bluuebunny/crossref_metadata_2025 huggingface dataset:
KRAS,NRASandBRAFmutations in Greek and Romanian patients with colorectal cancer: a cohort study
Authors: Negru Serban , Papadopoulou Eirini , Apessos Angela , Stanculeanu Dana Lucia , Ciuleanu Eliade , Volovat Constantin , Croitoru Adina , Kakolyris Stylianos , Aravantinos Gerasimos , Ziras Nikolaos , Athanasiadis Elias , Touroutoglou Nikolaos , Pavlidis Nikolaos , Kalofonos Haralabos P , Nasioulas George
Published: May 2014

Objectives

Treatment decision-making in colorectal cancer is often guided by tumour tissue molecular analysis. The aim of this study was the development and validation of a high-resolution melting (HRM) method for the detection ofKRAS,NRASandBRAFmutations in Greek and Romanian patients with colorectal cancer and determination of the frequency of these mutations in the respective populations.

Setting

Diagnostic molecular laboratory located in Athens, Greece.

Participants

2425 patients with colorectal cancer participated in the study.

Primary and secondary outcome measures

2071 patients with colorectal cancer (1699 of Greek and 372 of Romanian origin) were analysed forKRASexon 2 mutations. In addition, 354 tumours from consecutive patients (196 Greek and 161 Romanian) were subjected to fullKRAS(exons 2, 3 and 4),NRAS(exons 2, 3 and 4) andBRAF(exon 15) analysis.KRAS,NRASandBRAFmutation detection was performed by a newly designed HRM analysis protocol, followed by Sanger sequencing.

Results

KRASexon 2 mutations (codons 12/13) were detected in 702 of the 1699 Greek patients with colorectal carcinoma analysed (41.3%) and in 39.2% (146/372) of the Romanian patients. Among the 354 patients who were subjected to fullKRAS,NRASandBRAFanalysis, 40.96% hadKRASexon 2 mutations (codons 12/13). Among theKRASexon 2 wild-type patients 15.31% harboured additionalRASmutations and 12.44%BRAFmutations. The newly designed HRM method used showed a higher sensitivity compared with the sequencing method.

Conclusions

The HRM method developed was shown to be a reliable method forKRAS,NRASandBRAFmutation detection. Furthermore, no difference in the mutation frequency ofKRAS,NRASandBRAFwas observed between Greek and Romanian patients with colorectal cancer.
Which features of primary care affect unscheduled secondary care use? A systematic review
Authors: Huntley Alyson , Lasserson Daniel , Wye Lesley , Morris Richard , Checkland Kath , England Helen , Salisbury Chris , Purdy Sarah
Published: May 2014

Objectives

To conduct a systematic review to identify studies that describe factors and interventions at primary care practice level that impact on levels of utilisation of unscheduled secondary care.

Setting

Observational studies at primary care practice level.

Participants

Studies included people of any age of either sex living in Organisation for Economic Co-operation and Development (OECD) countries with any health condition.

Primary and secondary outcome measures

The primary outcome measure was unscheduled secondary care as measured by emergency department attendance and emergency hospital admissions.

Results

48 papers were identified describing potential influencing features on emergency department visits (n=24 studies) and emergency admissions (n=22 studies). Patient factors associated with both outcomes were increased age, reduced socioeconomic status, lower educational attainment, chronic disease and multimorbidity. Features of primary care affecting unscheduled secondary care were more complex. Being able to see the same healthcare professional reduced unscheduled secondary care. Generally, better access was associated with reduced unscheduled care in the USA. Proximity to healthcare provision influenced patterns of use. Evidence relating to quality of care was limited and mixed.

Conclusions

The majority of research was from different healthcare systems and limited in the extent to which it can inform policy. However, there is evidence that continuity of care is associated with reduced emergency department attendance and emergency hospital admissions.
Endometrial biopsy in women with abnormal uterine bleeding: inadequate and unassessable categorisation is not clinically relevant
Authors: Ewies Ayman A A , Shaaban Kadry A A , Merard Reena , Zanetto Ulises
Published: May 2014

Aims

Inadequate endometrial biopsy comprises a dilemma for gynaecologists and histopathologists alike. This study was conducted to assess the clinical merit of classifying scant endometrial biopsy into inadequate and unassessable using McCluggage criteria.

Methods

We retrospectively classified 268 endometrial biopsies, initially reported as inadequate, into inadequate (n=74) and unassessable (n=174) using McCluggage criteria after excluding 20 cases; all taken from patients aged ≥50 years with abnormal uterine bleeding attending Sandwell and West Birmingham Hospitals, UK from 1 January 2007 until 30 September 2012. The electronic clinical records were reviewed to find out the consequent clinical decisions and final outcomes. The follow-up period was 15 months after including the last patient.

Results

The median age was 57 years (range: 50–97), and the median number of visits to hospital till the diagnosis was achieved was 2 (range: 1–4). The final diagnosis of endometrial hyperplasia or cancer was reported in 9 cases; 5 (7.1%) with an initial finding of inadequate and 4 with unassessable (2.4%); the difference was statistically insignificant (p=0.13). More patients in the inadequate category (82.4%) underwent further investigations when compared with the unassessable category (68.4%); the difference was statistically significant (p=0.029). There was no statistically significant difference in the inadequate to unassessable ratio when the endometrial thickness was ≥5 mm or <5 mm within the Pipelle group (p=0.46) or the curettage group (p=0.34).

Conclusions

Our findings suggest that categorising scant endometrial specimens into inadequate or unassessable has no clinical implications. The gynaecologist should interpret the histopathology report in the light of clinical scenario.
Diverse forms of pulmonary hypertension remodel the arterial tree to a high shear phenotype
Authors: Allen Roblee P. , Schelegle Edward S. , Bennett Stephen H.
Published: May 2014

Pulmonary hypertension (PH) is associated with progressive changes in arterial network complexity. An allometric model is derived that integrates diameter branching complexity between pulmonary arterioles of generation n and the main pulmonary artery (MPA) via a power-law exponent ( X) in dn= dMPA2− n/ Xand the arterial area ratio β = 21–2/ X. Our hypothesis is that diverse forms of PH demonstrate early decrements in X independent of etiology and pathogenesis, which alters the arteriolar shear stress load from a low-shear stress ( X > 2, β > 1) to a high-shear stress phenotype (X < 2, β < 1). Model assessment was accomplished by comparing theoretical predictions to retrospective morphometric and hemodynamic measurements made available from a total of 221 PH-free and PH subjects diagnosed with diverse forms (World Health Organization; WHO groups I-IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial hypertension (IPAH), familial (FPAH), collagen vascular disease, and methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA), cardiac output (Q) and body weight (M), utilizing an allometric power-law prediction of X relative to a PH-free state. Comparisons of X between PAH-free and PAH subjects indicates a characteristic reduction in area that elevates arteriolar shear stress, which may contribute to mechanisms of endothelial dysfunction and injury before clinically defined thresholds of pulmonary vascular resistance and PH. We conclude that the evaluation of X may be of use in identifying reversible and irreversible phases of PH in the early course of the disease process.
Physiological interdependence of the cardiovascular and postural control systems under orthostatic stress
Authors: Garg Amanmeet , Xu Da , Laurin Alexandre , Blaber Andrew P.
Published: May 2014

The cardiovascular system has been observed to respond to changes in human posture and the environment. On the same lines, frequent fallers have been observed to suffer from cardiovascular deficits. The present article aims to demonstrate the existence of interactions between the cardiovascular and postural control systems. The behavior of the two systems under orthostatic challenge was studied through novel adaptations of signal processing techniques. To this effect, the interactions between the two systems were assessed with two metrics, coherence and phase lock value, based on the wavelet transform. Measurements from the cardiovascular system (blood pressure), lower limb muscles (surface electromyography), and postural sway (center of pressure) were acquired from young healthy adults ( n = 28, men = 12, age = 20–28 yr) during quiet stance. The continuous wavelet transform was applied to decompose the representative signals on a time-scale basis in a frequency region of 0.01 to 0.1 Hz. Their linear coupling was quantified through a coherence metric, and the synchrony was characterized via the phase information. The outcomes of this study present evidence that the cardiovascular and postural control systems work together to maintain homeostasis under orthostatic challenge. The inferences open a new direction of study for effects under abnormalities and extreme environmental conditions.
A method for noninvasive longitudinal measurements of [Ca2+] in arterioles of hypertensive optical biosensor mice
Authors: Mauban Joseph R. H. , Fairfax Seth T. , Rizzo Mark A. , Zhang Jin , Wier Withrow Gil
Published: May 2014

We used two-photon (2-p) Förster resonance energy transfer (FRET) microscopy to provide serial, noninvasive measurements of [Ca2+] in arterioles of living “biosensor” mice. These express a genetically encoded Ca2+ indicator (GECI), either FRET-based exMLCK or intensity-based GCaMP2. The FRET ratios, Rmin and Rmax, required for in vivo Ca2+ calibration of exMLCK were obtained in isolated arteries. For in vivo experiments, mice were anesthetized (1.5% isoflurane), and arterioles within a depilated ear were visualized through the intact skin (i.e., noninvasively), by 2-p excitation of exMLCK (at 820 nm) or GCaMP2 (at 920 nm). Spontaneous or agonist-evoked [Ca2+] transients in arteriolar smooth muscle cells were imaged (at 2 Hz) with both exMLCK and GCaMP2. To examine changes in arteriolar [Ca2+] that might accompany hypertension, five exMLCK mice were implanted with telemetric blood pressure transducers and osmotic minipumps containing ANG II (350 ng·kg−1·min−1) and fed a high (6%)-salt diet for 9 days. [Ca2+] was measured every other day in five smooth muscle cells of two to three arterioles in each animal. Prior to ANG II/salt, [Ca2+] was 246 ± 42 nM. [Ca2+] increased transiently to 599 nM on day 2 after beginning ANG II/salt, then remained elevated at 331 ± 42 nM for 4 more days, before returning to 265 ± 47 nM 6 days after removal of ANG II/salt. In summary, two-photon excitation of exMLCK and GCaMP2 provides a method for noninvasive, longitudinal quantification of [Ca2+] dynamics and vascular structure in individual arterioles of a particular animal over an extended period of time, a capability that should enhance future studies of hypertension and vascular function.
Obesity increases inflammation and impairs lymphatic function in a mouse model of lymphedema
Authors: Savetsky Ira L. , Torrisi Jeremy S. , Cuzzone Daniel A. , Ghanta Swapna , Albano Nicholas J. , Gardenier Jason C. , Joseph Walter J. , Mehrara Babak J.
Published: May 2014

Although obesity is a major clinical risk factor for lymphedema, the mechanisms that regulate this effect remain unknown. Recent reports have demonstrated that obesity is associated with acquired lymphatic dysfunction. The purpose of this study was to determine how obesity-induced lymphatic dysfunction modulates the pathological effects of lymphatic injury in a mouse model. We used a diet-induced model of obesity in adult male C57BL/6J mice in which experimental animals were fed a high-fat diet and control animals were fed a normal chow diet for 8–10 wk. We then surgically ablated the superficial and deep lymphatics of the midportion of the tail. Six weeks postoperatively, we analyzed changes in lymphatic function, adipose deposition, inflammation, and fibrosis. We also compared responses to acute inflammatory stimuli in obese and lean mice. Compared with lean control mice, obese mice had baseline decreased lymphatic function. Lymphedema in obese mice further impaired lymphatic function and resulted in increased subcutaneous adipose deposition, increased CD45+ and CD4+ cell inflammation ( P < 0.01), and increased fibrosis, but caused no change in the number of lymphatic vessels. Interestingly, obese mice had a significantly increased acute inflammatory reaction to croton oil application. In conclusion, obese mice have impaired lymphatic function at baseline that is amplified by lymphatic injury. This effect is associated with increased chronic inflammation, fibrosis, and adipose deposition. These findings suggest that obese patients are at higher risk for lymphedema due to impaired baseline lymphatic clearance and an increased propensity for inflammation in response to injury.
Ca2+/calmodulin-dependent protein kinase II increases the susceptibility to the arrhythmogenic action potential alternans in spontaneously hypertensive rats
Authors: Mitsuyama Hirofumi , Yokoshiki Hisashi , Watanabe Masaya , Mizukami Kazuya , Shimokawa Junichi , Tsutsui Hiroyuki
Published: May 2014

Action potential duration alternans (APD-ALT), defined as long-short-long repetitive pattern of APD, potentially leads to lethal ventricular arrhythmia. However, the mechanisms of APD-ALT in the arrhythmogenesis of cardiac hypertrophy remain undetermined. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is known to modulate the function of cardiac sarcoplasmic reticulum and play an important role in Ca2+ cycling. We thus aimed to determine the role of CaMKII in the increased susceptibility to APD-ALT and arrhythmogenesis in the hypertrophied heart. APD was measured by high-resolution optical mapping in left ventricular (LV) anterior wall from normotensive Wistar-Kyoto (WKY; n = 10) and spontaneously hypertensive rats (SHR; n = 10) during rapid ventricular pacing. APD-ALT was evoked at significantly lower pacing rate in SHR compared with WKY (382 ± 43 vs. 465 ± 45 beats/min, P < 0.01). These changes in APD-ALT in SHR were completely reversed by KN-93 (1 μmol/l; n = 5), an inhibitor of CaMKII, but not its inactive analog, KN-92 (1 μmol/l; n = 5). The magnitude of APD-ALT was also significantly greater in SHR than WKY and was completely normalized by KN-93. Ventricular fibrillation (VF) was induced by rapid pacing more frequently in SHR than in WKY (60 vs. 10%; P < 0.05), which was also abolished by KN-93 (0%, P < 0.05). Western blot analyses indicated that the CaMKII autophosphorylation at Thr287 was significantly increased in SHR compared with WKY. The increased susceptibility to APD-ALT and VF during rapid pacing in hypertrophied heart was prevented by KN-93. CaMKII could be an important mechanism of arrhythmogenesis in cardiac hypertrophy.
Dynamic phosphorylation of VE-cadherin Y685 throughout mouse estrous cycle in ovary and uterus
Authors: Sidibé Adama , Polena Helena , Razanajatovo Jeremy , Mannic Tiphaine , Chaumontel Nicolas , Bama Soumalamaya , Maréchal Irène , Huber Philippe , Gulino-Debrac Danielle , Bouillet Laurence , Vilgrain Isabelle
Published: May 2014

We previously reported that vascular endothelial growth factor induced vascular endothelial (VE)-cadherin tyrosine phosphorylation at Y685 in a Src-dependent manner in vitro. Here, we studied the occurrence of Y685 phosphorylation in vivo in the female reproductive tract because it is a unique model of physiological vascular remodeling dependent on vascular endothelial growth factor. We first developed and characterized an anti-phospho-specific antibody against the site Y685 of VE-cadherin to monitor VE-cadherin phosphorylation along the four phases of mouse estrous cycle, termed proestrus, estrus, metestrus, and diestrus. A dynamic profile of tyrosine phosphorylated proteins was observed in both uterus and ovary throughout mouse estrous cycle, including kinase Src, which was found highly active at the estrus phase. The extent of tyrosine phosphorylated VE-cadherin was low at proestrus but strongly increased at estrus and returned to baseline at metestrus and diestrus, suggesting a potent hormonal regulation of this specific process. Indeed, C57Bl/6 female mice treatment with pregnant mare serum gonadotropin and human chorionic gonadotropin confirmed a significant increase in phosphoY685-VE-cadherin compared with that in untreated mice. These results demonstrate that VE-cadherin tyrosine phosphorylation at Y685 is a physiological and hormonally regulated process in female reproductive organs. In addition, this process was concomitant with the early steps of vascular remodeling taking place at estrus stage, suggesting that phosphoY685-VE-cadherin is a biomarker of endothelial cell activation in vivo.
VE-cadherin Y685F knock-in mouse is sensitive to vascular permeability in recurrent angiogenic organs
Authors: Sidibé Adama , Polena Helena , Pernet-Gallay Karin , Razanajatovo Jeremy , Mannic Tiphaine , Chaumontel Nicolas , Bama Soumalamaya , Maréchal Irène , Huber Philippe , Gulino-Debrac Danielle , Bouillet Laurence , Vilgrain Isabelle
Published: May 2014

Covalent modifications such as tyrosine phosphorylation are associated with the breakdown of endothelial cell junctions and increased vascular permeability. We previously showed that vascular endothelial (VE)-cadherin was tyrosine phosphorylated in vivo in the mouse reproductive tract and that Y685 was a target site for Src in response to vascular endothelial growth factor in vitro. In the present study, we aimed to understand the implication of VE-cadherin phosphorylation at site Y685 in cyclic angiogenic organs. To achieve this aim, we generated a knock-in mouse carrying a tyrosine-to-phenylalanine point mutation of VE-cadherin Y685 (VE-Y685F). Although homozygous VE-Y685F mice were viable and fertile, the nulliparous knock-in female mice exhibited enlarged uteri with edema. This phenotype was observed in 30% of females between 4 to 14 mo old. Histological examination of longitudinal sections of the VE-Y685F uterus showed an extensive disorganization of myometrium and endometrium with highly edematous uterine glands, numerous areas with sparse cells, and increased accumulation of collagen fibers around blood vessels, indicating a fibrotic state. Analysis of cross section of ovaries showed the appearance of spontaneous cysts, which suggested increased vascular hyperpermeability. Electron microscopy analysis of capillaries in the ovary showed a slight but significant increase in the gap size between two adjacent endothelial cell membranes in the junctions of VE-Y685F mice (wild-type, 11.5 ± 0.3, n = 78; and VE-Y685F, 12.48 ± 0.3, n = 65; P = 0.045), as well as collagen fiber accumulation around capillaries. Miles assay revealed that either basal or vascular endothelial growth factor-stimulated permeability in the skin was increased in VE-Y685F mice. Since edema and fibrotic appearance have been identified as hallmarks of initial increased vascular permeability, we conclude that the site Y685 in VE-cadherin is involved in the physiological regulation of capillary permeability. Furthermore, this knock-in mouse model is of potential interest for further studies of diseases that are associated with abnormal vascular permeability.
Sympathetic predominance is associated with impaired endothelial progenitor cells and tunneling nanotubes in controlled-hypertensive patients
Authors: de Cavanagh Elena M. V. , González Sergio A. , Inserra Felipe , Forcada Pedro , Castellaro Carlos , Chiabaut-Svane Jorge , Obregón Sebastián , Casarini María Jesús , Kempny Pablo , Kotliar Carol
Published: May 2014

Early endothelial progenitor cells (early EPC) and late EPC are involved in endothelial repair and can rescue damaged endothelial cells by transferring organelles through tunneling nanotubes (TNT). In rodents, EPC mobilization from the bone marrow depends on sympathetic nervous system activity. Indirect evidence suggests a relation between autonomic derangements and human EPC mobilization. We aimed at testing whether hypertension-related autonomic imbalances are associated with EPC impairment. Thirty controlled-essential hypertensive patients [systolic blood pressure/diastolic blood pressure = 130(120–137)/85(61–88) mmHg; 81.8% male] and 20 healthy normotensive subjects [114(107–119)/75(64–79) mmHg; 80% male] were studied. Mononuclear cells were cultured on fibronectin- and collagen-coated dishes for early EPC and late EPC, respectively. Low (LF)- and high (HF)-frequency components of short-term heart rate variability were analyzed during a 5-min rest, an expiration/inspiration maneuver, and a Stroop color-word test. Modulations of cardiac sympathetic and parasympathetic activities were evaluated by LF/HF (%) and HF power (ms2), respectively. In controlled-hypertensive patients, the numbers of early EPC, early EPC that emitted TNT, late EPC, and late EPC that emitted TNT were 41, 77, 50, and 88% lower than in normotensive subjects ( P < 0.008), respectively. In controlled-hypertensive patients, late EPC number was positively associated with cardiac parasympathetic reserve during the expiration/inspiration maneuver (rho = 0.45, P = 0.031) and early EPC with brachial flow-mediated dilation (rho = 0.655; P = 0.049); also, late TNT number was inversely related to cardiac sympathetic response during the stress test (rho = −0.426, P = 0.045). EPC exposure to epinephrine or norepinephrine showed negative dose-response relationships on cell adhesion to fibronectin and collagen; both catecholamines stimulated early EPC growth, but epinephrine inhibited late EPC growth. In controlled-hypertensive patients, sympathetic overactivity/parasympathetic underactivity were negatively associated with EPC, suggesting that reducing sympathetic/increasing parasympathetic activation might favor endothelial repair.
Estrogen regulation of the brain renin-angiotensin system in protection against angiotensin II-induced sensitization of hypertension
Authors: Xue Baojian , Zhang Zhongming , Beltz Terry G. , Guo Fang , Hay Meredith , Johnson Alan Kim
Published: May 2014

This study investigated sex differences in the sensitization of angiotensin (ANG) II-induced hypertension and the role of central estrogen and ANG-(1–7) in this process. Male and female rats were implanted for telemetered blood pressure (BP) recording. A subcutaneous subpressor dose of ANG II was given alone or concurrently with intracerebroventricular estrogen, ANG-(1–7), an ANG-(1–7) receptor antagonist A-779 or vehicle for 1 wk (induction). After a 1-wk rest (delay), a pressor dose of ANG II was given for 2 wk (expression). In males and ovariectomized females, subpressor ANG II had no sustained effect on BP during induction, but produced an enhanced hypertensive response to the subsequent pressor dose of ANG II during expression. Central administration of estrogen or ANG-(1–7) during induction blocked ANG II-induced sensitization. In intact females, subpressor ANG II treatment produced a decrease in BP during induction and delay, and subsequent pressor ANG II treatment given during expression produced only a slight but significant increase in BP. However, central blockade of ANG-(1–7) by intracerebroventricular infusion of A-779 during induction restored the decreased BP observed in females during induction and enhanced the pressor response to the ANG II treatment during expression. RT-PCR analyses indicated that estrogen given during induction upregulated mRNA expression of the renin-angiotensin system (RAS) antihypertensive components, whereas both central estrogen and ANG-(1–7) downregulated mRNA expression of RAS hypertensive components in the lamina terminalis. The results indicate that females are protected from ANG II-induced sensitization through central estrogen and its regulation of brain RAS.
Mechanisms Promoting Escape from Mitotic Stress–Induced Tumor Cell Death
Authors: Sinnott Rebecca , Winters Leah , Larson Brittany , Mytsa Daniela , Taus Patrick , Cappell Kathryn M. , Whitehurst Angelique W.
Published: May 2014

Non–small cell lung cancer (NSCLC) is notorious for its paltry responses to first-line therapeutic regimens. In contrast to acquired chemoresistance, little is known about the molecular underpinnings of the intrinsic resistance of chemo-naïve NSCLC. Here we report that intrinsic resistance to paclitaxel in NSCLC occurs at a cell-autonomous level because of the uncoupling of mitotic defects from apoptosis. To identify components that permit escape from mitotic stress–induced death, we used a genome-wide RNAi-based strategy, which combines a high-throughput toxicity screen with a live-cell imaging platform to measure mitotic fate. This strategy revealed that prolonging mitotic arrest with a small molecule inhibitor of the APC/cyclosome could sensitize otherwise paclitaxel-resistant NSCLC. We also defined novel roles for CASC1 and TRIM69 in supporting resistance to spindle poisons. CASC1, which is frequently co-amplified with KRAS in lung tumors, is essential for microtubule polymerization and satisfaction of the spindle assembly checkpoint. TRIM69, which associates with spindle poles and promotes centrosomal clustering, is essential for formation of a bipolar spindle. Notably, RNAi-mediated attenuation of CASC1 or TRIM69 was sufficient to inhibit tumor growth in vivo. On the basis of our results, we hypothesize that tumor evolution selects for a permissive mitotic checkpoint, which may promote survival despite chromosome segregation errors. Attacking this adaptation may restore the apoptotic consequences of mitotic damage to permit the therapeutic eradication of drug-resistant cancer cells. Cancer Res; 74(14); 3857–69. ©2014 AACR.
Validating Self-Reported Mammography Use in Vulnerable Communities: Findings and Recommendations
Authors: Allgood Kristi L. , Rauscher Garth H. , Whitman Steven , Vasquez-Jones Giselle , Shah Ami M.
Published: May 2014

Background: Most health surveys ask women whether they have had a recent mammogram, all of which report mammography use (past 2 years) at about 70% to 80% regardless of race or residence. We examined the potential extent of overreporting of mammography use in low income African-American and Latina women, and whether self-report inaccuracies might bias estimated associations between patient characteristics and mammography use.

Methods: Using venue-based sampling in two poor communities on the west side of Chicago, we asked eligible women living in two west side communities of Chicago to complete a survey about breast health (n = 2,200) and to provide consent to view their medical record. Of the 1,909 women who screened eligible for medical record review, 1,566 consented (82%). We obtained medical records of all women who provided both permission and a valid local mammography facility (n = 1,221). We compared the self-reported responses from the survey with the imaging reports found in the medical record (documented). To account for missing data, we conducted multiple imputations for key demographic variables and report standard measures of accuracy.

Results: Although 73% of women self-reported a mammogram in the last 2 years, only 44% of self-reports were documented. Overreporting of mammography use was observed for all three ethnic groups.

Conclusions: These results suggest considerable overestimation of prevalence of use in these vulnerable populations.

Impact: Relying on known faulty self-reported mammography data as a measure of mammography use provides an overly optimistic picture of utilization, a problem that may be exacerbated in vulnerable minority communities. Cancer Epidemiol Biomarkers Prev; 23(8); 1649–58. ©2014 AACR.
Increased Lung and Bladder Cancer Incidence in Adults after In Utero and Early-Life Arsenic Exposure
Authors: Steinmaus Craig , Ferreccio Catterina , Acevedo Johanna , Yuan Yan , Liaw Jane , Durán Viviana , Cuevas Susana , García José , Meza Rodrigo , Valdés Rodrigo , Valdés Gustavo , Benítez Hugo , VanderLinde Vania , Villagra Vania , Cantor Kenneth P. , Moore Lee E. , Perez Saida G. , Steinmaus Scott , Smith Allan H.
Published: May 2014

Background: From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer.

Methods: We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls.

Results: ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and >800 μg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96–3.71], and 5.24 (3.05–9.00; Ptrend < 0.001) for lung cancer, and 1.00, 2.94 (1.29–6.70), and 8.11 (4.31–15.25; Ptrend < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed.

Conclusion: Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure.

Impact: Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. Cancer Epidemiol Biomarkers Prev; 23(8); 1529–38. ©2014 AACR.
Dietary Insulin Index and Insulin Load in Relation to Endometrial Cancer Risk in the Nurses' Health Study
Authors: Prescott Jennifer , Bao Ying , Viswanathan Akila N. , Giovannucci Edward L. , Hankinson Susan E. , De Vivo Immaculata
Published: May 2014

Background: Although unopposed estrogen exposure is considered the main driver of endometrial carcinogenesis, factors associated with states of insulin resistance and hyperinsulinemia are independently associated with endometrial cancer risk. We used dietary insulin load and insulin index scores to represent the estimated insulin demand of overall diets and assessed their association with endometrial cancer risk in the prospective Nurses' Health Study.

Methods: We estimated incidence rate ratios (RR) and 95% confidence intervals (CI) for risk of invasive endometrial cancer using Cox proportional hazards models. Between the baseline dietary questionnaire (1980) and 2010, we identified a total of 798 incident-invasive epithelial endometrial adenocarcinomas over 1,417,167 person-years of follow-up.

Results: Dietary insulin scores were not associated with overall risk of endometrial cancer. Comparing women in the highest with the lowest quintile, the multivariable-adjusted RRs of endometrial cancer were 1.07 (95% CI, 0.84–1.35) for cumulative average dietary insulin load and 1.03 (95% CI, 0.82–1.31) for cumulative average dietary insulin index. Findings did not vary substantially by alcohol consumption, total dietary fiber intake, or body mass index and/or physical activity (Pheterogeneity ≥ 0.10).

Conclusions: Intake of a diet predicted to stimulate a high postprandial insulin response was not associated with endometrial cancer risk in this large prospective study. Considering the complex interplay of diet, lifestyle, and genetic factors contributing to the hyperinsulinemic state, dietary measures alone may not sufficiently capture absolute long-term insulin exposure.

Impact: This study is the first to investigate dietary insulin scores in relation to endometrial cancer risk. Cancer Epidemiol Biomarkers Prev; 23(8); 1512–20. ©2014 AACR.
Manipulating the Epigenome in Germinal Center Lymphomas: Is It Getting Easier and EZier?
Authors: Amengual Jennifer E. , O'Connor Owen A.
Published: May 2014

Mutations affecting key epigenetic modifiers tend to cluster in malignancies in which cells of origin lie in the germinal center (GC). EZH2, as transcriptional repressor, is mutated in high frequency in Chinese and Western patients with follicular lymphoma and may represent a rational target for GC-derived lymphomas. Clin Cancer Res; 20(12); 3047–9. ©2014 AACR.
Targeting Mitochondrial Metabolism by Inhibiting Autophagy in BRAF-Driven Cancers
Authors: Strohecker Anne M. , White Eileen
Published: May 2014

Metabolomic analyses of human tumors and mouse models of cancer have identified key roles for autophagy in supporting mitochondrial metabolism and homeostasis. In this review, we highlight data suggesting that autophagy inhibition may be particularly effective in BRAF-driven malignancies. Catalytic BRAF inhibitors have profound efficacy in tumors carrying activating mutations in Braf but are limited by the rapid emergence of resistance due in part to increased mitochondrial biogenesis and heightened rates of oxidative phosphorylation. We suggest that combined inhibition of autophagy and BRAF may overcome this limitation.

Significance: Braf V600E-driven tumors require autophagy and likely autophagy-provided substrates to maintain mitochondrial metabolism and to promote tumor growth, suggesting that autophagy ablation may improve cancer therapy. Cancer Discov; 4(7); 766–72. ©2014 AACR.
Ablation of Epicardial Ganglionated Plexi Increases Atrial Vulnerability to Arrhythmias in Dogs
Authors: Mao Jun , Yin Xiandong , Zhang Ying , Yan Qian , Dong Jianzeng , Ma Changsheng , Liu Xingpeng
Published: May 2014

Background—

Previous studies have suggested that systematic ablation of ganglionated plexi (GP) could increase the short-term success rate of radiofrequency ablation for atrial fibrillation, but the long-term efficacy of this approach is not fully established.

Methods and Results—

Twenty-four mongrel dogs were divided into 3 groups: epicardial GP ablation group 1 (n=8), epicardial GP ablation group 2 (n=8), and a sham operation group (n=8). In the 2 epicardial GP ablation groups, the 4 major GP and the ligament of Marshall were systematically ablated. The effective refractory period and inducibility of tachyarrhythmias were measured before and immediately after GP ablation in epicardial GP ablation group 1 and 8 weeks later in the other 2 groups. Tyrosine hydroxylase and choline acetyltransferase expressions were also determined immunohistochemically 8 weeks later in the latter groups. Compared with epicardial GP ablation group 1 and the sham operation group, epicardial GP ablation group 2 had the shortest atrial and ventricular effective refractory period and the highest inducibility of atrial tachyarrhythmias. The inducibility of ventricular tachyarrhythmias among the 3 groups was comparable. The density of tyrosine hydroxylase– and choline acetyltransferase–positive nerves in the atrium was the highest in epicardial GP group 2, whereas there were no significant intergroup differences in the densities of these 2 types of nerves in the ventricle.

Conclusions—

After 8 weeks of healing, epicardial GP ablation without additional atrial ablation was potentially proarrhythmic, which may be attributable to decreased atrial effective refractory period and hyper-reinnervation involving both sympathetic and parasympathetic nerves.
Functions of Dysfunction
Authors: Ashforth Blake E. , Reingen Peter H.
Published: May 2014

We report the results of an ethnographic study of a natural food cooperative in which we found an inherent tension in its mission between idealism and pragmatism, and we explore the dynamics through which that tension was managed and engaged in day-to-day governance and activities. Insights from participant observation, archival data, semi-structured interviews, and surveys provide a detailed and holistic account of the intergroup and intragroup processes through which the co-op negotiated its dualistic nature, as embodied in its hybrid organizational identity. The findings suggest that the value of each side of the duality was recognized at both the individual and organizational levels. Members’ discomfort with the duality, however, led them to split the mission in two and identify with one part, while projecting their less-favored part on others, creating an identity foil (an antithesis). This splitting resulted in ingroups and outgroups and heated intergroup conflict over realizing cooperative ideals vs. running a viable business. Ingroup members favoring one part of the mission nonetheless identified with the outgroup favoring the other because it embodied a side of themselves they continued to value. Individuals who exemplified their ingroup’s most extreme attributes were seen by the outgroup as prototypical, thus serving as “lightning rods” for intergroup conflict; this dynamic paradoxically enabled other ingroup members to work more effectively with moderate members of the outgroup. The idealist–pragmatist duality was kept continually in play over time through oscillating decisions and actions that shifted power from one group to the other, coupled with ongoing rituals to repair and maintain relationships disrupted by the messiness of the process. Thus ostensible dysfunctionality at the group level fostered functionality at the organizational level.
Civil Compliance and “Political Luddism”
Authors: Pappas Takis S. , O’Malley Eoin
Published: May 2014

When badly hit by the same global financial and economic crisis in the early 2000s, the Irish and the Greek societies reacted in quite different ways. Whereas Ireland remained largely acquiescent and displayed a high degree of civil compliance, Greeks took massively to the streets using violence and attacking specifically the state and the state personnel, a phenomenon we refer to as “political Luddism.” It is shown that the two countries are quite similar in terms of their economic condition, cultural background, social composition, ideological profiling, and party system dynamics, among other factors. What, then, explains the two countries’ dissimilar reactions to crisis? Through a detailed analysis of the cases, the article offers evidence that the most compelling explanation relates to the varying ability of the Greek and Irish states to continue providing basic public goods and other state-related services to their respective societies.
Educational Segregation, Tea Party Organizations, and Battles over Distributive Justice
Authors: McVeigh Rory , Beyerlein Kraig , Vann Burrel , Trivedi Priyamvada
Published: May 2014

Competing visions of who is deserving of rewards and privileges, and different understandings of the fairness of reward allocation processes, are at the heart of political conflict. Indeed, social movement scholars generally agree that a key component of most, if not all, social movements is a shared belief that existing conditions are unfair and subject to change (Gamson 1992; McAdam 1982; Snow et al. 1986; Turner and Killian 1987). In this article we consider the role that residential segregation by education level plays in shaping perceptions of distributive justice and, in turn, providing a context conducive to conservative political mobilization. We apply these ideas in an analysis of Tea Party activism and show that educational segregation is a strong predictor of the number of Tea Party organizations in U.S. counties. In a complementary analysis, we find that individuals with a bachelor’s degree are more likely than people who do not have any college education to support the Tea Party; this relationship is strongest in counties with higher levels of educational segregation.
Fecal Overflow Often Affects Children With Chronic Constipation That Appears After the Age of 2 Years
Authors: Kammacher Guerreiro Mélissa , Bettinville Aurore , Herzog Denise
Published: May 2014

Chronic functional constipation with or without encopresis is a common problem in the pediatric population, and the prevalence of encopresis may be underestimated. The aim of this study was to assess the prevalence and risk factors for overflow incontinence in patients with chronic constipation seen at a pediatric gastroenterology consultation. A retrospective study of 270 files of patients seen between 1997 and 2012 was conducted, and a classification according to Rome III criteria was done. Among 145 (53.7%) boys and 125 (46.2%) girls, 117 had overflow incontinence (43.3%) - 41 (35%) girls and 76 (65%) boys. The first symptoms of chronic constipation appeared at a median age of 30 and 33 months in encopretic and 16 and 12 months in nonencopretic girls and boys, respectively. The first specialized consultation took place after a median disease duration of 26.5 and 24 months in encopretic and 16 and 9 months in nonencopretic girls and boys, respectively. A history of stool retention and the presence of scybala at examination, but not of pain at defecation or anal fissure, were associated with encopresis. The onset of chronic constipation after the age of 2 years, a longer disease duration, male gender, and a history of stool retention were seen as risk factors for the development of encopresis in patients with chronic functional constipation.
Civil society: A multi-layered concept
Authors: Pérez-Díaz Víctor
Published: May 2014

This article analyses the connections between social developments and the evolution of the theory of civil society (CS) (classical background, semantic shifts, re-emergence and open questions regarding future research). The author distinguishes four layers of meanings of CS and focuses on selected research areas of CS qua associations (third sector, social capital, public sphere, civility). The aim is to provide access points and a frame of reference, and to emphasize the need for a culture-centered perspective, for a wide debate on a problematic in flux.
The new mobilities paradigm for a live sociology
Authors: Sheller Mimi
Published: May 2014

This article offers an overview of the field of mobilities research, tracing the theoretical antecedents to the study of mobilities both within the classical sociological tradition and at its borders with other disciplines or theoretical schools. It examines how ‘the new mobilities paradigm’ differs from earlier approaches to globalization, nomadism, and flow, and outlines some of the key themes and research areas within the field, in particular the concepts of mobility systems, mobility capital, mobility justice, and movement-space. In addressing new developments in mobile methodologies and realist ontologies, this review of the field concludes with a call for an emergent vital sociology that is attentive to its own autopoiesis.
Cultural sociology in perspective: Linking culture and power
Authors: Lima Neto Fernando
Published: May 2014

Cultural sociology aims at incorporating the central role of meaning-making into the analysis of social phenomena. The article presents an overview of cultural sociology, focusing on its main theoretical frameworks, methodological strategies and empirical investigations. The interplay between the cultural and the social and the focus on meaning variations are two central principles of analysis based on which cultural sociologists seek to revitalize the notion of culture in sociology. Since these principles can be combined in different manners, the article compares the two main current approaches to connect cultural codes and social interactions in the symbolical analysis of social phenomena.
Political sociology: State–society relations
Authors: Botelho André
Published: May 2014

Taking the contemporary debate about the status of political sociology as a starting point, the article presents some of the alternative views, and discusses the relationships between sociology and political science. It claims that, despite persistent controversies, looking into the research tradition of political sociology is a useful resource to grasp the identity of the sub-discipline. Accordingly, the author takes the relationship between state and society as the central issue that everywhere cuts across theoretical and methodological diversity. Finally, the text takes the nation-state as the most typical configuration of the relationship between state and society in modern history, and one that remains so in the present, despite the many historical and analytical challenges we observe today.
Religion and contemporary sociological theories
Authors: Turner Bryan S
Published: May 2014

In the late 20th and early 21st centuries, the sociology of religion enjoyed a remarkable growth in both theory and empirical research. The scholarly consensus argues that the early secularization thesis associated with modernization theory was misleading and simplistic, or that it was primarily relevant to northern Europe. Beyond the European framework, there is ample evidence that religion continues to play a major role in society, culture and politics. With urbanization in the developing world, there has come increasing piety and religious revivalism. Religion will be a major factor in political and ideological struggles across the globe in this century. One negative aspect of this focus on political conflict, however, has been an over-concentration on radical Islam and other manifestations of religious violence.
Is Viewing a Nature Video After Work Restorative? Effects on Blood Pressure, Task Performance, and Long-Term Memory
Authors: Pilotti Maura , Klein Eric , Golem Devon , Piepenbrink Eric , Kaplan Katie
Published: May 2014

Can a brief exposure to nature at the end of a workday enhance sustained attention and long-term memory? Student advisors viewed a video of either a natural environment or a busy city street after work. Then they performed a tone-detection task that was intended to mimic a key feature of their job (being on the telephone). After the nature video, systolic blood pressure increased and response latencies remained stable across time. After the city video, systolic blood pressure remained unchanged from baseline, whereas response latencies increased over time. Self-reports of arousal and emotional state did not differ significantly between videos, whereas memory of the experimental setting was better after viewing the nature video. In sum, a brief contact with nature at the end of a workday may give an individual vigor to complete additional tasks but not improve his or her affect.