bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic coupling between TRPV4 and Ca2+-activated SK1/3 and IK1 K+ channels plays a critical role in regulating the K+-secretory BK channel in kidney collecting duct cells
Authors: Li Yue , Hu Hongxiang , Tian Jin-Bin , Zhu Michael X. , O’Neil Roger G.
Published: March 2017

The large-conductance Ca2+-activated K+ channel, BK (KCNMA1), is expressed along the connecting tubule (CNT) and cortical collecting duct (CCD) where it underlies flow- and Ca2+-dependent K+ secretion. Its activity is partially under the control of the mechanosensitive transient receptor potential vanilloid type 4 (TRPV4) Ca2+-permeable channel. Recently, we identified three small-/intermediate-conductance Ca2+-activated K+ channels, SK1 (KCNN1), SK3 (KCNN3), and IK1 (KCNN4), with notably high Ca2+-binding affinities, that are expressed in CNT/CCD and may be regulated by TRPV4-mediated Ca2+ influx. The K+-secreting CCD mCCDcl1 cells, which express these channels, were used to determine whether SK1/3 and IK1 are activated on TRPV4 stimulation and whether they contribute to Ca2+ influx and activation of BK. Activation of TRPV4 (GSK1016790A) modestly depolarized the membrane potential and robustly increased intracellular Ca2+, [Ca2+]i. Inhibition of both SK1/3 and IK1 by application of apamin and 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), respectively, further depolarized the membrane potential and markedly suppressed the TRPV4-mediated rise in [Ca2+]i. Application of BK inhibitor iberiotoxin after activation of TRPV4 without apamin/TRAM-34 also reduced [Ca2+]i and further intensified membrane depolarization, demonstrating BK involvement. However, the BK-dependent effects on [Ca2+]i and membrane potential were largely abolished by pretreatment with apamin and TRAM-34, identical to that observed by separately suppressing TRPV4-mediated Ca2+ influx, demonstrating that SK1/3-IK1 channels potently contribute to TRPV4-mediated BK activation. Our data indicate a direct correlation between TRPV4-mediated Ca2+ signal and BK activation but where early activation of SK1/3 and IK1 channels are critical to sufficiently enhanced Ca2+ entry and [Ca2+]i levels required for activation of BK.
Endothelial dysfunction correlates with exaggerated exercise pressor response during whole body maximal exercise in chronic kidney disease
Authors: Downey Ryan M. , Liao Peizhou , Millson Erin C. , Quyyumi Arshed A. , Sher Salman , Park Jeanie
Published: March 2017

Chronic kidney disease (CKD) patients have exercise intolerance associated with increased cardiovascular mortality. Previous studies demonstrate that blood pressure (BP) and sympathetic nerve responses to handgrip exercise are exaggerated in CKD. These patients also have decreased nitric oxide (NO) bioavailability and endothelial dysfunction, which could potentially lead to an impaired ability to vasodilate during exercise. We hypothesized that CKD patients have exaggerated BP responses during maximal whole body exercise and that endothelial dysfunction correlates with greater exercise pressor responses in these patients. Brachial artery flow-mediated dilation (FMD) was assessed before maximal treadmill exercise in 56 participants: 38 CKD (56.7 ± 1.2 yr old, 38 men) and 21 controls (52.8 ± 1.8 yr old, 20 men). During maximal treadmill exercise, the slope-of-rise in systolic BP (+10.32 vs. +7.75 mmHg/stage, P < 0.001), mean arterial pressure (+3.50 vs. +2.63 mmHg/stage, P = 0.004), and heart rate (+11.87 vs. +10.69 beats·min−1·stage−1, P = 0.031) was significantly greater in CKD compared with controls. Baseline FMD was significantly lower in CKD (2.76 ± 0.42% vs. 5.84 ± 0.97%, P = 0.008). Lower FMD values were significantly associated with a higher slope-of-rise in systolic BP (+11.05 vs. 8.71 mmHg/stage, P = 0.003) during exercise in CKD, as well as poorer exercise capacity measured as peak oxygen uptake (V̇o2peak; 19.47 ± 1.47 vs. 24.57 ± 1.51 ml·min−1·kg−1, P < 0.001). These findings demonstrate that low FMD in CKD correlates with augmented BP responses during exercise and lower V̇o2peak, suggesting that endothelial dysfunction may contribute to exaggerated exercise pressor responses and poor exercise capacity in CKD patients.
Activity-dependent increases in [Ca2+]i contribute to digital-analog plasticity at a molluscan synapse
Authors: Ludwar Bjoern Ch. , Evans Colin G. , Cambi Monica , Cropper Elizabeth C.
Published: March 2017

In a type of short-term plasticity that is observed in a number of systems, synaptic transmission is potentiated by depolarizing changes in the membrane potential of the presynaptic neuron before spike initiation. This digital-analog form of plasticity is graded. The more depolarized the neuron, the greater the increase in the efficacy of synaptic transmission. In a number of systems, including the system presently under investigation, this type of modulation is calcium dependent, and its graded nature is presumably a consequence of a direct relationship between the intracellular calcium concentration ([Ca2+]i) and the effect on synaptic transmission. It is therefore of interest to identify factors that determine the magnitude of this type of calcium signal. We studied a synapse in Aplysia and demonstrate that there can be a contribution from currents activated during spiking. When neurons spike, there are localized increases in [Ca2+]i that directly trigger neurotransmitter release. Additionally, spiking can lead to global increases in [Ca2+]i that are reminiscent of those induced by subthreshold depolarization. We demonstrate that these spike-induced increases in [Ca2+]i result from the activation of a current not activated by subthreshold depolarization. Importantly, they decay with a relatively slow time constant. Consequently, with repeated spiking, even at a low frequency, they readily summate to become larger than increases in [Ca2+]i induced by subthreshold depolarization alone. When this occurs, global increases in [Ca2+]i induced by spiking play the predominant role in determining the efficacy of synaptic transmission.

NEW & NOTEWORTHY We demonstrate that spiking can induce global increases in the intracellular calcium concentration ([Ca2+]i) that decay with a relatively long time constant. Consequently, summation of the calcium signal occurs even at low firing frequencies. As a result there is significant, persistent potentiation of synaptic transmission.
Clinical Decision Support Systems for Comorbidity: Architecture, Algorithms, and Applications
Authors: Fan Aihua , Lin Di , Tang Yu
Published: March 2017

In this paper, we present the design of a clinical decision support system (CDSS) for monitoring comorbid conditions. Specifically, we address the architecture of a CDSS by characterizing it from three layers and discuss the algorithms in each layer. Also we address the applications of CDSSs in a few real scenarios and analyze the accuracy of a CDSS in consideration of the potential conflicts when using multiple clinical practice guidelines concurrently. Finally, we compare the system performance in our design with that in the other design schemes. Our study shows that our proposed design can achieve a clinical decision in a shorter time than the other designs, while ensuring a high level of system accuracy.
A 64-Year-Old Woman with Chest Pain, Limb Weakness, and Endometrial Cancer
Authors: Ponthus Simon , Kherad Omar , Petriccioli Nicole , Lobrinus Johannes Alexander , Guerne Pierre-André A.
Published: March 2017

Necrotizing autoimmune myopathy (NAM) is a rare subgroup of idiopathic inflammatory myopathies (IIM). This pathology usually affects proximal limb muscles and in some cases the myocardium. Patients usually display proximal limb weakness. Muscular biopsy is required to confirm the diagnosis. We report the case of a 64-year-old woman with an atypical first presentation of NAM, manifested by chest pain in the context of metastatic endometrial cancer. The diagnosis of NAM was however made when she returned a second time with proximal limb weakness. A treatment with prednisone was then initiated, to which rituximab was rapidly associated, beside a specific chemotherapy.
Human Excretion of Polybrominated Diphenyl Ether Flame Retardants: Blood, Urine, and Sweat Study
Authors: Genuis Shelagh K. , Birkholz Detlef , Genuis Stephen J.
Published: March 2017

Commonly used as flame retardants, polybrominated diphenyl ethers (PBDEs) are routinely detected in the environment, animals, and humans. Although these persistent organic pollutants are increasingly recognized as having serious health implications, particularly for children, this is the first study, to our knowledge, to investigate an intervention for human elimination of bioaccumulated PBDEs. Objectives. To determine the efficacy of blood, urine, and perspiration as PBDE biomonitoring mediums; assess excretion of five common PBDE congeners (28, 47, 99, 100, and 153) in urine and perspiration; and explore the potential of induced sweating for decreasing bioaccumulated PBDEs. Results. PBDE congeners were not found in urine samples; findings focus on blood and perspiration. 80% of participants tested positive in one or more body fluids for PBDE 28, 100% for PBDE 47, 95% for PBDE 99, and 90% for PBDE 100 and PBDE 153. Induced perspiration facilitated excretion of the five congeners, with different rates of excretion for different congeners. Conclusion. Blood testing provides only a partial understanding of human PBDE bioaccumulation; testing of both blood and perspiration provides a better understanding. This study provides important baseline evidence for regular induced perspiration as a potential means for therapeutic PBDE elimination. Fetotoxic and reproductive effects of PBDE exposure highlight the importance of further detoxification research.
Buyang Huanwu Decoction Ameliorates Poststroke Depression via Promoting Neurotrophic Pathway Mediated Neuroprotection and Neurogenesis
Authors: Luo Lin , Deng Shuhua , Yi Jian , Zhou Sainan , She Yan , Liu Baiyan
Published: March 2017

Objective. The aim of the present research is to investigate the therapeutic effect of Buyang Huanwu Decoction (BHD) in poststroke depression (PSD) animal model and illustrate its underlying mechanism via promoting neurotrophic pathway mediated neuroprotection and neurogenesis. Methods. To induce PSD rat model, isolation housed rats that received middle cerebral artery occlusion (MCAO) surgery successively suffered from chronic mild stress (CMS) treatment for consecutive twenty‐one days. Meanwhile, rats were correspondingly given vehicle, BHD, and fluoxetine. Then, neurologic function was scored and depressive‐like behaviors were assessed by sucrose preference test, locomotor activity, novelty‐suppressed feeding test, and forced swim test. Thereafter, the neuroprotection and neurogenesis related molecular markers and signaling were detected. Results. We firstly observed a significant neurological function recovery and antidepressants effect of BHD after MCAO together with CMS treatment. Our study also found that treatment with BHD and fluoxetine can significantly rescue neurons from apoptosis and promote neurogenesis in the CA3 and DG regions in the hippocampus. Notably, BHD and fluoxetine treatment can activate BDNF/ERK/CREB signaling. Conclusion. The results suggest that BHD is a promising candidate for treating PSD. Its curative effects can be attributed to neurotrophic pathway mediated neuroprotection and neurogenesis.
Distributions and Community Composition of Birds in Iraq’s Central Marsh
Authors: Fazaa Nadheer A. , Dunn Jonathon C. , Whittingham Mark J.
Published: March 2017

The Central Marsh (CM) in southern Iraq is known to provide important habitats for both resident and migrant birds. The CM has been used extensively by humans, in part due to its high levels of productivity and biodiversity. It was drained in the 1990s by the government and reflooded and restored in 2003. Recent brief surveys of the CM from 2005 to 2010 recorded 94 bird species. Our study combined transects and point counts in detailed monthly surveys from October 2013 to June 2014 in the CM. We found a total of 125 bird species in the CM across all surveys, with 31 species recorded for the first time in the CM and 11 species categorised as red listed by the IUCN. Fourteen species were confirmed breeding in the CM. Cluster analysis using NMDS ordination showed that the study area can be divided into three main clusters of bird assemblages which are presented here. We provide management recommendations based on our findings.
Evaluation of a Compact Hybrid Brain-Computer Interface System
Authors: Shin Jaeyoung , Müller Klaus-Robert , Schmitz Christoph H. , Kim Do-Won , Hwang Han-Jeong
Published: March 2017

We realized a compact hybrid brain-computer interface (BCI) system by integrating a portable near-infrared spectroscopy (NIRS) device with an economical electroencephalography (EEG) system. The NIRS array was located on the subjects’ forehead, covering the prefrontal area. The EEG electrodes were distributed over the frontal, motor/temporal, and parietal areas. The experimental paradigm involved a Stroop word-picture matching test in combination with mental arithmetic (MA) and baseline (BL) tasks, in which the subjects were asked to perform either MA or BL in response to congruent or incongruent conditions, respectively. We compared the classification accuracies of each of the modalities (NIRS or EEG) with that of the hybrid system. We showed that the hybrid system outperforms the unimodal EEG and NIRS systems by 6.2% and 2.5%, respectively. Since the proposed hybrid system is based on portable platforms, it is not confined to a laboratory environment and has the potential to be used in real-life situations, such as in neurorehabilitation.
Complete Response after Treatment with Neoadjuvant Chemoradiation with Prolonged Chemotherapy for Locally Advanced, Unresectable Adenocarcinoma of the Pancreas
Authors: Pompa Tiffany A. , Morano William F. , Jeurkar Chetan , Li Hui , Soundararajan Suganthi , Poli Jaganmohan , Bowne Wilbur B. , Styler Michael
Published: March 2017

Surgery is the only chance for cure in pancreatic ductal adenocarcinoma. In unresectable, locally advanced pancreatic cancer (LAPC), the National Comprehensive Cancer Network (NCCN) suggests chemotherapy and consideration for radiation in cases of unresectable LAPC. Here we present a rare case of unresectable LAPC with a complete histopathological response after chemoradiation followed by surgical resection. A 54-year-old female presented to our clinic in December 2013 with complaints of abdominal pain and 30-pound weight loss. An MRI demonstrated a mass in the pancreatic body measuring6.2×3.2 cm; biopsy revealed proven ductal adenocarcinoma. Due to splenic vein/artery and contiguous celiac artery encasement, she was deemed surgically unresectable. She was started on FOLFIRINOX therapy (three cycles), intensity modulated radiation to a dose of 54 Gy in 30 fractions concurrent with capecitabine, followed by FOLFIRI, and finally XELIRI. After 8 cycles of ongoing XELIRI completed in March 2015, restaging showed a remarkable decrease in tumor size, along with PET-CT revealing no FDG-avid uptake. She was reevaluated by surgery and taken for definitive resection. Histopathological evaluation demonstrated a complete R0 resection and no residual tumor. Based on this patient and literature review, this strategy demonstrates potential efficacy of neoadjuvant chemoradiation with prolonged chemotherapy, followed by surgery, which may improve outcomes in patients deemed previously unresectable.
Inhibition of Horseradish Peroxidase Activity by Boroxine Derivative, Dipotassium-trioxohydroxytetrafluorotriborate K2[B3O3F4OH]
Authors: Ostojic Jelena , Herenda Safija , Galijasevic Semira , Galic Borivoj , Milos Mladen
Published: March 2017

Recently research shows that horseradish peroxidase, HRP, when combined with other compounds, is highly reactive toward different human tumour cells and that better understanding of catalytic mechanism and inhibition HPR could lead to a new targeted cancer therapy. Thus, the inhibition of HRP activity by dipotassium-trioxohydroxytetrafluorotriborate K2[B3O3F4OH] was investigated for possible explanation of previously observed antitumour activities of this promising drug. HRP activity was studied under steady-state kinetic conditions by a spectrophotometric method. In the absence of the inhibitor values of Km = 0.47 mM and Vmax = 0.34 mM min−1, respectively, were determined. The hydrogen peroxide H2O2 kinetic measurements show a competitive inhibition with the inhibition constant KI = 2.56 mM. The activation energy Ea values were found to be very similar for both reactions; in the absence of inhibitor activation energy was 17.7 kJ mol−1 and in the presence of inhibitor activation energy was 16.3 kJ mol−1. The values of Arrhenius constants were found to be different; A = 4.635 s−1 was measured in the absence of inhibitor while in the presence of inhibitor Arrhenius constant was 1.745 s−1 showing that K2[B3O3F4OH] initiates conformational change in the structure of the HRP and subsequently reduces its activity.
Study on the Preparation and Anisotropic Distribution of Mechanical Properties of Well-Aligned PMIA Nanofiber Mats Reinforced Composites
Authors: He Bin , Tan Dongyi , Liu Tao , Wang Zexing , Zhou Hengshu
Published: March 2017

Well-aligned PMIA nanofiber mats were fabricated by electrospinning and then hot-pressing was used to produce PMIA nanofiber mats reinforced PLA matrix by layer-by-layer with the interlayer angles of 0, 45, and 90°. Orthogonal experimental design was employed to fix the effect of the hot-pressing parameters on the tensile strength of nanocomposites, and SEM was used to characterize the broken sections of the nanocomposites after tensile test. The optimized process parameters were achieved of pressure as 1000 Pa, temperature as 180°C, and time as 30 min. The SEM images of broken sections showed that the different laminate forms and the state of bearing load of nanofibers resulted in the different morphologies of broken sections. The break strength of PMIA/PLA nanocomposites with any of interlayer angles at different tensile testing directions was revealed as follows: axial > oblique > transverse, and the initial modulus also showed the same except the angle of 90° with the approach initial modulus at the axial and transverse directions. The maximum tensile strength and modulus of the nanocomposites were 17.12 MPa and 1642.17 MPa, respectively, of the axial tensile testing directions of the interlayer angle of 0°.
Semianalytical Solution for the Deformation of an Elastic Layer under an Axisymmetrically Distributed Power-Form Load: Application to Fluid-Jet-Induced Indentation of Biological Soft Tissues
Authors: Lu Minhua , Huang Shuai , Yang Xianglong , Yang Lei , Mao Rui
Published: March 2017

Fluid-jet-based indentation is used as a noncontact excitation technique by systems measuring the mechanical properties of soft tissues. However, the application of these devices has been hindered by the lack of theoretical solutions. This study developed a mathematical model for testing the indentation induced by a fluid jet and determined a semianalytical solution. The soft tissue was modeled as an elastic layer bonded to a rigid base. The pressure of the fluid jet impinging on the soft tissue was assumed to have a power-form function. The semianalytical solution was verified in detail using finite-element modeling, with excellent agreement being achieved. The effects of several parameters on the solution behaviors are reported, and a method for applying the solution to determine the mechanical properties of soft tissues is suggested.
The Checkpoint Kinase 1 Inhibitor Prexasertib Induces Regression of Preclinical Models of Human Neuroblastoma
Authors: Lowery Caitlin D. , VanWye Alle B. , Dowless Michele , Blosser Wayne , Falcon Beverly L. , Stewart Julie , Stephens Jennifer , Beckmann Richard P. , Bence Lin Aimee , Stancato Louis F.
Published: March 2017

Purpose: Checkpoint kinase 1 (CHK1) is a key regulator of the DNA damage response and a mediator of replication stress through modulation of replication fork licensing and activation of S and G2–M cell-cycle checkpoints. We evaluated prexasertib (LY2606368), a small-molecule CHK1 inhibitor currently in clinical testing, in multiple preclinical models of pediatric cancer. Following an initial assessment of prexasertib activity, this study focused on the preclinical models of neuroblastoma.

Experimental Design: We evaluated the antiproliferative activity of prexasertib in a panel of cancer cell lines; neuroblastoma cell lines were among the most sensitive. Subsequent Western blot and immunofluorescence analyses measured DNA damage and DNA repair protein activation. Prexasertib was investigated in several cell line–derived xenograft mouse models of neuroblastoma.

Results: Within 24 hours, single-agent prexasertib promoted γH2AX–positive double-strand DNA breaks and phosphorylation of DNA damage sensors ATM and DNA–PKcs, leading to neuroblastoma cell death. Knockdown of CHK1 and/or CHK2 by siRNA verified that the double-strand DNA breaks and cell death elicited by prexasertib were due to specific CHK1 inhibition. Neuroblastoma xenografts rapidly regressed following prexasertib administration, independent of starting tumor volume. Decreased Ki67 and increased immunostaining of endothelial and pericyte markers were observed in xenografts after only 6 days of exposure to prexasertib, potentially indicating a swift reduction in tumor volume and/or a direct effect on tumor vasculature.

Conclusions: Overall, these data demonstrate that prexasertib is a specific inhibitor of CHK1 in neuroblastoma and leads to DNA damage and cell death in preclinical models of this devastating pediatric malignancy. Clin Cancer Res; 23(15); 4354–63. ©2017 AACR.
A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67
Authors: Jovanović Bojana , Mayer Ingrid A. , Mayer Erica L. , Abramson Vandana G. , Bardia Aditya , Sanders Melinda E. , Kuba M. Gabriela , Estrada Monica V. , Beeler J. Scott , Shaver Timothy M. , Johnson Kimberly C. , Sanchez Violeta , Rosenbluth Jennifer M. , Dillon Patrick M. , Forero-Torres Andres , Chang Jenny C. , Meszoely Ingrid M. , Grau Ana M. , Lehmann Brian D. , Shyr Yu , Sheng Quanhu , Chen Sheau-Chiann , Arteaga Carlos L. , Pietenpol Jennifer A.
Published: March 2017

Purpose: Because of inherent disease heterogeneity, targeted therapies have eluded triple-negative breast cancer (TNBC), and biomarkers predictive of treatment response have not yet been identified. This study was designed to determine whether the mTOR inhibitor everolimus with cisplatin and paclitaxel would provide synergistic antitumor effects in TNBC.

Methods: Patients with stage II/III TNBC were enrolled in a randomized phase II trial of preoperative weekly cisplatin, paclitaxel and daily everolimus or placebo for 12 weeks, until definitive surgery. Tumor specimens were obtained at baseline, cycle 1, and surgery. Primary endpoint was pathologic complete response (pCR); secondary endpoints included clinical responses, breast conservation rate, safety, and discovery of molecular features associated with outcome.

Results: Between 2009 and 2013, 145 patients were accrued; 36% of patients in the everolimus arm and 49% of patients in the placebo arm achieved pCR; in each arm, 50% of patients achieved complete responses by imaging. Higher rates of neutropenia, mucositis, and transaminase elevation were seen with everolimus. Clinical response to therapy and long-term outcome correlated with increased frequency of DNA damage response (DDR) gene mutations, Basal-like1 and Mesenchymal TNBC-subtypes, AR-negative status, and high Ki67, but not with tumor-infiltrating lymphocytes.

Conclusions: The paclitaxel/cisplatin combination was well tolerated and active, but addition of everolimus was associated with more adverse events without improvement in pCR or clinical response. However, discoveries made from correlative studies could lead to predictive TNBC biomarkers that may impact clinical decision-making and provide new avenues for mechanistic exploration that could lead to clinical utility. Clin Cancer Res; 23(15); 4035–45. ©2017 AACR.
Focal Adhesion Kinase as a Potential Target in AML and MDS
Authors: Carter Bing Z. , Mak Po Yee , Wang Xiangmeng , Yang Hui , Garcia-Manero Guillermo , Mak Duncan H. , Mu Hong , Ruvolo Vivian R. , Qiu Yihua , Coombes Kevin , Zhang Nianxiang , Ragon Brittany , Weaver David T. , Pachter Jonathan A. , Kornblau Steven , Andreeff Michael
Published: March 2017

Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P = 2 × 10−4) and relapse (P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3-ITD (P = 0.0024) or RAS (P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34+ (P = 5.42 × 10−20) and CD34+CD38− MDS (P = 7.62 × 10−9) cells compared with normal CD34+ cells. MDS patients with higher FAK in CD34+ cells tended to have better overall survival (P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia–stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133–44. ©2017 AACR.
Metabolic Obesity, Adipose Inflammation and Elevated Breast Aromatase in Women with Normal Body Mass Index
Authors: Iyengar Neil M. , Brown Kristy A. , Zhou Xi Kathy , Gucalp Ayca , Subbaramaiah Kotha , Giri Dilip D. , Zahid Heba , Bhardwaj Priya , Wendel Nils K. , Falcone Domenick J. , Wang Hanhan , Williams Samantha , Pollak Michael , Morrow Monica , Hudis Clifford A. , Dannenberg Andrew J.
Published: March 2017

Obesity is associated with breast white adipose tissue (WAT) inflammation, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that have been linked to the pathogenesis of breast cancer. Here, we determined whether metabolic obesity, including changes in breast biology and systemic effects, occurs in a subset of women with normal body mass index (BMI). Breast WAT and fasting blood were collected from 72 women with normal BMI (<25 kg/m2) undergoing mastectomy for breast cancer risk reduction or treatment. WAT inflammation was defined by the presence of crown-like structures of the breast (CLS-B) which are composed of dead or dying adipocytes surrounded by macrophages. Severity of inflammation was measured as CLS-B/cm2. The primary objective was to determine whether breast WAT inflammation is associated with aromatase expression and activity. Secondary objectives included assessment of circulating factors and breast adipocyte size. Breast WAT inflammation was present in 39% of women. Median BMI was 23.0 kg/m2 (range, 18.4–24.9 kg/m2) in women with breast WAT inflammation versus 21.8 kg/m2 (range, 17.3–24.6 kg/m2) in those without inflammation (P = 0.04). Breast WAT inflammation was associated with elevated aromatase expression and activity, which increased with severity of inflammation (P < 0.05). Breast WAT inflammation correlated with larger adipocytes (P = 0.01) and higher circulating levels of C-reactive protein, leptin, insulin, and triglycerides (P ≤ 0.05). A subclinical inflammatory state associated with elevated aromatase in the breast, adipocyte hypertrophy, and systemic metabolic dysfunction occurs in some normal BMI women and may contribute to the pathogenesis of breast cancer. Cancer Prev Res; 10(4); 235–43. ©2017 AACR.

See related article by Berger, p. 223–25.
A High Ki67/BCL2 Index Could Predict Lower Disease-Free and Overall Survival in Intestinal-Type Gastric Cancer
Authors: Min Kyueng-Whan , Kim Dong-Hoon , Son Byoung Kwan , Kim Dong Hyun , Kim Eun-Kyung , Seo Jinwon , Ahn Sang Bong , Jo Yun Ju , Park Young Sook , Ha Junghoon
Published: March 2017

Background: The heterogeneity of gastric cancer makes the identification of potential prognostic indicators particularly important. The Ki67 and BCL2 proteins are known prognostic markers for different types of cancer. Ki67 is associated with cell proliferation, whereas BCL2 has antiproliferative roles. A combined marker based on these opposite functions might provide improved prognostic information in gastric cancer. Method: Ki67 and BCL2 expression was assessed in 276 gastric adenocarcinoma tissue microarrays. A Ki67/BCL2 index based on the relative expression of each protein was divided into low- and high-risk groups using receiver operating characteristic curves. Results: A high Ki67/BCL2 index significantly correlated with advanced stage, recurrence, intestinal type, high histologic grade, and lymphatic and perineural invasion (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between disease-free or overall survival and the Ki67/BCL2 index in intestinal-type gastric cancer (all p < 0.05). Conclusions: A combined marker using Ki67 and BCL2 could be a useful indicator for predicting survival in patients with intestinal-type gastric cancer.
How to Differentiate Borderline Hepatic Nodules in Hepatocarcinogenesis: Emphasis on Imaging Diagnosis
Authors: Park Hyun Jeong , Choi Byung Ihn , Lee Eun Sun , Park Sung Bin , Lee Jong Beum
Published: March 2017

Background: Rapid advances in liver imaging have improved the evaluation of hepatocarcinogenesis and early diagnosis and treatment of hepatocellular carcinoma (HCC). In this situation, detection of early-stage HCC in its development is important for the improvement of patient survival and optimal treatment strategies. Because early HCCs are considered precursors of progressed HCC, precise differentiation between a dysplastic nodule (DN), especially a high-grade DN, and early HCC is important. In clinical practice, these nodules are frequently called “borderline hepatic nodules.” Summary: This article discusses radiological and pathological characteristics of these borderline hepatic nodules and offers an understanding of multistep hepatocarcinogenesis by focusing on the descriptions of the imaging changes in the progression of DN and early HCC. Detection and accurate diagnosis of borderline hepatic nodules are still a challenge with contrast enhanced ultrasonography, CT, and MRI with extracellular contrast agents. However, gadoxetic acid-enhanced MRI may be useful for improving the diagnosis of these borderline nodules. Key Messages: Since there is a net effect of incomplete neoangiogenesis and decreased portal venous flow in the early stage of hepatocarcinogenesis, borderline hepatic nodules commonly show iso- or hypovascularity. Therefore, precise differentiation of these nodules remains a challenging issue. In MRI using hepatobiliary contrast agents, signal intensity of HCCs on hepatobiliary phase (HBP) is regarded as a potential imaging biomarker. Borderline hepatic nodules are seen as nonhypervascular and hypointense nodules on the HBP, which is important for predicting tumor behavior and determining appropriate therapeutic strategies.
PBL: uma solução para integração e gerenciamento dos diversos tipos de projetos na engenharia civil
Authors: Lopes Paulo Adeildo , Martins Daiana Bragueto
Published: March 2017

O presente trabalho tem por objetivo averiguar a integração e gerenciamento dos diversos tipos de projetos na engenharia civil utilizando o método Problem-Based Learning (PBL) no processo de ensino-aprendizagem. A abordagem ocorreu por meio da disciplina de Síntese e Integração dos Conhecimentos (SIC) que integra o quarto ano da grade curricular do Curso de Engenharia Civil de uma Instituição de Ensino Superior particular brasileira. A disciplina em questão compõe a grade curricular com a finalidade de integrar as diversas disciplinas da série e também a grande maioria das disciplinas já estudadas pelos discentes do curso nos demais anos. A pesquisa de campo foi desenvolvida por meio da pesquisa-ação durante o ano letivo de 2013 e os dados utilizados nesta pesquisa foram coletados pelo docente em duas turmas de quarto ano, composta por 38 discentes. A implantação do PBL nesta disciplina ocorreu por meio de um problema no qual os discentes em um contexto simulado do cenário real da prática profissional da engenharia civil desenvolveram como produto final a integração dos diversos tipos de projetos necessários à execução de uma obra residencial em dois pavimentos. Observa-se que foram realizadas sessões tutoriais semanais, nas quais as equipes tinham metas a serem desenvolvidas e apresentadas ao professor. Estas soluções eram discutidas e, por meio de trocas de experiências entre os discentes e o docente poderiam ser melhoradas se necessárias e reapresentadas junto com as metas da próxima semana. Enfim, a melhoria envolvendo a integração foi um processo cíclico até a composição de uma solução tecnicamente satisfatória, considerando que o problema foi comum para todos e que as soluções apresentadas são diferentes entre si, possibilitando uma riqueza nos debates. Os resultados evidenciam que foi possível sair da metodologia de ensino tradicional que permeia a grande maioria dos cursos de engenharia civil do Brasil, melhorar o nível de ensino e aprendizagem, desenvolver a capacidade de trabalhar em equipe, desenvolver a percepção de que os projetos podem ter excelente qualidade, contudo se forem desenvolvidos isoladamente, sem integração entre eles, tornam as obras caras, geram desperdícios e deixam a desejar em relação a sua funcionalidade e finalidade.
Integração de tecnologias CAD/CAE/CAM no ateliê de arquitetura: Uma aplicação no projeto de edifícios altos
Authors: Celani Gabriela , Monteiro Ana Maria Góes , Franco Juarez , Calixto Victor
Published: March 2017

Este artigo descreve uma disciplina de ateliê do 9º semestre do curso de Arquitetura e Urbanismo da Universidade Estadual de Campinas – Unicamp – em que foi adotada uma estratégia de projeto paramétrico e baseado em desempenho para o desenvolvimento de edifícios altos. A disciplina envolveu o uso de programas de análise ambiental e estrutural, além da modelagem paramétrica e algorítmica como maneira de incorporar os resultados dessas análises à geração da forma, com base no desempenho. Além disso, a disciplina fez um uso intensivo de equipamentos de fabricação digital para a produção de maquetes. Os resultados obtidos demonstram a importância da presença de uma equipe interdisciplinar de instrutores no ateliê de projeto, além da viabilidade de se reproduzir, ainda que de maneira simplificada, o processo de projeto integrado, com o uso de tecnologias CAD/CAE/CAM, que vem se tornando cada vez mais presente nos escritórios de arquitetura.
A semiótica hoje: avanços e perspectivas
Authors: Fontanille Jacques
Published: March 2017

A pesquisa, de modo geral, deixou de pertencer apenas ao domínio de pesquisadores profissionais, na medida em que, atualmente, é uma das grandes funções das sociedades globalizadas, participando, consequentemente, dos modos de construção de identidades que essas sociedades propõem. Se a semiótica quer reconhecer-se ainda como disciplina de vocação científica, não pode escapar desse movimento global. Ao propor um corpo de conceitos e de métodos para questionar as práticas, os textos, os objetos, as interações sociais, as formas de vida e os modos de existência coletivos e da coletividade, a semiótica tem condições de construir esses sentidos, especialmente se trabalhar em colaboração com as outras ciências humanas e sociais que contribuem para edificar, cada uma de seu próprio ponto de vista, essa arquitetura das significações humanas. Neste artigo, tendo em vista esse cenário, buscaremos apontar quais são alguns dos desafios, dos avanços e das perspectivas da semiótica para o mundo de hoje. Ainda que não esgotemos as possibilidades de um projeto integral no âmbito da semiótica, acreditamos que pudemos escolher alguns exemplos que ocupam lugar de destaque nas preocupações atuais de nossa sociedade e que são objetos de uma demanda social e política mais urgente. Esperamos, portanto, que nossa reflexão seja suficiente para chamar a atenção de outros pesquisadores para os desafios sociais do século XXI, o que, ao nosso ver, deve ser uma das “vocações” da semiótica.
249 construtores de cidades
Authors: Ficher Sylvia
Published: March 2017

Cidades não se resumem à sua materialidade, ainda que tal materialidade seja bem mais do que um cenário inerte diante do qual se desenrola o drama da vida em sociedade. E aqueles envolvidos diretamente na sua concretude podem ser considerados reais construtores de cidades. Conhecer melhor suas trajetórias profissionais é ferramenta útil para os estudos urbanos. Aqui é apresentada uma descrição sumária das atividades de alguns desses construtores da metrópole paulistana: 120 engenheiros-arquitetos diplomados pela Escola Politécnica (1899-1954); 90 arquitetos e engenheiros-arquitetos diplomados pela Escola de Engenharia Mackenzie (1919-46); e 39 arquitetos diplomados pela Escola de Belas Artes (1929-34).
O urbanismo e os urbanistas na história urbana brasileira: percursos e perguntas para pensar a história urbana da América Latina
Authors: Faria Rodrigo de
Published: March 2017

Quais são os temas e os objetos da pesquisa em história do urbanismo no Brasil? Essa pergunta orientou uma análise sobre a pesquisa em história do urbanismo no Brasil pelo interesse na pesquisa das trajetórias profissionais de urbanistas. A partir de um levantamento sobre abordagens já realizadas pela historiografia brasileira, foram formuladas algumas considerações nesse campo de investigação. As recorrências e as permanências da pesquisa foram problematizadas para que pudéssemos apontar uma necessidade de articulação com a historiografia latino-americana, para que a construção-intepretação histórica urbanística da América Latina seja realizada com a presença mais direta dos estudos realizados no Brasil.
Um paradoxo patrimonial: a Catedral Metropolitana do Rio de Janeiro
Authors: Segre Roberto , Santos João Henrique dos , Souza Estela Maris de
Published: March 2017

A Catedral do Rio de Janeiro foi construída na Esplanada de Santo Antônio na segunda metade do século XX. A nova Catedral rompe com a tipologia das igrejas coloniais e traz a influência das pirâmides maias em um edifício moderno. A Esplanada de Santo Antônio traduz a grande ruptura que o tecido urbano sofreu nessa área onde é significativo o contraste entre o passado e o presente deixando em aberto o desafio de integrá-los em um conjunto patrimonial que recupere os valores humanísticos que sempre caracterizaram a cidade do Rio de Janeiro.
Comparison of glycemic and lipid profiles indicators among obese children and adolescents treated at public or private services from the city of Ribeirão Preto (SP)
Authors: Nogueira-de-Almeida Carlos A. , Pires Lara A. F. , Santos Rafaela G. dos
Published: March 2017

Design: Observational cross-sectional. Objectives: To compare the lipid and glycemic profiles of obese children and adolescents, followed at a public or a private health service. Methods: A cross-sectional study involving 113 obese patients, aged 7 to 18 years, conducted at two clinics, one public (n = 51) and the other private ( n = 62). Anthropometric data and blood samples were collected and glucose, insulin, HOMA and lipid profile have been compared between groups. Results: regarding averages, it was observed differences only for HDL, with lower values for public service. The prevalence of indicators outside the normal range, has always been above 45%, with the exception of hyperglycemia witch was rare. Only the prevalence of individuals with low HDL was different between groups, being lower at the private service. Conclusions: there was almost no hyperglycemia, but the prevalence of dyslipidemia and insulin resistance were high in both services. HDL was the only indicator that showed differences between the two groups and, considering that it is the most sensitive to the quality of nutrition and physical activity, it may be suggested that at the public health and on the individual management, these aspects should be better managed in lower income populations
Meta-analysis of the effectiveness of exercise in reducing blood pressure of postmenopausal hypertensive women
Authors: Costa Janine Araújo da , Borges Grasiely Faccin
Published: March 2017

Study design: Systematic review/metanalysis. Objective: To determine the effectiveness of exercise in reducing systolic and diastolic systemic blood pressure in postmenopausal hypertensive women. Methodology: A metanalysis type review of original articles published between 2004-2014 in the databases LILACS, SCIELO, PubMed and BIREME.. Results: Ten studies that evaluated the effect of exercise in postmenopausal hypertensive women were considered in the present metanalysis totalizing 192 women in the experimental group and 177 women in the control group. The majority of the studies (five) determined the effect of aerobic exercise combined with resistance exercise. Data metanalysis showed that physical exercise promoted a reduction in systolic and diastolic systemic blood pressure [systolic:-7,4 (-10,4 a -4,5) mmHg; mean and CI95% respectively P<0,0001; Z= 4,95] and [diastolic: -4,4 (-6,1 a -2,7) mmHg, mean and CI95% respectively; P<0,0001; Z= 5,22]. Conclusion: Physical exercise is effective in reducing high blood pressure in hypertensive postmenopausal women. Better results were observed in the studies in which exercise was practiced for longer periods particularly in those that combined aerobic exercise with resistance exercise
Translocalidades menonitas na América Latina e Caribe
Authors: Löwen Sahr Cicilian Luiza , Heidrich Álvaro Luiz
Published: March 2017

Desde o início da globalização na modernidade, na virada entre o século XV e XVI, os menonitas participam na produção de espaços translocais e globais. Surgidos nas controvérsias teológicas da Grande Reforma religiosa, eles defendiam o batizado adulto e um pacifismo extremo, que os submetiam a fortes rejeições e perseguições. Consequentemente, sua formação social tem por base uma intensa coerência interna que os leva, muitas vezes, a constituição de comunidades conservadoras. Assim, os menonitas desenvolveram ao longo de sua história uma dispersão mundial que se estende até hoje, funcionando através de um sistema de “translocalidade”. A análise dessas redes complexas de translocalidade se estabelece a partir da observação dos fluxos migratório, sobretudo aqueles que convergem para a América Latina e Caribe. Um foco específico é dado à organização interna dessa pluralidade a partir de exemplos do Paraguai.
Mudanças na dinâmica fluvial da bacia hidrográfica do Ribeirão Araquá: eventos tectônicos e climáticos no quaternário
Authors: Souza André De Oliveira , Perez Filho Archimedes
Published: March 2017

O presente trabalho apresenta os resultados dos estudos sobre a dinâmica geomorfológica quaternária da bacia do Ribeirão Araquá, municípios de São Pedro e Charqueada-SP. O trabalho parte do pressuposto que eventos neotectônicos e climáticos influenciaram na mudança da dinâmica fluvial desta bacia. Deste modo, o objetivo principal dessa pesquisa foi investigar a relação destes eventos com a elaboração de dois níveis de altos terraços e das linhas de cascalhos identificadas nos mesmos. Foram utilizados parâmetros fluvio-morfométricos e datações de sedimentos fluviais através da Luminescência Opticamente Estimulada (LOE). Os resultados apontaram para a coalescência de eventos neotectônicos durante o Pleistoceno Superior e climáticos na transição Pleistoceno Superior-Holoceno, sendo responsáveis pelas alterações no nível de base e formação dos terraços fluviais.
Geografia da mortalidade infantil do Brasil: variações espaciais e desigualdades territoriais
Authors: Faria Rivaldo
Published: March 2017

O objetivo deste artigo é analisar as variações espaciais e as desigualdades territoriais nos indicadores de mortalidade infantil do Brasil. O estudo foi feito com todos os óbitos infantis e nascidos vivos registrados em sistemas oficiais nos anos de 2012 e 2013 nas 558 microrregiões brasileiras. Os indicadores foram calculados e estimados através do método bayesiano empírico. As características do território foram analisadas através de um indicador multicritério denominado Índice de Privação Social. Os resultados indicaram elevados coeficientes de mortalidade infantil (CMI) nas microrregiões dos estados do nordeste e norte do país e fatores associados relacionados à idade da mãe, doenças infecciosas, vazios assistenciais e falta de acompanhamento pré-natal. Nas microrregiões dos estados do sudeste e sul e parte do centro-oeste os CMI são menos elevados e os fatores associados estão mais relacionados com a prematuridade e baixo peso à nascença.
A dendeicultura na Amazônia paraense
Authors: Nahum Joao Santos , Santos Cleison Bastos dos
Published: March 2017

Analisamos a expansão da dendeicultura na microrregião de Tomé-Açu, na Amazônia paraense. Em que transformações da paisagem, da configuração espacial, da dinâmica social, enfim, do território, podemos identificar esse boom? Partimos do território usado, o que nos permite considerar a dendeicultura um evento e afirmar que estamos diante de um boom do dendê materializado por territórios-rede do dendê. Baseamo-nos em entrevistas, coleta de dados, mapas e trabalho de campo levantados desde 2008 nos municípios de Moju, Acará, Tailândia, Tomé-Açu e Concórdia do Pará, lugares onde a monocultura da palma africana se expande e exige um olhar geográfico, atento aos usos e abusos do território.
Empreendimento hidrelétrico e famílias ribeirinhas na Amazônia: desterritorialização e resistência à construção da hidrelétrica Belo Monte, na Volta Grande do Xingu
Authors: Herrera José Antonio , Santana Nelivaldo Cardoso
Published: March 2017

Neste texto, evidenciam-se dois elementos percebidos no início da pesquisa sobre o impacto do empreendimento de Belo Monte: (a) a necessidade de valorizar a história das famílias que estão sendo desterritorializadas e (b) a resistência dos movimentos sociais à construção da UHE Belo Monte. Para isso, arrolam-se fragmentos de entrevistas que permitem entender o processo vivido pelas famílias da Volta Grande do Xingu e as ações de resistência dos movimentos sociais à implantação do empreendimento. A pesquisa está em curso desde 2012 e conta com o auxílio financeiro do CNPq e da Fapespa, o que permitiu verificar a supressão dos direitos das famílias afetadas e a sobreposição dos empreendedores aos movimentos de resistência, de modo que a obra não atende adequadamente às condicionantes básicas reivindicadas pela sociedade local