bluuebunny/crossref_metadata_2025 huggingface dataset:
Descriptive analysis of central sleep apnea in childhood at a single center
Authors: Kritzinger Fiona E. , Al‐Saleh Suhail , Narang Indra
Published: April 2011

Data on central sleep apnea (CSA) and its significance in children are limited. Our objectives were to describe the polysomnogram (PSG) characteristics and clinical features of children with significant CSA at a single pediatric sleep center.

Study Design and Methods

A retrospective chart review of children diagnosed with CSA on a PSG, from January 2007 to December 2008, was performed. All the PSG's were performed in the pediatric sleep laboratory at The Hospital for Sick Children in Toronto, Canada. All children diagnosed with significant CSA with a PSG was eligible for inclusion. Each PSG was conducted and scored according to the American Academy of Sleep Medicine standard. Significant CSA was defined as a central apnea index (CAI) of >5 events/hr. Outcome for each patient was defined by the percentage change in the CAI at follow up.

Results

52/969 (5.4%) patients had a CAI > 5/hr on a baseline PSG. Of the 25/52 (13 males) patients who met inclusion criteria, the median age was 19 months (range 3–156 months) and their median BMI z score was +0.27 (range −2.95 to 3.02). The median CAI was 11 events/hr (range 6–198/hr). The mean oxygen saturations ranged from 92.8% to 98.5%, with a median of 97%. Six (24%) patients had associated sleep‐related hypoventilation and none of the patients had periodic breathing. The commonest identifiable risk factor for CSA in the study population was a neurological disorder.

Conclusions

This study confirms that CSA is an important finding in a significant number of young children referred for an evaluation for suspected sleep related disordered breathing. Any child diagnosed with CSA warrants full clinical assessment, including neuro‐imaging. Future research should aim to evaluate the long term outcome of significant CSA. Pediatr. Pulmonol. 2011; 46:1023–1030. © 2011 Wiley‐Liss, Inc.
Physical activity, fitness, and dyspnea perception in children with congenital diaphragmatic hernia
Authors: Turchetta Attilio , Fintini Danilo , Cafiero Giulia , Calzolari Armando , Giordano Ugo , Cutrera Renato , Morini Francesco , Braguglia Annabella , Bagolan Pietro
Published: April 2011

We assessed whether physical activity could influence the performance and perception of dyspnea in children who were operated on for high risk congenital diaphragmatic hernia (CDH). We hypothesized that CDH children with normal activity would have better lung function and exercise performance level when compared to sedentary CDH subjects.

We studied 18 children (11 males and 7 females, mean age 6.6 ± 2.6 years) who were surgically corrected. All children underwent physical examination, ECG at rest, and a maximal exercise stress test on a treadmill to measure the duration of exercise, maximal heart rate and blood pressure, maximal oxygen uptake (VO2 max and VO2 ml/kg/min). Lung function testing to measure forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and peak expiratory flow (PEF) was also performed. Following the stress test, the Dalhousie dyspnea and effort scale was shown to children as a pictorial panel with three groups of increasing (from 1 to 7) levels of effort perception, throat discomfort, and chest dyspnea. Children were divided into group A (sedentary) and group B (regular physical participation). There was no difference in CDH severity between the two groups. Group A had a statistically significant lower duration of exercise (P < 0.01), maximal oxygen consumption (VO2 max P < 0.0001), VO2 ml/kg/min (P < 0.001), higher throat closing feeling (P < 0.004), chest dyspnea (P < 0.001), and effort perception (P < 0.04) compared to group B. No differences were found in lung function tests.

In conclusion, our data may suggest that children with a history of CDH who are active maintain a higher level of performance with less perception of dyspnea and effort. Pediatr. Pulmonol. 2011; 46:1000–1006. © 2011 Wiley‐Liss, Inc.
Not all children with nodular interstitial lung patterns in South Africa have TB—A rare case of paediatric “Bird Fanciers' disease”
Authors: Andronikou Savvas , Goussard Pierre , Gie Robert P.
Published: April 2011

Bird Fancier's disease is an allergic alveolitis that is rare in children. We describe the relevance of adequate history for making the diagnosis in children and the difficulty distinguishing this entity on chest radiographs and CT from imaging patterns caused by infections such as tuberculosis and HIV in developing countries. Pediatr. Pulmonol. 2011; 46:1134–1136. © 2011 Wiley Periodicals, Inc.
Salivary cortisol levels in prepubertal children using inhaled corticosteroids with or without concurrent intranasal corticosteroids
Authors: Heijsman Sigrid M. , de Vries Tjalling W. , Wolthuis Albert , Kamps Arvid W.A.
Published: April 2011

Background

Inhaled corticosteroids (ICS) and intranasal steroids (INS) are frequently co‐administered in children with asthma and rhinitis. In contrast to monotherapy with ICS or INS, little is known about the safety of concurrent use of topical steroids on hypothalamic–pituitary–adrenal (HPA) axis function in prepubertal children.

Objective

Comparison of morning salivary cortisol levels in prepubertal children using maintenance treatment with ICS with and without concurrent use of INS to steroid naïve control groups (healthy children, and children with constipation who are under pediatric care).

Methods

Cross‐sectional observational study in prepubertal children (6–12 years) using ICS alone (n = 41) or in combination with INS (n = 22), compared to different control groups with no steroid treatment (18 healthy children, and 28 children with constipation). Morning salivary cortisol levels were determined from saliva samples collected at home.

Results

The morning salivary cortisol levels of the healthy children (8.7 nmol/L; 95% CI 5.9–18.8), and the children with constipation (8.9 nmol/L; 8.0–11.3) were comparable. The salivary cortisol levels of prepubertal children using ICS (median 4.7 nmol/L; 95% CI 4.6–6.9) or a combination of ICS and INS (5.1 nmol/L; 4.2–7.6) were comparable, but significantly reduced compared to both control groups. There was no correlation between salivary cortisol level and age, duration of disease, or cumulative daily dose of topical steroids.

Conclusion

Salivary cortisol levels in prepubertal children using ICS, with or without concurrent use of INS, were comparable. However, salivary cortisol levels were significantly reduced compared to steroid naïve controls, irrespective of the cumulative daily dose of topical steroids. Pediatr. Pulmonol. 2011; 46:1055–1061. © 2011 Wiley Periodicals, Inc.
The myristoylation of guanylate cyclase‐activating protein‐2 causes an increase in thermodynamic stability in the presence but not in the absence of Ca2+
Authors: Schröder Thomas , Lilie Hauke , Lange Christian
Published: April 2011

Guanylate cyclase activating protein‐2 (GCAP‐2) is a Ca2+‐binding protein of the neuronal calcium sensor (NCS) family. Ca2+‐free GCAP‐2 activates the retinal rod outer segment guanylate cyclases ROS‐GC1 and 2. Native GCAP‐2 is N‐terminally myristoylated. Detailed structural information on the Ca2+‐dependent conformational switch of GCAP‐2 is missing so far, as no atomic resolution structures of the Ca2+‐free state have been determined. The role of the myristoyl moiety remains poorly understood. Available functional data is incompatible with a Ca2+‐myristoyl switch as observed in the prototype NCS protein, recoverin. For the homologous GCAP‐1, a Ca2+‐independent sequestration of the myristoyl moiety inside the proteins structure has been proposed. In this article, we compare the thermodynamic stabilities of myristoylated and non‐myristoylated GCAP‐2 in their Ca2+‐bound and Ca2+‐free forms, respectively, to gain information on the nature of the Ca2+‐dependent conformational switch of the protein and shed some light on the role of its myristoyl group. In the absence of Ca2+, the stability of the myristoylated and non‐myristoylated forms was indistinguishable. Ca2+ exerted a stabilizing effect on both forms of the protein, which was significantly stronger for myr GCAP‐2. The stability data were corroborated by dye binding experiments performed to probe the solvent‐accessible hydrophobic surface of the protein. Our results strongly suggest that the myristoyl moiety is permanently solvent‐exposed in Ca2+‐free GCAP‐2, whereas it interacts with a hydrophobic part of the protein's structure in the Ca2+‐bound state.
A Three‐Gene panel on urine increases PSA specificity in the detection of prostate cancer
Authors: Rigau Marina , Ortega Israel , Mir Maria Carmen , Ballesteros Carlos , Garcia Marta , Llauradó Marta , Colás Eva , Pedrola Núria , Montes Melania , Sequeiros Tamara , Ertekin Tugce , Majem Blanca , Planas Jacques , Ruiz Anna , Abal Miguel , Sánchez Alex , Morote Juan , Reventós Jaume , Doll Andreas
Published: April 2011

BACKGROUND

Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post‐prostate massage (PM) urine for increasing the specificity of prostate‐specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa.

METHODS

We analyzed post‐PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real‐time PCR in post‐PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic “gray zone” (4–10 ng/ml) on a target subset of 82 men with no prior biopsy.

RESULTS

By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver‐operating characteristic curve was 0.74 versus 0.82 in the diagnostic “gray zone.” Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone.

CONCLUSIONS

Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine‐based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum‐PSA test, could be used to determine better which patients should undergo biopsy. Prostate 71:1736–1745, 2011. © 2011 Wiley Periodicals, Inc.
Passive bioelectrical properties for assessing high‐ and low‐grade prostate adenocarcinoma
Authors: Halter Ryan J. , Schned Alan R. , Heaney John A. , Hartov Alex
Published: April 2011

BACKGROUND

The electrical properties of prostate tissues are dependent on cellular morphology and have been demonstrated to distinguish between benign and malignant formations. Because Gleason grading is also based on tissue architecture we explored the hypothesis that the electrical properties might also provide discriminating power between high‐ and low‐Gleason grade cancers.

METHODS

Electrical properties (σ, ε, Δσ, σ∞, fc, and α) were gauged from 546 prostate tissue samples and correlated with histopathological assessment. Primary and secondary Gleason grades and a Gleason score were assigned to the tissues identified as cancer. We evaluated how well differently graded cancers were separable from benign tissues and from each other on the basis of these properties using ROC curves.

RESULTS

Of the 546 prostate tissue samples, 71 were identified as cancer and 465 as benign. ε, Δσ, σ∞, and fc provided the most discriminatory power with area under the curves (AUCs) ranging from 0.77–0.82 for detecting any cancer, 0.72–0.8 for low‐grade cancer, and increasing to 0.87–0.9 for detecting high‐grade cancer. Further, ε, Δσ, and σ∞, provided AUCs ranging from 0.74 to 0.75 for discriminating between low‐ and high‐grade cancers.

CONCLUSIONS

Using the electrical properties to identify prostate cancer is improved when high‐grade cancers are sought. These electrical properties can also discriminate between different grades of tumors. These findings suggest that technologies being developed to sense and image these properties in vivo may discriminate between aggressive and indolent lesions. Prostate 71:1759–1767, 2011. © 2011 Wiley Periodicals, Inc.
BRCA1 mutations do not increase prostate cancer risk: Results from a meta‐analysis including new data
Authors: Fachal Laura , Gómez‐Caamaño Antonio , Celeiro‐Muñoz Catuxa , Peleteiro Paula , Blanco Ana , Carballo Ana , Forteza Jerónimo , Carracedo Ángel , Vega Ana
Published: April 2011

BACKGROUND

Although in recent years deleterious BRCA1 mutations have been extensively studied as a prostate cancer risk factor, results are inconclusive. To assess the contribution of the BRCA1 Galician founder mutation c.211A>G in prostate cancer morbidity we conducted a case‐control study. Moreover, to better elucidate whether deleterious BRCA1 mutations are involved in the development of prostate cancer, we performed a systematic review and a meta‐analysis of BRCA1 studies on prostate cancer.

METHODS

A total of 905 unselected men diagnosed with adenocarcinoma of the prostate and a control group of 936 unrelated men without history of prostate cancer were evaluated for c.211A>G. Adjusted by age Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. To construct the meta‐analysis, genotype‐based epidemiological studies reporting BRCA1 founder mutations on prostate cancer were identified by comprehensive and systematic bibliographic search. After extraction of relevant data, main and subgroup analysis by mutation were performed to assess the effect of BRCA1 on prostate cancer risk.

RESULTS

Four c.211A>G heterozygous individuals, one patient and three controls, were detected (OR = 0.27; 95% CI: 0.01–2.36; P = 0.28). Meta‐analysis results from the integration of our data and other seven studies with BRCA1 genotyping data (5,705 prostate cancer cases and 13,218 controls) did not detect an association with prostate cancer risk (OR = 1.36; 95% CI: 0.87–2.14; P = 0.18).

CONCLUSIONS

Our conclusive trial demonstrates the lack of association between Galician splicing mutation c.211A>G in the BRCA1 gene and prostate cancer risk. Moreover, the result of the meta‐analysis also discards the involvement of BRCA1 mutations in the development of prostate cancer. Prostate 71:1768–1779, 2011. © 2011 Wiley Periodicals, Inc.
Identification of AKAP‐4 as a new cancer/testis antigen for detection and immunotherapy of prostate cancer
Authors: Chiriva‐Internati Maurizio , Yu Yuefei , Mirandola Leonardo , D'Cunha Nicholas , Hardwicke Fred , Cannon Martin J. , Cobos Everardo , Kast W. Martin
Published: April 2011

BACKGROUND

Prostate cancer (PC) is the second most common cancer in older men, after skin cancer. PC is difficult to diagnose because the prostate‐specific antigen screening method is associated with many false positives. In addition there is a need to develop new and more effective treatments. Among presently available new treatments, immunotherapy is a promising approach. We investigated the expression of the cancer/testis antigen, AKAP‐4, in PC patients to evaluate the possibility of exploiting AKAP‐4 as a target for immunotherapy.

METHODS

We analyzed normal prostate tissues, 15 patients with PC and the LnCAP PC cell line by immunohistochemistry. We tested AKAP‐4 immunogenicity through indirect ELISA on sera from patients and healthy subjects, and we generated in vitro AKAP‐4‐specific cytotoxic lymphocytes from peripheral blood mononuclear cells.

RESULTS

AKAP‐4 was shown both at the cytoplasmic and surface levels of the LnCAP PC cell line. AKAP‐4 was also highly expressed in PC cells from patients. We detected specific anti‐AKAP‐4 circulating immunoglobulins in AKAP‐4 positive subjects. Using recombinant AKAP‐4 loaded autologous dendritic cells, we generated AKAP‐4‐specific and HLA‐I‐restricted cytotoxic T lymphocytes able to kill PC cells in vitro. Further characterization indicated a Th‐1 skewing in the cytokine secretion profile of these cells.

CONCLUSIONS

We demonstrate the aberrant expression of AKAP‐4 in PC, which will potentially be developed as a biomarker in PC. We provide evidence that AKAP‐4 is a potential target for PC adoptive immunotherapy or anti‐tumor vaccination. Prostate 72:12–23, 2012. © 2011 Wiley Periodicals, Inc.
The Association between pre‐operative PSA and prostate cancer‐specific mortality in patients with long‐term follow‐up after radical prostatectomy
Authors: Lewinshtein Dan , Teng Brandon , Valencia Ashley , Gibbons Robert , Porter Christopher R.
Published: April 2011

BACKGROUND

The clinical and pathologic predictors of prostate cancer‐specific mortality (PCSM) many years after radical prostatectomy (RP) remain to be fully elucidated. We explored the association between pre‐operative prostate‐specific antigen (PSA) and other pathologic predictors and PCSM in men who have undergone (RP).

METHODS

We report on 459 patients with PCSM data after RP who were followed prospectively over a 23‐year period between 1987 and 1997. Cox regression and Kaplan–Meier analysis were used to evaluate pre‐operative PSA, pathologic Gleason sum, pathologic stage, and surgical margin status as predictors of PCSM.

RESULTS

The median PSA was 6.6 ng/ml (±9.9) and the median follow‐up time was 9.4 (±4.9) years. Fourteen patients (3.1%) died of PC. On multivariate analysis, only PSA (HR: 1.050; P = 0.001) and binary Gleason sum (HR: 3.402; P = 0.043) remained significant predictors of PCSM. The predicted 10‐year PCSM was significantly worse in those patients in the highest PSA tertile compared to those in other tertiles [PSA > 9.9: 87% (82–92%) vs. PSA = 4–9.9: 95% (93.0–97.0%) vs. PSA = 0–3.9: 100.0% (100.0–100.0%)].

CONCLUSIONS

We have highlighted the importance of pre‐operative PSA in predicting PCSM many years after RP. It is a more significant predictor than Gleason sum and pathologic stage. Thus, PSA may help identify patients with life‐threatening PC at a time when their disease is curable with definitive therapy. Prostate 72:24–29, 2012. © 2011 Wiley Periodicals, Inc.
Prostate cancer risk variants are not associated with disease progression
Authors: Szulkin Robert , Holmberg Erik , Stattin Pär , Xu Jianfeng , Zheng Sigun , Palmgren Juni , Grönberg Henrik , Wiklund Fredrik
Published: April 2011

BACKGROUND

Currently used prognostic markers are limited in their ability to accurately predict disease progression among patients with localized prostate cancer. We examined 23 reported prostate cancer susceptibility variants for association with disease progression.

METHODS

Disease progression was explored among 4,673 Swedish patients treated for clinically localized prostate cancer between 1997 and 2002. Prostate cancer progression was defined according to primary treatment as a composed event reflecting termination of deferred treatment, biochemical recurrence, local progression, or presence of distant metastasis. Association between single variants, and all variants combined, were performed in Cox regression analysis assuming both log‐additive and co‐dominant genetic models.

RESULTS

Three of the 23 genetic variants explored were nominally associated with prostate cancer progression; rs9364554 (P = 0.041) on chromosome 6q25 and rs10896449 (P = 0.029) on chromosome 11q13 among patients treated with curative intent; and rs4054823 (P = 0.008) on chromosome 17p12 among patients on surveillance. However, none of these associations remained statistically significant after correction for multiple testing. The combined effect of all susceptibility variants was not associated with prostate cancer progression neither among patients receiving treatment with curative intent (P = 0.14) nor among patients on surveillance (P = 0.92).

CONCLUSIONS

We observed no evidence for an association between any of 23 established prostate cancer genetic risk variants and disease progression. Accumulating evidence suggests separate genetic components for initiation and progression of prostate cancer. Future studies systematically searching for genetic risk variants associated with prostate cancer progression and prognosis are warranted. Prostate 72:30–39, 2012. © 2011 Wiley Periodicals, Inc.
Expression of NF‐κB‐related proteins and their modulation during TNF‐α‐provoked apoptosis in prostate cancer cells
Authors: Rodríguez‐Berriguete Gonzalo , Fraile Benito , Paniagua Ricardo , Aller Patricio , Royuela Mar
Published: April 2011

BACKGROUND

The involvement of TNF‐α in cancer development is controversial, since this cytokine was reported to act either as tumor promoter or suppressor. TNF‐α may activate signaling pathways critical for life/death decisions, such as mitogen‐activated protein kinases (MAPKs) and the anti‐apoptotic NF‐κB pathway. In this work, we investigate the activation status of NF‐κB‐related proteins in human prostate cancerous versus normal epithelium, and the alterations in the NF‐κB pathway in relation to cell death in TNF‐α‐treated LNCaP (androgen‐independent cells) and PC3 (androgen‐independent) prostate cancer cell lines.

METHODS

The expression of phospho‐p38‐MAPK, phospho‐IKK‐α/β and phospho‐IκB‐α, total IκB‐α, and p65‐ and p50‐NF‐κB, were analyzed by immunohistochemistry in cancerous and normal prostate samples. The toxicity of TNF‐α in LNCaP and PC3 cells, with or without kinase and NF‐κB inhibitors, was assessed by changes on viability (MTT assay) and apoptosis (loss of DNA, annexin‐V binding, and caspase cleavage/activation). Expression of NF‐κB‐related proteins in these cell lines was measured by Western blot.

RESULTS

Phospho‐IκB‐α, phospho‐IKK‐α/β and phospho‐p38 levels, cytoplasmic p50 to IκB‐α ratio, and nuclear p50 and p65, levels, were increased in cancerous epithelium, suggesting activation of the NF‐κB pathway in prostatic malignance. TNF‐α caused apoptosis with higher efficacy in LNCaP cells, and this response was potentiated by p38‐MAPK inhibitor (LNCaP cells) and IKK‐β inhibitor (both cell lines). However, the protective action of IKK‐β was mediated by NF‐κB only in LNCaP cells.

CONCLUSIONS

IKK‐β mediates both NF‐κB‐dependent and ‐independent anti‐apoptotic functions in prostate cancerous epithelium. IKK‐β and p38‐MAPK may represent useful therapeutic targets against prostate cancer. Prostate 72:40–50, 2012. © 2011 Wiley Periodicals, Inc.
Treatment decision‐making for localized prostate cancer: What younger men choose and why
Authors: Sidana Abhinav , Hernandez David J. , Feng Zhaoyong , Partin Alan W. , Trock Bruce J. , Saha Surajit , Epstein Jonathan I.
Published: April 2011

BACKGROUND AND OBJECTIVE

The literature lacks knowledge about information preferences and decision‐making in young prostate cancer patients. This study provides insight into information sources consulted and factors dictating treatment decision‐making in young prostate cancer patients.

METHODS

Subjects were identified from pathology consult service of a National Center of Excellence. Questionnaires were mailed to 986 men, under 50 years of age, diagnosed with Gleason score 6 prostate cancer between 2001 and 2005.

RESULTS

Four hundred ninety‐three men responded. The most common primary therapies were surgery 397 (81.4%), radiation 52 (10.7%), and active surveillance (AS) 26 (5.3%). Participants with at least some college education (P = 0.003) or annual income >$100,000 (P = 0.003) were more likely to consult three or more doctors. Amongst all treatments, “doctor's recommendation” was the most influential information source, although relatively less important in the AS group. Internet was the second most frequent information source. Participants with higher education (P = 0.0003) and higher income (P = 0.002) considered sexual function more important while making a treatment choice. Only 2% of the men preferred a passive role in the decision‐making. Informed decision‐making was preferred more by patients who chose radiation and AS while shared decision‐making was preferred more by surgery patients (P < 0.05). The majority (89%) of the respondents did not regret their decision. No difference in satisfaction levels was found between different treatment modalities.

CONCLUSIONS

This study provides insight into information sources consulted, such as the greater internet use, and various factors dictating treatment decision‐making in young prostate cancer patients. There was an overall very high satisfaction rate regardless of the therapy chosen. Prostate 72:58–64, 2012. © 2011 Wiley Periodicals, Inc.
The association between inflammation‐related genes and serum androgen levels in men: The prostate, lung, colorectal, and ovarian study
Authors: Meyer Tamra E. , Chu Lisa W. , Li Qizhai , Yu Kai , Rosenberg Philip S. , Menashe Idan , Chokkalingam Anand P. , Quraishi Sabah M. , Huang Wen‐Yi , Weiss Jocelyn M. , Kaaks Rudolf , Hayes Richard B. , Chanock Stephen J. , Hsing Ann W.
Published: April 2011

BACKGROUND

Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation‐related genes.

METHODS

In this report, we evaluated associations between 9,932 single nucleotide polymorphisms (SNPs) marking common genetic variants in 774 inflammation‐related genes and four serum androgen levels (total testosterone [T], bioavailable T [BioT]; 5α‐androstane‐3α, 17β‐diol glucuronide [3αdiol G], and 4‐androstene‐3,17‐dione [androstenedione]), in 560 healthy men (median age 64 years) drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Baseline serum androgens were measured by radioimmunoassay. Genotypes were determined as part of the Cancer Genetic Markers of Susceptibility Study genome‐wide scan. SNP‐hormone associations were evaluated using linear regression of hormones adjusted for age. Gene‐based P values were generated using an adaptive rank truncated product (ARTP) method.

RESULTS

Suggestive associations were observed for two inflammation‐related genes and circulating androgen levels (false discovery rate [FDR] q‐value <0.1) in both SNP and gene‐based tests. Specifically, T was associated with common variants in MMP2 and CD14, with the most significant SNPs being rs893226G > T in MMP2 and rs3822356T > C in CD14 (FDR q‐value = 0.09 for both SNPs). Other genes implicated in either SNP or gene‐based tests were IK with T and BioT, PRG2 with T, and TNFSF9 with androstenedione.

CONCLUSION

These results suggest possible cross‐talk between androgen levels and inflammation pathways, but larger studies are needed to confirm these findings and to further clarify the interrelationship between inflammation and androgens and their effects on cancer risk. Prostate 72:65–71, 2012. © 2011 Wiley Periodicals, Inc.
Preoperative insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) blood level predicts gleason sum upgrading
Authors: Terracciano Daniela , Bruzzese Dario , Ferro Matteo , Mazzarella Claudia , Di Lorenzo Giuseppe , Altieri Vincenzo , Mariano Angela , Macchia Vincenzo , Di Carlo Angelina
Published: April 2011

BACKGROUND

About 43% of men with low Gleason grade prostate cancer (PCa) at biopsy will be finally diagnosed with high‐grade PCa at radical prostatectomy (RP). Gleason sum at RP is a good indicator of biochemical recurrence and poor clinical outcome. Therefore, there is a need to improve clinical evaluation of PCa aggressiveness in order to choice appropriate treatment. To this aim an easy‐available tool is represented by circulating biomarkers. Among these, the best candidates are some molecules involved in PCa pathogenesis such as IGFBP‐2 and IGFBP‐3, IL‐6, and its soluble receptor (SIL‐6R).

METHODS

In this study, we evaluated the ability of preoperative IGFBP‐2, IGFBP‐3, IL‐6, and SIL‐6R serum levels to predict Gleason score upgrade in 52 PCa patients.

RESULTS

We found that IGFBP‐3 median levels were significantly lower in patients who showed Gleason upgrading from biopsy to RP (P = 0.024). We also found an association between biopsy T‐stage and Gleason Upgrade (P = 0.011). Using multivariate logistic regression model, we demonstrated that the association of IGFBP‐3 serum levels together with biopsy T‐stage and biopsy Gleason score was useful to calculate a prognostic risk score. ROC curve analysis of risk score showed a good ability to predict GSU (AUC = 0.81; 95% CI 0.69–0.93).

CONCLUSIONS

Our results suggest that preoperative IGFBP‐3 circulating levels determination may be useful to predict Gleason score upgrading alone and/or in combination with biopsy T‐stage and biopsy Gleason score. Prostate 72:100–107, 2012. © 2011 Wiley Periodicals, Inc.
Resveratrol Inhibits Periodontal Pathogens In Vitro
Authors: O'Connor D. J. , Wong R. W. K. , Rabie A. B. M.
Published: April 2011

The gram‐negative anaerobic bacteria A. actinomycetemcomitans (Aa) and P. gingivalis (Pg) are key components in the aetiology of periodontal disease, and associated hard‐tissue destruction. Resveratrol is a phytoalexin, produced naturally by several plants when under attack by bacterial or fungal pathogens. It is found in many foods including mulberries, peanuts and the skin of labrusca and muscadine grapes. The objective of this study was to evaluate the effect of resveratrol on the in vitro growth of periodontal pathogens Aa and Pg. For comparison, resveratrol's effect on a variety of other oral microorganisms was also evaluated. Resveratrol demonstrates a poor solubility in water, thus different concentrations of resveratrol in the solvent dimethyl sulphoxide (DMSO) were added to calibrated suspensions of Aa and Pg. As a control, a parallel series of dilutions containing the vehicle DMSO alone was made to measure the effect of the solvent. Minimum inhibitory concentrations of the periodontal pathogens were calculated. All suspensions were incubated for 1, 3, 6 and 24 h in an anaerobic chamber at 37 °C. At each time interval, selected dilutions from each culture broth were plated on blood agar plates. Colonies appearing on blood agar plates were visually counted at 3 days for Aa, and at 5 days for Pg. The periodontal bacteria showed a significant decrease (p < 0.05) in viable counts after 1 h, whilst no colony forming units could be observed after 24 h. The results suggest that resveratrol possesses significant antimicrobial properties on periodontal pathogens in vitro. Copyright © 2011 John Wiley & Sons, Ltd.
Photoprotective Effects of Topical Formulations Containing a Combination of Ginkgo biloba and Green Tea Extracts
Authors: Belo Susi Elaine Dal , Gaspar Lorena Rigo , Campos Patrícia Maria Berardo Gonçalves Maia
Published: April 2011

The beneficial photoprotective effects of topical formulations containing combined extracts of Ginkgo biloba (GB) and green tea (GT) have not been investigated. The present study aims to assess the photoprotective effects of topical formulations containing GB and GT combined or not by applications on the dorsal skin of hairless mice prior to UVA/B irradiation. After 20 h, skin barrier damage (TEWL), erythema, histological alterations and sunburn cell formation were evaluated. The results showed that only extract supplemented formulations protected the skin against the UV‐induced damage. Formulations containing GB provided total protection of the skin barrier function avoiding UV radiation damage such as TEWL and erythema and were more effective than those containing GT. However, it is suggested that formulations containing combined GB and GT may provide substantial photoprotective effects since different aspects of skin damage were influenced by each extract. Copyright © 2011 John Wiley & Sons, Ltd.
Full‐configuration‐interaction study of the metal‐insulator transition in a model system: Hn linear chains n=4, 6,…, 16
Authors: Bendazzoli Gian Luigi , Evangelisti Stefano , Monari Antonio
Published: April 2011

The metal‐insulator transition induced by electron correlation (Mott transition) is studied with ab initio full CI methods in model systems. These are linear chains of equally spaced hydrogen atoms. Different indicators of the metal‐insulator transition (maximum of the localization tensor or of the polarizability) areused and discussed. It is shown that the different indicators give concordant results, and that the transition is associated to a change in electron correlation, measured by the “particle‐hole” symmetric correlation entropy. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem 111:3416–3423, 2011
Unique QM/MM potential energy surface exploration using microiterations
Authors: Melaccio Federico , Olivucci Massimo , Lindh Roland , Ferré Nicolas
Published: April 2011

The determination and the characterization of important points of a potential energy surface can be carried out routinely using any molecular modelling software based on either a quantum mechanical (QM) or a classical (molecular mechanics, MM) description of the particle interactions. However the coupling of the QM and MM descriptions (QM/MM) gives rise to severe efficiency limitations during a geometry optimization of the whole system, especially when both subsystems are coupled electrostatically. This work introduces two simple improvements, mainly developed in the framework of the electrostatic potential fitted method to ensure the uniqueness of the QM/MM potential energy surface. The first one aims to improve the approximate Hessian matrix used in the QM optimization step. The second one tries to recouple electrostatically the QM and MM subsystems when microiterations are used. These methods are tested on a very simple system (a QM water molecule in a MM water box) before to be applied to the investigation of the light absorption in the rhodopsin protein at the multireference second‐order perturbation level of theory (CASPT2). This work is dedicated to the memory of Prof. B. O. Roos. He was a great support for the implementation of the QM/MM method in the Molcas package. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem 111:3339–3346, 2011
How to select active space for multiconfigurational quantum chemistry?
Authors: Veryazov Valera , Malmqvist Per Åke , Roos Björn O.
Published: April 2011

Björn Roos is one of the pioneers in the development and usage of multiconfigurational methods, in particular, the complete active space self‐consistent field method and the perturbational complete active space perturbation theory through second order. To perform multiconfigurational calculations using these methods, a set of active orbitals must be selected, and the success of the methods depends on the choice of this set. This is not only sometimes easy but also sometimes difficult, especially for use of the more recent RASSCF and RASPT2 methods (which use a “restricted active space” rather than the complete one). Although an automated procedure for selecting the active orbitals would be a preferable solution, this does not seem feasible yet. An account of the problem is given, with examples and some approaches that usually work. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem 111:3329–3338, 2011
Electronic spectra of nitroethylene
Authors: Borges Itamar , Barbatti Mario , Aquino Adélia J.A. , Lischka Hans
Published: April 2011

A systematic study of the electronic excited states of nitroethylene (C2H3NO2) was carried out using the approximate coupled‐cluster singles‐and‐doubles approach with the resolution of the identity (RI‐CC2), the time dependent density functional theory with the CAMB3LYP functional (TDDFT/CAMB3LYP) and the DFT multireference configuration interaction (DFT/MRCI) method. Vertical transition energies and optical oscillator strengths were computed for a maximum of 20 singlet transitions. Semiclassical simulations of the ultraviolet (UV) spectra were performed at the RI‐CC2 and DFT/MRCI levels. The main features in the UV spectrum were assigned to a weak n‐π* transition, and two higher energy πCC+O‐π* bands. These characteristics are common to molecules containing NO2 groups. Simulated spectra are in good agreement with the experimental spectrum. The energy of the bands in the DFT/MRCI simulation agrees quite well with the experiment, although it overestimates the band intensities. RI‐CC2 produced intensities comparable to the experiment, but the bands were blue shifted. A strong πCC+O‐π* band, not previously measured, was found in the 8–9 eV range. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012
Interesting periodic variations in physical and chemical properties of homonuclear diatomic molecules
Authors: Kamal C. , Banerjee Arup , Ghanty Tapan K. , Chakrabarti Aparna
Published: April 2011

We carry out a systematic study of various ground state and response properties of homonuclear diatomic molecules (from hydrogen to rubidium, including transition metals) as a function of atomic number of constituent atoms. We perform the ground state and response property calculations by using state of the art density functional theory/time dependent density functional theory. We observe that several properties of homonuclear diatomic molecules show periodic variations along rows and columns of the periodic table. The periodic variations in the ground state properties of diatomic molecules may be explained by the nature and type of the bond that exists between the constituent atoms. Similarly, the periodic variations in the response properties such as static dipole polarizability and strength of the van der Waals interaction between diatomic molecules have been correlated with the variations in metallic/nonmetallic character of the elements along the periodic table. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012
General solution of the coulomb–dirac problem: calculation of a divergence‐free lamb shift
Authors: Ritchie Burke
Published: April 2011

Paul Dirac's time‐dependent equation is inferred from the scalar product of an electron's four‐momentum and an electromagnetic four‐potential on identifying an electromagnetic carrier‐wave energy with the electron's rest‐mass energy (Maxwell–Dirac equivalency). Dirac's Schroedinger‐like temporally harmonic solution is not the general solution to his time‐dependent equation, because it constrains all four components of his vector wave function to oscillate in time at a single frequency. In fact, it is equivalent to an approximation method known as adiabatic elimination, which is widely used in the optical‐physics literature to solve temporally coupled equations. The general time‐dependent solution for the Coulomb problem includes coupled positive‐ and negative‐energy states whose wave function is a mixture of bound and unbound components. The Maxwell–Dirac equivalency permits the unbound component, which is known as Zitterbewegung in the free‐elecron problem, to be interpreted as a photonic component, which conserves energy for a ground state in which the electron simultaneously occupies two states whose separation is of order 2mc2. Equations of motion for a photon, which are formed from the scalar product of a photon's four‐momentum and an electromagnetic four‐potential, are also presented and used to calculate a divergence‐free Lamb shift. Finally, Dirac's general time‐dependent solution is shown to contain subatomic bound states for the Coulomb problem, even though such states are forbidden in Dirac's standard solution. These states exist for an electron, whose positive‐ (negative‐) energy motion is attractive (repulsive), or for a positron, whose positive‐ (negative‐) energy motion is repulsive (attractive), respectively. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2012
EVALUATING DAM RE‐OPERATION FOR FRESHWATER CONSERVATION IN THE SUSTAINABLE RIVERS PROJECT
Authors: Konrad C. P. , Warner A. , Higgins J. V.
Published: April 2011

Sustainable management of global water resources requires changing of dam operations to maintain river, floodplain and estuary ecosystems. Re‐operating dams for ecological objectives must be evaluated rigorously because of the complexity of ecological responses to streamflow, uncertainty in the long‐term and large‐scale conservation impacts on freshwater ecosystems and the foregone environmental or social benefits from other uses of water. Prescribed releases at five demonstration sites in the Sustainable Rivers Project, a partnership between the US Army Corps of Engineers (Corps) and The Nature Conservancy to plan and implement environmental flow prescriptions at Corps dams nationwide, have been evaluated in terms of their immediate and direct ecological outcomes. Advancing dam re‐operation as a freshwater conservation strategy at these and other sites will require additional evidence about longer‐term and broader impacts on biodiversity and ecosystems. A pragmatic framework for monitoring and evaluating dam re‐operation as a conservation strategy includes a balanced assessment of direct responses and long‐term effects, institutional partnerships that can implement monitoring and evaluation at an ecosystem scale and improved reporting of scientific investigations to facilitate long‐term monitoring and cross‐site learning. Copyright © 2011 John Wiley & Sons, Ltd.
Platform envelopment
Authors: Eisenmann Thomas , Parker Geoffrey , Van Alstyne Marshall
Published: April 2011

Due to network effects and switching costs in platform markets, entrants generally must offer revolutionary functionality to win substantial market share. We explore a second entry path that does not rely upon Schumpeterian innovation: platform envelopment. Through envelopment, a provider in one platform market can enter another platform market, and combine its own functionality with that of the target in a multi‐platform bundle that leverages shared user relationships. Envelopers capture market share by foreclosing an incumbent's access to users; in doing so, they harness the network effects that previously had protected the incumbent. We present a typology of envelopment attacks based on whether platform pairs are complements, weak substitutes, or functionally unrelated and we analyze conditions under which these attack types are likely to succeed. Copyright © 2011 John Wiley & Sons, Ltd.
Rivalry within strategic groups and consequences for performance: the firm‐size effects
Authors: Mas‐Ruiz Francisco , Ruiz‐Moreno Felipe
Published: April 2011

Our study examines how, in a given industry, rivalry functions within strategic groups defined according to the size of their member firms and how this rivalry affects performance. We hypothesize that, owing to several forms of group‐level effects including market power, efficiency, differentiation, and multimarket contact, strategic groups that comprise smaller firms will exhibit both increased rivalry and decreased performance compared with strategic groups that comprise larger firms. We test our hypotheses by estimating the effect of group‐level strategic interactions (i.e., conjectural variations) on firm performance. Ultimately, our analysis of empirical data on loans in the Spanish banking industry demonstrates that increased rivalry and decreased performance indeed characterizes firms belonging to a strategic group that comprises smaller firms. Copyright © 2011 John Wiley & Sons, Ltd.
Biogenesis of spliceosomal small nuclear ribonucleoproteins
Authors: Fischer Utz , Englbrecht Clemens , Chari Ashwin
Published: April 2011

Virtually, all eukaryotic mRNAs are synthesized as precursor molecules that need to be extensively processed in order to serve as a blueprint for proteins. The three most prevalent processing steps are the capping reaction at the 5′‐end, the removal of intervening sequences by splicing, and the formation of poly (A)‐tails at the 3′‐end of the message by polyadenylation. A large number of proteins and small nuclear ribonucleoprotein complexes (snRNPs) interact with the mRNA and enable the different maturation steps. This chapter focuses on the biogenesis of snRNPs, the major components of the pre‐mRNA splicing machinery (spliceosome). A large body of evidence has revealed an intricate and segmented pathway for the formation of snRNPs that involves nucleo‐cytoplasmic transport events and elaborates assembly strategies. We summarize the knowledge about the different steps with an emphasis on trans‐acting factors of snRNP maturation of higher eukaryotes. WIREs RNA 2011 2 718–731 DOI: 10.1002/wrna.87

This article is categorized under:

RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes

RNA Processing > Splicing Mechanisms

RNA Export and Localization > Nuclear Export/Import

RNA in Disease and Development > RNA in Disease
Updated database for L x‐ray production by protons and extraction of L‐subshell ionization cross sections from only Lγ and Lα + Lβ cross sections
Authors: Lapicki Gregory , Miranda Javier
Published: April 2011

Database from pre‐1995 compilations of L x‐ray production and ionization by protons is enlarged by 53% with the present update. Semiempirical formulas for Lγ and Lαβ are developed and used to extract L1, L2, and L3 subshell ionization cross sections. The extracted ionization cross sections are shown for a sample of elements and compared with the database ionization cross sections in gold. Copyright © 2011 John Wiley & Sons, Ltd.
PIXE characterisation of prehistoric pigments from Abri Pataud (Dordogne, France)
Authors: Beck L. , Lebon M. , Pichon L. , Menu M. , Chiotti L. , Nespoulet R. , Paillet P.
Published: April 2011

Abri Pataud is a prehistoric rock‐shelter now largely collapsed. Archaeological excavations have revealed more than 40 settlements between 35 000 and 20 000 years ago corresponding to the first half of Upper Palaeolithic (Aurignacian, Gravettian and Solutrean archaeological cultures). During the excavations, remains of painted rock flakes coming from the collapsed shelter walls, painted objects, ochre pencils as well as raw pigments were found in archaeological levels. After preliminary non‐destructive investigation of the samples by scanning electron microscopy (SEM) and X‐ray diffraction, non‐destructive analyses were performed by ion beam analysis (IBA). In this paper, PIXE results obtained on red pigment material are reported. Minor and trace elements were used to compare pigments present on the decorated rock flakes or on painted objects, with raw pigment materials discovered in the same archaeological site. PIXE results provide new data for the interpretation of the Abri Pataud prehistoric site. This study confirms the ability of PIXE to characterize prehistoric pigments and to discriminate possible sources on the basis of the trace elements associated with the iron oxide phase. Copyright © 2011 John Wiley & Sons, Ltd.
Depth profiling techniques: how PIXE compares to NRP and MEIS?
Authors: Dos Santos C. E. I. , Shubeita S. M. , Amaral L. , Grande P. L. , Dias J. F.
Published: April 2011

The aim of the present work is to check the potentialities of particle‐induced X‐ray emission (PIXE) as an analytical tool for measurement of ultra‐thin film thicknesses in the nanometer scale. To that end, several different thin oxide films (HfO2, LaScO3, LaAlO3 and Al2O3) in the range of 2–60 nm were grown on crystalline Si. Film thickness measurements using 2.0 and 0.4 MeV proton PIXE, 40 and 200 keV proton medium energy ion scattering (MEIS), and 991.9 keV proton nuclear reaction profiling (NRP) were compared. For the simple target structures studied in this work, the results indicate that PIXE provides thicknesses compatible to those obtained with NRP and MEIS. However, PIXE analysis proved to be difficult in some cases, particularly when close‐by elements with overlapping X‐ray peaks are involved. For such cases, MEIS and NRP present clear advantages over PIXE. Copyright © 2011 John Wiley & Sons, Ltd.