bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone‐metabolizing genes
Authors: Chia V. M. , Li Y. , Quraishi S. M. , Graubard B. I. , Figueroa J. D. , Weber J‐P. , Chanock S. J. , Rubertone M. V. , Erickson R. L. , McGlynn K. A. 
Published: July 2009

SummaryIt has been hypothesized that the increased prevalence of testicular germ cell tumours (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone‐metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p′‐dichlorodiphenyldichloroethylene, chlordane‐related compounds and polychlorinated biphenyls (PCBs), modified by polymorphisms in five hormone‐metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4 and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans‐nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR = 1.90, 95% CI, 1.01–3.56) compared with those with the lowest; there was no increased risk among men with the homozygous major allele genotype (p‐interactions = 0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB‐118 and PCB‐138 concentrations: the 45–55% reductions in TGCT risk for men with the highest quartiles compared with the lowest quartiles were only present in those who had a major homozygous allele genotype (p‐interactions < 0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.
Does hybridization between divergent progenitors drive whole‐genome duplication?
Authors: BUGGS RICHARD J. A. , SOLTIS PAMELA S. , SOLTIS DOUGLAS E. 
Published: July 2009

AbstractHybridization and whole‐genome duplication are both potential mechanisms of rapid speciation which sometimes act in concert. Recent surveys, showing that homoploid hybrid species tend to be derived from parents that are less evolutionarily divergent than parents of polyploid hybrid species (allopolyploids), have been interpreted as supporting a hypothesis that high divergence between hybridizing species drives whole‐genome duplication. Here, we argue that such conclusions stem from problems in sampling (especially the omission of autopolyploids) and null model selection, and underestimate the importance of selection. The data simply demonstrate that hybridization between divergent parents has a higher probability of successfully producing a species if followed by polyploidization.
Identification of a Campylobacter jejuni‐secreted protein required for maximal invasion of host cells
Authors: Christensen Jeffrey E. , Pacheco Sophia A. , Konkel Michael E. 
Published: July 2009

SummaryThe food‐borne pathogen Campylobacter jejuni is dependent on a functional flagellum for motility and the export of virulence proteins that promote maximal host cell invasion. Both the flagellar and non‐flagellar proteins exported via the flagellar type III secretion system contain a sequence within the amino‐terminus that directs their export from the bacterial cell. Accordingly, we developed a genetic screen to identify C. jejuni genes that encode a type III secretion amino‐terminal sequence that utilizes the flagellar type III secretion system of Yersinia enterocolitica and a phospholipase reporter (yplA). We screened a library of 321 C. jejuni genes and identified proteins with putative type III secretion amino‐terminal sequences. One gene identified by the screen was Cj1242. We generated a mutation in Cj1242, and performed growth rate, motility, secretion and INT 407 cell adherence and internalization assays. The C. jejuni Cj1242 mutant was not altered in growth rate or motility when compared with the wild‐type strain, but displayed an altered secretion profile and a reduction in host cell internalization. Based on the phenotype of the C. jejuni Cj1242 mutant, we designated the protein Campylobacter invasion antigen C (CiaC). Collectively, our findings indicate that CiaC is a potentially important virulence factor.
Impact of delayed introduction of sulfadoxine–pyrimethamine and arthemeter–lumefantrine on malaria epidemiology in KwaZulu‐Natal, South Africa
Authors: Knight S. E. , Anyachebelu E. J. , Geddes R. , Maharaj R. 
Published: July 2009

SummaryObjective  To investigate how delayed introduction of sulfadoxine–pyrimethamine (Fansidar®) and arthemeter–lumefantrine (Coartem®) as first‐line drugs for malaria in KwaZulu‐Natal contributed to the reported epidemics of 1985–1988 and 1997–2001.Methods  Ecological study assessing the association between malaria incidence and the emergence and degree of resistance to chloroquine from 1982 to 1988 and to sulfadoxine–pyrimethamine from 1991 to 2001, when each was the first‐line malaria treatment.Results  The relative risk for malaria infection after the level of drug resistance reached 10% was 4.5 (95% CI: 4.0–5.2) in the chloroquine period and 5.9 (95% CI: 5.7–6.1) in the sulfadoxine–pyrimethamine period. In the chloroquine period, the relative risk of death from malaria was tenfold (95% CI: 1.3–78.1) and the case fatality doubled after drug resistance had reached 10%. The risk of death during the sulfadoxine–pyrimethamine period was 10.8 (95% CI: 5.9–19.2) and case fatality 1.8 times higher after drug resistance had reached 10%, than before.Conclusion  Malaria epidemics in KwaZulu‐Natal, South Africa have been exacerbated by failing drug regimens. The establishment of sentinel sites for monitoring drug failure and the prompt adoption of guidelines based on World Health Organization standards in drug resistance should improve malaria control.
Accuracy of WHO CD4 cell count criteria for virological failure of antiretroviral therapy
Authors: Keiser Olivia , MacPhail Patrick , Boulle Andrew , Wood Robin , Schechter Mauro , Dabis François , Sprinz Eduardo , Egger Matthias ,   for the ART‐LINC Collaboration of the International Databases to Evaluate AIDS (IeDEA)
Published: July 2009

SummaryObjectives  To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment.Methods  Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV‐1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non‐nucleoside reverse transcriptase inhibitor‐based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/μl, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements ≥10 0000 copies/ml (higher threshold) or ≥500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated.Results  A total of 2009 patients were included. During 1856 person‐years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6–33.6%) for the higher and 12.6% (6.7–21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3–97.8%) and 97.3% (96.5–98.0%), for positive predictive value 9.5% (3.6–19.6%) and 19.0% (10.2–30.9%) and for negative predictive value 98.5% (97.9–99.0%) and 95.7% (94.7–96.6%).Conclusions  The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource‐limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource‐limited settings.
Low level genotypic chloroquine resistance near Malawi’s northern border with Tanzania
Authors: Bridges Daniel J. , Molyneux Malcolm , Nkhoma Standwell 
Published: July 2009

SummaryWe conducted a prevalence study of mutations in Plasmodium falciparum that are associated with antimalarial drug resistance at a rural site in Karonga near Malawi’s northern border with Tanzania. We found a higher prevalence of the key chloroquine resistance‐conferring mutation in the pfcrt gene (K76T) at this site in comparison with the prevalence in Blantyre, a city in the south of Malawi, far from an international border (9%vs. 0%; P < 0.0005). In contrast we found a lower prevalence of the quintuple dhfr/dhps mutation, which is highly predictive of SP treatment failure, at the Karonga site compared to Blantyre (76%vs. 88%; P < 0.005). The prevalence of the K76T pfcrt mutation at two Tanzanian sites close to the border with Malawi was recently reported to be over 50%. Our findings suggest a considerable ‘leakage’ of parasite antimalarial drug resistance across the border between two countries with different national malaria control policies and with different levels of resistance. Neighbouring countries should consider implementing common regional rather than national malaria treatment policies to prevent the spread of antimalarial drug resistance alleles across their borders.
Instability of the structure and allergenic protein content in Arizona cypress pollen
Authors: Shahali Y. , Pourpak Z. , Moin M. , Mari A. , Majd A. 
Published: July 2009

Background:  The allergenic characteristics of pollen and their levels of expression may vary depending on the plant species, the degree of maturation and the influence of environmental factors such as climate and atmospheric pollution. The objective of this survey was the comparison of the structure and allergenic protein content in Arizona cypress (Cupressus arizonica, CA) pollen collected just after microsporangia dehiscence and 2 weeks later in urban areas.Methods:  The morphology and structure of pollen were examined by scanning electron microscopy. Pollen protein content was quantitatively and qualitatively investigated by Bradford protein assay, SDS‐PAGE and densitometric analysis respectively. Fifteen allergic subjects, according to their clinical history of seasonal rhino‐conjunctivitis and bronchial asthma have been selected for skin prick testing and ImmunoCap using CA standard allergen and for immunoblotting using extracts of CA mature pollen collected from Tehran.Results:  After 2 weeks, numerous cracks and collapses appeared in pollen surfaces. Western blotting performed by using extracts of pollen collected from Tehran, revealed that sera‐specific immunoglobulin E of all allergic subjects reacted to a 35 kDa protein. The presence of this new major allergen and the decrease of Cup a 1 provide reliable explications about the low efficiency of standard commercial allergens in the diagnosis of the CA pollen allergy in Tehran.Conclusion:  The instability of the pollen structure and protein content affects CA pollen allergenic properties. This study also suggests that to optimize CA standard allergen preparations, the eventual variability of pollen allergenic components have to be considered for each region.
Clostridium difficile‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations, protective associations, and outcomes
Authors: Dubberke Erik R. , Reske Kimberlay A. , Srivastava Anand , Sadhu Justin , Gatti Robert , Young Rebecca M. , Rakes Lauren C. , Dieckgraefe Brian , DiPersio John , Fraser Victoria J. 
Published: July 2009

Dubberke ER, Reske KA, Srivastava A, Sadhu J, Gatti R, Young RM, Rakes LC, Dieckgraefe B, DiPersio J, Fraser VJ. Clostridium difficile‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations, protective associations, and outcomes. Clin Transplant 2009. DOI: 10.1111/j.1399‐0012.2009.01035.x © 2009 John Wiley & Sons A/S.Abstract: The purpose of this study was to evaluate risk factors, protective factors, and outcomes associated with Clostridium difficile‐associated disease (CDAD) in allogeneic hematopoietic stem‐cell transplant (HSCT) recipients. A case–control study was performed with 37 CDAD cases and 67 controls. In the multivariable logistic regression analysis, receipt of a third or fourth generation cephalosporin was associated with increased risk of CDAD (OR = 4.6, 95% CI 1.6–13.1). Receipt of growth factors was associated with decreased risk of CDAD (OR=0.1, 95% CI 0.02–0.3). Cases were more likely to develop a blood stream infection after CDAD than were controls at any point before discharge (p < 0.001). CDAD cases were more likely than controls to develop new onset graft‐vs.‐host disease (GVHD) (p < 0.001), new onset severe GVHD (p < 0.001), or new onset gut GVHD (p = 0.007) after CDAD/discharge. Severe CDAD was a risk factor for death at 180 d in multivariable Cox proportional hazards regression (HR=2.6, 95% CI 1.1–6.2). CDAD is a significant cause of morbidity and mortality in allogeneic HSCT patients, but modifiable risk factors exist. Further study is needed to determine the best methods of decreasing patients’ risk of CDAD.
Effects of acorn tannin content on infection by the fungus Ciboria batschiana
Authors: Takahashi A. , Ichihara Y. , Isagi Y. , Shimada T. 
Published: July 2009

Summary Ciboria batschiana, a fructicolous Discomycete, is a pathogen of Quercus serrata acorns, which contain considerable amounts of tannins in the cotyledons. It was hypothesized that the severity of C. batschiana infection may differ according to individual acorn tannin content. To examine this hypothesis, we investigated the relationship between survival of acorns to C. batschiana and tannin content, estimated non‐destructively using near infrared spectroscopy analysis. In addition, an inoculation experiment showed that acorns with higher tannin contents were more resistant to C. batschiana than those with lower tannin contents. We conclude that infection success of C. batschiana differs with tannin content of individual acorns.
Abnormal Expression of TIMP‐2, SOD, Vimentin and PAI Proteins in Cloned Bovine Placentae
Authors: Kim H‐R , Naruse K , Lee H‐R , Han R‐X , Park C‐S , Jin D‐I 
Published: July 2009

ContentsCloned mammals suffer from high rates of placental abnormality and foetal loss during pregnancy. We previously used 2‐D gel electrophoresis and mass spectrometry for global proteomic analysis of cloned and normal bovine placentae to identify differential protein expression patterns. Here, we used Western blot analysis to confirm the expression levels of several pregnancy‐related proteins putatively identified as being differentially expressed in somatic cell nuclear transfer (SCNT) vs normal bovine placentae. The expression levels of tissue inhibitor of metalloproteinase‐2 (TIMP‐2), its downstream protein, matrix metalloproteinase‐2 (MMP‐2), superoxide dismutase (SOD), vimentin and plasminogen activator inhibitor‐1 (PAI) were analysed in the placentae of SCNT cloned Korean native cattle that died immediately after birth and in normal placentae obtained by AI. Our results revealed that TIMP‐2 and SOD were up‐regulated in SCNT placenta compared with normal placenta, whereas MMP‐2 levels were comparable in cloned and normal placentae, and vimentin and PAI were significantly down‐regulated in SCNT compared with normal placentae. Our results suggest that key proteins of placental development are abnormally expressed in SCNT cloned bovine placentae, probably resulting in abnormal placental function and clonal mortality.
Breast‐feeding and overweight in Singapore school children
Authors: Sabanayagam Charumathi , Shankar Anoop , Chong Yap‐Seng , Wong Tien Yin , Saw Seang Mei 
Published: July 2009

AbstractBackground:  Studies from developed Western countries have shown inconsistent associations between breast‐feeding and overweight/obesity in children and adolescents. Few data are available from Asian populations. The purpose of the present study was therefore to evaluate the association between breast‐feeding and overweight/obesity in a study of 10–12‐year‐old children in Singapore.Methods:  A total of 797 school children (49% girls, 76% Chinese) who participated in the Singapore Cohort Study of the Risk Factors for Myopia (SCORM) were examined. Overweight/obesity (n = 179) was defined as age–sex‐specific body mass index (BMI) cut‐offs corresponding to BMI of 25 kg/m2 for overweight and 30 kg/m2 for obesity at age 18 based on the International Obesity Task Force (IOTF) reference.Results:  The prevalence of overweight/obesity was 22.5%. Overall, breast‐feeding was not found to be associated with overweight/obesity. After adjusting for potential confounders, the multivariable odds ratio (95% confidence interval) of overweight/obesity was 1.14 (0.80–1.63) for ever breast‐fed compared with never breast‐fed, 1.00 (0.57–1.72) for breast‐fed for >3 months compared to ≤3 months and 0.79 (0.47–1.34) for exclusive/mostly breast‐fed compared to partly breast‐fed.Conclusions:  No significant associations were detected among breast‐feeding, its type, and duration with overweight/obesity in this Asian cohort of 10–12‐year‐old children.
Pediatric models for adult target‐controlled infusion pumps
Authors: ANDERSON BRIAN J. 
Published: July 2009

SummaryTarget‐controlled infusion (TCI) pumps currently do not satisfactorily cater for the pediatric population, particularly for those under 5 years. Growth and development are two major aspects of children not readily apparent in adults, and these two aspects influence clearance (CL) and volume of distribution (V). In simple terms, V determines initial dose, and CL determines infusion rate at steady state. Three major covariates (size, age, and organ function) contribute to parameter variability in children. Size can be standardized for clearance in a 70‐kg person using the allometric ¾ power model. Remifentanil, a drug cleared by hydrolysis, can be modeled in all age groups by simple application of this model using a standardized clearance of 2790 ml·min−1 for a 70‐kg person. Allometry alone is insufficient to predict clearance in neonates and infants from adult parameters for most drugs used in anesthesia. The addition of a model describing maturation is required. The sigmoid Emax or Hill model has been found useful for describing this maturation process. Propofol maturation has been described with a mature clearance of 1.83 l·min−1·70kg−1, a maturation half‐time (TM50) of 44 weeks and a Hill coefficient of 4.9. Organ function also affects clearance, and propofol clearance is reduced in neonates and infants after cardiac surgery. Although pharmacokinetics (PK) in children is receiving increasing attention and is eminently programmable into a TCI device, pharmacodynamic (PD) measures in children remain poorly defined, partly because the depth of anesthesia monitoring are inadequate. Both PK and PD are necessary for safe use of TCI pumps.
GeoChip‐based analysis of functional microbial communities during the reoxidation of a bioreduced uranium‐contaminated aquifer
Authors: Van Nostrand Joy D. , Wu Wei‐Min , Wu Liyou , Deng Ye , Carley Jack , Carroll Sue , He Zhili , Gu Baohua , Luo Jian , Criddle Craig S. , Watson David B. , Jardine Philip M. , Marsh Terence L. , Tiedje James M. , Hazen Terry C. , Zhou Jizhong 
Published: July 2009

SummaryA pilot‐scale system was established for in situ biostimulation of U(VI) reduction by ethanol addition at the US Department of Energy's (DOE's) Field Research Center (Oak Ridge, TN). After achieving U(VI) reduction, stability of the bioreduced U(IV) was evaluated under conditions of (i) resting (no ethanol injection), (ii) reoxidation by introducing dissolved oxygen (DO), and (iii) reinjection of ethanol. GeoChip, a functional gene array with probes for N, S and C cycling, metal resistance and contaminant degradation genes, was used for monitoring groundwater microbial communities. High diversity of all major functional groups was observed during all experimental phases. The microbial community was extremely responsive to ethanol, showing a substantial change in community structure with increased gene number and diversity after ethanol injections resumed. While gene numbers showed considerable variations, the relative abundance (i.e. percentage of each gene category) of most gene groups changed little. During the reoxidation period, U(VI) increased, suggesting reoxidation of reduced U(IV). However, when introduction of DO was stopped, U(VI) reduction resumed and returned to pre‐reoxidation levels. These findings suggest that the community in this system can be stimulated and that the ability to reduce U(VI) can be maintained by the addition of electron donors. This biostimulation approach may potentially offer an effective means for the bioremediation of U(VI)‐contaminated sites.
Key targets of hormonal treatment of prostate cancer. Part 2: the androgen receptor and 5α‐reductase
Authors: Vis André N. , Schröder Fritz H. 
Published: July 2009

OBJECTIVEThe inhibition of 5α‐reductase (5AR) blocks the synthesis of the most powerful intracellular androgen, dihydrotestosterone (DHT). The prostate has two 5AR isoenzymes (5AR1 and 5AR2) that change in expression and cellular location during the development of prostate cancer and tumour progression. The objective of this review is to provide an understanding of the pharmacological properties and the potential clinical benefits of 5AR inhibition.METHODSWe searched Pubmed for data obtained from pharmacological, preclinical and clinical studies.RESULTS5AR1 expression increases with increasing aggressiveness and extension of malignant prostatic disease. Conversely, 5AR2 expression decreases from benign prostatic tissue to localized prostate cancer. The efficacy of 5AR2 monotherapy with finasteride alone or in combination with an androgen receptor antagonist on more final outcome measures seems to be limited. Combining an androgen receptor antagonist with a 5AR inhibitor in patients with asymptomatic, locally advanced or recurrent prostate cancer might be a reasonable first therapeutic hormonal approach. As plasma testosterone levels are maintained, beneficial effects on quality of life, potency and sexual function are expected. From studies on the dual 5AR inhibitor dutasteride, the drug produces a biochemical response in some men who progressed under androgen‐deprivation therapy, and is generally well tolerated.CONCLUSIONSAchieving more potent suppression of intracellular DHT synthesis by 5AR inhibition is expected to provide clinical benefit to patients. Previous studies have shown that 5AR inhibition, by dutasteride in particular, halts/delays the progression of disease, and might even cause regression of disease in patients with advanced prostate cancer.