bluuebunny/crossref_metadata_2025 huggingface dataset:
Global gene expression profiling in early-stage polycystic kidney disease in the Han:SPRD Cy rat identifies a role for RXR signaling
Authors: Kugita Masanori , Nishii Kazuhiro , Morita Miwa , Yoshihara Daisuke , Kowa-Sugiyama Hiroe , Yamada Kouji , Yamaguchi Tamio , Wallace Darren P. , Calvet James P. , Kurahashi Hiroki , Nagao Shizuko
Published: October 2010

Han:SPRD Cy is a spontaneous rat model of polycystic kidney disease (PKD) caused by a missense mutation in Pkdr1. Cystogenesis in this model is not clearly understood. In the current study, we performed global gene expression profiling in early-stage PKD cyst development in Cy/Cy kidneys and normal (+/+) kidneys at 3 and 7 days of postnatal age. Expression profiles were determined by microarray analysis, followed by validation with real-time RT-PCR. Genes were selected with over 1.5-fold expression changes compared with age-matched +/+ kidneys for canonical pathway analysis. We found nine pathways in common between 3- and 7-day Cy/Cy kidneys. Three significantly changed pathways were designated “Vitamin D Receptor (VDR)/Retinoid X Receptor (RXR) Activation,” “LPS/IL-1-Mediated Inhibition of RXR Function,” and “Liver X Receptor (LXR)/RXR Activation.” These results suggest that RXR-mediated signaling is significantly altered in developing kidneys with mutated Pkdr1. In gene ontology analysis, the functions of these RXR-related genes were found to be involved in regulating cell proliferation and organ morphogenesis. With real-time RT-PCR analysis, the upregulation of Ptx2, Alox15b, OSP, and PCNA, major markers of cell proliferation associated with the RXR pathway, were confirmed in 3- and 7-day Cy/Cy kidneys compared with 3-day +/+ kidneys. The increased RXR protein was observed in both the nucleus and cytoplasm of cystic epithelial cells in early-stage Cy/Cy kidneys, and the RXR-positive cells were strongly positive for PCNA staining. Taken together, cell proliferation and organ morphogenesis signals transduced by RXR-mediated pathways may have important roles for cystogenesis in early-stage PKD in this Pkdr1-mutated Cy rat.
Differing Neurophysiologic Mechanosensory Input From Glabrous and Hairy Skin in Juvenile Rats
Authors: Boada M. Danilo , Houle Timothy T. , Eisenach James C. , Ririe Douglas G.
Published: October 2010

Sensory afferents in skin encode and convey thermal and mechanical conditions, including those that threaten tissue damage. A small proportion of skin, the glabrous skin of the distal extremities, is specialized to explore the environment in fine detail. Aside from increased innervation density, little is known regarding properties of mechanosensory afferents to glabrous skin in younger animals that explain the exquisite precision and high contrast in rapidly sampling physical structures, including those that threaten injury. To assess this, we obtained intact neuronal intracellular recordings in vivo from 115 mechanosensitive afferent neurons from lumbar and thoracic dorsal root ganglia in juvenile rats. Two characteristics were unique to glabrous skin: a threefold higher proportion of fast-conducting to slow-conducting afferents that were high-threshold mechanosensitive nociceptors compared with hairy skin and a twofold faster conduction velocity of fast-conducting nociceptors compared with hairy skin. Additionally differences were found in mechanical thresholds between glabrous skin and hairy skin for each fiber type. These differences reflect and help explain the rapid response of skin specialized to explore the physical environment. Additionally, these results highlight potential limitations of using passive electrical properties and conduction velocity alone to characterize primary afferents without knowledge of the skin type they innervated.
Social and Ecological Regulation of a Decision-Making Circuit
Authors: Neumeister H. , Whitaker K. W. , Hofmann H. A. , Preuss T.
Published: October 2010

Ecological context, sensory inputs, and the internal physiological state are all factors that need to be integrated for an animal to make appropriate behavioral decisions. However, these factors have rarely been studied in the same system. In the African cichlid fish Astatotilapia burtoni, males alternate between two phenotypes based on position in a social hierarchy. When dominant (DOM), fish display bright body coloration and a wealth of aggressive and reproductive behavioral patterns that make them conspicuous to predators. Subordinate (SUB) males, on the other hand, decrease predation risk by adopting cryptic coloration and schooling behavior. We therefore hypothesized that DOMs would show enhanced startle-escape responsiveness to compensate for their increased predation risk. Indeed, behavioral responses to sound clicks of various intensities showed a significantly higher mean startle rate in DOMs compared with SUBs. Electrophysiological recordings from the Mauthner cells (M-cells), the neurons triggering startle, were performed in anesthetized animals and showed larger synaptic responses to sound clicks in DOMs, consistent with the behavioral results. In addition, the inhibitory drive mediated by interneurons (passive hyperpolarizing potential [PHP] cells) presynaptic to the M-cell was significantly reduced in DOMs. Taken together, the results suggest that the likelihood for an escape to occur for a given auditory stimulus is higher in DOMs because of a more excitable M-cell. More broadly, this study provides an integrative explanation of an ecological and social trade-off at the level of an identifiable decision-making neural circuit.
Selective Decontamination of the Digestive Tract Reduces Pneumonia and Mortality
Authors: Haas Lenneke E. M. , Schultz Marcus J.
Published: October 2010

Selective decontamination of the digestive tract (SDD) has been subject of numerous randomized controlled trials in critically ill patients. Almost all clinical trials showed SDD to prevent pneumonia. Nevertheless, SDD has remained a controversial strategy. One reason for why clinicians remained reluctant to implement SDD into daily practice could be that mortality was reduced in only 2 trials. Another reason could be the heterogeneity of trials of SDD. Indeed, many different prophylactic antimicrobial regimes were tested, and dissimilar diagnostic criteria for pneumonia were applied amongst the trials. This heterogeneity impeded interpretation and comparison of trial results. Two other hampering factors for implementation of SDD have been concerns over the risk of antimicrobial resistance and fear for escalation of costs associated with the use of prophylactic antimicrobials. This paper describes the concept of SDD, summarizes the results of published trials of SDD in mixed medical-surgical intensive care units, and rationalizes the risk of antimicrobial resistance and rise of costs associated with this potentially life-saving preventive strategy.
Angiogenesis and Breast Cancer
Authors: Longatto Filho Adhemar , Lopes José Manuel , Schmitt Fernando C.
Published: October 2010

Angiogenesis is an essential step for breast cancer progression and dissemination. The development of new blood vessels in cancer setting (angiogenesis) is conducted by numerous physiological and pathological stimuli, where the main stimulus is hypoxia. The knowledge of different molecular pathways regulating angiogenesis is constantly growing. An increased and complex scenario of angiogenesis is nowadays available in breast cancer, specifically, and permits not only to understand most of the important phases of neoplastic growth but also offer an exciting perspective for new therapeutic proposals based on blocking new blood vessels sprouting. This review focused on historical and recent understanding of angiogenesis occurrence in breast cancer.
Technical Note on (Q, r, L) Inventory Model with Defective Items
Authors: Tung Cheng-Tan , Wou Yu-Wen , Lin Shih-Wei , Deng Peter
Published: October 2010

Under a reasonable assumption, we derive an analytical approach that verifies uniqueness of the optimal solution for stochastic inventory models with defective items. Our approach implies a robust method to find the optimal solution.
Blood Vessel Density in Basal Cell Carcinomas and Benign Trichogenic Tumors as a Marker for Differential Diagnosis in Dermatopathology
Authors: Winter Julia , Kneitz Hermann , Bröcker Eva-B.
Published: October 2010

In order to get insight into the density of blood vessels in the stroma of benign and malignant trichogenic neoplasms, immunohistological quantification of CD 31 positive vessels was performed in 112 tumors, comprised of 50 BCCs of nodular (35) or morphoeic (15) growth patterns, 17 Pinkus' tumors, as well as 17 trichoepitheliomas of which 6 were desmoplastic, 8 trichofolliculomas, and 20 trichoblastomas.Methods. Vessel density was counted within the tumors, in the tumor-surrounding stroma, and, as a control, in the normal skin of the operation specimen. The results were compared using statistical methods.Results. Whereas, irrespective of the patients' age and location of tumors, the vessel density in normal skin showed no significant differences (), the counts in the peritumoral stroma revealed significant differences between the different tumors investigated. The highest counts were obtained in BCC () and the lowest in benign trichogenic neoplasms (around 14) Pinkus' tumors revealed intermediate counts (). The vessel densities within the tumors were generally low, and no correlation to the dignity was found.Conclusion. Determination of blood vessel density in the peritumoral stroma may be an additional parameter for differential diagnosis of trichogenic tumors of uncertain dignity.
Conditional Regulatory T-Cell Depletion Releases Adaptive Immunity Preventing Carcinogenesis and Suppressing Established Tumor Growth
Authors: Teng Michele W.L. , Ngiow Shin Foong , von Scheidt Bianca , McLaughlin Nicole , Sparwasser Tim , Smyth Mark J.
Published: October 2010

Foxp3 is a central control element in the development and function of regulatory T cells (Treg), and mice expressing a diphtheria toxin (DT) receptor–enhanced green fluorescent protein fusion protein under the control of the foxp3 gene locus (DEREG mice) allow conditional and efficient depletion of Foxp3+ Treg by DT injection. Herein, we use DEREG mice and a mouse model of carcinogenesis to show that conditional and effective Treg depletion can both protect mice from carcinogenesis by innate control, yet permanently eradicate a proportion of de novo–established tumors in mice in a largely CD8+ T-cell– and IFN-γ–dependent manner. Tumors displayed a heterogeneous response to Treg depletion, and suppression of established tumors was accompanied by an increase in the tumor-infiltrating CD8+ T-cell/B-cell ratio. Tumor rejection occurred in the absence of overt autoimmunity, suggesting that effective transient Treg depletion strategies may be therapeutic in at least a proportion of spontaneous tumors developing in the host. Cancer Res; 70(20); 7800–9. ©2010 AACR.
Optical Detection of Buccal Epithelial Nanoarchitectural Alterations in Patients Harboring Lung Cancer: Implications for Screening
Authors: Roy Hemant K. , Subramanian Hariharan , Damania Dhwanil , Hensing Thomas A. , Rom William N. , Pass Harvey I. , Ray Daniel , Rogers Jeremy D. , Bogojevic Andrej , Shah Maitri , Kuzniar Tomasz , Pradhan Prabhakar , Backman Vadim
Published: October 2010

We have recently developed a novel optical technology, partial wave spectroscopic (PWS) microscopy, which is exquisitely sensitive to the nanoarchitectural manifestation of the genetic/epigenetic alterations of field carcinogenesis. Our approach was to screen for lung cancer by assessing the cheek cells based on emerging genetic/epigenetic data which suggests that the buccal epithelium is altered in lung field carcinogenesis. We performed PWS analysis from microscopically normal buccal epithelial brushings from smokers with and without lung cancer (n = 135). The PWS parameter, disorder strength of cell nanoarchitecture (Ld), was markedly (>50%) elevated in patients harboring lung cancer compared with neoplasia-free smokers. The performance characteristic was excellent with an area under the receiver operator characteristic curve of >0.80 and was equivalent for both disease stage (early versus late) and histologies (small cell versus non–small cell lung cancers). An independent data set validated the findings with only a minimal degradation of performance characteristics. Our results offer proof of concept that buccal PWS may potentially herald a minimally intrusive prescreening test that could be integral to the success of lung cancer population screening programs. Cancer Res; 70(20); 7748–54. ©2010 AACR.
Selective Depletion of Foxp3+ Regulatory T Cells Improves Effective Therapeutic Vaccination against Established Melanoma
Authors: Klages Katjana , Mayer Christian T. , Lahl Katharina , Loddenkemper Christoph , Teng Michele W.L. , Ngiow Shin Foong , Smyth Mark J. , Hamann Alf , Huehn Jochen , Sparwasser Tim
Published: October 2010

Tumor-bearing individuals have been reported to harbor increased numbers of Foxp3+ regulatory T cells (Treg), which prevent the development of efficient antitumor immune responses. Thus, Treg depletion has already been tested as a promising therapeutic approach in various animal models and entered clinical trials. However, the use of nonspecific Treg targeting agents such as CD25 depleting antibodies, which in addition to CD25+ Tregs also deplete recently activated CD25+ effector T cells, potentially masked the tremendous potential of this therapeutic strategy. To avoid such nonspecific effects, we used transgenic DEREG (depletion of regulatory T cells) mice, which express a diphtheria toxin receptor under control of the Foxp3 locus, allowing selective depletion of Foxp3+ Tregs even during ongoing immune responses. We showed that Foxp3+ Treg depletion induced partial regression of established ovalbumin (OVA)-expressing B16 melanoma, which was associated with an increased intratumoral accumulation of activated CD8+ cytotoxic T cells. The antitumor effect could be significantly enhanced when Treg depletion was combined with vaccination against OVA. To further assess whether this therapeutic approach would break self-tolerance, we crossed DEREG mice with RipOVAlow mice, expressing OVA as neo–self-antigen under control of the rat insulin promoter. In these mice, combined Treg depletion and vaccination also induced tumor regression without the onset of diabetes. Together, our data suggest that selective Treg targeting strategies combined with vaccinations against tumor-associated (self) antigens have the potential to evoke efficient antitumor responses without inducing overt autoimmunity. These findings might have implications for future therapeutic interventions in cancer patients. Cancer Res; 70(20); 7788–99. ©2010 AACR.
A Population-based Study on the Risks of Cervical Lesion and Human Papillomavirus Infection among Women in Beijing, People's Republic of China
Authors: Li Changdong , Wu Minghui , Wang Jiandong , Zhang Songwen , Zhu Li , Pan Jing , Zhang Weiyuan
Published: October 2010

Background: Few population-based studies have investigated premalignant and malignant cervical abnormalities in Beijing.

Methods: A total of 6,385 randomly selected sexually active women were interviewed and examined. Cervical lesion was diagnosed using cytology and histology. High-risk human papillomavirus (HPV) was detected by the second-generation hybrid capture test and typed by gene chip of DNA from paraffin-embedded tissue.

Results: The cervical lesion prevalence diagnosed by histology was 5.8%. High-risk HPV overall prevalence was 9.9%, 50.5% with cervical lesion and 7.4% without cervical lesion. High-risk HPV DNA load increased with increasing degree of lesions. HPV 16 was the most common type (26.5%) among women with cervical lesion, followed by HPV 58 (8.8%), HPV 33 (7.8%), and HPV 56 (5.3%). Women under 50 years of age, married status, pregnancy and delivery status, couple's sexual behavior, contraceptive history, columnar ectopy, and bacterial vaginosis or trichomonas vaginitis history were more risk factors for HPV infection. Factors for cervical lesion were similar, but in comparison with HPV infection, all associations were weakened. Only middle-aged women, husband's sexual partners, oral contraceptives, columnar ectopy, and history of trichomonas vaginitis remained associated with cervical lesion.

Conclusion: In Beijing, the prevalence of cervical lesion and high-risk HPV is higher than estimated in previous reports. HPV 16, 58, and 33 were the most prevalent types. This is relevant for work related to cervical cancer vaccination.

Impact: The study was conducted to understand the current status and epidemiologic characteristics of women with cervical lesion and HPV infection in Beijing. Cancer Epidemiol Biomarkers Prev; 19(10); 2655–64. ©2010 AACR.
Adherence to a Breast Cancer Screening Program and Its Predictors in Underserved Women in Southern Brazil
Authors: Caleffi Maira , Ribeiro Rodrigo A. , Bedin Ademar J. , Viegas-Butzke Júlia M.P. , Baldisserotto Fernanda D.G. , Skonieski Giovana P. , Giacomazzi Juliana , Camey Suzi A. , Ashton-Prolla Patrícia
Published: October 2010

Background: Adherence to breast cancer screening is a key element to ensure effectiveness of programs aiming at downstaging of breast cancer. In this study, we evaluated adherence to a screening program and its predictors in underserved women in southern Brazil.

Methods: Attendance to the program, which is based on yearly mammogram and clinical examination, was evaluated prospectively. Mean time frames between visits were calculated. Possible predictors of adherence (defined as mean intervals ≤18 mo), such as socioeconomic indicators and health/lifestyle behaviors, were investigated.

Results: A total of 3,749 women (age 51 ± 8 y, illiteracy rate of 6.8%, 57.4% with parity ≥3) were analyzed. Median time between screening rounds was 16.5 months (interquartile range, 13.1-25.7), and median number of rounds attended was 3 (interquartile range, 2-4); 57.6% had mean intervals ≤18, and 71% ≤24 months. The most important independent predictors of adherence were high genetic risk [relative risk (RR), 1.25; 95% confidence interval (95% CI), 1.11-1.40], illiteracy (RR, 0.77; 95% CI, 0.67-0.90), parity ≥5 (RR, 0.89; 95% CI, 0.83-0.96), and smoking (RR, 0.82; 95% CI, 0.77-0.88).

Conclusions: Although the proposed screening interval was 1 year, compliance to biannual screening (accepted in several international programs) was high, especially when considering the low socioeconomic level of the sample.

Impact: This project aims to test a breast cancer screening model for underserved populations in limited-resource countries where adherence is an issue. The identification of worst adherence predictors can point to interventions to improve outcomes of similar public health screening strategies. Cancer Epidemiol Biomarkers Prev; 19(10); 2673–9. ©2010 AACR.
A Prospective Study on Dietary Acrylamide Intake and the Risk for Breast, Endometrial, and Ovarian Cancers
Authors: Wilson Kathryn M. , Mucci Lorelei A. , Rosner Bernard A. , Willett Walter C.
Published: October 2010

Background: Acrylamide is a probable human carcinogen formed during cooking of many common foods. Epidemiologic studies on acrylamide and breast cancer risk have been null; however, positive associations with ovarian and endometrial cancers have been reported. We studied acrylamide intake and risk for breast, endometrial, and ovarian cancers in a prospective cohort study.

Methods: We assessed acrylamide intake among 88,672 women in the Nurses' Health Study using food frequency questionnaires administered every 4 years. Between 1980 and 2006, we identified 6,301 cases of invasive breast cancer, 484 cases of invasive endometrial adenocarcinoma, and 416 cases of epithelial ovarian cancer. We used Cox proportional hazards models to study the association between acrylamide and cancer risk.

Results: We found no association between acrylamide intake and breast cancer overall or according to estrogen and progesterone receptor status. We found an increased risk for endometrial cancer among high acrylamide consumers (adjusted relative risk for highest versus lowest quintile = 1.41; 95% CI, 1.01-1.97; P for trend = 0.03). We observed a nonsignificant suggestion of increased risk for ovarian cancer overall (relative risk, 1.25; 95% CI, 0.88-1.77; P trend = 0.12), with a significantly increased risk for serous tumors (relative risk, 1.58; 95% CI, 0.99-2.52; P trend = 0.04). Associations did not differ by smoking status.

Conclusions: We observed no association between acrylamide and breast cancer. Risk for endometrial cancer and possibly ovarian cancer was greater among high acrylamide consumers.

Impact: This is the second prospective study to report positive associations with endometrial and ovarian cancers. These associations should be further evaluated to inform public health policy. Cancer Epidemiol Biomarkers Prev; 19(10); 2503–15. ©2010 AACR.
Prospective Study of Human Papillomavirus (HPV) Types, HPV Persistence, and Risk of Squamous Cell Carcinoma of the Cervix
Authors: Sundström Karin , Eloranta Sandra , Sparén Pär , Arnheim Dahlström Lisen , Gunnell Anthony , Lindgren Anders , Palmgren Juni , Ploner Alexander , Sanjeevi Carani B. , Melbye Mads , Dillner Joakim , Adami Hans-Olov , Ylitalo Nathalie
Published: October 2010

Background: The link between squamous cell cervical carcinoma and human papillomavirus (HPV) 16/18 is well established, but the magnitude of the risk association is uncertain and the importance of other high-risk HPV (HRHPV) types is unclear.

Methods: In two prospective nested case-control series among women participating in cytologic screening in Sweden, we collected 2,772 cervical smears from 515 women with cancer in situ (CIS), 315 with invasive squamous cell carcinoma (SCC), and individually matched controls. All smears were tested for HPV with PCR assays, and the median follow-up until diagnosis was 5 to 7 years. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (95% CI).

Results: The presence of HPV16/18 in the first smear was associated with 8.5-fold (95% CI, 5.3-13.7) and 18.6-fold (95% CI, 9.0-38.9) increased risks of CIS and SCC, respectively, compared with women negative for HPV. Infection with other HRHPV types in the first smear was also associated with significantly increased risks for both CIS and SCC. Persistence of HPV16 infection conferred a RR of 18.5 (95% CI, 6.5-52.9) for CIS and 19.5 (95% CI, 4.7-81.7) for SCC. The HPV16/18 attributable risk proportion was estimated at 30% to 50% for CIS, and 41% to 47% for SCC. Other HRHPV types also conferred significant proportions.

Conclusions: Our large population-based study provides quantification of risks for different HPV types and prospective evidence that non-16/18 HRHPV types increase the risk for future cervical cancer.

Impact: This study gives further insights into cervical cancer risk stratification with implications for HPV-based prevention strategies. Cancer Epidemiol Biomarkers Prev; 19(10); 2469–78. ©2010 AACR.
A Common Prostate Cancer Risk Variant 5′ of Microseminoprotein-β (MSMB) Is a Strong Predictor of Circulating β-Microseminoprotein (MSP) Levels in Multiple Populations
Authors: Waters Kevin M. , Stram Daniel O. , Le Marchand Loic , Klein Robert J. , Valtonen-André Camilla , Peltola Mari T. , Kolonel Laurence N. , Henderson Brian E. , Lilja Hans , Haiman Christopher A.
Published: October 2010

Background: β-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5′ region of the gene that encodes MSP (MSMB) has recently been identified as a risk factor for prostate cancer.

Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer–free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels.

Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P < 10−8), with carriers of the C allele having lower geometric mean MSP levels (ng/mL; CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans, 25.8/16.4/6.7). We estimated the variant accounts for 30% to 50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P = 3.5 × 10−6), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans.

Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations.

Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele. Cancer Epidemiol Biomarkers Prev; 19(10); 2639–46. ©2010 AACR.
Comparison Study on the Complete Sequence of Hepatitis B Virus Identifies New Mutations in Core Gene Associated with Hepatocellular Carcinoma
Authors: Zhu Yu , Jin Yan , Guo Xia , Bai Xin , Chen Taoyang , Wang Jinbing , Qian Gengsun , Groopman John D. , Gu Jianren , Li Jinjun , Tu Hong
Published: October 2010

Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC).

Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls.

Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W.

Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC.

Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC. Cancer Epidemiol Biomarkers Prev; 19(10); 2623–30. ©2010 AACR.
Lipophilic Statin Use and Risk of Breast Cancer Subtypes
Authors: Woditschka Stephan , Habel Laurel A. , Udaltsova Natalia , Friedman Gary D. , Sieh Weiva
Published: October 2010

Background/Aims: Statins are widely used and of high interest as potential chemopreventive agents for cancer. Preclinical studies suggest that lipophilic statins have anticancer properties targeting hormone receptor (HR)-negative breast cancer. Few epidemiologic studies have investigated the relationship between lipophilic statin use and risk for breast cancer, stratified by HR status. We conducted a large case-control study within Kaiser Permanente of Northern California (KPNC) to determine whether chronic use of lipophilic statins is associated with decreased risk of HR-negative breast cancer or other breast cancer subtypes.

Methods: We identified 22,488 breast cancer cases diagnosed from 1997 to 2007, and 224,860 controls matched to cases based upon birth year and duration of KPNC pharmacy coverage. Use of lipophilic statins was ascertained using the comprehensive electronic pharmacy records of KPNC.

Results: We found no association between lipophilic statin use (≥2 y versus never) and overall breast cancer risk (odds ratioadj, 1.02; 95% CI, 0.97-1.08) in conditional logistic regression models adjusted for oral contraceptive and hormone therapy use. Women who used lipophilic statins did not have a decreased risk of HR-negative breast cancer (odds ratioadj, 0.98; 95% CI, 0.84-1.14) nor altered risk of HR-positive disease (odds ratioadj, 1.03; 95% CI, 0.97-1.10). Furthermore, lipophilic statin use was not associated with risk of any of the intrinsic subtypes, luminal A, luminal B, human epidermal growth factor receptor 2 positive/estrogen receptor negative, or triple negative.

Conclusions: Our results do not support an association of lipophilic statin use with the risk for breast cancer in general or with risks of HR-negative or other breast cancer subtypes specifically.

Impact: These findings do not confirm previous reports of a possible preventive association. Cancer Epidemiol Biomarkers Prev; 19(10); 2479–87. ©2010 AACR.
Mammographic Density and Risk of Second Breast Cancer after Ductal Carcinoma In situ
Authors: Habel Laurel A. , Capra Angela M. , Achacoso Ninah S. , Janga Aradhana , Acton Luana , Puligandla Balaram , Quesenberry Charles P.
Published: October 2010

Background: We examined whether mammographic density predicts risk of second breast cancers among patients with ductal carcinoma in situ (DCIS).

Methods: The study included DCIS patients diagnosed during 1990 to 1997 and treated with breast-conserving surgery at Kaiser Permanente Northern California. Medical records were reviewed for clinical factors and subsequent breast cancers (DCIS and invasive). Ipsilateral mammograms from the index DCIS were assessed for density without knowledge of subsequent cancer status. Cox regression modeling was used to examine the association between mammographic density and risk of breast cancer events.

Results: Of the 935 eligible DCIS patients, 164 (18%) had a subsequent ipsilateral breast cancer, and 59 (6%) had a new primary cancer in the contralateral breast during follow-up (median, 103 mo). Those with the greatest total area of density (upper 20% of values) were at increased risk for invasive disease in either breast [hazard ratio (HR), 2.1; 95% confidence interval (95% CI), 1.2-3.8] or any cancer (DCIS or invasive) in the ipsilateral (HR, 1.7; 95% CI, 1.0-2.9) or contralateral (HR, 3.0; 95% CI, 1.3-6.9) breast compared with those with the smallest area of density (bottom 20%). HRs for these same end points comparing those in the highest with those in the lowest American College of Radiology Breast Imaging Reporting and Data System category were 1.6 (95% CI, 0.7-3.6), 1.3 (95% CI, 0.7-2.6), and 5.0 (95% CI, 1.4-17.9), respectively. There was a suggestion of increasing risk of contralateral, but not ipsilateral, cancer with increasing percent density.

Conclusions: Women with mammographically dense breasts may be at higher risk of subsequent breast cancer, especially in the contralateral breast.

Impact: Information about mammographic density may help with DCIS treatment decisions. Cancer Epidemiol Biomarkers Prev; 19(10); 2488–95. ©2010 AACR.
MSH6 and MUTYH Deficiency Is a Frequent Event in Early-Onset Colorectal Cancer
Authors: Giráldez María Dolores , Balaguer Francesc , Bujanda Luis , Cuatrecasas Miriam , Muñoz Jenifer , Alonso-Espinaco Virginia , Larzabal Mikel , Petit Anna , Gonzalo Victoria , Ocaña Teresa , Moreira Leticia , Enríquez-Navascués José María , Boland C. Richard , Goel Ajay , Castells Antoni , Castellví-Bel Sergi
Published: October 2010

Purpose: Early-onset colorectal cancer (CRC) is suggestive of a hereditary predisposition. Lynch syndrome is the most frequent CRC hereditary cause. The MUTYH gene has also been related to hereditary CRC. A systematic characterization of these two diseases has not been reported previously in this population.

Experimental Design: We studied a retrospectively collected series of 140 patients ≤50 years old diagnosed with nonpolyposis CRC. Demographic, clinical, and familial features were obtained. Mismatch repair (MMR) deficiency was determined by microsatellite instability (MSI) analysis, and immunostaining for MLH1, MSH2, MSH6, and PMS2 proteins. Germline MMR mutations were evaluated in all MMR-deficient cases. Tumor samples with loss of MLH1 or MSH2 protein expression were analyzed for somatic methylation. Germline MUTYH mutations were evaluated in all cases. BRAF V600E and KRAS somatic mutational status was also determined.

Results: Fifteen tumors (11.4%) were MSI, and 20 (14.3%) showed loss of protein expression (7 for MLH1/PMS2, 2 for isolated MLH1, 3 for MSH2/MSH6, 7 for isolated MSH6, and 1 for MSH6/PMS2). We identified 11 (7.8%) germline MMR mutations, 4 in MLH1, 1 in MSH2, and 6 in MSH6. Methylation analysis revealed one case with somatic MLH1 methylation. Biallelic MUTYH mutations were detected in four (2.8%) cases. KRAS and BRAF V600E mutations were present in 39 (27.9%) and 5 (3.6%) cases, respectively.

Conclusions: Loss of MSH6 expression is the predominant cause of MMR deficiency in early-onset CRC. Our findings prompt the inclusion of MSH6 and MUTYH screening as part of the genetic counseling of these patients and their relatives. Clin Cancer Res; 16(22); 5402–13. ©2010 AACR.
‘Naming the Demon’: The ‘Structure’ of Evil in Lonergan and Girard
Authors: Dadosky John D.
Published: October 2010

This article explores basic insights from René Girard and Bernard Lonergan on the ‘structure’ of evil in human living. For Girard, the root of human evil lies in rivalries, affections of the human heart that lead to mimetic competition, and in the extreme, to the scapegoating of innocent or vulnerable people. For Lonergan, evil is the opposite of the good, so that there is a sense in which he identifies evil as it opposes the good at every level of its structure. In the case of both thinkers, the hope of a solution to the persistence of evil lies in the positive mimesis or imitation and participation in the Triune life of God.
Capabilities and the Common Good
Authors: Mulligan Suzanne
Published: October 2010

The author explores some of the connections that can be made between the concept of the common good and the capabilities approach to development. Although widely used in the social teaching of the Church, the definition of the common good found in the social encyclicals is often vague and requires further explanation. In drawing from the work of Amartya Sen and Martha Nussbaum the author seeks to show how the idea of capabilities can assist our understanding of the common good. In addition, it is suggested that the language of capabilities and the common good could contribute significantly to current public debate. Both concepts place an emphasis on integral human development which provides a starting point for a more holistic social discourse.
Stem Cell-Calcium Phosphate Constructs for Bone Engineering
Authors: Xu H.H.K. , Zhao L. , Weir M.D.
Published: October 2010

While human bone-marrow-derived mesenchymal stem cells (hBMSCs) have been investigated, human umbilical cord mesenchymal stem cells (hUCMSCs) are a relatively new cell source. Little has been reported on hUCMSC encapsulation in scaffolds for bone tissue engineering. The objective of this study was to encapsulate hBMSCs and hUCMSCs in calcium phosphate cement (CPC) scaffolds for dental, craniofacial, and orthopedic applications. Stem-cell-encapsulating CPC construct with chitosan and fiber reinforcement reached the strength of cancellous bone, which was much stronger than previous injectable carriers for cell delivery. hUCMSCs and hBMSCs inside the constructs showed excellent viability and osteo-differentiation. The encapsulated hUCMSCs synthesized nearly three-fold more bone minerals than the hBMSCs in vitro. Hence, stem-cell-encapsulating CPC-chitosan-fiber construct may be promising for dental and orthopedic applications. This study indicated that the hUCMSCs were a potent alternative to the gold-standard hBMSCs, which may have a broad impact on regenerative medicine and dental tissue engineering.
Do Men and Women Differ in Their Retirement Planning? Testing a Theoretical Model of Gendered Pathways to Retirement Preparation
Authors: Noone Jack , Alpass Fiona , Stephens Christine
Published: October 2010

Previous literature has situated retirement and retirement planning within the male’s domain by positioning women as unconcerned and therefore ill prepared for retirement. However, women’s increasing representation in the workforce requires a reexamination of their retirement plans and the factors that enable them. In this study, a subsample of 2,277 working men and women from the New Zealand Health, Work, and Retirement Survey provides the basis for a structural equation model examining the effects of socioeconomic status, work involvement, and retirement perceptions on retirement planning. This model also tests for gender differences to assess the extent to which women are disadvantaged in terms of their retirement planning and the factors that may affect retirement plans. Results indicated that perceptions of retirement and economic living standards were associated with financial preparedness. However, women were still economically disadvantaged compared to men and this impacted negatively on their financial preparations. Retirement and retirement planning is now of greater concern for women. Future promotional initiatives should be aimed at these groups to assist their financial preparations for the future.
Sibling Influence on Care Given by Children to Older Parents
Authors: Tolkacheva Natalia , Broese van Groenou Marjolein , van Tilburg Theo
Published: October 2010

This study examines the degree to which siblings’ behaviors and characteristics influence a child’s caregiving. A sample of 186 older parents in need of care with at least two adult children reported on characteristics and caregiving of all their children ( N = 703). Multilevel regression models show that there is evidence of children’s joint caregiving efforts: The more care siblings give, the more care the child gives. Results demonstrate that the more sisters a child has, the less care that child gives. Children also substitute and support each other: The greater the number of siblings with partners and the lower the frequency of sibling emotional support exchanges with a parent, the more care the child gives. The study reflects the various outcomes of sibling solidarity when older parents become dependent.
No Follow-Up After Positive Newborn Screening: Medical Neglect?
Authors: Merrick Melissa T. , Butt Sakina M. , Jent Jason F. , Cano Nicole M. , Lambert Walter F. , Chapman Ana V. , Griffith Joseph F. , Ciener Daisy , Dandes Susan K. , Sanders Lee M.
Published: October 2010

The current study examined medical professionals’ behaviors related to reporting medical neglect when a family is noncompliant with follow-up services after a positive newborn screening result. Pediatric medical professionals within an urban medical campus were provided with five case vignettes in relation to different diseases. Medical professionals rated the severity of family noncompliance with follow-up services and indicated whether they would report suspected medical neglect to Child Protective Services (CPS). Physicians were more likely to report medical neglect than the other mandated reporters in the study. Logistic regression analyses found that medical professionals’ perceptions of the severity of family noncompliance with services were significantly predictive of decisions to report medical neglect. Respondent gender and the method by which families were notified of screening results also significantly affected reporting behaviors in certain instances. Although all vignettes included information that met legal statutes for reporting neglect, medical professionals indicated that they would only report neglect 40—61% of the time across vignettes. Continued investigation of the rationale behind medical professionals’ decision-making process and training protocols designed to improve mandated reporter knowledge and reporting behaviors are needed to further reduce bias and improve objectivity when considering ethical and professional obligations to report medical neglect.
Learners’ use of first language (Arabic) in pair work in an EFL class
Authors: Storch Neomy , Aldosari Ali
Published: October 2010

One of the concerns foreign language teachers may have about using small group (and pair) work is that students will use their shared first language (L1) instead of the target language. This study investigated the effect of learner proficiency pairing and task type on the amount of L1 used by learners of English as a foreign language (EFL) in pair work and the functions that the L1 served. Learners in this study ( n = 15 pairs) formed three proficiency groupings based on the teacher’s assessment of their second language proficiency: high—high (H—H), high—low (H—L), and low—low (L—L). All pairs completed three tasks — jigsaw, composition and text-editing — and their talk was audio-recorded. The transcribed pair talk was analysed for the quantity of L1 used (L1 words and L1 turns), and the functions the L1 served. The study found that overall, there was a modest use of L1 in pair work activity and that task type had a greater impact on the amount of L1 used than proficiency pairing. L1 was mainly used for the purpose of task management and to facilitate deliberations over vocabulary. When used for task management, L1 tended to reflect the kind of relationship the learners formed. When used for vocabulary deliberations, L1 was used not only to provide explanations to peers but also for private speech.
Contextualizing corrective feedback in second language writing pedagogy
Authors: Evans Norman W. , Hartshorn K. James , McCollum Robb M. , Wolfersberger Mark
Published: October 2010

Although effective writing skills are vital to the success of university-level students, second language (L2) writers face unique challenges in developing these skills. This is particularly relevant to their ability to produce writing that is linguistically accurate. While many writing teachers feel a great commitment to these students, much of the research has either led to conflicting results or provided teachers with limited practical guidelines that can be utilized effectively in the classroom. This is especially true regarding written corrective feedback (WCF). Therefore, this article provides L2 writing teachers with a paradigm for understanding the WCF debate and interpreting the available research. We emphasize three contextual variables that must be considered if we are to understand the current research and maximize the utility of future research. These include the learner, the situation, and the instructional methodology. As an examination of how one of these contextual variables might affect L2 writing accuracy, this article presents an innovative instructional methodology specifically designed to improve L2 writing accuracy. We refer to the central component of this methodology as dynamic written corrective feedback. The article concludes with the preliminary results from an exploratory pilot study using this instructional methodology.
Ten Steps in Training Volunteer Support Group Facilitators
Authors: Greif Geoffrey L.
Published: October 2010

Caregiver support groups are often led by volunteer lay leaders who might have personal experiences with Alzheimer’s disease. This article offers 10 steps in what to consider and how to conduct training for these lay leaders so that the success of the support groups can be maximized. Steps include helping trainees understand their own feelings and the feelings of their group members as well as teaching about the stages that groups typically experience from beginning to termination and the role of the leader at each stage.
Suppression of Proliferation and Invasive Behavior of Human Metastatic Breast Cancer Cells by Dietary Supplement BreastDefend
Authors: Jiahua Jiang  , Wojnowski Rachael , Jedinak Andrej , Sliva Daniel
Published: October 2010

Aim: The study was to evaluate the effect of the dietary supplement BreastDefend (BD) on the proliferation and invasive behavior of highly metastatic human breast cancer cells in vitro. Methods: Cell proliferation and cytotoxicity of BD was evaluated in MDA-MB-231 cells treated with BD (0-40 μg/mL) by MTT assay and trypan blue staining, respectively. Expression of cell cycle regulatory genes were determined by DNA-microarray analysis. Effect of BD on invasiveness was assessed by cellular adhesion, migration, and invasion assays. Results: BD treatment of cells MDA-MB-231 resulted in the cytostatic inhibition of cell proliferation with IC50 22.2, 19.1, and 17.5 μg/mL for 24, 48, and 72 hours, respectively. The inhibition of proliferation was mediated by the upregulation expression of CCNG1, CHEK1, CDKN1C, GADD45A, and E2F2, whereas BD downregulated expression of CCNA1 and CDK6 genes. The induction of expression of GADD45A and inhibition of expression of cyclin A1 (gene CCNA1) by BD was also confirmed on the protein level. BD treatment suppressed the invasive behavior of MDA-MB-231 cells by the inhibition of cellular adhesion, migration, and invasion. This inhibition of invasiveness was mediated by the suppression of secretion of urokinase plasminogen activator (uPA), and by the downregulation of expression of CXCR4 in breast cancer cells treated with BD. Conclusion: BD inhibits proliferation and invasive behavior of the highly metastatic human breast cancer cells in vitro. BD may have a therapeutic potential for prevention or treatment of highly metastatic breast cancers.
Overcoming Personal and Academic Challenges: Perspectives From Latina/o College Students
Authors: Cavazos Javier , Johnson Michael B. , Sparrow Gregory Scott
Published: October 2010

Eleven Latina/o college students were interviewed to provide insight into what kind of coping responses they used to overcome challenges and when such responses were employed. The following responses emerged: positive reframing, acceptance, self-talk, maintaining focus on final goals, using low expectations as motivation, self-reflection, taking action, and seeking support. A discussion regarding the importance of these findings is provided and implications for practice are presented.
Immunomodulatory impact of a synbiotic in Th1 and Th2 models of infection
Authors: Cazzola Mario , Tompkins Thomas A. , Matera Maria G.
Published: October 2010

Background and methods: The immunomodulatory activity of a synbiotic combination containing three bacterial strains (Lactobacillus helveticus R0052, Bifidobacterium longum subsp. infantis R0033 and Bifidobacterium bifidum R0071) and short-chain fructooligosaccharide was examined in two distinct infectious rat models. In the Th1 model, Wistar rats were administered the synbiotic combination for 2 weeks prior to challenge with a single oral dose of enterotoxigenic Escherichia coli or vehicle. In the Th2 model, pretreated rats were challenged with a single subcutaneous dose of hook worm, Nippostrongylus brasiliensis. Blood samples were collected 3 hours or 4 days postchallenge and serum levels of pro- and anti-inflammatory cytokines were measured.

Results: Significant reductions in pro-inflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6, and tumour necrosis factor (TNF)-α were observed in both models suggesting a single, unifying mode of action on an upstream regulator. The N. brasiliensis study also compared the effect of the individual strains to synbiotic. For most of cytokines the combination appeared to average the effect of the individual strains with the exception of IL-4 and IL-10 where there was apparent synergy for the combination. Furthermore, the cytokine response varied by strain.

Conclusions: It was concluded that this synbiotic combination of these three microbes could be beneficial in both Th1 and Th2 diseases.