bluuebunny/crossref_metadata_2025 huggingface dataset:
Wavelength Dependence of the Polarization Singularities in a Two-Mode Optical Fiber
Authors: Inavalli V. V. G. Krishna , Pottapinjara Vijay , Viswanathan Nirmal K.
Published: September 2011

We present here an experimental demonstration of the wavelength dependence of the polarization singularities due to linear combination of the vector modes excited directly in a two-mode optical fiber. The coherent superposition of the vector modes excited by linearly polarized Gaussian beam as offset skew rays propagated in a helical path inside the fiber results in the generation of phase singular beams with edge dislocation in the fiber output. The polarization character of these beams is found to change dramatically with wavelength—from left-handed elliptically polarized edge dislocation to right-handed elliptically polarized edge-dislocation through disclinations. The measured behaviour is understood as being due to intermodal dispersion of the polarization corrections to the propagating vector modes, as the wavelength of the input beam is scanned.
Characterization of Porcine Endogenous Retrovirus Clones from the NIH Miniature Pig BAC Library
Authors: Yu Seong-Lan , Jung Woo-Young , Jung Kie-Chul , Cho In-Cheol , Lim Hyun-Tae , Jin Dong-Il , Lee Jun-Heon
Published: September 2011

Pigs have been considered as donors for xenotransplantation in the replacement of human organs and tissues. However, porcine endogenous retroviruses (PERVs) might transmit new infectious disease to humans during xenotransplantation. To investigate PERV integration sites, 45 PERV-positive BAC clones, including 12 PERV-A, 16 PERV-B, and 17 PERV-C clones, were identified from the NIH miniature pig BAC library. The analysis of 12 selected full-length sequences of PERVs, including the long terminal repeat (LTR) region, identified the expected of open reading frame length, an indicative of active PERV, in all five PERV-C clones and one of the four PERV-B clones. Premature stop codons were observed in only three PERV-A clones. Also, eleven PERV integration sites were mapped using a 5000-rad IMpRH panel. The map locations of PERV-C clones have not been reported before, thus they are novel PERV clones identified in this study. The results could provide basic information for the elimination of site-specific PERVs in selection of pigs for xenotransplantation.
Previous Leisure-Time Physical Activity Dose Dependently Decreases Ischemic Stroke Severity
Authors: Deplanque Dominique , Masse Isabelle , Libersa Christian , Leys Didier , Bordet Régis
Published: September 2011

In the present subanalysis of a cross-sectional study showing the favorable effect of prior transient ischemia, leisure-time physical activity, and lipid-lowering drug therapy on stroke severity, we aimed to evaluate whether previous physical activity was dose dependently associated to minor stroke (NIHSS 0–3) and to identify possible underlying factors. Among 362 consecutive patients, less severe stroke was related to weekly exercise duration prior to stroke (no exercise: 36.1%; <2 hours: 49.3%; 2–5 hours: 58.8%; >5 hours: 64.0%; ). Only weak and moderate exercise practices were protective (weak: 50.0%; moderate: 79.3%; heavy: 22.2%; ). Such a beneficial effect was observed independently of age and was associated with a trend to a lower frequency of arterial hypertension, alcohol abuse, and a better metabolic profile. Besides other therapeutic approaches, physical activity may be a simple way to decrease cerebral ischemia severity.
Protective Effect of Proanthocyanidin against Diabetic Oxidative Stress
Authors: Yokozawa Takako , Cho Eun Ju , Park Chan Hum , Kim Ji Hyun
Published: September 2011

We investigated the antidiabetic potential of proanthocyanidin and its oligomeric form in STZ-induced diabetic model rats anddb/dbtype 2 diabetic mice. Proanthocyanidin ameliorated the diabetic condition by significant decreases of serum glucose, glycosylated protein, and serum urea nitrogen as well as decreases of urinary protein and renal-AGE in STZ-induced diabetic rats and decrease of serum glucose as well as significant decrease of glycosylated protein indb/dbtype 2 diabetic mice. The suppression of ROS generation and elevation of the GSH/GSSG ratio were also observed in the groups administered proanthocyanidin. Moreover, proanthocyanidin, especially its oligomeric form, affected the inflammatory process with the regulation of related protein expression, iNOS, COX-2 and upstream regulators, NF-κB, and the IκB-α. In addition, it had a marked effect on hyperlipidemia through lowering significant levels of triglycerides, total cholesterol, and NEFA. Moreover, expressions in the liver of SREBP-1 and SREBP-2 were downregulated by the administration of proanthocyanidins. The protective effect against hyperglycemia and hyperlipidemia in type 1 and 2 diabetic models was significantly strong in the groups administered the oligomeric rather than polymeric form. This suggests that oligomers act as a regulator in inflammatory reactions caused by oxidative stress in diabetes.
Role of Adaptive Immunity in Alcoholic Liver Disease
Authors: Albano Emanuele
Published: September 2011

Stimulation of innate immunity is increasingly recognized to play an important role in the pathogenesis of alcoholic liver disease (ALD), while the contribution of adaptive immunity has received less attention. Clinical and experimental data show the involvement of Th-1 and Th-17 T-lymphocytes in alcoholic hepatitis. Nonetheless, the mechanisms by which alcohol triggers adaptive immunity are still incompletely characterized. Patients with advanced ALD have circulating IgG and T-lymphocytes recognizing epitopes derived from protein modification by hydroxyethyl free radicals and end products of lipid-peroxidation. High titers of IgG against lipid peroxidation-derived antigens are associated with an increased hepatic production of proinflammatory cytokines/chemokines. Moreover, the same antigens favor the breaking of self-tolerance towards liver constituents. In particular, autoantibodies against cytochrome P4502E1 (CYP2E1) are evident in a subset of ALD patients. Altogether these results suggest that allo- and autoimmune reactions triggered by oxidative stress might contribute to hepatic inflammation during the progression of ALD.
Affective-Cognitive Behavioral Therapy for Fibromyalgia: A Randomized Controlled Trial
Authors: Woolfolk Robert L. , Allen Lesley A. , Apter Jeffrey T.
Published: September 2011

A randomized controlled trial was conducted to assess the efficacy of an individually administered form of cognitive behavioral treatment for fibromyalgia. In an additive design, 76 patients diagnosed with fibromyalgia were randomly assigned to either the experimental treatment (affective-cognitive behavioral therapy, 10 individual sessions, one per week) administered concurrently with treatment-as-usual or to an unaugmented treatment-as-usual condition. Statistical analysis conducted at the end of treatment (3 months after the baseline assessment) and at a followup (9 months after the baseline assessment) indicated that the patients receiving the experimental treatment reported less pain and overall better functioning than control patients, both at posttreatment and at followup. The implications of these findings for future research are discussed.
Mast Cell Targeting Hampers Prostate Adenocarcinoma Development but Promotes the Occurrence of Highly Malignant Neuroendocrine Cancers
Authors: Pittoni Paola , Tripodo Claudio , Piconese Silvia , Mauri Giorgio , Parenza Mariella , Rigoni Alice , Sangaletti Sabina , Colombo Mario P.
Published: September 2011

Mast cells (MC) are c-Kit–expressing cells, best known for their primary involvement in allergic reactions, but recently reappraised as important players in either cancer promotion or inhibition. Here, we assessed the role of MCs in prostate tumor development. In prostate tumors from both tumor-prone transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and human patients, MCs are specifically enriched and degranulated in areas of well-differentiated (WD) adenocarcinoma but not around poorly differentiated (PD) foci that coexist in the same tumors. We derived novel TRAMP tumor cell lines, representative of WD and PD variants, and through pharmacologic stabilization or genetic ablation of MCs in recipients mice, we showed that MCs promote WD adenocarcinoma growth but are dispensable for PD tumors. WD tumors rely on MCs for matrix metalloprotease 9 (MMP-9) provision, as reconstitution of MC-deficient mice with wild-type but not MMP-9−/− MCs was sufficient to promote their growth. In contrast, PD tumors are MMP-9 self-competent, consistently with epithelial-to-mesenchymal transition. Such a dual source of MMP-9 was confirmed in human tumors, suggesting that MCs could be a good target for early-stage prostate cancer. Interestingly, in testing whether MC targeting could block or delay tumorigenesis in tumor-prone TRAMP mice, we observed a high incidence of early and aggressive tumors, characterized by a neuroendocrine (NE) signature and c-Kit expression. Taken together, these data underscore the contribution of MCs in tumor progression and uncover a new, opposite role of MCs in protecting against the occurrence of aggressive NE variants in prostate cancer. Cancer Res; 71(18); 5987–97. ©2011 AACR.
Mathematical Modeling Predicts the Effect of Folate Deficiency and Excess on Cancer-Related Biomarkers
Authors: Neuhouser Marian L. , Nijhout H. Frederik , Gregory Jesse F. , Reed Michael C. , James S. Jill , Liu Amy , Shane Barry , Ulrich Cornelia M.
Published: September 2011

Background: Folate is an essential B-vitamin that mediates one-carbon metabolism reactions, including nucleotide synthesis and others related to carcinogenesis. Both low- and high-folate status influences carcinogenesis.

Methods: We used a mathematical model of folate-mediated one-carbon metabolism to predict the effect of a range of intracellular epithelial folate concentrations (0.25–15.0 μmol/L) on methylation rate and purine and thymidylate synthesis. We also examined the interaction of these folate concentrations with polymorphisms in two enzymes [methylene tetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS)] in relation to the biochemical products.

Results: TS enzyme reaction rate increased markedly in response to the modeled higher intracellular folate concentrations. Changes in methylation rate were modest, whereas purine synthesis was only minimally related to increases in folate concentrations with an apparent threshold effect at 5.0 to 6.0 μmol/L. The relationship between folate concentrations and thymidylate synthesis was modified by genetic variation in TS but less so by variation in MTHFR. These gene–folate interactions modestly influenced purine synthesis in a nonlinear manner but only affected methylation rate under conditions of very high MTHFR activity.

Conclusion: Thymidylate synthesis is very sensitive to changes in epithelial intracellular folate and increased nearly fivefold under conditions of high intracellular folate. Individuals with genetic variations causing reduced TS activity may present even greater susceptibility to excessive folate.

Impact: Our observation that thymidylate synthesis increases dramatically under conditions of very elevated intracellular folate provides biological support to observations that excessive folic acid intake increases risk of both precursor lesions (i.e., colorectal adenomas) and cancer. Cancer Epidemiol Biomarkers Prev; 20(9); 1912–7. ©2011 AACR.
No Association of Type 2 Diabetes Risk Variants and Prostate Cancer Risk: the Multiethnic Cohort and PAGE
Authors: Waters Kevin M. , Wilkens Lynne R. , Monroe Kristine R. , Stram Daniel O. , Kolonel Laurence N. , Henderson Brian E. , Le Marchand Loïc , Haiman Christopher A.
Published: September 2011

Background: Epidemiologic studies have found evidence of an inverse association between diabetes status and prostate cancer risk. We explored the hypothesis that common genetic variation may explain, in part, the inverse association between diabetes and prostate cancer.

Methods: We tested 17 diabetes risk variants for association with prostate cancer risk in a prostate cancer case–control study of 2,746 cases and 3,317 controls from five racial/ethnic groups in the Multiethnic Cohort (MEC) study.

Results: After adjustment for multiple testing, none of the alleles were statistically significantly associated with prostate cancer risk. Aggregate scores that sum the risk alleles were also not significantly associated with risk.

Conclusions: We did not find evidence of association of this set of diabetes risk alleles with prostate cancer.

Impact: Resequencing and fine-mapping of the loci for diabetes and prostate cancer that were identified by genome-wide association studies are necessary to understand any genetic contribution for the inverse association between these common diseases. Cancer Epidemiol Biomarkers Prev; 20(9); 1979–81. ©2011 AACR.
Investigation of the Prevalence and Number of Aberrant Crypt Foci Associated with Human Colorectal Neoplasm
Authors: Sakai Eiji , Takahashi Hirokazu , Kato Shingo , Uchiyama Takashi , Hosono Kunihiro , Endo Hiroki , Maeda Shin , Yoneda Masato , Taguri Masataka , Nakajima Atsushi
Published: September 2011

Background: Aberrant crypt foci (ACF) are considered to be useful as surrogate biomarker for colorectal cancer (CRC), but the biological significance of ACF remains controversial. We attempted to investigate the relationship between the presence of ACF and human colorectal carcinogenesis using a relatively large sample size.

Methods: We carried out high-magnification chromoscopic colonoscopy to identify ACFs in 861 subjects undergoing a diagnostic endoscopy at the Yokohama City University Hospital. The present study compared the prevalence and number of ACFs in three subject groups (normal subjects, adenoma cases, and CRC cases). The correlations between the demographic and behavioral characteristics of the subjects and the prevalence of ACFs were also assessed.

Results: The prevalence of ACF was 64%, 88%, and 95%, and the mean number of ACF was 3.6, 6.2, and 10.1, in normal subjects, adenoma cases, and CRC cases, respectively. When differences in the prevalence and number of ACFs among age- and sex-stratified subject groups were examined, significant stepwise increments from normal subjects to adenoma cases to CRC cases were apparent (P < 0.001). Moreover, an age- and sex-adjusted multiple logistic regression analysis revealed that smoking and alcohol habits had a synergistic effect, increasing the prevalence of ACFs as well as the risk of CRC (P < 0.001).

Conclusions: These results suggested that ACF may serve as a reliable surrogate biomarker for human colorectal carcinogenesis.

Impact: The use of ACF as an endpoint may enable the size, duration, and cost of CRC chemoprevention studies to be reduced. Cancer Epidemiol Biomarkers Prev; 20(9); 1918–24. ©2011 AACR.
Polymorphisms in Nucleotide Excision Repair Genes and Endometrial Cancer Risk
Authors: Doherty Jennifer A. , Weiss Noel S. , Fish Sherianne , Fan Wenhong , Loomis Melissa M. , Sakoda Lori C. , Rossing Mary Anne , Zhao Lue Ping , Chen Chu
Published: September 2011

Background: Exposure to estrogens increases the risk of endometrial cancer. Certain estrogen metabolites can form bulky DNA adducts, which are removed via nucleotide excision repair (NER), and the ability to carry out this repair might be related to endometrial cancer risk.

Methods: We examined 64 tag and functional single-nucleotide polymorphisms (SNPs) in the NER genes ERCC1, ERCC2 (XPD), ERCC3 (XPB), ERCC4 (XPF), ERCC5 (XPG), LIG1, XPA, and XPC in a population-based case–control study in Washington state, with 783 endometrial cancer cases and 795 controls.

Results: The presence of ERCC5 rs4150386 C, LIG1 rs3730865 C, XPA rs2808667 T, or XPC rs3731127 T alleles was associated with risk of endometrial cancer, with respective age-, county-, and reference year–adjusted per-allele ORs and 95% CIs of 0.68 (0.53–0.87, P = 0.002), 1.46 (1.02–2.10, P = 0.04), 0.71 (0.52–0.97, P = 0.03), and 1.57 (1.13–2.17, P = 0.007), respectively.

Conclusions: Certain ERCC5, LIG1, XPA, and XPC genotypes might influence endometrial cancer risk.

Impact: Because of multiple redundancies in DNA repair pathways (and therefore a low prior probability) and the large number of associations examined, false-positive findings are likely. Further characterization of the relation between variation in NER genes and endometrial cancer risk is warranted. Cancer Epidemiol Biomarkers Prev; 20(9); 1873–82. ©2011 AACR.
Genetic Variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF Genes Are Prognostic Markers of Prostate Cancer-Specific Mortality
Authors: Lin Daniel W. , FitzGerald Liesel M. , Fu Rong , Kwon Erika M. , Zheng Siqun Lilly , Kolb Suzanne , Wiklund Fredrik , Stattin Pär , Isaacs William B. , Xu Jianfeng , Ostrander Elaine A. , Feng Ziding , Grönberg Henrik , Stanford Janet L.
Published: September 2011

Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer.

Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 top-ranking SNPs (P ≤ 0.01, FDR ≤ 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients.

Results: Five SNPs were validated (P ≤ 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2–1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (Ptrend = 0.001), adjusting for clinicopathologic factors known to influence prognosis.

Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer.

Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated. Cancer Epidemiol Biomarkers Prev; 20(9); 1928–36. ©2011 AACR.
Physical, Mental, and Neurocognitive Status and Employment Outcomes in the Childhood Cancer Survivor Study Cohort
Authors: Kirchhoff Anne C. , Krull Kevin R. , Ness Kirsten K. , Armstrong Gregory T. , Park Elyse R. , Stovall Marilyn , Robison Leslie L. , Leisenring Wendy
Published: September 2011

Introduction: We examined the relationship of physical, mental, and neurocognitive function with employment and occupational status in the Childhood Cancer Survivor Study.

Methods: We included survivors 25 years or older with available short form-36 (physical and mental health component scores), brief symptom inventory (depression, anxiety, and somatization), and neurocognitive questionnaire (task efficiency, emotional regulation, organization, and memory). We generated relative risks (RR) from generalized linear models for these measures on unemployment (n = 5,386) and occupation (n = 3,763) outcomes adjusted for demographic and cancer-related factors and generated sex-stratified models.

Results: Poor physical health was associated with an almost eightfold higher risk of health-related unemployment (P < 0.001) compared to survivors with normal physical health. Male survivors with somatization and memory problems were approximately 50% (P < 0.05 for both) more likely to report this outcome, whereas task efficiency limitations were significant for both sexes (males: RR = 2.43, P < 0.001; females: RR = 2.28, P < 0.001). Employed female survivors with task efficiency, emotional regulation, and memory limitations were 13% to 20% (P < 0.05 for all) less likely to work in professional or managerial occupations than unaffected females.

Conclusions: Physical problems may cause much of the health-related unemployment among childhood cancer survivors. Whereas both male and female survivors with neurocognitive deficits—primarily in task efficiencies—are at risk for unemployment, employed female survivors with neurocognitive deficits may face poor occupational outcomes more often than males.

Impact: Childhood cancer survivors are at risk for poor employment outcomes. Screening and intervention for physical, mental, and neurocognitive limitations could improve employment outcomes for this population. Cancer Epidemiol Biomarkers Prev; 20(9); 1838–49. ©2011 AACR.
Serum 25-Hydroxy Vitamin D and Prostate Cancer Risk in a Large Nested Case–Control Study
Authors: Albanes Demetrius , Mondul Alison M. , Yu Kai , Parisi Dominick , Horst Ronald L. , Virtamo Jarmo , Weinstein Stephanie J.
Published: September 2011

Background: Vitamin D compounds inhibit prostate tumorigenesis experimentally, but epidemiologic data are inconsistent with respect to prostate cancer risk, with some studies suggesting nonsignificant positive associations.

Methods: The 25-hydroxy vitamin D [25(OH)D]–prostate cancer relation was examined in a nested case–control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of 50- to 69-year-old Finnish men. We matched 1,000 controls to 1,000 cases diagnosed during up to 20 years of follow-up on the basis of age (±1 year) and fasting blood collection date (±30 days). Conditional multivariate logistic regression models estimated ORs and 95% CIs. All statistical significance testing was 2-sided.

Results: Cases had nonsignificantly 3% higher serum 25(OH)D levels (P = 0.19). ORs (95% CIs) for increasing season-specific quintiles of 25(OH)D concentrations were 1.00 (reference), 1.29 (0.95–1.74), 1.34 (1.00–1.80), 1.26 (0.93–1.72), and 1.56 (1.15–2.12), with Ptrend = 0.01. Analyses based on prespecified clinical categories and season-adjusted values yielded similar results. These findings seemed stronger for aggressive disease [OR (95% CI) for fifth quintile of serum 25(OH)D [1.70 (1.05–2.76), Ptrend = 0.02], among men with greater physical activity [1.85 (1.26–2.72), Ptrend = 0.002], higher concentrations of serum total cholesterol [2.09 (1.36–3.21), Ptrend = 0.003] or α-tocopherol [2.00 (1.30–3.07), Ptrend = 0.01] and higher intakes of total calcium [1.82 (1.20–2.76), Ptrend = 0.01] or vitamin D [1.69 (1.04–2.75), Ptrend = 0.08], or among those who had received the trial α-tocopherol supplements [1.74 (1.15–2.64), Ptrend = 0.006].

Conclusion: Our findings indicate that men with higher vitamin D blood levels are at increased risk of developing prostate cancer.

Impact: Greater caution is warranted with respect to recommendations for high-dose vitamin D supplementation and higher population target blood levels. Cancer Epidemiol Biomarkers Prev; 20(9); 1850–60. ©2011 AACR.
Parity and Lactation in Relation to Estrogen Receptor Negative Breast Cancer in African American Women
Authors: Palmer Julie R. , Boggs Deborah A. , Wise Lauren A. , Ambrosone Christine B. , Adams-Campbell Lucile L. , Rosenberg Lynn
Published: September 2011

Background: Estrogen receptor (ER)-negative breast tumors and progesterone receptor (PR)-negative breast tumors occur more commonly in women of African ancestry. Recent research indicates that the effects of reproductive factors may differ by hormone receptor status. We assessed the relation of parity and lactation to incidence of ER−/PR− and ER+/PR+ breast cancer in a cohort of African American women.

Methods: From 1995–2009, 457 incident cases of ER+/PR+ and 318 cases of ER−/PR− breast cancer were confirmed by review of pathology data among 59,000 African American women followed in the Black Women's Health Study through biennial questionnaires. HRs and two-sided 95% CIs for the incidence of breast cancer subtypes were derived from proportional hazards regression models that controlled for age, reproductive variables, and breast cancer risk factors.

Results: Higher parity was associated with an increased risk of ER−/PR− breast cancer (HR = 1.48, 95% CI: 0.98–1.84 for 3+ versus 0 births, Ptrend = 0.009), and with a reduced risk of ER+/PR+ cancer (HR = 0.53, 95% CI: 0.39–0.73 for 3+ versus 0 births, Ptrend = 0.0002). Among women who had breastfed, high parity was no longer associated with increased incidence of ER−/PR− breast, but the inverse association with ER+/PR+ cancer persisted.

Conclusions: The higher incidence of ER−/PR− breast cancer in African American women may be explained in part by their higher parity and lower prevalence of breastfeeding relative to white women.

Impact: Increased breastfeeding may lead to a reduction in the incidence of this breast cancer subtype. Cancer Epidemiol Biomarkers Prev; 20(9); 1883–91. ©2011 AACR.
Increased Mortality in Women with Breast Cancer Detected during Pregnancy and Different Periods Postpartum
Authors: Johansson Anna L.V. , Andersson Therese M-L. , Hsieh Chung-Cheng , Cnattingius Sven , Lambe Mats
Published: September 2011

Background: Because of a continued trend toward postponed childbearing, the incidence of pregnancy-associated breast cancer (PABC) is likely to increase. This study investigated the mortality in women with PABC in relation to when the tumor was detected (during pregnancy, different postpartum periods) and by time since diagnosis, compared with women with non-PABC.

Methods: A population-based cohort study of 15,721 Swedish women diagnosed with breast cancer between ages 15 to 44 years, of whom 1,110 (7%) had a PABC (diagnosed during or within two years after pregnancy). Information on outcome and potential confounders was obtained from population-based health registers. Mortality rates and HRs with 95% CIs were estimated.

Results: Women with PABC had higher mortality compared with women with non-PABC diagnosed at the same age and calendar period. Among women with PABC, 46% died within 15 years after diagnosis, whereas 34% died among non-PABC patients. The mortality in both groups peaked at around two years after diagnosis, with the highest peak occurring in women diagnosed 4 to 6 months after delivery (HR = 3.8, 95% CI: 2.4–5.9). An increased mortality among women with PABC remained until 10 years after diagnosis.

Conclusions: Women with PABC had a poorer prognosis compared with women with breast cancer and no recent birth. The mortality increase was most pronounced in the subgroup of women diagnosed shortly after delivery.

Impact: An increased awareness among clinicians may help reduce the mortality in women with PABC, for example, by avoiding undue delays in diagnosis and treatment. Cancer Epidemiol Biomarkers Prev; 20(9); 1865–72. ©2011 AACR.
Cancer Disparities: Unmet Challenges in the Elimination of Disparities
Authors: Gehlert Sarah , Colditz Graham A.
Published: September 2011

Background: The first 20 years of publication of Cancer Epidemiology, Biomarkers & Prevention occurred during a period of increased attention to health disparities and advances in knowledge about their determinants. Yet, despite clear documentation of disparities and advanced understanding of determinants, we have made little headway in reducing disparities at the population level. Multilevel models, such as one produced by the Centers for Population Health and Health Disparities (CPHHD), hold promise for understanding the complex determinants of cancer disparities and their interactions as well as translating scientific discoveries into solutions. The CPHHD model maps across a range of scientific disciplines, from the biological to the social, each with its own disciplinary language and methods. The ability to work effectively across disciplinary boundaries is essential to framing comprehensive solutions.

Methods: After briefly characterizing the current state of knowledge about health disparities, we outline three major challenges faced by disparities researchers and practitioners and offer suggestions for addressing these challenges.

Results: These challenges are how to consider race and ethnicity in disparities research, how best to translate discoveries into public health solutions to cancer disparities, and how to create a research environment that supports the successful execution of multilevel research.

Conclusions: Attention to all three of the challenges outlined above is urgently needed to advance our efforts to eliminate cancer disparities.

Impact: Addressing the challenges outlined above will help to eliminate disparities in the future.Cancer Epidemiol Biomarkers Prev; 20(9); 1809–14. ©2011 AACR.
Bronchial Allergen Challenge Using the Medicaid Dosimeter
Authors: Schulze Johannes , Rosewich Martin , Dressler Melanie , Riemer Carsten , Rose Markus A. , Zielen Stefan
Published: September 2011

Background: Bronchial allergen provocations are well established in asthma research. We evaluated the reproducibility of single-concentration, single-step allergen challenges in volunteers with grass pollen allergy. Methods: Forty-seven subjects underwent bronchial challenges using the aerosol provocation system nebulizer (Medicaid Sidestream) with incremental doses of grass pollen to define the individual allergen dose that causes a 20% drop in FEV1 (PD20FEV1). In 39 subjects this procedure was followed by single-step challenges. Early and late asthmatic responses were monitored, and increases in exhaled nitric oxide were measured before and 24 h after single-step challenges. Results: After the first single-step challenge, the maximum drop in FEV1 was 21.3% ± 8.0. A comparison of the drop in FEV1 to the initial incremental challenge (29.7% ± 7.5) revealed an intraclass correlation of –0.30 (p < 0.05). In the second single-step challenge, the mean drop in FEV1 was 20.9% ± 7.2. Compared with the first single-step challenge, the intraclass correlation was 0.37 (p < 0.05) and the 95% limits of agreement according to Bland and Altman were –17.5 to 18.1%. The increases in exhaled nitric oxide revealed substantial agreement in repeated single-step challenges (26.8 ppb ± 27.8 and 21.8 ppb ± 21.9, ICC 0.62, p < 0.001). Conclusions: The use of aerosol provocation system to calculate the PD20FEV1 allergen is a timesaving procedure and is less prone to errors because only one dilution of the allergen is used. The repeatability in well-defined subjects is excellent to study the mechanisms of allergen-induced airway inflammation and the development of new treatments for allergic diseases.
IgG to Various Beta-Glucans in a Human Adult Population
Authors: Noss Ilka , Wouters Inge M. , Smit Lidwien A.M. , Meijer Evert , Pronk Anjoeka , Heederik Dick J.J. , Doekes Gert
Published: September 2011

Background: Fungal β-(1,3)-glucans are pro-inflammatory agents, and exposures to β-(1,3)-glucans are associated with respiratory tract symptoms. IgG anti-(1,3)-glucan titers are measured in diagnosis of fungal infections. Although other β-glucan structures exist, like β-(1,6)-glucans, little is known about their antigenic or pro-inflammatory properties. We aimed to investigate IgG titers and specificities in human sera against different β-glucans with varying structures. Methods: IgG anti-β-glucan was measured by enzyme immunoassay in a random sample of 40 sera from healthy adults, with a panel of 8 differently structured glucans. In a subsequent larger series, IgG anti-β-(1,6)-glucan was measured in a random sample of 667 sera from three occupational populations with different organic dust exposures. Possible determinants of IgG anti-β-(1,6)-glucan titers were explored with linear-regression analysis. Results: We found wide variation in anti-β-glucan IgG levels. The highest titers were found for pure β-(1,6)-glucan pustulan. Moderate to strong reactions with other β-(1,6)-containing structures appeared to be due to cross-reacting anti-β-(1,6)-glucan antibodies. Surprisingly, the mean IgG anti-β-(1,6)-glucan titer was significantly lower in agricultural workers – with highest organic dust exposure – than in spray painters and bakery workers. Smoking status was associated with lower IgG anti-β-(1,6)-glucan titers in all populations. Conclusions: IgG to β-(1,3)- and β-(1,6)-glucans can be found in normal human sera. β-(1,6)-glucans appear to be much more potent antigens. The health impact of high anti-β-(1,6)-glucan antibody levels remains unclear and further investigations are needed.
Effect of Vitamin E Administration on the Elevated Oxygen Stress and the Telomeric and Subtelomeric Status in Alzheimer’s Disease
Authors: Guan Jing-Zhi , Guan Wei-Ping , Maeda Toyoki , Makino Naoki
Published: September 2011

Background: Oxidative stress (OS) may be involved in the neurodegenerative process in Alzheimer’s disease (AD). Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, are sensitive to OS, and serve as markers of a cell’s replicative history. Telomere length shortening has been reported to relate to OS with aging process and aging-associated diseases, but the telomeric changes were not always identical, especially in change of telomere length distribution and subtelomeric methylation. The involvement of an OS-associated telomere change in the pathogenesis of AD has been discussed for decades, and the telomere length and telomerase activity were analyzed. However, other telomeric factors, such as the telomere distribution and subtelomeric methylation status, have not yet been analyzed. Objective: The subtelomeric methylation status as well as the telomere length were studied in AD with an antioxidant vitamin in terms of OS. Methods: We measured urinary 8-iso-PGF2α, a lipid-peroxidation product as an OS marker, and methylated and non-methylated telomere lengths in the peripheral blood mononuclear cells by Southern blotting in AD patients before and after vitamin E treatment. Results: The level of urinary 8-iso-PGF2α was found to have increased in AD. Middle-ranged telomeres (4.4–9.4 kb) increased and the shortest telomeres (<4.4 kb) decreased in AD patients. Telomeres were more methylated in both long telomeres and in short telomeres in AD compared with the control. The oral administration of the antioxidant vitamin E in 400 mg/day for 6 months in AD patients partly reversed AD-associated alterations in OS marker levels. Conclusions: AD patients showed an elevated OS marker level, and vitamin E lowered the OS level. In comparison with controls, AD patients showed shorter telomere lengths. Cells with short and long telomeres bore relatively hypermethylated subtelomeres in AD patients. Aging-associated accumulation of cells bearing short telomeres was not observed in AD. These results imply that long telomeres with hypomethylation tend to shorten faster, and cells bearing short telomeres with hypomethylation tend to more easily enter into a senescent state under elevated OS stress in AD. However, no significant effect on the altered telomeric profiles in AD patients could be detected after a 6-month administration of vitamin E.
Genetic Testing of the Short Child
Authors: Johnston Rohrbasser L.B.
Published: September 2011

Increased understanding of the pathogenetics of short stature and readily available genetic testing have changed the face of diagnostic endocrinology. It remains essential, however, that each short child undergoes detailed clinical, auxological and traditional endocrine assessment to determine which gene (or genes) to study. Diagnostic algorithms and clinical scoring systems are reviewed and the implications of genetic testing for determination of therapy type are discussed. At present, results from genetic testing do not reliably indicate which growth-promoting therapy would be most effective. However, pharmacogenetic testing may play a future role in the individualisation of therapy.
Short Stature: Psychosocial Interventions
Authors: Sandberg David E.
Published: September 2011

The use of the term ‘psychosocial interventions’ in the title implies that short stature (SS) carries with it a burden predisposing the person to problems of psychological adjustment. Because of the visible salience of SS and its potential to serve as a lightning rod for false causal attributions, there is a need to differentiate assumptions and stereotypes from evidence. This brief overview examines the evidence regarding stature-related experiences and the psychosocial adaptations of children and adolescents with SS. These observations are discussed in the context of common developmental experiences, such as ‘teasing,’ and the prevalence of behavioral or emotional disturbance in the general population. Guidance is provided for the psychosocial evaluation of children and adolescents with SS who show psychological adjustment difficulties, and recommendations for evidence-based mental health treatments tailored to the presenting problem are offered.
Review of Growth Hormone Randomized Controlled Trials in Children with Idiopathic Short Stature
Authors: Deodati Annalisa , Peschiaroli Emanuela , Cianfarani Stefano
Published: September 2011

Recombinant human growth hormone (GH) has been used to increase growth and adult height in children with idiopathic short stature (ISS) despite the lack of definitive, long-term studies of efficacy. Our aim was to systematically review all randomized controlled trials (RCTs) of GH use in children with ISS.We performeda formal search of the Cochrane Central Register of Controlled Trials, Medline and the bibliographic references from all retrieved articles describing such trials up to August 2009. Three long-term RCTs conducted to the achievement of adult height were identified. The mean age at start of treatment in the three trials was 10.1 ± 3.4 years. The mean duration of GH therapy was 5.4 ± 0.9 years. The mean difference between treated and untreated children was 0.77 ± 0.4 standard deviation score (SDS) (approximately 5.5 cm). The mean adult height achievedafter GH therapy at conventional doses was –1.5 ± 0.3 SDS. GH improves adult height in children with ISS. However, treated individuals remain relatively short compared with peers of normal height. The individual response to therapy is highly variable and further studies are required to identify responders. Lastly, high-quality evidence from long-term RCTs of GH therapy that continue until achievement of adult height is necessary to determine the ideal dosage and long-term safety.
The Basis for Optimising Growth with Growth Hormone Usage in Children with Idiopathic Short Stature: Analysis of Data from KIGS (Pfizer International Growth Study Database)
Authors: Ranke Michael B. , Lindberg Anders ,   on behalf of the KIGS International Board
Published: September 2011

Many children with idiopathic short stature (ISS) remain short as adults. Height can be improved permanently by growth hormone (GH) treatment, as in children with Turner syndrome or born small for gestational age. Although GH treatment for ISS is an approved indication in the United States, there is ongoing controversy in Europe about approving GH treatment for this indication as well as determining the optimal mode of treatment. In addition to data from randomized controlled trials, data from pharmacoepidemiological surveys such as the Pfizer International Growth Study Database (KIGS) have provided substantial information about the short-term and long-term effects of GH on growth and adult height in children with ISS. Based on published articles and a recent survey from KIGS on 454 patients who have reached adult height, we attempted to categorize those children with ISS who have the greatest chances of achieving a normal adult height, or at least gain the most height following GH treatment. This analysis provides a rational basis for discussion about the most efficacious and cost-effective uses of GH treatment in children with ISS.
Low Urine pH Is a Predictor of Chronic Kidney Disease
Authors: Nakanishi Naoko , Fukui Michiaki , Tanaka Muhei , Toda Hitoshi , Imai Saeko , Yamazaki Masahiro , Hasegawa Goji , Oda Yohei , Nakamura Naoto
Published: September 2011

Background/Aims: A variety of risk factors for chronic kidney disease (CKD), including the metabolic syndrome, were recently reported. It has been suggested that a low urine pH is another characteristic of the metabolic syndrome. However, the relationship between urine pH and CKD remains to be elucidated. Methods: A cohort study was performed on 1,811 subjects who underwent a health check-up, and we examined whether low urine pH could be a predictor of CKD. The following risk factors for CKD were evaluated: age, gender, history of alcohol intake and smoking, BMI, systolic blood pressure, fasting plasma glucose, total cholesterol, uric acid, total leukocyte count, CKD stage, fasting urine pH, and protein at baseline. Results: We followed 1,811 subjects for a median period of 7.7 years. Three hundred and thirty-nine subjects developed stage 3 CKD defined as progression to estimated glomerular filtration rate <60 ml/min/1.73 m2. Multiple Cox regression analysis revealed that the adjusted HR (95% CI) for stage 3 CKD was 1.32 (1.06–1.65; p = 0.0129) in subjects with fasting urine pH 5.0–5.5 compared to subjects with pH 6.5–7.0. Conclusion: Our study suggests that low urine pH is an independent predictor of stage 3 CKD.
Sensitivity and Specificity of Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 for the Diagnosis of Renal Cell Carcinoma
Authors: Morrissey Jeremiah J. , London Amy N. , Lambert Matthew C. , Kharasch Evan D.
Published: September 2011

Background/Aims: Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are urinary biomarkers of diagnostic relevance in a wide variety of acute and chronic kidney diseases. Their diagnostic sensitivity and specificity for kidney cancer are largely unknown and therefore the subject of this investigation. Methods: A prospective cohort study was performed to evaluate urine biomarkers for clear-cell and papillary subtypes of renal cancer (67 patients undergoing nephrectomy) and 55 control patients undergoing non-kidney surgery. Urinary KIM-1 and NGAL concentrations were determined by sensitive and specific ELISAs. Results: In renal cancer patients, median NGAL excretion was 0.52 (1st to 3rd quartiles: 0.28–0.82) ng/mg urinary creatinine (UCr) before nephrectomy compared to 0.15 (0.04–0.31) ng/mg UCr in controls (p < 0.001), and there was a modest decrease of 30% after nephrectomy (p < 0.008). NGAL was not correlated to tumor size (r = 0.19, p = 0.27) or stage. Before nephrectomy, KIM-1 excretion was 0.68 (0.40–1.12) ng/mg UCr compared to 0.03 (0.01–0.06) in controls (p < 0.001). There was a linear correlation between KIM-1 excretion before nephrectomy and tumor size (Spearman’s r = 0.66, p < 0.001), tumor stage, and a 50% decrease in median KIM-1 concentration 1 month following tumor excision (p < 0.01). Biomarker concentration ranges for renal cancer patients and controls overlapped substantially for NGAL but not KIM-1. Conclusion: NGAL is not a sensitive or specific urinary biomarker of kidney cancer. Although KIM-1 had diagnostic sensitivity for kidney cancer, it is well known to reflect many types of kidney injuries, thus limiting its specificity as a diagnostic biomarker for renal cancer.
Impact of Serial Troponin Release on Outcomes in Patients With Acute Heart Failure
Authors: O'Connor Christopher M. , Fiuzat Mona , Lombardi Carlo , Fujita Kenji , Jia Gang , Davison Beth A. , Cleland John , Bloomfield Daniel , Dittrich Howard C. , DeLucca Paul , Givertz Michael M. , Mansoor George , Ponikowski Piotr , Teerlink John R. , Voors Adriaan A. , Massie Barry M. , Cotter Gad , Metra Marco
Published: September 2011

Background—

Cardiac troponin T (cTnT) elevation is common and is a predictor of outcomes in patients with acute heart failure (AHF). The degree and progression of cTnT release during hospitalization of patients with AHF is unclear. We evaluated the incidence of cTnT release during AHF hospitalization and the relationship of cTnT release with outcomes.

Methods and Results—

The
P
lacebo-controlled
R
andomized study of the selective A(1) adenosine receptor antagonist rolofylline for patients hospitalized with acute heart failure and volume
O
verload to assess
T
reatment
E
ffect on
C
ongestion and renal func
T
ion (PROTECT) pilot study was a multicenter, double-blind study of patients with AHF. Measurements of cTnT were collected at randomization and days 2, 3, 4, and 7. Patients were classified on the basis of their serum cTnT levels at baseline: positive (>0.03 ng/mL), detectable (>0.01 ng/mL), and negative (≤0.01 ng/mL). A detectable cTnT level developed during the study (after baseline) was classified as cTnT conversion: 288 patients were included; 172 (60%) patients had detectable cTnT levels and 97 (34%) had positive values (>0.03 ng/mL) at baseline. Of the 116 patients with negative troponin at baseline, 24 (21%) had elevated cTnT levels by day 7. On multivariable analysis, positive cTnT at baseline was an independent predictor of the composite end point of cardiovascular/renal rehospitalization or death at 60 days (hazard ratio, 1.84; 95% confidence interval, 1.04–3.26;
P
=0.036). Kaplan-Meier curves showed similar worse outcomes in patients with troponin conversion and positive troponin at baseline.

Conclusions—

There was a high prevalence of baseline cTnT elevation in this cohort; 21% of those negative at baseline converted to detectable levels by day 7. Positive troponin at baseline, and conversion to positive levels, were associated with worse outcomes at 60 days.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00328692 and NCT00354458.
Predictors of Response to Cardiac Resynchronization Therapy in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT)
Authors: Goldenberg Ilan , Moss Arthur J. , Hall W. Jackson , Foster Elyse , Goldberger Jeffrey J. , Santucci Peter , Shinn Timothy , Solomon Scott , Steinberg Jonathan S. , Wilber David , Barsheshet Alon , McNitt Scott , Zareba Wojciech , Klein Helmut
Published: September 2011

Background—

We hypothesized that combined assessment of factors that are associated with favorable reverse remodeling after cardiac resynchronization-defibrillator therapy (CRT-D) can be used to predict clinical response to the device.

Methods and Results—

The study population comprised 1761 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). Best-subset regression analysis was performed to identify factors associated with echocardiographic response (defined as percent reduction in left ventricular end-diastolic volume 1 year after CRT-D implantation) and to create a response score. Cox proportional hazards regression analysis was used to evaluate the CRT-D versus defibrillator-only reduction in the risk of heart failure or death by the response score. Seven factors were identified as associated with echocardiographic response to CRT-D and made up the response score (female sex, nonischemic origin, left bundle-branch block, QRS ≥150 milliseconds, prior hospitalization for heart failure, left ventricular end-diastolic volume ≥125 mL/m
2
, and left atrial volume <40 mL/m
2
). Multivariate analysis showed a 13% (
P
<0.001) increase in the clinical benefit of CRT-D per 1-point increment in the response score (range, 0–14) and a significant direct correlation between risk reduction associated with CRT-D and response score quartiles: Patients in the first quartile did not derive a significant reduction in the risk of heart failure or death with CRT-D (hazard ratio=0.87;
P
=0.52); patients in the second and third quartiles derived 33% (
P
=0.04) and 36% (
P
=0.03) risk reductions, respectively; and patients in the upper quartile experienced a 69% (
P
<0.001) risk reduction (
P
for trend=0.005).

Conclusion—

Combined assessment of factors associated with reverse remodeling can be used for improved selection of patients for cardiac resynchronization therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00180271.