removal of its zeolitic water, ∼1·7 H2O, does not degrade the structure. Monosulfoaluminate, AFm, is reduced from 12 to 10 H2O with shrinkage of its basal spacing from ∼9·0 to ∼8·2 Å. However, D-drying of pastes from commercial calcium sulfoaluminate rich in AFm usually gives mixtures of the ∼9·0 and ∼8·2 Å phases.
Reliability of the X-ray diffraction quantitative determination of the fraction unhydrated in the hardened paste of Portland cement
Authors: Sideris K. K.
Published: October 2009

The data from several studies concerning the non-evaporable water hydration criterion (as a reference criterion) and the fraction unhydrated in the hardened paste of Portland cement determined by the X-ray diffraction quantitative analysis are analysed in order to investigate the reliability of the X-ray method. The residue unhydrated in the hardened paste of Portland cement or of the major individual phases determined by the X-ray direct method does not agree with the residue estimated on the basis of the non-evaporable water criterion. The results of this study point to the unreliability of the X-ray diffraction quantitative analysis for determining the correct fraction hydrated in the hardened paste of Portland cement.