bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relevance of the Affordable Care Act for Improving Mental Health Care
Authors: Mechanic David , Olfson Mark
Published: December 2015

Provisions of the Affordable Care Act provide unprecedented opportunities for expanded access to behavioral health care and for redesigning the provision of services. Key to these reforms is establishing mental and substance abuse care as essential coverage, extending Medicaid eligibility and insurance parity, and protecting insurance coverage for persons with preexisting conditions and disabilities. Many provisions, including Accountable Care Organizations, health homes, and other structures, provide incentives for integrating primary care and behavioral health services and coordinating the range of services often required by persons with severe and persistent mental health conditions. Careful research and experience are required to establish the services most appropriate for primary care and effective linkage to specialty mental health services. Research providing guidance on present evidence and uncertainties is reviewed. Success in redesign will follow progress building on collaborative care and other evidence-based practices, reshaping professional incentives and practices, and reinvigorating the behavioral health workforce.
Exosomes: Fundamental Biology and Roles in Cardiovascular Physiology
Authors: Ibrahim Ahmed , Marbán Eduardo
Published: December 2015

Exosomes are nanosized membrane particles that are secreted by cells that transmit information from cell to cell. The information within exosomes prominently includes their protein and RNA payloads. Exosomal microRNAs in particular can potently and fundamentally alter the transcriptome of recipient cells. Here we summarize what is known about exosome biogenesis, content, and transmission, with a focus on cardiovascular physiology and pathophysiology. We also highlight some of the questions currently under active investigation regarding these extracellular membrane vesicles and their potential in diagnostic and therapeutic applications.
Representation and Consent: Why They Arose in Europe and Not Elsewhere
Authors: Stasavage David
Published: December 2015

Medieval Western Europeans developed two practices that are the bedrock of modern democracy: representative government and the consent of the governed. Why did this happen in Europe and not elsewhere? I ask what the literature has to say about this question, focusing on the role of political ideas, on economic development, and on warfare. I consider Europe in comparison with the Byzantine Empire, the Abbasid Caliphate, and Song Dynasty China. I argue that ultimately Europe's different path may have been an accident. It was produced by Western Europe's experience of outside invasion that replaced the Western Roman Empire with a set of small, fragmented polities in which rulers were relatively weak. Small size meant low transaction costs for maintaining assemblies. The relatively weak position of rulers meant that consent of the governed was necessary. I also suggest how these conclusions should influence our understanding of democracy today.
Dynamic Modeling of Steam Condenser and Design of PI Controller Based on Grey Wolf Optimizer
Authors: Li Shu-Xia , Wang Jie-Sheng
Published: December 2015

Shell-and-tube condenser is a heat exchanger for cooling steam with high temperature and pressure, which is one of the main kinds of heat exchange equipment in thermal, nuclear, and marine power plant. Based on the lumped parameter modeling method, the dynamic mathematical model of the simplified steam condenser is established. Then, the pressure PI control system of steam condenser based on the Matlab/Simulink simulation platform is designed. In order to obtain better performance, a new metaheuristic intelligent algorithm, grey wolf optimizer (GWO), is used to realize the fine-tuning of PI controller parameters. On the other hand, the Z-N engineering tuning method, genetic algorithm, and particle swarm algorithm are adopted for tuning PI controller parameters and compared with GWO algorithm. Simulation results show that GWO algorithm has better control performance than other four algorithms.
The Effect of Lumbar Lordosis on Screw Loosening in Dynesys Dynamic Stabilization: Four-Year Follow-Up with Computed Tomography
Authors: Kuo Chao-Hung , Chang Peng-Yuan , Tu Tsung-Hsi , Fay Li-Yu , Chang Hsuan-Kan , Wu Jau-Ching , Huang Wen-Cheng , Cheng Henrich
Published: December 2015

Introduction. This study aimed to evaluate the effects of Dynesys dynamic stabilization (DDS) on clinical and radiographic outcomes, including spinal pelvic alignment.Method. Consecutive patients who underwent 1- or 2-level DDS for lumbar spondylosis, mild degenerative spondylolisthesis, or degenerative disc disease were included. Clinical outcomes were evaluated by Visual Analogue Scale for back and leg pain, Oswestry Disability Index, and the Japanese Orthopedic Association scores. Radiographic outcomes were assessed by radiographs and computed tomography. Pelvic incidence and lumbar lordosis (LL) were also compared.Results. In 206 patients with an average follow-up of 51.1 ± 20.8 months, there were 87 screws (8.2%) in 42 patients (20.4%) that were loose. All clinical outcomes improved at each time point after operation. Patients with loosened screws were 45 years older. Furthermore, there was a higher risk of screw loosening in DDS involving S1, and these patients were more likely to have loosened screws if the LL failed to increase after the operation.Conclusions. The DDS screw loosening rate was overall 8.2% per screw and 20.4% per patient at more than 4 years of follow-up. Older patients, S1 involvement, and those patients who failed to gain LL postoperatively were at higher risk of screw loosening.
System Reliability Evaluation Based on Convex Combination Considering Operation and Maintenance Strategy
Authors: Li Lijie , Jia Limin , Wang Yanhui
Published: December 2015

The approaches to the system reliability evaluation with respect to the cases, where the components are independent or the components have interactive relationships within the system, were proposed in this paper. Starting from the higher requirements on system operational safety and economy, the reliability focused optimal models of multiobjective maintenance strategies were built. For safety-critical systems, the pessimistic maintenance strategies are usually taken, and, in these cases, the system reliability evaluation has also to be tackled pessimistically. For safety-uncritical systems, the optimistic maintenance strategies were usually taken, and, in these circumstances, the system reliability evaluation had also to be tackled optimistically, respectively. Besides, the reasonable maintenance strategies and their corresponding reliability evaluation can be obtained through the convex combination of the above two cases. With a high-speed train system as the example background, the proposed method is verified by combining the actual failure data with the maintenance data. Results demonstrate that the proposed study can provide a new system reliability calculation method and solution to select and optimize the multiobjective operational strategies with the considerations of system safety and economical requirements. The theoretical basis is also provided for scientifically estimating the reliability of a high-speed train system and formulating reasonable maintenance strategies.
Exact Periodic Wave, Bisoliton, and Various Breather Solutions for the Zakharov Equations
Authors: Wang Heng , Chen Longwei , Liu Hongjiang , Zheng Shuhua
Published: December 2015

The Zakharov equations, which involve the interactions between Langmuir and ion acoustic waves in plasma, are analytically studied. By using the method of Exp-function, the periodic wave, bisoliton, Akhmediev breather, Ma breather, and Peregrine breather of the Zakharov equations are obtained. These results presented in this paper enrich the diversity of solution structures of the Zakharov equations. Furthermore, based on the numerical simulations of these solutions, some physics analysis of bisolitons and various breathers are given.
Osseous Scaphotrapezial Coalition
Authors: Weathers William M. , Spence Susanna C. , Beckmann Nicholas M.
Published: December 2015

Osseous scaphotrapezial coalition is one of the rarest forms of carpal coalition of the hand. Often discovered incidentally, pain and functional limitation have not been reported. Carpal coalitions occurring across the carpal rows are thought to occur as a result of some insult or congenital anomaly. Isolated scaphotrapezial coalition calls into question the traditional thinking that fusion between the proximal and distal carpal rows must be acquired or associated with congenital syndromes.
Testicular and Related Size Evaluations in Nigerian Sahel Goats with Optimal Cauda Epididymal Sperm Reserve
Authors: Abba Y. , Igbokwe I. O.
Published: December 2015

Testicular sizes of animals are important for identification of those with adequate sperm production. The aim of this study was to define the testicular and related size estimates that would be associated with optimal cauda epididymal sperm counts (ESC) in Sahel goats based on postmortem evaluations. A stratified quota sample population of 125 male goats inclusive of all testicular sizes was taken at a slaughterhouse in Maiduguri, Nigeria. The bucks were aged 18–30 months and weighed 17.04 ± 2.99 (12–25) kg. Body, testicular, and epididymal weights of each goat with other related size measurements were estimated. ESC was determined from homogenized tissue using a manual cytometer. At the cut-off ESC of >1.1 × 109sperm heads, 66 (52.80%) of the goats had optimal ESC which was associated with testicular weight of 59.90 ± 16.10 (31.40–86.20) g, gonadosomatic index of 3.51 ± 0.69 (2.00–4.50) g/kg, and scrotal circumference of 19.07 ± 1.29 (17.00–21.80) cm. The size variables of the scrotum and testis correlated with one another and with the ESC. These findings provide data that may be used to anticipate adequate antemortem sperm reserve based on testicular size during preliminary selection of sires for breeding from a sexually mature Sahel buck population.
Structural Determinants in Family Planning Service Utilization in Ethiopia: EDHS 2011 Analysis
Authors: Gizachew Balew Jembere , Cho Yongtae , Tammy Kim Clara , Ko Woorim
Published: December 2015

Family planning coverage has improved in Ethiopia in the last decade, though fertility is still about 5.8 in the rural setup. In this paper, the major structural determinants of family planning service were analyzed using a multilevel model from 8906 individual women observation in the 2011 EDHS data. The results show that there is a big variation in family planning use both at the individual and between group levels. More than 39% of the variation in FP use is explained by contextual cluster level differences. Most of the socioeconomic predictors; respondent’s education, ethnicity, and partners’ education as well as employment status and urbanization were found to be significant factors that affect FP use. Similarly health extension visit and media access were found to be strong factors that affect FP service at both individual and cluster levels. This evidence concludes that addressing these contextual factors is very crucial to strengthen FP use and fertility reduction in the nation, beyond individual behavioral changes.
Obstacles Regions 3D-Perception Method for Mobile Robots Based on Visual Saliency
Authors: Xu Tao , Jia Songmin , Dong Zhengyin , Li Xiuzhi
Published: December 2015

A novel mobile robots 3D-perception obstacle regions method in indoor environment based on Improved Salient Region Extraction (ISRE) is proposed. This model acquires the original image by the Kinect sensor and then gains Original Salience Map (OSM) and Intensity Feature Map (IFM) from the original image by the salience filtering algorithm. The IFM was used as the input neutron of PCNN. In order to make the ignition range more exact, PCNN ignition pulse input was further improved as follows: point multiplication algorithm was taken between PCNN internal neuron and binarization salience image of OSM; then we determined the final ignition pulse input. The salience binarization region abstraction was fulfilled by improved PCNN multiple iterations finally. Finally, the binarization area was mapped to the depth map obtained by Kinect sensor, and mobile robot can achieve the obstacle localization function. The method was conducted on a mobile robot (Pioneer3-DX). The experimental results demonstrated the feasibility and effectiveness of the proposed algorithm.
Experimental Investigation on Mechanical and Turning Behavior of Al 7075/x% wt. TiB2-1% Gr In Situ Hybrid Composite
Authors: Ramkumar K. R. , Bekele Habtamu , Sivasankaran S.
Published: December 2015

The present research work involves the study of AA 7075-TiB2-Gr in situ composite through stir casting route. This in situ method involves formation of reinforcements within the matrix by the chemical reaction of two or more compounds which also produces some changes in the matrix material within the vicinity. Titanium Diboride (TiB2) and graphite were the reinforcement in a matrix of AA 7075 alloy. The composite was prepared with the formation of the reinforcement inside the molten matrix by adding salts of Potassium Tetrafluoroborate (KBF4) and Potassium Hexafluorotitanate (K2TiF6). The samples were taken under casted condition and the properties of the composite were tested by conducting characterization using X-ray diffraction (XRD), hardness test, flexural strength by using three-point bend test, scanning electron microscope (SEM), optical microstructure, grain size analysis, and surface roughness. It was found that good/excellent mechanical properties were obtained in AA 7075-TiB2-Gr reinforced in situ hybrid composite compared to alloy due to particulate strengthening of ceramic particles of TiB2in the matrix. Further, Al 7075-3% TiB2-1% Gr hybrid in situ composite exhibited improved machinability over the alloy and composites due to self-lubricating property given by the Gr particles in the materials.
Hopf Bifurcation Characteristics of Dual-Front Axle Self-Excited Shimmy System for Heavy Truck considering Dry Friction
Authors: Wei Daogao , Xu Ke , Jiang Yibin , Chen Changhe , Zhao Wenjing , Zhou Fugeng
Published: December 2015

Multiaxle steering is widely used in commercial vehicles. However, the mechanism of the self-excited shimmy produced by the multiaxle steering system is not clear until now. This study takes a dual-front axle heavy truck as sample vehicle and considers the influences of mid-shift transmission and dry friction to develop a 9 DOF dynamics model based on Lagrange’s equation. Based on the Hopf bifurcation theorem and center manifold theory, the study shows that dual-front axle shimmy is a self-excited vibration produced from Hopf bifurcation. The numerical method is adopted to determine how the size of dry friction torque influences the Hopf bifurcation characteristics of the system and to analyze the speed range of limit cycles and numerical characteristics of the shimmy system. The consistency of results of the qualitative and numerical methods shows that qualitative methods can predict the bifurcation characteristics of shimmy systems. The influences of the main system parameters on the shimmy system are also discussed. Improving the steering transition rod stiffness and dry friction torque and selecting a smaller pneumatic trail and caster angle can reduce the self-excited shimmy, reduce tire wear, and improve the driving stability of vehicles.
Nanosized Particles of Silica and Its Derivatives for Applications in Various Branches of Food and Nutrition Sectors
Authors: Kasaai Mohammad Reza
Published: December 2015

Nanosized particles of silica and its derivatives have been identified as versatile for a broad range of science, technology, and engineering applications. In this paper, an effort has been made to provide a short review from the available literature information on their applications in various branches of food and nutrition sectors. The information provided in this paper describes various parameters affecting their performances and efficiencies. The properties and applications of nanosilica and its derivatives have been compared with microsilica and bulk-silica for their performances. The use of nanosized particles of silica and its derivatives provides a number of advantages. Their efficiencies and performances are significantly higher than those of the traditional ones.
Modeling and Analysis of Static and Dynamic Characteristics of Nonlinear Seat Suspension for Off-Road Vehicles
Authors: Yan Zhenhua , Zhu Bing , Li Xuefei , Wang Guoqiang
Published: December 2015

Low-frequency vibrations (0.5–5 Hz) that harm drivers occur in off-road vehicles. Thus, researchers have focused on finding methods to effectively isolate or control low-frequency vibrations. A novel nonlinear seat suspension structure for off-road vehicles is designed, whose static characteristics and seat-human system dynamic response are modeled and analyzed, and experiments are conducted to verify the theoretical solutions. Results show that the stiffness of this nonlinear seat suspension could achieve real zero stiffness through well-matched parameters, and precompression of the main spring could change the nonlinear seat suspension performance when a driver’s weight changes. The displacement transmissibility curve corresponds with the static characteristic curve of nonlinear suspension, where the middle part of the static characteristic curve is gentler and the resonance frequency of the displacement transmissibility curve and the isolation minimum frequency are lower. Damping should correspond with static characteristics, in which the corresponding suspension damping value should be smaller given a flatter static characteristic curve to prevent vibration isolation performance reduction.
Iron Deprivation Affects Drug Susceptibilities of Mycobacteria Targeting Membrane Integrity
Authors: Pal Rahul , Hameed Saif , Fatima Zeeshan
Published: December 2015

Multidrug resistance (MDR) acquired byMycobacterium tuberculosis(MTB) through continuous deployment of antitubercular drugs warrants immediate search for novel targets and mechanisms. The ability of MTB to sense and become accustomed to changes in the host is essential for survival and confers the basis of infection. A crucial condition that MTB must surmount is iron limitation, during the establishment of infection, since iron is required by both bacteria and humans. This study focuses on how iron deprivation affects drug susceptibilities of known anti-TB drugs inMycobacterium smegmatis, a “surrogate of MTB.” We showed that iron deprivation leads to enhanced potency of most commonly used first line anti-TB drugs that could be reverted upon iron supplementation. We explored that membrane homeostasis is disrupted upon iron deprivation as revealed by enhanced membrane permeability and hypersensitivity to membrane perturbing agent leading to increased passive diffusion of drug and TEM images showing detectable differences in cell envelope thickness. Furthermore, iron seems to be indispensable to sustain genotoxic stress suggesting its possible role in DNA repair machinery. Taken together, we for the first time established a link between cellular iron and drug susceptibility of mycobacteria suggesting iron as novel determinant to combat MDR.
Positive Modulation of Pink Nelumbo nucifera Flowers on Memory Impairment, Brain Damage, and Biochemical Profiles in Restraint Rats
Authors: Prabsattroo Thawatchai , Wattanathorn Jintanaporn , Somsapt Pichet , Sritragool Opass
Published: December 2015

Due to the crucial role of oxidative stress in the stress‐induced memory deficit, the benefit of substance possessing antioxidant effect is focused. Since no data are available, we aimed to determine the effect of Nelumbo nucifera flowers extract on spatial memory and hippocampal damage in stressed rats. Male Wistar rats, weighing 250–350 g, were orally given N. nucifera extract at doses of 10, 10, and 200 mg·kg−1 45 minutes before the exposure to 12‐hour restraint stress. The spatial memory and serum corticosterone were assessed at 7 and 14 days of study period. At the end of study, acetylcholinesterase (AChE), monoamine oxidase type A and monoamine oxidase type B (MAO‐A and MAO‐B), oxidative stress status, neuron density, and Ki67 expression in hippocampus were also assessed. The results showed that N. nucifera extract decreased memory deficit and brain damage, serum corticosterone, oxidative stress status, AChE, and MAO‐A and MAO‐B activities but increased neuron density and Ki67 expression in hippocampus. These suggested that the improved oxidative stress status, adult neurogenesis, and cholinergic and monoaminergic functions might be responsible for the protective effect against stress‐related brain damage and dysfunction of the extract. Therefore, N. nucifera extract is the potential neuroprotective and memory enhancing agent. However, further researches are still required.
From Wireless Sensor Networks to Wireless Body Area Networks: Formal Modeling and Verification on Security Using PAT
Authors: Chen Tieming , Yu Zhenbo , Li Shijian , Chen Bo
Published: December 2015

Model checking has successfully been applied on verification of security protocols, but the modeling process is always tedious and proficient knowledge of formal method is also needed although the final verification could be automatic depending on specific tools. At the same time, due to the appearance of novel kind of networks, such as wireless sensor networks (WSN) and wireless body area networks (WBAN), formal modeling and verification for these domain-specific systems are quite challenging. In this paper, a specific and novel formal modeling and verification method is proposed and implemented using an expandable tool called PAT to do WSN-specific security verification. At first, an abstract modeling data structure for CSP#, which is built in PAT, is developed to support the node mobility related specification for modeling location-based node activity. Then, the traditional Dolev-Yao model is redefined to facilitate modeling of location-specific attack behaviors on security mechanism. A throughout formal verification application on a location-based security protocol in WSN is described in detail to show the usability and effectiveness of the proposed methodology. Furthermore, also a novel location-based authentication security protocol in WBAN can be successfully modeled and verified directly using our method, which is, to the best of our knowledge, the first effort on employing model checking for automatic analysis of authentication protocol for WBAN.
SIGMAR1 Regulates Membrane Electrical Activity in Response to Extracellular Matrix Stimulation to Drive Cancer Cell Invasiveness
Authors: Crottès David , Rapetti-Mauss Raphael , Alcaraz-Perez Francisca , Tichet Mélanie , Gariano Giuseppina , Martial Sonia , Guizouarn Hélène , Pellissier Bernard , Loubat Agnès , Popa Alexandra , Paquet Agnès , Presta Marco , Tartare-Deckert Sophie , Cayuela Maria Luisa , Martin Patrick , Borgese Franck , Soriani Olivier
Published: December 2015

The sigma 1 receptor (Sig1R) is a stress-activated chaperone that regulates ion channels and is associated with pathologic conditions, such as stroke, neurodegenerative diseases, and addiction. Aberrant expression levels of ion channels and Sig1R have been detected in tumors and cancer cells, such as myeloid leukemia and colorectal cancer, but the link between ion channel regulation and Sig1R overexpression during malignancy has not been established. In this study, we found that Sig1R dynamically controls the membrane expression of the human voltage-dependent K+ channel human ether-à-go-go-related gene (hERG) in myeloid leukemia and colorectal cancer cell lines. Sig1R promoted the formation of hERG/β1-integrin signaling complexes upon extracellular matrix stimulation, triggering the activation of the PI3K/AKT pathway. Consequently, the presence of Sig1R in cancer cells increased motility and VEGF secretion. In vivo, Sig1R expression enhanced the aggressiveness of tumor cells by potentiating invasion and angiogenesis, leading to poor survival. Collectively, our findings highlight a novel function for Sig1R in mediating cross-talk between cancer cells and their microenvironment, thus driving oncogenesis by shaping cellular electrical activity in response to extracellular signals. Given the involvement of ion channels in promoting several hallmarks of cancer, our study also offers a potential strategy to therapeutically target ion channel function through Sig1R inhibition. Cancer Res; 76(3); 607–18. ©2015 AACR.
A Small-Molecule Antagonist of the β-Catenin/TCF4 Interaction Blocks the Self-Renewal of Cancer Stem Cells and Suppresses Tumorigenesis
Authors: Fang Liang , Zhu Qionghua , Neuenschwander Martin , Specker Edgar , Wulf-Goldenberg Annika , Weis William I. , von Kries Jens P. , Birchmeier Walter
Published: December 2015

Wnt/β-catenin signaling is a highly conserved pathway essential for embryogenesis and tissue homeostasis. However, deregulation of this pathway can initiate and promote human malignancies, especially of the colon and head and neck. Therefore, Wnt/β-catenin signaling represents an attractive target for cancer therapy. We performed high-throughput screening using AlphaScreen and ELISA techniques to identify small molecules that disrupt the critical interaction between β-catenin and the transcription factor TCF4 required for signal transduction. We found that compound LF3, a 4-thioureido-benzenesulfonamide derivative, robustly inhibited this interaction. Biochemical assays revealed clues that the core structure of LF3 was essential for inhibition. LF3 inhibited Wnt/β-catenin signals in cells with exogenous reporters and in colon cancer cells with endogenously high Wnt activity. LF3 also suppressed features of cancer cells related to Wnt signaling, including high cell motility, cell-cycle progression, and the overexpression of Wnt target genes. However, LF3 did not cause cell death or interfere with cadherin-mediated cell–cell adhesion. Remarkably, the self-renewal capacity of cancer stem cells was blocked by LF3 in concentration-dependent manners, as examined by sphere formation of colon and head and neck cancer stem cells under nonadherent conditions. Finally, LF3 reduced tumor growth and induced differentiation in a mouse xenograft model of colon cancer. Collectively, our results strongly suggest that LF3 is a specific inhibitor of canonical Wnt signaling with anticancer activity that warrants further development for preclinical and clinical studies as a novel cancer therapy. Cancer Res; 76(4); 891–901. ©2015 AACR.
Impact of Screening on Breast Cancer Mortality: The UK Program 20 Years On
Authors: Massat Nathalie J. , Dibden Amanda , Parmar Dharmishta , Cuzick Jack , Sasieni Peter D. , Duffy Stephen W.
Published: December 2015

Background: With changes in diagnosis, treatment, and management of breast cancer since the mammography screening trials, there is a need to evaluate contemporary breast screening programs. A case–control study was set up to assess the current impact of attendance in the English Breast Screening Program on breast cancer mortality.

Methods: Cancer registry cases who died from primary breast cancer ages 47 to 89 years in London in 2008 to 2009 (869 women) were matched to 1 or 2 general population controls (1,642 women) with no diagnosis of breast cancer at the time of the case's diagnosis, who were alive at the case's death. Cases and controls were matched for date of birth and screening area, and had been invited to breast screening at least once prior to the case's diagnosis. ORs were estimated using conditional logistic regression. Self-selection bias was addressed using contemporaneous attendance at the cervical screening program. Sensitivity analyses were undertaken to assess the likely effect of lead time bias.

Results: Attendance at breast screening resulted in a breast cancer mortality reduction of 39% [OR, 0.61; 95% confidence interval (CI), 0.44–0.85] after self-selection correction. Attendance in the last 3 years prior to diagnosis resulted in a 60% mortality reduction (OR, 0.40; 95% CI, 0.31–0.51). Lead time bias effects were negligible.

Conclusion: Our results suggest that community breast screening programs provide their expected benefit in terms of reducing the risk of breast cancer death among women participating.

Impact: Mammography is an important tool for reducing breast cancer mortality and its impact could be increased by encouraging regular attendance. Cancer Epidemiol Biomarkers Prev; 25(3); 455–62. ©2015 AACR.

See related article by Massat et al., p. 479
Relationship of Terminal Duct Lobular Unit Involution of the Breast with Area and Volume Mammographic Densities
Authors: Gierach Gretchen L. , Patel Deesha A. , Pfeiffer Ruth M. , Figueroa Jonine D. , Linville Laura , Papathomas Daphne , Johnson Jason M. , Chicoine Rachael E. , Herschorn Sally D. , Shepherd John A. , Wang Jeff , Malkov Serghei , Vacek Pamela M. , Weaver Donald L. , Fan Bo , Mahmoudzadeh Amir Pasha , Palakal Maya , Xiang Jackie , Oh Hannah , Horne Hisani N. , Sprague Brian L. , Hewitt Stephen M. , Brinton Louise A. , Sherman Mark E.
Published: December 2015

Elevated mammographic density (MD) is an established breast cancer risk factor. Reduced involution of terminal duct lobular units (TDLU), the histologic source of most breast cancers, has been associated with higher MD and breast cancer risk. We investigated relationships of TDLU involution with area and volumetric MD, measured throughout the breast and surrounding biopsy targets (perilesional). Three measures inversely related to TDLU involution (TDLU count/mm2, median TDLU span, median acini count/TDLU) assessed in benign diagnostic biopsies from 348 women, ages 40–65, were related to MD area (quantified with thresholding software) and volume (assessed with a density phantom) by analysis of covariance, stratified by menopausal status and adjusted for confounders. Among premenopausal women, TDLU count was directly associated with percent perilesional MD (P trend = 0.03), but not with absolute dense area/volume. Greater TDLU span was associated with elevated percent dense area/volume (P trend<0.05) and absolute perilesional MD (P = 0.003). Acini count was directly associated with absolute perilesional MD (P = 0.02). Greater TDLU involution (all metrics) was associated with increased nondense area/volume (P trend ≤ 0.04). Among postmenopausal women, TDLU measures were not significantly associated with MD. Among premenopausal women, reduced TDLU involution was associated with higher area and volumetric MD, particularly in perilesional parenchyma. Data indicating that TDLU involution and MD are correlated markers of breast cancer risk suggest that associations of MD with breast cancer may partly reflect amounts of at-risk epithelium. If confirmed, these results could suggest a prevention paradigm based on enhancing TDLU involution and monitoring efficacy by assessing MD reduction. Cancer Prev Res; 9(2); 149–58. ©2015 AACR.
Cryptic 13q34 and 4q35.2 Deletions in an Italian Family
Authors: Riccardi Federica , Rivolta Gianna F. , Uliana Vera , Grati Francesca R. , La Starza Roberta , Marcato Livia , Di Perna Caterina , Quintavalle Gabriele , Garavelli Livia , Rosato Simonetta , Sammarelli Gabriella , Neri Tauro M. , Tagliaferri Annarita , Martorana Davide
Published: December 2015

Variations of DNA sequences in the human genome range from large, microscopically visible chromosome anomalies to single nucleotide changes. Submicroscopic genomic copy number variations, i.e. chromosomal imbalances which are undetectable by conventional cytogenetic analysis, play an intriguing clinical role. In this study, we describe the clinical consequences of the concurrent presence of an interstitial deletion in 13q34 and a terminal deletion in 4q35.2 in an Italian family. The index patient, a 19-year-old male, as well as his 12-year-old sister are carriers of both deletions, one of maternal and the other of paternal origin. The phenotype includes language delay, multiorgan involvement and bleeding diathesis with mild deficiency of factors X and VII. In the sister, the concomitant presence of Noonan syndrome may partly explain the clinical symptoms. The deleted region on chromosome 13 involves several genes (ATP11A, MCF2L, F7, F10, PROZ, PCID2, CUL4A, and LAMP1); some of these seem to play a role in the proband's phenotype. The terminal deletion in 4q35.2 contains other OMIM genes (FRG1, FRG2 and DBET); moreover, the 4q region is reported as a susceptibility locus for Crohn's disease, diagnosed in the proband's father. To our knowledge, this is the first report of a family with these 2 submicroscopic copy number changes. We tried to relate the clinical phenotype of the proband and his family to the molecular function of the involved genes.
Screening for Helicobacter pylori in Idiopathic Pulmonary Fibrosis Lung Biopsies
Authors: Kreuter Michael , Kirsten Detlef , Bahmer Thomas , Penzel Roland , Claussen Martin , Ehlers-Tenenbaum Svenja , Muley Thomas , Palmowski Karin , Eichinger Monika , Leider Marta , Herth Felix J.F. , Rabe Klaus F. , Bittmann Iris , Warth Arne
Published: December 2015

Background: Increasing evidence suggests a role of gastro-oesophageal reflux (GER) in idiopathic pulmonary fibrosis (IPF) pathogenesis. Recently, an association between serum Helicobacter pylori (HP) antibody positivity and more severe disease was described, but HP has not been directly analysed in lung tissue so far. Objective: To investigate the presence of HP in the lung tissue of IPF patients. Methods: Two tertiary interstitial lung disease care centre databases were screened for available lung biopsy material from IPF patients. Clinical and radiological data, including presence of GER and antiacid medication, were evaluated. HP-specific PCR was carried out on the IPF lung biopsy specimens. Results: A total of 39 IPF patients were included, of whom 85% were male. The patients' median age was 66 years, their vital capacity was 79% predicted, and their diffusing capacity for carbon monoxide was 53% predicted. In all, 82% of the lung biopsies were surgical and 18% transbronchial. Comorbidities were GER disease in 23% (n = 9), sleep apnoea in 13% (n = 5) and hiatal hernia in 38% of the cases (n = 15). Proton pump inhibitors were prescribed at the time of biopsy in 21% of the cases (n = 9). After a median follow-up of 25 months (range 6-69), there were 1 death, 1 lung transplantation and 8 acute exacerbations without relevant differences between the GER and non-GER subgroups. HP DNA was not detected in any of the lung tissue samples. Conclusion: The fact that no HP DNA was detected in the lung tissues calls into question the proposed relevance of HP to the direct pathogenesis of IPF.
Delayed Boston Keratoprosthesis Exchange due to a Preceding Vitreoretinal Surgery with Intraoperative Choroidal Detachment
Authors: Relimpio López María Isabel , Gessa Sorroche María , Garrido Hermosilla Antonio Manuel , Laborda Guirao Teresa , Espejo Arjona Francisco , Rodríguez de la Rúa Franch Enrique
Published: December 2015

Purpose: The aim is to describe the main characteristics of an anterior/posterior segment surgery and how to resolve intraoperative complications. Setting/Venue: The anterior and posterior segment surgical video was created at the Department of Ophthalmology, Virgin Macarena University Hospital, Seville, Spain. Methods: We present the case of a male with Stevens-Johnson syndrome and severe limbal deficiency who needed a Boston type 1 keratoprosthesis, reaching a visual acuity of 0.4 (0.05 before surgery). In the course of follow-up, he developed corneal melting with perforation, immune vitritis, and a large epimacular membrane. We decided to perform a 23-gauge vitrectomy associated with keratoprosthesis exchange. As a consequence of inappropriate anesthesia, the patient woke up during the surgery, provoking a retinal tear besides a choroidal detachment. These damages needed endolaser photocoagulation as well as silicone oil tamponade, forcing us to postpone the exchange. An intravitreal dexamethasone implant was also injected. Two months later, the silicone oil was removed, and the Boston keratoprosthesis was replaced by a new type 1 model with a titanium back plate, which likely improves biocompatibility and retention and may reduce complications such as retroprosthetic membranes and stromal corneal melts. Results: Good anatomical results were achieved, and visual acuity slightly improved to 0.2. Conclusions: Combined anterior and posterior segment surgery represents a great challenge that can improve not only visual acuity but also quality of life in patients with severe diseases such as Stevens-Johnson syndrome.
“Pensar em cidadania é pensar em cooperação social”
Authors: Pozzi Diana Helena De Benedetto , Padovano Bruno Roberto , Borelli Primavera , Gomes Suzana Helena de Avelar , Caldas Waldenyr , Vitti Isadora , Abreu Sérgio França Adorno de
Published: December 2015

Cidadania é o exercício dos direitos e deveres civis, políticos e sociais estabelecidos em uma sociedade, e, ao contrário do pensamento de muitos, exercê-la vai além da escolha eleitoral. Em um contexto complexo como o atual, muitas dúvidas acerca do tema vêm à tona: Como exercer a cidadania em tempos de crise? Qual a relação entre cidadania e as instituições nacionais vigentes? E como as manifestações sociais se incluem no exercício cidadão e democrático?
Saúde e Bem-estar na Obesidade: Paradoxo ou Possibilidade?
Authors: Ulian Mariana Dimitrov , Scagliusi Fernanda Baeza , Sato Priscila De Morais , Modesto Bruno , Benatti Fabiana , Gualano Bruno , Roble Odilon , Unsain Ramiro Fernandez
Published: December 2015

O presente artigo relata, brevemente, a história de um curso comunitário destinado a oferecer intervenções não farmacológicas a mulheres com excesso de peso. Ênfase é dada ao formato atual do curso, que conta com equipe multidisciplinar na área de Saúde apta a oferecer suporte amplo à mulher obesa que encontra dificuldade para se enquadrar o padrão de beleza requerido pela sociedade. Em nosso curso, propomos um programa centrado na saúde e na qualidade de vida do indivíduo obeso, sem foco na perda de peso, de acordo com os princípios da filosofia “Health at Every Size”. Os resultados qualitativos preliminares indicam que tal abordagem é promissora, oferecendo aos profissionais de saúde uma alternativa à proposta vigente de "perda de peso a qualquer custo". Os avanços no ensino, na pesquisa e na extensão associados ao curso também são discutidos ao longo do artigo.
Comparison of Right and Left Upper Limb Arterial Variants in Patients Undergoing Bilateral Transradial Procedures
Authors: Burzotta Francesco , Brancati Marta Francesca , Porto Italo , Saffioti Silvia , Aurigemma Cristina , Niccoli Giampaolo , Leone Antonio Maria , Coluccia Valentina , Crea Filippo , Trani Carlo
Published: December 2015

Background—

Transradial approach (TRA), when compared with transfemoral, improves the safety of percutaneous coronary procedures. Arterial axis variants are known to hinder the performance of transradial approach percutaneous coronary procedures. Data on the occurrence of arterial axis variants in the right and left arm arterial axes of individual patients are lacking.

Methods and Results—

From a single-center prospective registry, we selected all patients in whom bilateral upper limb arterial anatomy was assessed based on the performance of left and right radial catheterization obtained during the same or during repeat coronary diagnostic or interventional procedure(s). The occurrence of upper right and left limb arterial axis variants was classified according to the previously described operative ABC classification. A total of 610 patients were identified. An ABC upper limb arterial axis variant was detected in 156 (25.6%) patients. Variants were right-sided only in 65 (11.0%), left-sided only in 40 (6.6%), and bilateral in 46 (7.5%) patients. Thus, arterial axis variants were significantly more common in the right side (
P
=0.02). Bilateral arterial variants were significantly associated with age, female sex, and valvulopathy. Both A (radial/brachial) and B (axillary/subclavian/innominate) variants exhibited concordance across the 2 sides (odds ratio, 7.2; 95% confidence interval, 4.1–12.7 and 8.0; 95% confidence interval, 2.1–30.9, respectively).

Conclusions—

The occurrence of an anatomic variant potentially hindering transradial approach coronary diagnostic or interventional procedures is bilateral in <8% of cases and is more common in the right arm. Such information may guide, during the clinical practice, the access selection in the case of repeat procedures or need for additional accesses.
Multimodal SHG-2PF Imaging of Microdomain Ca
2+
-Contraction Coupling in Live Cardiac Myocytes
Authors: Awasthi Samir , Izu Leighton T. , Mao Ziliang , Jian Zhong , Landas Trevor , Lerner Aaron , Shimkunas Rafael , Woldeyesus Rahwa , Bossuyt Julie , Wood Brent M. , Chen Yi-Je , Matthews Dennis L. , Lieu Deborah K. , Chiamvimonvat Nipavan , Lam Kit S. , Chen-Izu Ye , Chan James W.
Published: December 2015

Rationale:

Cardiac myocyte contraction is caused by Ca
2+
binding to troponin C, which triggers the cross-bridge power stroke and myofilament sliding in sarcomeres. Synchronized Ca
2+
release causes whole cell contraction and is readily observable with current microscopy techniques. However, it is unknown whether localized Ca
2+
release, such as Ca
2+
sparks and waves, can cause local sarcomere contraction. Contemporary imaging methods fall short of measuring microdomain Ca
2+
-contraction coupling in live cardiac myocytes.

Objective:

To develop a method for imaging sarcomere level Ca
2+
-contraction coupling in healthy and disease model cardiac myocytes.

Methods and Results:

Freshly isolated cardiac myocytes were loaded with the Ca
2+
-indicator fluo-4. A confocal microscope equipped with a femtosecond-pulsed near-infrared laser was used to simultaneously excite second harmonic generation from A-bands of myofibrils and 2-photon fluorescence from fluo-4. Ca
2+
signals and sarcomere strain correlated in space and time with short delays. Furthermore, Ca
2+
sparks and waves caused contractions in subcellular microdomains, revealing a previously underappreciated role for these events in generating subcellular strain during diastole. Ca
2+
activity and sarcomere strain were also imaged in paced cardiac myocytes under mechanical load, revealing spontaneous Ca
2+
waves and correlated local contraction in pressure-overload–induced cardiomyopathy.

Conclusions:

Multimodal second harmonic generation 2-photon fluorescence microscopy enables the simultaneous observation of Ca
2+
release and mechanical strain at the subsarcomere level in living cardiac myocytes. The method benefits from the label-free nature of second harmonic generation, which allows A-bands to be imaged independently of T-tubule morphology and simultaneously with Ca
2+
indicators. Second harmonic generation 2-photon fluorescence imaging is widely applicable to the study of Ca
2+
-contraction coupling and mechanochemotransduction in both health and disease.
Fruit and Vegetable Consumption and the Incidence of Hypertension in Three Prospective Cohort Studies
Authors: Borgi Lea , Muraki Isao , Satija Ambika , Willett Walter C. , Rimm Eric B. , Forman John P.
Published: December 2015

Increased fruit and vegetable intake lowers blood pressure in short-term interventional studies. However, data on the association of long-term intake of fruits and vegetables with hypertension risk are scarce. We prospectively examined the independent association of whole fruit (excluding juices) and vegetable intake, as well as the change in consumption of whole fruits and vegetables, with incident hypertension in 3 large longitudinal cohort studies: Nurses’ Health Study (n=62 175), Nurses’ Health Study II (n=88 475), and Health Professionals Follow-up Study (n=36 803). We calculated hazard ratios and 95% confidence intervals for fruit and vegetable consumption while controlling for hypertension risk factors. Compared with participants whose consumption was ≤4 servings/week, the pooled hazard ratios among those whose intake was ≥4 servings/day were 0.92(0.87–0.97) for total whole fruit intake and 0.95(0.86–1.04) for total vegetable intake. Similarly, compared with participants who did not increase their fruit or vegetable consumption, the pooled hazard ratios for those whose intake increased by ≥7 servings/week were 0.94(0.90–0.97) for total whole fruit intake and 0.98(0.94–1.01) for total vegetable. Analyses of individual fruits and vegetables yielded different results. Consumption levels of ≥4 servings/week (as opposed to <1 serving/month) of broccoli, carrots, tofu or soybeans, raisins, and apples was associated with lower hypertension risk. In conclusion, our results suggest that greater long-term intake and increased consumption of whole fruits may reduce the risk of developing hypertension.
Early Weight Gain, Linear Growth, and Mid-Childhood Blood Pressure
Authors: Perng Wei , Rifas-Shiman Sheryl L. , Kramer Michael S. , Haugaard Line K. , Oken Emily , Gillman Matthew W. , Belfort Mandy B.
Published: December 2015

In recent years, the prevalence of hypertension and prehypertension increased markedly among children and adolescents, highlighting the importance of identifying determinants of elevated blood pressure early in life. Low birth weight and rapid early childhood weight gain are associated with higher future blood pressure. However, few studies have examined the timing of postnatal weight gain in relation to later blood pressure, and little is known regarding the contribution of linear growth. We studied 957 participants in Project Viva, an ongoing US prebirth cohort. We examined the relations of gains in body mass index z-score and length/height z-score during 4 early life age intervals (birth to 6 months, 6 months to 1 year, 1 to 2 years, and 2 to 3 years) with blood pressure during mid-childhood (6–10 years) and evaluated whether these relations differed by birth size. After accounting for confounders, each additional z-score gain in body mass index during birth to 6 months and 2 to 3 years was associated with 0.81 (0.15, 1.46) and 1.61 (0.33, 2.89) mm Hg higher systolic blood pressure, respectively. Length/height gain was unrelated to mid-childhood blood pressure, and there was no evidence of effect modification by birth size for body mass index or length/height z-score gain. Our findings suggest that more rapid gain in body mass index during the first 6 postnatal months and in the preschool years may lead to higher systolic blood pressure in mid-childhood, regardless of size at birth. Strategies to reduce accrual of excess adiposity during early life may reduce mid-childhood blood pressure, which may also impact adult blood pressure and cardiovascular health.