bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifestyle Intervention in Men with Advanced Prostate Cancer Receiving Androgen Suppression Therapy: A Feasibility Study
Authors: Bourke Liam , Doll Helen , Crank Helen , Daley Amanda , Rosario Derek , Saxton John M.
Published: March 2011

Background: Healthy lifestyle behaviors could have a role in ameliorating some of the adverse effects of androgen suppression therapy (AST) in men with prostate cancer. The primary aim of this study was to assess the feasibility of a tapered supervised exercise program in combination with dietary advice in men with advanced prostate cancer receiving AST.

Methods: Advanced prostate cancer patients receiving AST for a minimum of 6 months were randomized to a 12-week lifestyle program comprising aerobic and resistance exercise, plus dietary advice (n = 25), or standard care (n = 25). Exercise behavior, dietary macronutrient intake, quality of life, fatigue, functional fitness, and biomarkers associated with disease progression were assessed at baseline, after the intervention, and at 6 months.

Results: The lifestyle group showed improvements in exercise behavior (P < 0.001), dietary fat intake (P = 0.001), total energy intake (P = 0.005), fatigue (P = 0.002), aerobic exercise tolerance (P < 0.001), and muscle strength (P = 0.033) compared with standard care controls. Although a high rate of attrition (44%) was observed at 6 months, the improvements in key health outcomes were sustained. No effects on clinical prostate cancer disease markers were observed.

Conclusions: This preliminary evidence suggests that pragmatic lifestyle interventions have potential to evoke improvements in exercise and dietary behavior, in addition to other important health outcomes in men with advanced prostate cancer receiving AST.

Impact: This study shows for the first time that pragmatic lifestyle interventions are feasible and could have a positive impact on health behaviors and other key outcomes in men with advanced prostate cancer receiving AST. Cancer Epidemiol Biomarkers Prev; 20(4); 647–57. ©2011 AACR.
Can UV Exposure Reduce Mortality?
Authors: Berwick Marianne
Published: March 2011

A Swedish cohort analysis in this issue (1) demonstrates a significant reduction in all cause mortality and in cardiovascular mortality associated with several measures of sun exposure. In addition, ultraviolet exposure from tanning beds is associated with a significant increase in all cause mortality and cancer mortality. A potential explanation for the protective association is that UV exposure results in high levels of serum vitamin D which may improve survival. However, that explanation does not hold for ultraviolet exposure from tanning beds, which in this study is associated with a significant increase in all cause mortality and cancer mortality. Such a finding is curious and inconsistent with a vitamin D hypothesis. These results should impel investigators to study further the biology of ultraviolet radiation, both natural and artificial, and its health effects. Cancer Epidemiol Biomarkers Prev; 20(4); 582–4. ©2011 AACR.
Oral Contraceptive Use and Parity Associations with Uncommon Breast Cancer Histologies in the Breast Cancer Family Registry: the Role of Family History
Authors: Work ME , John EM , Andrulis IL , Hopper JL , Liao Y , Hibshoosh H , Terry MB
Published: March 2011

Purpose: The effect of parity and oral contraceptive (OC) use on breast cancer risk differs by cancer subtype as defined by histology. Family history of breast cancer impacts decisions regarding both parity and oral contraceptive use; it is unknown whether reproductive risk factors are related to uncommon histologies in women with and without a strong family history.

Methods: Using population-based data from the Breast Cancer Family Registry, we conducted analyses using unordered polytomous regression to determine the role of family history in associations between parity, OC use, and breast cancer histologic subtype, among 3,260 cases and 2,997 controls. Histologic types examined included ductal and lobular as well as the uncommon histologies of mucinous, tubular, and medullary cancer.

Results: Twenty-eight percent of cases and 9% of controls had a family history (defined as at least 1 first-degree relative with breast cancer). Cases with and without family history were similar in regards to OC use (75% and 73%, respectively were ever-users) and parity (2.08 children in cases with family history, 2.10 in cases without). In a multivariable model, when compared with controls, OC use was inversely associated with tumors of mucinous histology (OR = 0.43, 95% CI 0.23–0.79 for use ≥5 years vs. never use). There was a stronger inverse association with OC use and the mucinous subtype among those without a family history (OR = 0.27, 95% CI 0.13–0.57), and a nonsignificant positive association in those with family history (OR = 2.19, 95% CI 0.40–11.84). High parity (≥3 children) was positively associated with medullary histology (OR = 2.62, 95% CI 1.16–5.91, compared with nulliparity); the association was stronger among women without a family history (OR = 4.31, 95% CI 1.67–11.12), and was not significantly associated among those with a family history (OR = 0.36, 95% CI 0.06–2.29). Parity was inversely associated with the mucinous type (OR = 0.45, 95% CI 0.21–0.96, compared with nulliparity), and this effect remained stable in women with and without family history.

Conclusion: This study suggests that selected reproductive risk factors may only be related to uncommon breast cancer histologies among women without a family history of breast cancer.
Change in Colorectal Cancer Screening Decision Stage
Authors: Njoku A , Cocroft J , Daskalakis C , Sifri R , Bittner-Fagan H , Myers R
Published: March 2011

Introduction: Colorectal cancer screening (CRC) screening decision stage (SDS) is a measure of proximity to screening. Predictors of change in SDS have not been reported in the literature.

Objective: To assess SDS change and predictors of SDS among primary care patients 50 to 74 years of age who are enrolled in a randomized, controlled trial of behavioral interventions designed to increase CRC screening.

Methods: On a baseline survey, study participants reported on perceptions about CRC screening and SDS (i.e., decided to screen vs. had not decided to screen). Participants were randomized to one of three study groups: Control Group (usual care), Standard Intervention (SI) Group [mailed screening materials (i.e., informational booklet, a stool blood test kit, instructions for scheduling a screening colonoscopy, and a reminder)]; and a Tailored Navigation Intervention (TNI) Group (mailed screening materials tailored to baseline SDS and a navigation telephone call). TNI Group participants were asked to report current SDS, including current screening status, at navigation. We assessed change in SDS from baseline to navigation and performed multivariable analyses to identify predictors of SDS change.

Results: Of 248 TNI Group participants, 205 (83%) received a navigation call. Background characteristics of these participants were as follows: white (76%), female (64%), aged 50–59 (67%), >high school education (52%), and married (62%). At baseline, 43 (21%) participants reported that they had not decided to screen, and 162 (79%) reported that they had decided to screen. At navigation, 55 (27%) participants reported a positive change in SDS (26 moved forward in SDS but did not screen and 29 screened). Participants who had not decided to screen at baseline were more likely to exhibit positive change in SDS than those who had decided to screen at baseline (63% and 17%, respectively, P < 0.0001). Among participants who had not decided to screen at baseline, only one reported actual screening. Of those participants who had decided to screen, 28 actually screened.

Discussion: More than a quarter of participants reported a positive change in SDS in response to the mailed tailored intervention materials sent before the navigation call. Baseline SDS was a strong predictor of SDS change.
Sigmoidoscopy and Colonoscopy are Inversely Associated with Both Left- and Right-sided Advanced Adenomas
Authors: Burnett-Hartman A , Newcomb P , Phipps A , Passarelli M , Mandelson M , Zhu L , Upton M
Published: March 2011

Background: The U.S. Preventive Services Task Force recommends routine colorectal cancer screening starting at age 50; however, evidence is insufficient to recommend one screening method over the other methods. Common colorectal cancer screening methods include fecal occult blood tests (FOBT), sigmoidoscopy, and colonoscopy.

Objective: We examined the association between advanced adenomas, known precursors to colorectal cancer, and history of screening by FOBT, sigmoidoscopy, and colonoscopy.

Methods: We conducted a case-control study of advanced colorectal adenomatous polyps, which included 306 advanced adenoma cases and 2,287 controls without advanced adenomas, aged 24 to 79, who received an index colonoscopy from 1998 to 2007. All participants completed a questionnaire covering screening history and other colorectal cancer risk factors. Participants with polyps underwent a standard pathology review; adenomas ≥10 mm or at with at least 20% villous components were considered advanced adenomas. We used separate logistic regression models to estimate adjusted odds ratios (ORs) and 95% CIs for the associations between advanced adenomas and previous FOBT, sigmoidoscopy, and colonoscopy at least 2 years before the index colonoscopy.

Results: Each screening method was associated with decreased odds of advanced adenomas; however, only associations for sigmoidoscopy and colonoscopy were statistically significant. The OR for advanced adenomas, comparing participants with at least one previous FOBT to those who had never had FOBT, was 0.82 (95% CI: 0.63–1.06); for sigmoidoscopy, OR = 0.59 (95% CI: 0.46–0.77); and for colonoscopy, OR = 0.53 (95% CI: 0.39–0.72). These associations were similar with respect to left- and right-sided advanced adenomas.

Discussion: Our findings suggest colonoscopy and sigmoidoscopy have similar inverse associations with advanced adenomas in both left and right sides of the colon. This is in contrast to studies of colorectal cancer that suggest endoscopy is associated with a decreased risk for tumors of the left but not right side. The discrepancy between our findings and these studies may be explained if right-sided colorectal cancers are more likely to have nonadenoma precursors that are overlooked by screening.
Single Nucleotide Polymorphisms in Genes of One-Carbon Metabolism Pathway and Bladder Cancer Survival
Authors: Chang SC , Yang YC , Zhang ZF
Published: March 2011

One-carbon metabolism pathway plays an important role in carcinogenesis through its involvement in DNA methylation and biosynthesis. Epidemiologic studies have indicated the associations between genetic polymorphisms in this pathway and the susceptibility of various cancers, including bladder cancer. However, few studies have focused on their associations with bladder cancer prognosis. Using follow-up data from 249 bladder cancer patients who have been treated at the Memorial Sloan-Kettering Cancer Center from 1993 to 1997, we investigated the associations between survival time of bladder cancer patients and single nucleotide polymorphisms (SNPs) involved in the one-carbon metabolism pathway. Epidemiologic data were collected by trained interviewers. Genotyping of seven SNPs in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), DNA methyltransferase 1 (DNMT1), and aldehyde dehydrogenase 2 (ALDH2) genes was performed using SNPlex and Taqman assays (Applied Biosystems) with DNA isolated from blood samples collected at time-of-interview. Survival curves were estimated using the Kaplan-Meier method, and differences in distributions were evaluated by log-rank tests and Cox proportional hazards models. Overall, no obvious associations were observed between the studied SNPs and all-cause mortality among bladder cancer patients after adjustment on age, gender, race/ethnicity, smoking status, and tumor stage. However, after stratification on smoking status, increased survival time was found among ever-smoked carriers of MTRR rs1532268 and rs1801394 variant allele, with adjusted HRs of 0.65 (95% CI = 0.45–0.95) and 0.65 (95% CI = 0.43–0.98), respectively. Increased survival time was also observed among never smokers with ALDH2 rs2238151 C/T or T/T genotypes, compared to those with the C/C genotype (HR = 0.23, 95% CI = 0.06–0.90). Our findings suggest that smoking may interact with one-carbon metabolism pathway related genetic polymorphisms on survival among bladder cancer patients. Future studies with larger sample sizes are needed to confirm the associations.
The Cancer Stroop Task as an Implicit Measure of Cognitive Interference in Head and Neck Cancer Patients
Authors: Milbury K , Badr H
Published: March 2011

Given the stigmatizing and debilitating nature of head and neck cancer (HNC) and its treatment, patients are at risk of developing trauma symptoms such as cognitive interference (unwanted, disturbing thoughts) that can increase their risk for distress. Most measures of cognitive interference employ a self-report format making them susceptible to self-presentation and defensive biases. To address these limitations, we developed and implemented an implicit measure, a cancer Stroop task (CST), with the goal to establish a link between implicit intrusive cognitions and distress (BSI) and self-reported intrusive cognitions (Impact of Events Scale, IES). As part of an observational spousal support study, 70 patients (87% male) completed self-report measures and then engaged in problem-solving discussions with their spouses about cancer-related concerns in the lab. Afterward, the computerized CST was administered. Participants were instructed to color-name each stimulus word while ignoring word meaning. Slower responses to emotionally salient (cancer) versus neutral words reflect their power to automatically capture attention and become intrusive. Results revealed a significant inverse association between response time to cancer words and distress (P < 0.001) and self-reported cognitive intrusion (P < 0.01) so that individuals who responded more slowly revealed greater distress and cognitive intrusion compared to individuals with faster responses. These findings suggest that the CST is a promising measure of cognitive interference as it is associated with self-report measures of distress and cognitive intrusion. Unlike self-report measures assessing intrusive cognitions over the past 7 days, this implicit measure allows to examine the effects of immediate environmental antecedents on cognitive interference. Thus, our next step in this ongoing study will be to behaviorally code the cancer discussion for supportiveness on the spouse as a predictor of cognitive interference as measured by the CST.
Prenatal Tobacco Smoke Exposure and Genomewide Methylation in Adulthood
Authors: Flom J , Ferris J , Gonzalez K , Santella R , Terry MB
Published: March 2011

Genomic DNA demethylation, including demethylation of repetitive elements (which comprise 45% of the human genome), has been linked to increased risk of breast and other cancers. Genomic DNA methylation can be altered prenatally and throughout life and may be a mechanism through which the environment alters disease risk. There is evidence that prenatal tobacco smoke exposure has a persistent impact on genomic DNA methylation; however, no study to date has assessed the association between prenatal smoke exposure and adult repetitive element methylation. We measured repetitive element methylation of Alu, LINE-1, and Sat2 using MethyLight in 92 members of the New York Women's Birth Cohort, a follow-up of former female participants of the New York site of the U.S. National Collaborative Perinatal Project (mean age at blood draw = 43.5, SD = 1.8). Prenatal smoke exposure was reported prospectively. We estimated associations using multivariable linear regression, and used the natural log of Alu, LINE-1, and Sat2 methylation level. Thirty-one (36%) participants were exposed to prenatal smoke. These participants were more likely to smoke at the time of interview (P < 0.01). Prenatal smoke exposure was inversely associated with genomic DNA methylation of Sat2 and Alu, adjusted for age, childhood environmental tobacco smoke exposure (ETS) and adult smoking status (exposed vs. unexposed to prenatal smoke: Sat2: β = −0.20, 95% CI = −0.39, −0.02; Alu: β = −0.09, 95% CI = −0.26, 0.08). In multivariable models, childhood ETS had a positive, borderline significant association with Sat2 methylation (β = 0.17, 95% CI −0.02, 0.37). If replicated in larger studies, these results suggest that prenatal smoke exposure may have a persistent impact on genomic DNA demethylation of Sat2 and Alu in adulthood, and thus may be a pathway through which prenatal smoke exposure impacts adult disease. Results are strengthened by the fact that prenatal smoke exposure data were collected prospectively in the early 1960s, before there was a stigma associated with maternal smoking during pregnancy. These results are consistent with the one study assessing this relation in children. Further studies are needed to confirm this finding and to investigate the underlying biological mechanism.
Pandemic 2009 H1N1 Influenza in Patients with Hematopoietic Stem Cell Transplantation and Hematologic Malignancy: Single Center Experience
Authors: Tekgündüz Emre , Yüksel Meltem Kurt , Erbay Çiğdem , Arıbaş Bilgin , Özdilekcan Çiğdem , Arslan Hülya , Koçubaba Şerife , Demiriz Itır , Tetik Ayşegül , Arda Kemal , Altuntaş Fevzi
Published: March 2011

Although valuable information on many aspects of the pandemic 2009 H1N1 influenza came to light in a relatively short period of time, the disease course among immunocompromised patients is largely unknown. In this study, we present the results of active H1N1 surveillance in 32 patients who were treated at our hematology/stem cell transplantation clinic between December 2009 and January 2010. We also report the clinical and laboratory features of patients with laboratory-proven disease and try to define the impact of novel H1N1 disease on their outcome. Eight patients in the hematology clinic and 7 patients in the hematology/stem cell transplantation unit tested positive for pandemic H1N1 infection. Patients were treated with oral oseltamivir for 5–15 days. In 10 patients the infection was limited to the upper respiratory tract. But in 5 patients it was complicated with lower respiratory diseases. Three of them required intensive care support with mechanic ventilation and all died during follow-up. As the clinical and radiological findings of H1N1 infection are nonspecific in nature, we should have a high index of suspicion in immunocompromised patients. Therefore, beginning empiric oseltamivir therapy while waiting for laboratory results and increasing the dose/duration of therapy in laboratory-confirmed cases could be life saving.
Low-Dose Weekly Docetaxel Is as Tolerable as Pemetrexed in Previously Treated Advanced Non-Small-Cell Lung Cancer
Authors: Chung Fu-Tsai , Lee Kang-Yun , Fang Yueh-Fu , Shieh Meng-Heng , Lin Shu-Min , Yu Chih-Teng , Lo Yun-Lun , Lin Ting-Yu , Kuo Chih-Hsi , Feng Po-Hao , Ni Yung-Lun , Kuo Han-Pin
Published: March 2011

Objectives: Docetaxel and pemetrexed have been validated as therapeutics for previously treated advanced non-small-cell lung cancer (NSCLC), but tolerability is a concern for standard treatment with docetaxel administered once every 3 weeks (tri-weekly 75-mg/m2 schedule). We conducted this retrospective study to compare the efficacy and toxicity of weekly low-dose docetaxel versus tri-weekly pemetrexed for previously treated advanced NSCLC. Methods: Consecutive patients who received low-dose single docetaxel (30 mg/m2 on days 1 and 8 every 3 weeks) or pemetrexed (500 mg/m2 every 3 weeks) at a single university-affiliated hospital following failure of previous treatment were retrospectively reviewed. Their outcomes and toxicity profiles were determined. Results: 179 patients were included between 2005 and 2008 (docetaxel, n = 79; pemetrexed, n = 100). Both groups had similar hematologic (16.5 vs. 15.0%; p = 0.84) and non-hematologic (20.3 vs. 24%; p = 0.55) toxicities. After controlling for confounding factors, docetaxel remained superior to pemetrexed for progression-free survival (median 4.0 vs. 2.4 months; hazard ratio 0.64; 95% CI 0.47–0.87; p = 0.005) and overall survival (median 15.0 vs.8.5 months; hazard ratio 0.54; 95% CI 0.38–0.77; p <0.001). Conclusion: Although this study showed that weekly low doses of docetaxel were as tolerable as pemetrexed for previously treated advanced NSCLC, a prospective design is needed to confirm this finding.
Infliximab in Drug-Naïve Patients with Failed Ileorectal Anastomosis for Crohn’s Disease: A New Chance for Sparing the Rectum?
Authors: Sciaudone G. , Pellino G. , Riegler G. , Selvaggi F.
Published: March 2011

The aim of this intervention study is to determine whether long-term infliximab therapy can decrease the proctectomy rate in patients with failed total colectomy and ileorectal anastomosis (IRA) for Crohn’s disease (CD). Twelve patients (5 females) – with a median age of 36.6 years (range 18–56 years), previously treated with IRA (5 in our institution and 7 referred) for colorectal and perianal CD (median Crohn’s Disease Activity Index 334.5, range 220–426), with rectal disease recurrence requiring proctectomy, no responders to conventional therapy but infliximab-naïve – were treated with infliximab infusions (Remicade™ 5 mg/kg at 0, 2, 6 weeks and then every 8 weeks) to avoid proctectomy. The main outcome measures consisted of IRA preservation and bowel function at study end. Mortality and major adverse reactions have not been observed. At the time of the median follow-up (57.4 months, range 36–92), the rectum was preserved in 10 patients (83.3%). One patient underwent proctectomy 6 weeks after the beginning of the treatment for unresponsiveness to drugs and another after 26 weeks for rectal stenosis. Anorectal function (maximum tolerated volume: 239 ± 43 vs. 294 ± 36 ml) and quality of life (Inflammatory Bowel Disease Questionnaire score 89.2 ± 20.6 vs. 173.8 ± 31.9) improved, and the Wexner Continence score (4.4 ± 2.4 vs. 1.7 ± 1.0) and daily defecations (5.2 ± 1.03 vs. 2.7 ± 1.05) decreased in 10 patients. Our results, although preliminary, are encouraging and seem to justify a less aggressive approach in patients with rectal and perianal recurrence after IRA for CD.
In vitro Reduction of Dental Erosion by Low-Concentration TiF4 Solutions
Authors: Vieira A.M. , Ruben J.L. , Bronkhorst E.M. , Huysmans M.C.D.N.J.M.
Published: March 2011

The aims of this study were to compare daily versus single applications of low-concentration TiF4 solutions for reduction of enamel erosion and to evaluate the enamel surface loss due to application of these solutions. Sixty bovine enamel samples were randomly divided into 2 groups: single versus daily treatment with TiF4 solution (ST vs. DT), which were subdivided into 5 subgroups (n = 6): 0% (control); 0.1, 0.5, 0.75 and 1% TiF4 concentration. Fluoride treatment was performed by immersing specimens in 10 ml of the TiF4 solutions for 5 min and rinsing them with tap water for 30 s. ST specimens were treated once only, DT specimens were treated before each erosion cycle. All specimens were subjected to 4 erosion cycles: 6 immersions of 2 min in Sprite, tap water rinse for 1 min and storage in artificial saliva for 1.5 h. Erosive enamel loss was measured using light profilometry, after each fluoride treatment and each erosive cycle. The values of surface loss/gain at application of the TiF4 solutions did not significantly differ from zero. At the end of the 4 erosion cycles, 0.5% showed the least (ST: 3.45 ± 0.27 µm, DT: 1.08 ± 1.69 µm) and 1% showed the most surface loss (ST: 4.87 ± 1.13 µm, DT: 6.56 ± 1.49 µm). A significant reduction of surface loss was found only for 0.5% DT (p = 0.009). Within the limitations of an in vitro study, it was concluded that multiple applications of a 0.5% TiF4 solution significantly reduced enamel erosion in vitro and caused no enamel loss at application.
Salvage Therapy with Mitomycin and Ifosfamide in Patients with Gemcitabine-Resistant Metastatic Pancreatic Cancer: A Phase II Trial
Authors: Cereda Stefano , Reni Michele , Rognone Alessia , Fugazza Clara , Ghidini Michele , Ceraulo Domenica , Brioschi Matteo , Nicoletti Roberto , Villa Eugenio
Published: March 2011

Background: At the time of upfront treatment failure, over half of the patients with advanced pancreatic cancer are candidates for further treatment. Methods: Patients with metastatic gemcitabine-resistant pancreatic cancer were treated with mitomycin 8 mg/m2 on day 1, ifosfamide 2,500 mg/m2 and mesna 3,000 mg/m2 on days 1–3 every 28 days until progressive disease. A positive responder was defined as a patient who was progression free at 6 months from trial enrolment. According to the Fleming design, a sample size of 34 patients was estimated assuming p0 = 0.05 and p1 = 0.20. Results: Between May 2006 and December 2007, 21 patients (median age 56 years; median Karnofsky performance score 80) were enrolled. One patient died before receiving any treatment. Eighteen patients interrupted chemotherapy due to progressive disease (n = 15), toxicity (n = 2) or refusal (n = 1). Grade >2 toxicity consisted of neutropenia in 80% of patients, thrombocytopenia and fatigue in 20% and anemia in 10%. Only 1 patient was progression free at 6 months (5%). One patient had a partial response (5%) and 2 patients had stable disease (10%). Median survival was 3.7 months. Conclusion: Based on the poor outcome observed and on the high level of grade 3–4 toxicity, the trial was prematurely stopped and the mitomycin and ifosfamide regimen was considered insufficiently active in gemcitabine-pretreated advanced pancreatic cancer.
Pathways of Lateral Spreading
Authors: Jacobi U. , Schanzer S. , Weigmann H.-J. , Patzelt A. , Vergou T. , Sterry W. , Lademann J.
Published: March 2011

In the case of topically applied substances, usually both lateral spreading and competitive penetration into the skin occur in parallel. In the present study, the pathways of lateral spreading were studied quantitatively and visually. The local distribution and lateral spreading of the UV filter substance butyl methoxydibenzoylmethane applied in an o/w emulsion was studied on the forearm and the back. The tape stripping procedure was used to determine the recovery rates inside and outside the area of application. The skin characteristics of transepidermal water loss, pH value, hydration of the stratum corneum and sebum rate were determined at both anatomic sites. Photography and laser scanning microscopy were used to visually investigate the lateral spreading of topically applied dyes. On the back, a preferred direction of lateral spreading parallel to the body axis was observed. This result was caused by differences in the network of furrows. The furrows functioned as a pathway for lateral spreading, whereas the follicles formed a reservoir for the topically applied substance.
3,5-Dimethyl-7H-Furo[3,2-g]Chromen-7-One as a Potential Anticancer Drug by Inducing p53-Dependent Apoptosis in Human Hepatoma HepG2 Cells
Authors: Sun Jian-guo , Chen Chao-yue , Luo Ke-wang , Yeung Chi-lam Au , Tsang Tsun-yee , Huang Zhi-zhen , Wu Ping , Fung Kwok-pui , Kwok Tim-tak , Liu Fei-yan
Published: March 2011

Background/Aims: Coumarins are natural compounds found in many plants that possess medical value by itself and its modified derivatives. Method: Six novel coumarin derivatives were synthesized and examined for their potential anticancer cytotoxicity. Result: Among the 6 derivatives, 3,5-dimethyl-7H-furo[3,2-g]chromen-7-one (DMFC) presented the strongest cytotoxicity against human hepatoma HepG2 cells in vitro with an IC50 value of 8.46 ± 0.28 µM in a 48-hour treatment. Further experiments revealed that DMFC induced apoptosis in HepG2 cells through both extrinsic and intrinsic apoptotic pathways in a p53-dependent manner. Mechanistically, DMFC activated caspases 3, 8 and 9, depolarized mitochondrial membrane potential and induced cytochrome c and apoptosis-inducing factor release. DMFC-induced apoptosis was also characterized by DNA fragmentation, phosphatidylserine externalization and sub-G1 peak in DNA histograms. Moreover, both caspase 8 and 9 inhibitors suppressed the apoptosis induced by DMFC. Western blot analyses revealed that DMFC also significantly increased the expression levels of p53, Fas death receptor, Fas-associated death domain protein and proapoptotic Bcl-2 family members such as Bax, Bad and tBid, as well as decreased the levels of pro-survival members such as Bcl-2 and Bcl-xl. Conclusion: DMFC is potentially an effective therapeutic agent in liver cancer therapy.
Maternally Inherited Essential Hypertension Is Associated With the Novel 4263A>G Mutation in the Mitochondrial tRNA
Ile
Gene in a Large Han Chinese Family
Authors: Wang Shiwen , Li Ronghua , Fettermann Andrea , Li Zongbin , Qian Yaping , Liu Yuqi , Wang Xinjian , Zhou Anna , Mo Jun Qin , Yang Li , Jiang Pingping , Taschner Andreas , Rossmanith Walter , Guan Min-Xin
Published: March 2011

Rational:

Despite maternal transmission of hypertension in some pedigrees, pathophysiology of maternally inherited hypertension remains poorly understood.

Objective:

To establish a causative link between mitochondrial dysfunction and essential hypertension.

Method and Results:

A total of 106 subjects from a large Chinese family underwent clinical, genetic, molecular, and biochemical evaluations. Fifteen of 24 adult matrilineal relatives exhibited a wide range of severity in essential hypertension, whereas none of the offspring of affected fathers had hypertension. The age at onset of hypertension in the maternal kindred varied from 20 years to 69 years, with an average of 44 years. Mutational analysis of their mitochondrial genomes identified a novel homoplasmic 4263A>G mutation located at the processing site for the tRNA
Ile
5′-end precursor. An in vitro processing analysis showed that the 4263A>G mutation reduced the efficiency of the tRNA
Ile
precursor 5′-end cleavage catalyzed by RNase P. tRNA Northern analysis revealed that the 4263A>G mutation caused ≈46% reduction in the steady-state level of tRNA
Ile
. An in vivo protein-labeling analysis showed ≈32% reduction in the rate of mitochondrial translation in cells carrying the 4263A>G mutation. Impaired mitochondrial translation is apparently a primary contributor to the reductions in the rate of overall respiratory capacity, malate/glutamate-promoted respiration, succinate/glycerol-3-phosphate-promoted respiration, or
N
,
N
,
N′
,
N′
-tetramethyl-
p
-phenylenediamine/ascorbate–promoted respiration and the increasing level of reactive oxygen species in cells carrying the 4263A>G mutation.

Conclusions:

These data provide direct evidence that mitochondrial dysfunction caused by mitochondrial tRNA
Ile
4263A>G mutation is involved in essential hypertension. Our findings may provide new insights into pathophysiology of maternally transmitted hypertension.
Phenotypical Manifestations of Mutations in the Genes Encoding Subunits of the Cardiac Sodium Channel
Authors: Wilde Arthur A.M. , Brugada Ramon
Published: March 2011

Variations in the gene encoding for the major sodium channel (Na
v
1.5) in the heart, SCN5A, has been shown to cause a number of arrhythmia syndromes (with or without structural changes in the myocardium), including the long-QT syndrome (type 3), Brugada syndrome, (progressive) cardiac conduction disease, sinus node dysfunction, atrial fibrillation, atrial standstill, and dilated cardiomyopathy. Of equal importance are variations in genes encoding for various subunits and regulatory proteins interacting with the α-subunit Na
v
1.5 and modifying its function. Based on detailed studies of genotype–phenotype relationships in these disease entities, on detailed studies of the basic electrophysiological phenotypes (heterologous expressed wild-type and mutant sodium channels and their interacting proteins), and on attempts to integrate the obtained knowledge, the past 15 years has witnessed an explosion of knowledge about these disease entities.
Nonalignment as Yugoslavia's Answer to Bloc Politics
Authors: Niebuhr Robert
Published: March 2011

This article focuses on Tito's effort to use foreign policy actions on behalf of his domestic goals. After a bitter rift emerged with the Soviet Union in 1948, Tito moved closer to the West for several years but never proved willing to shift to democratic politics. Although he did carry out reforms of Yugoslavia's Stalinist system in the 1960s, he maintained an authoritarian Communist polity until the end of his life. The article examines how Tito sought to use Yugoslavia's nonaligned status to boost his domestic legitimacy in the eyes of key elites and even, to a degree, in the eyes of the wider population. Yugoslavia's central role in the Bandung conference in 1955 and its subsequent hosting of the summit that formally set up the Nonaligned Movement in 1961 were used by Tito to try to legitimize the polity over which he presided. Yugoslavia's strategy of nonalignment is a valuable illustration of the connection between domestic politics and foreign policy in Communist as well as non-Communist states.
Anna Walentynowicz and the Legacy of Solidarity in Poland
Authors: Szporer Michael
Published: March 2011

The Polish historian Sławomir Cenckiewicz, formerly of the Institute of National Memory, has produced a book discussing the life and impact of Anna Walentynowicz, whose dismissal from the Lenin Shipyard in Gdańsk in early August 1980, five months before she was scheduled to retire, became the catalyst for the formation of Solidarity. The appendices to Cenckiewicz's book consist of more than 300 densely printed pages of crucial documents from the former state security archives, and these make the volume worthwhile. As a biography, the book has notable shortcomings, in part because it contains a good deal of extraneous material and fails to discuss numerous parts of Walentynowicz's life. Even so, Cenckiewicz does successfully capture some aspects of Walentynowicz's character and activities. In time, better books about Walentynowicz will appear, but Cenckiewicz's volume will be an important source for future biographers.
Reward Reduces Conflict by Enhancing Attentional Control and Biasing Visual Cortical Processing
Authors: Padmala Srikanth , Pessoa Luiz
Published: March 2011

How does motivation interact with cognitive control during challenging behavioral conditions? Here, we investigated the interactions between motivation and cognition during a response conflict task and tested a specific model of the effect of reward on cognitive processing. Behaviorally, participants exhibited reduced conflict during the reward versus no-reward condition. Brain imaging results revealed that a group of subcortical and fronto-parietal regions was robustly influenced by reward at cue processing and, importantly, that cue-related responses in fronto-parietal attentional regions were predictive of reduced conflict-related signals in the medial pFC (MPFC)/ACC during the upcoming target phase. Path analysis revealed that the relationship between cue responses in the right intraparietal sulcus (IPS) and interference-related responses in the MPFC during the subsequent target phase was mediated via signals in the left fusiform gyrus, which we linked to distractor-related processing. Finally, reward increased functional connectivity between the right IPS and both bilateral putamen and bilateral nucleus accumbens during the cue phase, a relationship that covaried with across-individual sensitivity to reward in the case of the right nucleus accumbens. Taken together, our findings are consistent with a model in which motivationally salient cues are employed to upregulate top–down control processes that bias the selection of visual information, thereby leading to more efficient stimulus processing during conflict conditions.
Enhanced Multisensory Integration and Motor Reactivation after Active Motor Learning of Audiovisual Associations
Authors: Butler Andrew J. , James Thomas W. , James Karin Harman
Published: March 2011

Everyday experience affords us many opportunities to learn about objects through multiple senses using physical interaction. Previous work has shown that active motor learning of unisensory items enhances memory and leads to the involvement of motor systems during subsequent perception. However, the impact of active motor learning on subsequent perception and recognition of associations among multiple senses has not been investigated. Twenty participants were included in an fMRI study that explored the impact of active motor learning on subsequent processing of unisensory and multisensory stimuli. Participants were exposed to visuo-motor associations between novel objects and novel sounds either through self-generated actions on the objects or by observing an experimenter produce the actions. Immediately after exposure, accuracy, RT, and BOLD fMRI measures were collected with unisensory and multisensory stimuli in associative perception and recognition tasks. Response times during audiovisual associative and unisensory recognition were enhanced by active learning, as was accuracy during audiovisual associative recognition. The difference in motor cortex activation between old and new associations was greater for the active than the passive group. Furthermore, functional connectivity between visual and motor cortices was stronger after active learning than passive learning. Active learning also led to greater activation of the fusiform gyrus during subsequent unisensory visual perception. Finally, brain regions implicated in audiovisual integration (e.g., STS) showed greater multisensory gain after active learning than after passive learning. Overall, the results show that active motor learning modulates the processing of multisensory associations.
Modulation of the Fusiform Face Area following Minimal Exposure to Motivationally Relevant Faces: Evidence of In-group Enhancement (Not Out-group Disregard)
Authors: Van Bavel Jay J. , Packer Dominic J. , Cunningham William A.
Published: March 2011

Studies have shown that fusiform face area (FFA) activity increases with visual expertise. We present an fMRI study showing that faces from a social category made relevant by an experimental manipulation (members of an experimentally created in-group) preferentially recruited the FFA even when they were matched in exposure to face stimuli from a less significant social category (members of an experimentally created out-group). Faces were randomly assigned to groups and fully counterbalanced so that no perceptual cues allowed participants to visually distinguish category membership. The results revealed a pattern of in-group enhancement (not out-group disregard), such that the FFA was selectively engaged following the presentation of in-group compared with out-group or unaffiliated control faces even when the intergroup distinction was arbitrary, and exposure to in-group and out-group faces was equivalent and brief. In addition, individual differences in FFA activity for in-group versus out-group faces were correlated with recognition memory differences for in-group and out-group faces. The effects of group membership on the FFA were not affected by task instruction to respond to in-group or out-group members and were functionally dissociated from early visual processing in the primary visual cortex. This study provides evidence that the FFA is sensitive to top–down influences and may be involved in subordinate level (vs. superordinate level) encoding of stimuli in the absence of long-term exposure or explicit task instructions.
Activation of Inhibition: Diminishing Impulsive Behavior by Direct Current Stimulation over the Inferior Frontal Gyrus
Authors: Jacobson Liron , Javitt Daniel C. , Lavidor Michal
Published: March 2011

A common feature of human existence is the ability to reverse decisions after they are made but before they are implemented. This cognitive control process, termed response inhibition, refers to the ability to inhibit an action once initiated and has been localized to the right inferior frontal gyrus (rIFG) based on functional imaging and brain lesion studies. Transcranial direct current stimulation (tDCS) is a brain stimulation technique that can facilitate as well as impair cortical function. To explore whether response inhibition can be improved through rIFG electrical stimulation, we administered focal tDCS before subjects performed the stop signal task (SST), which measures response inhibition. Notably, activation of the rIFG by unilateral anodal stimulation significantly improved response inhibition, relative to a sham condition, whereas the same tDCS protocol did not affect response time in the go trials of the SST and in a control task. Furthermore, the SST was not affected by tDCS at a control site, the right angular gyrus. Our results are the first demonstration of response inhibition improvement with brain stimulation over rIFG and further confirm the rIFG involvement in this task. Although this study was conducted in healthy subjects, present findings with anodal rIFG stimulation support the use of similar paradigms for the treatment of cognitive control impairments in pathological conditions.
Silent Reading of Direct versus Indirect Speech Activates Voice-selective Areas in the Auditory Cortex
Authors: Yao Bo , Belin Pascal , Scheepers Christoph
Published: March 2011

In human communication, direct speech (e.g., Mary said: “I'm hungry”) is perceived to be more vivid than indirect speech (e.g., Mary said [that] she was hungry). However, for silent reading, the representational consequences of this distinction are still unclear. Although many of us share the intuition of an “inner voice,” particularly during silent reading of direct speech statements in text, there has been little direct empirical confirmation of this experience so far. Combining fMRI with eye tracking in human volunteers, we show that silent reading of direct versus indirect speech engenders differential brain activation in voice-selective areas of the auditory cortex. This suggests that readers are indeed more likely to engage in perceptual simulations (or spontaneous imagery) of the reported speaker's voice when reading direct speech as opposed to meaning-equivalent indirect speech statements as part of a more vivid representation of the former. Our results may be interpreted in line with embodied cognition and form a starting point for more sophisticated interdisciplinary research on the nature of auditory mental simulation during reading.
The Neural Correlates of Inhibiting Pursuit to Smoothly Moving Targets
Authors: Burke Melanie Rose , Barnes Graham R.
Published: March 2011

A previous study has shown that actively pursuing a moving target provides a predictive motor advantage when compared with passive observation of the moving target while keeping the eyes still [Burke, M. R., & Barnes, G. R. Anticipatory eye movements evoked after active following versus passive observation of a predictable motion stimulus. Brain Research, 15, 74–81, 2008b]. By using a novel paradigm based on combining a smooth pursuit stimulus with a go/no-go task, we have been able to reveal significant differences in brain activity for the inhibition of pursuit during the presentation of a smoothly moving target. Areas that show specific inhibitory and retinocentric velocity storage activity for the passive (no-go) condition include the dorsolateral pFC, the caudate, and the posterior cingulate. The FEFs, the supramarginal gyrus, the medial occipital gyrus, and the superior parietal lobe were found to be more involved in both the acquisition and response generation during no-go trials when compared with go trials. The go trials revealed higher activity than the no-go during the acquisition phase in the uncus and posterior cingulate. Furthermore, higher motor-related activity in the go task was found in the cerebellum. In summary, the areas involved in inhibiting smooth pursuit are consistent with the findings from the saccade literature, providing further evidence in support of overlapping cortical control networks.
Face Processing Changes in Normal Aging Revealed by fMRI Adaptation
Authors: Lee Yunjo , Grady Cheryl L. , Habak Claudine , Wilson Hugh R. , Moscovitch Morris
Published: March 2011

We investigated the neural correlates of facial processing changes in healthy aging using fMRI and an adaptation paradigm. In the scanner, participants were successively presented with faces that varied in identity, viewpoint, both, or neither and performed a head size detection task independent of identity or viewpoint. In right fusiform face area (FFA), older adults failed to show adaptation to the same face repeatedly presented in the same view, which elicited the most adaptation in young adults. We also performed a multivariate analysis to examine correlations between whole-brain activation patterns and behavioral performance in a face-matching task tested outside the scanner. Despite poor neural adaptation in right FFA, high-performing older adults engaged the same face-processing network as high-performing young adults across conditions, except the one presenting a same facial identity across different viewpoints. Low-performing older adults used this network to a lesser extent. Additionally, high-performing older adults uniquely recruited a set of areas related to better performance across all conditions, indicating age-specific involvement of this added network. This network did not include the core ventral face-processing areas but involved the left inferior occipital gyrus, frontal, and parietal regions. Although our adaptation results show that the neuronal representations of the core face-preferring areas become less selective with age, our multivariate analysis indicates that older adults utilize a distinct network of regions associated with better face matching performance, suggesting that engaging this network may compensate for deficiencies in ventral face processing regions.
The Neural Sociometer: Brain Mechanisms Underlying State Self-esteem
Authors: Eisenberger Naomi I. , Inagaki Tristen K. , Muscatell Keely A. , Byrne Haltom Kate E. , Leary Mark R.
Published: March 2011

On the basis of the importance of social connection for survival, humans may have evolved a “sociometer”—a mechanism that translates perceptions of rejection or acceptance into state self-esteem. Here, we explored the neural underpinnings of the sociometer by examining whether neural regions responsive to rejection or acceptance were associated with state self-esteem. Participants underwent fMRI while viewing feedback words (“interesting,” “boring“) ostensibly chosen by another individual (confederate) to describe the participant's previously recorded interview. Participants rated their state self-esteem in response to each feedback word. Results demonstrated that greater activity in rejection-related neural regions (dorsal ACC, anterior insula) and mentalizing regions was associated with lower-state self-esteem. Additionally, participants whose self-esteem decreased from prescan to postscan versus those whose self-esteem did not showed greater medial prefrontal cortical activity, previously associated with self-referential processing, in response to negative feedback. Together, the results inform our understanding of the origin and nature of our feelings about ourselves.