Paradoxical Effects of MLL Paralogs in MLL-Rearranged Leukemia

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Michael J. Thirman
Conflicting data exist on the requirement for wild-type MLL1 in MLL-rearranged leukemia. In this issue of Cancer Cell, Chen et al. describe complementary approaches demonstrating that MLL1 is dispensable for MLL-fusion-mediated leukemogenesis. They also observe an unexpected role for MLL2 in MLL-rearranged leukemia cells and identify potential therapeutic targets.

Teaser

Conflicting data exist on the requirement for wild-type MLL1 in MLL-rearranged leukemia. In this issue of Cancer Cell, Chen et al. describe complementary approaches demonstrating that MLL1 is dispensable for MLL-fusion-mediated leukemogenesis. They also observe an unexpected role for MLL2 in MLL-rearranged leukemia cells and identify potential therapeutic targets.


http://ift.tt/2siewsG

Aberrant Glycosylation in Cancer: A Novel Molecular Mechanism Controlling Metastasis

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Ana Magalhães, Henrique O. Duarte, Celso A. Reis
Glycosylation alterations are involved in several steps of human cancer pathogenesis. In this issue of Cancer Cell, Agrawal et al. identified the glycosyltransferase FUT8 as a previously unrecognized mediator of melanoma metastasis, establishing core fucosylation as a potential therapeutic target for prevention and treatment of metastatic tumors.

Teaser

Glycosylation alterations are involved in several steps of human cancer pathogenesis. In this issue of Cancer Cell, Agrawal et al. identified the glycosyltransferase FUT8 as a previously unrecognized mediator of melanoma metastasis, establishing core fucosylation as a potential therapeutic target for prevention and treatment of metastatic tumors.


http://ift.tt/2tfPY0O

Intertumoral Heterogeneity within Medulloblastoma Subgroups

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Florence M.G. Cavalli, Marc Remke, Ladislav Rampasek, John Peacock, David J.H. Shih, Betty Luu, Livia Garzia, Jonathon Torchia, Carolina Nor, A. Sorana Morrissy, Sameer Agnihotri, Yuan Yao Thompson, Claudia M. Kuzan-Fischer, Hamza Farooq, Keren Isaev, Craig Daniels, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji Yeoun Lee, Wieslawa A. Grajkowska, Marta Perek-Polnik, Alexandre Vasiljevic, Cecile Faure-Conter, Anne Jouvet, Caterina Giannini, Amulya A. Nageswara Rao, Kay Ka Wai Li, Ho-Keung Ng, Charles G. Eberhart, Ian F. Pollack, Ronald L. Hamilton, G. Yancey Gillespie, James M. Olson, Sarah Leary, William A. Weiss, Boleslaw Lach, Lola B. Chambless, Reid C. Thompson, Michael K. Cooper, Rajeev Vibhakar, Peter Hauser, Marie-Lise C. van Veelen, Johan M. Kros, Pim J. French, Young Shin Ra, Toshihiro Kumabe, Enrique López-Aguilar, Karel Zitterbart, Jaroslav Sterba, Gaetano Finocchiaro, Maura Massimino, Erwin G. Van Meir, Satoru Osuka, Tomoko Shofuda, Almos Klekner, Massimo Zollo, Jeffrey R. Leonard, Joshua B. Rubin, Nada Jabado, Steffen Albrecht, Jaume Mora, Timothy E. Van Meter, Shin Jung, Andrew S. Moore, Andrew R. Hallahan, Jennifer A. Chan, Daniela P.C. Tirapelli, Carlos G. Carlotti, Maryam Fouladi, José Pimentel, Claudia C. Faria, Ali G. Saad, Luca Massimi, Linda M. Liau, Helen Wheeler, Hideo Nakamura, Samer K. Elbabaa, Mario Perezpeña-Diazconti, Fernando Chico Ponce de León, Shenandoah Robinson, Michal Zapotocky, Alvaro Lassaletta, Annie Huang, Cynthia E. Hawkins, Uri Tabori, Eric Bouffet, Ute Bartels, Peter B. Dirks, James T. Rutka, Gary D. Bader, Jüri Reimand, Anna Goldenberg, Vijay Ramaswamy, Michael D. Taylor
While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

Graphical abstract

Teaser

Cavalli et al. analyze 763 primary medulloblastoma samples using the similarity network fusion approach. They identify subtypes that have distinct somatic copy-number aberrations, activated pathways, and clinical outcomes within each of the four known subgroups and further delineate group 3 from group 4 MB.


http://ift.tt/2si7Uuw

MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Yufei Chen, Konstantinos Anastassiadis, Andrea Kranz, A. Francis Stewart, Kathrin Arndt, Claudia Waskow, Akihiko Yokoyama, Kenneth Jones, Tobias Neff, Yoo Lee, Patricia Ernst
The MLL1 histone methyltransferase gene undergoes many distinct chromosomal rearrangements to yield poor-prognosis leukemia. The remaining wild-type allele is most commonly, but not always, retained. To what extent the wild-type allele contributes to leukemogenesis is unclear. Here we show, using rigorous, independent animal models, that endogenous MLL1 is dispensable for MLL-rearranged leukemia. Potential redundancy was addressed by co-deleting the closest paralog, Mll2. Surprisingly, Mll2 deletion alone had a significant impact on survival of MLL-AF9-transformed cells, and additional Mll1 loss further reduced viability and proliferation. We show that MLL1/MLL2 collaboration is not through redundancy, but regulation of distinct pathways. These findings highlight the relevance of MLL2 as a drug target in MLL-rearranged leukemia and suggest its broader significance in AML.

Graphical abstract

Teaser

Chen et al. report that wild-type MLL1 is dispensable for MLL fusion leukemia, but instead loss of MLL2 reduces the survival of leukemia cells from human cell lines and in a mouse model of MLL-AF9 AML. Combined loss of MLL1 and MLL2 further reduces leukemia cell viability.


http://ift.tt/2siqdzu

From One to Many: Further Refinement of Medulloblastoma Subtypes Offers Promise for Personalized Therapy

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Abhishek Bavle, D. Williams Parsons
There is significant intertumoral heterogeneity within the four molecular subgroups of medulloblastoma. In this issue of Cancer Cell, Cavalli et al. apply similarity network fusion to gene expression and DNA methylation data to identify 12 medulloblastoma subtypes with distinct molecular and clinical profiles, making an important step toward molecularly tailored therapy.

Teaser

There is significant intertumoral heterogeneity within the four molecular subgroups of medulloblastoma. In this issue of Cancer Cell, Cavalli et al. apply similarity network fusion to gene expression and DNA methylation data to identify 12 medulloblastoma subtypes with distinct molecular and clinical profiles, making an important step toward molecularly tailored therapy.


http://ift.tt/2sijplJ

Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Detian Yuan, Shan Huang, Emanuel Berger, Lei Liu, Nina Gross, Florian Heinzmann, Marc Ringelhan, Tracy O. Connor, Mira Stadler, Michael Meister, Julia Weber, Rupert Öllinger, Nicole Simonavicius, Florian Reisinger, Daniel Hartmann, Rüdiger Meyer, Maria Reich, Marco Seehawer, Valentina Leone, Bastian Höchst, Dirk Wohlleber, Simone Jörs, Marco Prinz, Duncan Spalding, Ulrike Protzer, Tom Luedde, Luigi Terracciano, Matthias Matter, Thomas Longerich, Percy Knolle, Thomas Ried, Verena Keitel, Fabian Geisler, Kristian Unger, Einat Cinnamon, Eli Pikarsky, Norbert Hüser, Roger J. Davis, Darjus F. Tschaharganeh, Roland Rad, Achim Weber, Lars Zender, Dirk Haller, Mathias Heikenwalder
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant, heterogeneous cancer with poor treatment options. We found that mitochondrial dysfunction and oxidative stress trigger a niche favoring cholangiocellular overgrowth and tumorigenesis. Liver damage, reactive oxygen species (ROS) and paracrine tumor necrosis factor (Tnf) from Kupffer cells caused JNK-mediated cholangiocellular proliferation and oncogenic transformation. Anti-oxidant treatment, Kupffer cell depletion, Tnfr1 deletion, or JNK inhibition reduced cholangiocellular pre-neoplastic lesions. Liver-specific JNK1/2 deletion led to tumor reduction and enhanced survival in Akt/Notch- or p53/Kras-induced ICC models. In human ICC, high Tnf expression near ICC lesions, cholangiocellular JNK-phosphorylation, and ROS accumulation in surrounding hepatocytes are present. Thus, Kupffer cell-derived Tnf favors cholangiocellular proliferation/differentiation and carcinogenesis. Targeting the ROS/Tnf/JNK axis may provide opportunities for ICC therapy.

Graphical abstract

Teaser

Yuan et al. show that mitochondrial dysfunction and oxidative stress in the liver increase tumor necrosis factor (TNF) expression by Kupffer cells to cause JNK-mediated cholangiocellular proliferation and transformation. The ROS/TNF/JNK axis may be an effective target for intrahepatic cholangiocarcinoma therapy.


http://ift.tt/2tgcPZU

ACK1/TNK2 Regulates Histone H4 Tyr88-phosphorylation and AR Gene Expression in Castration-Resistant Prostate Cancer

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Kiran Mahajan, Pavani Malla, Harshani R. Lawrence, Zhihua Chen, Chandan Kumar-Sinha, Rohit Malik, Sudhanshu Shukla, Jongphil Kim, Domenico Coppola, Nicholas J. Lawrence, Nupam P. Mahajan
The androgen receptor (AR) is critical for the progression of prostate cancer to a castration-resistant (CRPC) state. AR antagonists are ineffective due to their inability to repress the expression of AR or its splice variant, AR-V7. Here, we report that the tyrosine kinase ACK1 (TNK2) phosphorylates histone H4 at tyrosine 88 upstream of the AR transcription start site. The WDR5/MLL2 complex reads the H4-Y88-phosphorylation marks and deposits the transcriptionally activating H3K4-trimethyl marks promoting AR transcription. Reversal of the pY88-H4 epigenetic marks by the ACK1 inhibitor (R)-9bMS-sensitized naive and enzalutamide-resistant prostate cancer cells and reduced AR and AR-V7 levels to mitigate CRPC tumor growth. Thus, a feedforward ACK1/pY88-H4/WDR5/MLL2/AR epigenetic circuit drives CRPC and is necessary for maintenance of the malignant state.

Graphical abstract

Teaser

Mahajan et al. report that ACK1 phosphorylates histone H4 at Y88 upstream of the AR transcription start site, leading to the WDR5/MLL2 complex-mediated increase of AR transcription. Inhibition of ACK1 reverses the pY88-H4 marks and reduces AR and AR-V7 levels to mitigate castration-resistant prostate tumor growth.


http://ift.tt/2tgcPJo

A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Praveen Agrawal, Barbara Fontanals-Cirera, Elena Sokolova, Samson Jacob, Christopher A. Vaiana, Diana Argibay, Veronica Davalos, Meagan McDermott, Shruti Nayak, Farbod Darvishian, Mireia Castillo, Beatrix Ueberheide, Iman Osman, David Fenyö, Lara K. Mahal, Eva Hernando
Association of aberrant glycosylation with melanoma progression is based mainly on analyses of cell lines. Here we present a systems-based study of glycomic changes and corresponding enzymes associated with melanoma metastasis in patient samples. Upregulation of core fucosylation (FUT8) and downregulation of α-1,2 fucosylation (FUT1, FUT2) were identified as features of metastatic melanoma. Using both in vitro and in vivo studies, we demonstrate FUT8 is a driver of melanoma metastasis which, when silenced, suppresses invasion and tumor dissemination. Glycoprotein targets of FUT8 were enriched in cell migration proteins including the adhesion molecule L1CAM. Core fucosylation impacted L1CAM cleavage and the ability of L1CAM to support melanoma invasion. FUT8 and its targets represent therapeutic targets in melanoma metastasis.

Graphical abstract

Teaser

Using a systems-based approach to assess glycosylation in matched primary and metastatic melanoma samples, Agrawal et al. find increased core fucosylation mediated by FUT8 in metastatic melanoma. FUT8 facilitates invasion and tumor dissemination, in part due to reduced cleavage of core-fucosylated L1CAM.


http://ift.tt/2tfKYck

Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Xiaoju Wang, Yuanyuan Qiao, Irfan A. Asangani, Bushra Ateeq, Anton Poliakov, Marcin Cieślik, Sethuramasundaram Pitchiaya, Balabhadrapatruni V.S.K. Chakravarthi, Xuhong Cao, Xiaojun Jing, Cynthia X. Wang, Ingrid J. Apel, Rui Wang, Jean Ching-Yi Tien, Kristin M. Juckette, Wei Yan, Hui Jiang, Shaomeng Wang, Sooryanarayana Varambally, Arul M. Chinnaiyan




http://ift.tt/2tfML1i

SnapShot: Immune Checkpoint Inhibitors

Publication date: 12 June 2017
Source:Cancer Cell, Volume 31, Issue 6
Author(s): Gabriel Abril-Rodriguez, Antoni Ribas
Immunotherapy has changed the landscape of cancer treatment. Checkpoint blockade therapies unleash breaks in the immune system and induce long-lasting responses. However, a significant number of patients do not respond (innate resistance), and a subset progress after responding (acquired resistance). A better understanding of the molecular mechanisms underlying checkpoint blockade therapies will facilitate the design of novel strategies to treat and prevent resistance. To view this SnapShot, open or download the PDF.

Teaser

Immunotherapy has changed the landscape of cancer treatment. Checkpoint blockade therapies unleash breaks in the immune system and induce long-lasting responses. However, a significant number of patients do not respond (innate resistance), and a subset progress after responding (acquired resistance). A better understanding of the molecular mechanisms underlying checkpoint blockade therapies will facilitate the design of novel strategies to treat and prevent resistance. To view this SnapShot, open or download the PDF.


http://ift.tt/2sipkHd

Structural Covariance Networks in Children with Autism or ADHD

Abstract

Background

While autism and attention-deficit/hyperactivity disorder (ADHD) are considered distinct conditions from a diagnostic perspective, clinically they share some phenotypic features and have high comorbidity. Regardless, most studies have focused on only one condition, with considerable heterogeneity in their results. Taking a dual-condition approach might help elucidate shared and distinct neural characteristics.

Method

Graph theory was used to analyse topological properties of structural covariance networks across both conditions and relative to a neurotypical (NT; n = 87) group using data from the ABIDE (autism; n = 62) and ADHD-200 datasets (ADHD; n = 69). Regional cortical thickness was used to construct the structural covariance networks. This was analysed in a theoretical framework examining potential differences in long and short-range connectivity, with a specific focus on relation between central graph measures and cortical thickness.

Results

We found convergence between autism and ADHD, where both conditions show an overall decrease in CT covariance with increased Euclidean distance between centroids compared with a NT population. The 2 conditions also show divergence. Namely, there is less modular overlap between the 2 conditions than there is between each condition and the NT group. The ADHD group also showed reduced cortical thickness and lower degree in hub regions than the autism group. Lastly, the ADHD group also showed reduced wiring costs compared with the autism groups.

Conclusions

Our results indicate a need for taking an integrated approach when considering highly comorbid conditions such as autism and ADHD. Furthermore, autism and ADHD both showed alterations in the relation between inter-regional covariance and centroid distance, where both groups show a steeper decline in covariance as a function of distance. The 2 groups also diverge on modular organization, cortical thickness of hub regions and wiring cost of the covariance network. Thus, on some network features the groups are distinct, yet on others there is convergence.

http://ift.tt/2rUUMe0

Places in the Brain: Bridging Layout and Object Geometry in Scene-Selective Cortex

Abstract

Diverse animal species primarily rely on sense (left–right) and egocentric distance (proximal–distal) when navigating the environment. Recent neuroimaging studies with human adults show that this information is represented in 2 scene-selective cortical regions—the occipital place area (OPA) and retrosplenial complex (RSC)—but not in a third scene-selective region—the parahippocampal place area (PPA). What geometric properties, then, does the PPA represent, and what is its role in scene processing? Here we hypothesize that the PPA represents relative length and angle, the geometric properties classically associated with object recognition, but only in the context of large extended surfaces that compose the layout of a scene. Using functional magnetic resonance imaging adaptation, we found that the PPA is indeed sensitive to relative length and angle changes in pictures of scenes, but not pictures of objects that reliably elicited responses to the same geometric changes in object-selective cortical regions. Moreover, we found that the OPA is also sensitive to such changes, while the RSC is tolerant to such changes. Thus, the geometric information typically associated with object recognition is also used during some aspects of scene processing. These findings provide evidence that scene-selective cortex differentially represents the geometric properties guiding navigation versus scene categorization.

http://ift.tt/2rpU0Cz

Specific Visual Subregions of TPJ Mediate Reorienting of Spatial Attention

Abstract

The temporo-parietal junction (TPJ) has been associated with various cognitive and social functions, and is critical for attentional reorienting. Attention affects early visual processing. Neuroimaging studies dealing with such processes have thus far concentrated on striate and extrastriate areas. Here, we investigated whether attention orienting or reorienting modulate activity in visually driven TPJ subregions. For each observer we identified 3 visually responsive subregions within TPJ: 2 bilateral (vTPJ_ant and vTPJ_post) and 1 right lateralized (vTPJ_cent). Cortical activity in these subregions was measured using fMRI while observers performed a 2-alternative forced-choice orientation discrimination task. Covert spatial endogenous (voluntary) or exogenous (involuntary) attention was manipulated using either a central or a peripheral cue with task, stimuli and observers constant. Both endogenous and exogenous attention increased activity for invalidly cued trials in right vTPJ_post; only endogenous attention increased activity for invalidly cued trials in left vTPJ_post and in right vTPJ_cent; and neither type of attention modulated either right or left vTPJ_ant. These results demonstrate that vTPJ_post and vTPJ_cent mediate the reorientation of covert attention to task relevant stimuli, thus playing a critical role in visual attention. These findings reveal a differential reorienting cortical response after observers' attention has been oriented to a given location voluntarily or involuntarily.

http://ift.tt/2rUYogm

Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: systematic review and meta-analysis

Abstract

Purpose

Non-alcoholic fatty liver disease (NAFLD) is an insidious pathologic condition that can manifest from simple steatosis to steatohepatitis (NASH) with potential progression to cirrhosis. Like the polycystic ovary syndrome (PCOS), NAFLD is associated with obesity, diabetes mellitus, insulin resistance and metabolic syndrome. PCOS women have an increased risk of NAFLD, but it is debatable which features of PCOS, either specific (androgen excess) or unspecific (metabolic derangements) affect the NAFLD risk.

Methods

We performed a systematic review and meta-analysis of studies that addressed the association of PCOS and NAFLD. We selected 17 studies published between 2007 and 2017 that included 2734 PCOS patients and 2561 controls of similar age and body mass index (BMI).

Results

PCOS patients have increased prevalence of NAFLD (odds ratio 2.54, 95% confidence interval 2.19–2.95). PCOS women with hyperandrogenism (classic phenotype) have a higher prevalence of NAFLD compared to women with PCOS without hyperandrogenism, even after correction for confounding variables. Among women with PCOS, those with NAFLD have higher serum total testosterone (mean difference 0.40 nmol/L, 95% CI 0.29–0.50 nmol/L) and free androgen index (mean difference 4.46, 95% CI 3.53–5.39) than those without NAFLD. The studies that used multivariate analysis controlling for age, BMI, triglycerides, and insulin resistance index confirmed that serum androgens are independent predictors of NAFLD in women with PCOS.

Conclusion

The prevalence of NAFLD is increased in women with PCOS and the presence of NAFLD is associated with high serum androgen levels, in addition to obesity and insulin resistance.

http://ift.tt/2rczzK5

Breast Implant Associated Anaplastic Large Cell Lymphoma: Impact and Implications

Publication date: Available online 12 June 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Lynda Wyld, Isabel T. Rubio




http://ift.tt/2svRZsQ

Molecular mechanisms of human papillomavirus-related carcinogenesis in head and neck cancer

Publication date: Available online 12 June 2017
Source:Microbes and Infection
Author(s): Farhoud Faraji, Munfarid Zaidi, Carole Fakhry, Daria A. Gaykalova
This review examines the general cellular and molecular underpinnings of human papillomavirus (HPV)-related carcinogenesis in the context of head and neck squamous cell carcinoma (HNSCC) and focuses on HPV-positive oropharyngeal squamous cell carcinoma in areas for which specific data is available. It covers the major pathways dysregulated in HPV-positive HNSCC and the genome-wide changes associated with this disease.



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An insight into the EANM technologist committee benchmark document on nuclear medicine technologists’ competencies

http://ift.tt/2s5561L

Is Usutu Virus Ready For Prime Time?

Publication date: Available online 12 June 2017
Source:Microbes and Infection
Author(s): Jason A. Tetro
Although considered a neglected tropical disease, the mosquitoborne Usutu virus has demonstrated signs of emergence from Africa to Europe. While human cases are infrequent, the potential for neuroinvasive infection, even in immunocompetent individuals, suggests a need for increased research into virus biology and pathogenesis, as well as rapid measures for diagnosis and environmental surveillance.



http://ift.tt/2rl9JY4

Superimposed effect of ovariectomy on type 2 diabetes mellitus in Wistar rats

Publication date: Available online 12 June 2017
Source:Alexandria Journal of Medicine
Author(s): Minerva K. Fahmy, Hayam G. Sayyed, Eman A. Abd Elrahim, Rana T.A. Farag
BackgroundEstrogen deprivation in the postmenopausal women plays a critical role in progression of type 2 diabetes mellitus (T2DM).AimThe present study investigated the overlaid effect of ovariectomy on T2DM and the possible underlying mechanism.MaterialsForty female Wistar rats were divided into four groups (10 rats each): sham control, ovariectomized control, sham diabetic and diabetic ovariectomized groups. At the end of experiment, estimation of body weight gain percentage, food intake, fasting blood glucose concentration, and insulin tolerance test were done. Then, rats were euthanized and blood samples were taken for measurement of serum concentration of insulin, HOMA-IR, lipid parameters, tumor necrosis factor-α, interleukin 1 beta, interleukin 4, interleukin 10, malondialdehyde and total thiol. Also, histopathological and immunohistochemical examination of the pancreas were done.ResultsThe present study revealed that ovariectomy aggravated the diabetic induced glucose metabolic disturbance as implied by impaired insulin tolerance test, increased insulin resistance alongside lipid dyshomeostasis. These metabolic disturbances might claim to exacerbation of oxidative stress and inflammatory response along with apparent histopathological and immunohistochemical changes on the pancreas.ConclusionWe concluded that metabolic disturbances induced by diabetes might be getting worse after ovariectomy via intensification of oxidative stress and inflammatory state.



http://ift.tt/2rcHwPd

At least eighty percent of brain grey matter is modifiable by physical activity: A review study

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Seyed Amir Hossein Batouli, Valiallah Saba
The human brain is plastic, i.e. it can show structural changes in response to the altered environment. Physical activity (PA) is a lifestyle factor which has significant associations with the structural and functional aspects of the human brain, as well as with the mind and body health. Many studies have reported regional/global brain volume increments due to exercising; however, a map which shows the overall extent of the influences of PAs on brain structure is not available. In this study, we collected all the reports on brain structural alterations in association with PA in healthy humans, and next, a brain map of the extent of these effects is provided. The results of this study showed that a large network of brain areas, equal to 82% of the total grey matter volume, were associated with PA. This finding has important implications in utilizing PA as a mediator factor for educational purposes in children, rehabilitation applications in patients, improving the cognitive abilities of the human brain such as in learning or memory, and preventing age-related brain deteriorations.



http://ift.tt/2sW1NK7

The effect of hippocampal NMDA receptor blockade by MK-801 on cued fear extinction

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Bo Zhang, Chuan-Yu Li, Xiu-Song Wang
Extinction of conditioned fear has been suggested to be a new form of learning instead of erasure of what was originally learned, and the process is NMDA (N-methyl d-aspartate) receptor (NMDAR) dependent. Most of studies have so far revealed the important roles of NMDARs in the amygdala and medial prefrontal cortex (mPFC) in cued fear extinction. Although the ventral hippocampus has intimately reciprocal connections with the amygdala and mPFC, the role of its NMDARs in cued fear extinction remains unclear. The present experiment explored the issue by bilateral pre-extinction microinjection of the noncompetitive NMDAR antagonist MK-801 into the ventral hippocampus. Four groups of rats were given habituation, tone cued fear conditioning, fear extinction training and extinction test. Prior to extinction training, rats received bilateral infusions of either MK-801 (1.5, 3, or 6μg/0.5μl) or saline. Our results showed that MK-801 reduced freezing on the first trial of extinction training with no impact on within-session acquisition of extinction, and that the lower doses of MK-801 resulted in increased freezing on the extinction retrieval test. These findings suggest that ventral hippocampal NMDARs are necessary for the consolidation of tone cued fear extinction.



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Perspectives on the Overall Risks of Living With Hypertrophic Cardiomyopathy.

Author: Maron, Barry J. MD; Maron, Martin S. MD; Rowin, Ethan J. MD

Page: 2317-2319

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Prognostic Value of Noninvasive Cardiovascular Testing in Patients With Stable Chest Pain: Insights From the PROMISE Trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain).

Author: Hoffmann, Udo MD, MPH; Ferencik, Maros MD, PhD; Udelson, James E. MD; Picard, Michael H. MD; Truong, Quynh A. MD, MPH; Patel, Manesh R. MD; Huang, Megan PhD; Pencina, Michael PhD; Mark, Daniel B. MD, MPH; Heitner, John F. MD; Fordyce, Christopher B. MD; Pellikka, Patricia A. MD; Tardif, Jean-Claude MD; Budoff, Matthew MD; Nahhas, George MD; Chow, Benjamin MD; Kosinski, Andrzej S. PhD; Lee, Kerry L. PhD; Douglas, Pamela S. MD; on behalf of the PROMISE Investigators

Page: 2320-2332

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New Promises for Refining Risk Stratification From Anatomical and Functional Assessment of Stable Chest Pain.

Author: Shaw, Leslee J. PhD; Mancini, G.B. John MD

Page: 2333-2335

http://ift.tt/2smzCqN

Loss of Cardioprotective Effects at the ADAMTS7 Locus as a Result of Gene-Smoking Interactions.

Author: Saleheen, Danish MBBS, PhD; Zhao, Wei MSc; Young, Robin PhD; Nelson, Christopher P. PhD; Ho, WeangKee PhD; Ferguson, Jane F. PhD; Rasheed, Asif MBBS; Ou, Kristy BS; Nurnberg, Sylvia T. PhD; Bauer, Robert C. PhD; Goel, Anuj MS; Do, Ron PhD; Stewart, Alexandre F.R. PhD; Hartiala, Jaana PhD; Zhang, Weihua PhD; Thorleifsson, Gudmar PhD; Strawbridge, Rona J. PhD; Sinisalo, Juha PhD; Kanoni, Stavroula PhD; Sedaghat, Sanaz PhD; Marouli, Eirini PhD; Kristiansson, Kati PhD; Hua Zhao, Jing PhD; Scott, Robert PhD; Gauguier, Dominique PhD; Shah, Svati H. MD; Smith, Albert Vernon PhD; van Zuydam, Natalie PhD; Cox, Amanda J. PhD; Willenborg, Christina PhD; Kessler, Thorsten MD; Zeng, Lingyao PhD; Province, Michael A. PhD; Ganna, Andrea PhD; Lind, Lars PhD; Pedersen, Nancy L. PhD; White, Charles C. PhD; Joensuu, Anni MSc; Edi Kleber, Marcus PhD; Hall, Alistair S. PhD; Marz, Winfried PhD; Salomaa, Veikko PhD; O'Donnell, Christopher MD; Ingelsson, Erik PhD; Feitosa, Mary F. PhD; Erdmann, Jeanette PhD; Bowden, Donald W. PhD; Palmer, Colin N.A. PhD; Gudnason, Vilmundur PhD; Faire, Ulf De PhD; Zalloua, Pierre PhD; Wareham, Nicholas PhD; Thompson, John R. PhD; Kuulasmaa, Kari PhD; Dedoussis, George PhD; Perola, Markus PhD; Dehghan, Abbas PhD; Chambers, John C. PhD; Kooner, Jaspal MD; Allayee, Hooman PhD; Deloukas, Panos PhD; McPherson, Ruth PhD; Stefansson, Kari PhD; Schunkert, Heribert MD; Kathiresan, Sekar MD; Farrall, Martin PhD; EPIC-CVD; Marcel Frossard, Philippe DSC; Rader, Daniel J. MD; Samani, Nilesh J. MD; PROMIS; CARDIoGRAMplusC4D; Reilly, Muredach P. MD.

Page: 2336-2353

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Holy Smokes-An Interaction!

Author: Mitchell, Braxton D. MPH, PhD

Page: 2354-2356

http://ift.tt/2smREt6

Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of Age: Cohort Study Using Electronic Health Records.

Author: Ravindrarajah, Rathi PhD; Hazra, Nisha C. MSc; Hamada, Shota DrPH; Charlton, Judith MSc; Jackson, Stephen H.D. MD; Dregan, Alex PhD; Gulliford, Martin C. MA

Page: 2357-2368

http://ift.tt/2sWsPRO

Reverse Causality in Cardiovascular Epidemiological Research: More Common Than Imagined?.

Author: Sattar, Naveed MD, PhD; Preiss, David MD, PhD

Page: 2369-2372

http://ift.tt/2smOpBO

Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.

Author: Dale, Caroline E. PhD *; Fatemifar, Ghazaleh PhD *; Palmer, Tom M. PhD; White, Jon PhD; Prieto-Merino, David PhD; Zabaneh, Delilah PhD; Engmann, Jorgen E.L. MSc; Shah, Tina PhD; Wong, Andrew PhD; Warren, Helen R. PhD; McLachlan, Stela PhD; Trompet, Stella PhD; Moldovan, Max PhD; Morris, Richard W. PhD; Sofat, Reecha MRCP; Kumari, Meena PhD; Hypponen, Elina PhD; Jefferis, Barbara J. PhD; Gaunt, Tom R. PhD; Ben-Shlomo, Yoav PhD; Zhou, Ang PhD; Gentry-Maharaj, Aleksandra PhD; Ryan, Andy PhD; UCLEB Consortium; METASTROKE Consortium; Mutsert, Renee de PhD; Noordam, Raymond PhD; Caulfield, Mark J. MBBS, MD; Jukema, J. Wouter MD, PhD; Worrall, Bradford B. MD, MSc; Munroe, Patricia B. PhD; Menon, Usha FRCOG, MD (Res); Power, Chris PhD; Kuh, Diana PhD; Lawlor, Debbie A. PhD; Humphries, Steve E. PhD; Mook-Kanamori, Dennis O. MD, PhD; Sattar, Naveed MD, PhD; Kivimaki, Mika PhD; Price, Jacqueline F. MD; Davey Smith, George DSc; Dudbridge, Frank PhD; Hingorani, Aroon D. MD, PhD; Holmes, Michael V. MD, PhD +; Casas, Juan P. MD, PhD +

Page: 2373-2388

http://ift.tt/2sW3Bmz

Ischemic Cerebroprotection Conferred by Myeloid Lineage-Restricted or Global CD39 Transgene Expression.

Author: Baek, Amy E. PhD; Sutton, Nadia R. MD; Petrovic-Djergovic, Danica MD, PhD; Liao, Hui MD; Ray, Jessica J. BA; Park, Joan BA; Kanthi, Yogendra MD; Pinsky, David J. MD

Page: 2389-2402

http://ift.tt/2smLY1V

A MicroRNA93-Interferon Regulatory Factor-9-Immunoresponsive Gene-1-Itaconic Acid Pathway Modulates M2-Like Macrophage Polarization to Revascularize Ischemic Muscle.

Author: Ganta, Vijay Chaitanya PhD; Choi, Min Hyub BS; Kutateladze, Anna BS; Fox, Todd E. PhD; Farber, Charles R. PhD; Annex, Brian H. MD

Page: 2403-2425

http://ift.tt/2sWE5NS

Pathophysiology of Takotsubo Syndrome.

Author: Pelliccia, Francesco MD, PhD; Kaski, Juan Carlos MD; Crea, Filippo MD; Camici, Paolo G. MD

Page: 2426-2441

http://ift.tt/2smLWqP

Cardiopulmonary Resuscitation in Adults and Children With Mechanical Circulatory Support: A Scientific Statement From the American Heart Association.

Author: Peberdy, Mary Ann MD, FAHA, Co-Chair; Gluck, Jason A. DO, Co-Chair; Ornato, Joseph P. MD, FAHA; Bermudez, Christian A. MD; Griffin, Russell E. LP, FP-C; Kasirajan, Vigneshwar MD; Kerber, Richard E. MD, FAHA +; Lewis, Eldrin F. MD, MPH, FAHA; Link, Mark S. MD; Miller, Corinne RN; Teuteberg, Jeffrey J. MD; Thiagarajan, Ravi MD, MPH; Weiss, Robert M. MD; O'Neil, Brian MD; On behalf of the American Heart Association Emergency Cardiovascular Care Committee; Council on Cardiopulmonary, Critical Care, Perioperative, and Resuscitation; Council on Cardiovascular Diseases in the Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology

Page: e1115-e1134

http://ift.tt/2sWyOWE

From the Literature.

Author: Hampton, Tracy PhD

Page: 2442-2443

http://ift.tt/2smOpli

How Pregnancy Impacts Adult Cyanotic Congenital Heart Disease: A Multicenter Observational Study.

Author: Ladouceur, Magalie MD, PhD; Benoit, Louise; Basquin, Adeline MD; Radojevic, Jelena MD; Hauet, Quentin MD; Hascoet, Sebastien MD; Moceri, Pamela MD, PhD; Le Gloan, Laurianne MD; Amedro, Pascal MD, PhD; Lucron, Hugues MD; Richard, Adelaide MD; Gouton, Marielle MD; Nizard, Jacky MD, PhD

Page: 2444-2447

http://ift.tt/2sWhalX

Targeting Cadherin-11 Prevents Notch1-Mediated Calcific Aortic Valve Disease.

Author: Clark, Cynthia R. PhD; Bowler, Meghan A. BS; Snider, J. Caleb BS; Merryman, W. David PhD

Page: 2448-2450

http://ift.tt/2smZuma

Letter by Stamler et al Regarding Article, "Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia".

Author: Stamler, Jonathan S. MD; Reynolds, James D. PhD; Hess, Douglas T. PhD

Page: e1135-e1136

http://ift.tt/2sWkkG4

Response by Bailey to Letter Regarding Article, "Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia".

Author: Bailey, Damian M. PhD

Page: e1137-e1138

http://ift.tt/2smKNjj

Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.

Author: Dale, Caroline E. PhD *; Fatemifar, Ghazaleh PhD *; Palmer, Tom M. PhD; White, Jon PhD; Prieto-Merino, David PhD; Zabaneh, Delilah PhD; Engmann, Jorgen E.L. MSc; Shah, Tina PhD; Wong, Andrew PhD; Warren, Helen R. PhD; McLachlan, Stela PhD; Trompet, Stella PhD; Moldovan, Max PhD; Morris, Richard W. PhD; Sofat, Reecha MRCP; Kumari, Meena PhD; Hypponen, Elina PhD; Jefferis, Barbara J. PhD; Gaunt, Tom R. PhD; Ben-Shlomo, Yoav PhD; Zhou, Ang PhD; Gentry-Maharaj, Aleksandra PhD; Ryan, Andy PhD; UCLEB Consortium; METASTROKE Consortium; Mutsert, Renee de PhD; Noordam, Raymond PhD; Caulfield, Mark J. MBBS, MD; Jukema, J. Wouter MD, PhD; Worrall, Bradford B. MD, MSc; Munroe, Patricia B. PhD; Menon, Usha FRCOG, MD (Res); Power, Chris PhD; Kuh, Diana PhD; Lawlor, Debbie A. PhD; Humphries, Steve E. PhD; Mook-Kanamori, Dennis O. MD, PhD; Sattar, Naveed MD, PhD; Kivimaki, Mika PhD; Price, Jacqueline F. MD; Davey Smith, George DSc; Dudbridge, Frank PhD; Hingorani, Aroon D. MD, PhD; Holmes, Michael V. MD, PhD +; Casas, Juan P. MD, PhD +

Page: 2373-2388

http://ift.tt/2sW3Bmz

Ischemic Cerebroprotection Conferred by Myeloid Lineage-Restricted or Global CD39 Transgene Expression.

Author: Baek, Amy E. PhD; Sutton, Nadia R. MD; Petrovic-Djergovic, Danica MD, PhD; Liao, Hui MD; Ray, Jessica J. BA; Park, Joan BA; Kanthi, Yogendra MD; Pinsky, David J. MD

Page: 2389-2402

http://ift.tt/2smLY1V

A MicroRNA93-Interferon Regulatory Factor-9-Immunoresponsive Gene-1-Itaconic Acid Pathway Modulates M2-Like Macrophage Polarization to Revascularize Ischemic Muscle.

Author: Ganta, Vijay Chaitanya PhD; Choi, Min Hyub BS; Kutateladze, Anna BS; Fox, Todd E. PhD; Farber, Charles R. PhD; Annex, Brian H. MD

Page: 2403-2425

http://ift.tt/2sWE5NS

Pathophysiology of Takotsubo Syndrome.

Author: Pelliccia, Francesco MD, PhD; Kaski, Juan Carlos MD; Crea, Filippo MD; Camici, Paolo G. MD

Page: 2426-2441

http://ift.tt/2smLWqP

Cardiopulmonary Resuscitation in Adults and Children With Mechanical Circulatory Support: A Scientific Statement From the American Heart Association.

Author: Peberdy, Mary Ann MD, FAHA, Co-Chair; Gluck, Jason A. DO, Co-Chair; Ornato, Joseph P. MD, FAHA; Bermudez, Christian A. MD; Griffin, Russell E. LP, FP-C; Kasirajan, Vigneshwar MD; Kerber, Richard E. MD, FAHA +; Lewis, Eldrin F. MD, MPH, FAHA; Link, Mark S. MD; Miller, Corinne RN; Teuteberg, Jeffrey J. MD; Thiagarajan, Ravi MD, MPH; Weiss, Robert M. MD; O'Neil, Brian MD; On behalf of the American Heart Association Emergency Cardiovascular Care Committee; Council on Cardiopulmonary, Critical Care, Perioperative, and Resuscitation; Council on Cardiovascular Diseases in the Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology

Page: e1115-e1134

http://ift.tt/2sWyOWE

From the Literature.

Author: Hampton, Tracy PhD

Page: 2442-2443

http://ift.tt/2smOpli

How Pregnancy Impacts Adult Cyanotic Congenital Heart Disease: A Multicenter Observational Study.

Author: Ladouceur, Magalie MD, PhD; Benoit, Louise; Basquin, Adeline MD; Radojevic, Jelena MD; Hauet, Quentin MD; Hascoet, Sebastien MD; Moceri, Pamela MD, PhD; Le Gloan, Laurianne MD; Amedro, Pascal MD, PhD; Lucron, Hugues MD; Richard, Adelaide MD; Gouton, Marielle MD; Nizard, Jacky MD, PhD

Page: 2444-2447

http://ift.tt/2sWhalX

Targeting Cadherin-11 Prevents Notch1-Mediated Calcific Aortic Valve Disease.

Author: Clark, Cynthia R. PhD; Bowler, Meghan A. BS; Snider, J. Caleb BS; Merryman, W. David PhD

Page: 2448-2450

http://ift.tt/2smZuma

Letter by Stamler et al Regarding Article, "Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia".

Author: Stamler, Jonathan S. MD; Reynolds, James D. PhD; Hess, Douglas T. PhD

Page: e1135-e1136

http://ift.tt/2sWkkG4

Response by Bailey to Letter Regarding Article, "Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia".

Author: Bailey, Damian M. PhD

Page: e1137-e1138

http://ift.tt/2smKNjj

Letter by Roozenbeek et al Regarding Article, "Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials".

Author: Roozenbeek, Bob MD, PhD; Dippel, Diederik W.J. MD, PhD; Lingsma, Hester F. PhD

Page: e1139-e1140

http://ift.tt/2sWoVrS

Response by Bivard et al to Letter Regarding Article, "Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials".

Author: Bivard, Andrew PhD; Muir, Keith MD; Parsons, Mark PhD

Page: e1141-e1142

http://ift.tt/2smOp4M

Correction to: Part 9: First Aid: 2015 International Consensus on First Aid Science With Treatment Recommendations.

Author:

Page: e1143

http://ift.tt/2sWp8eF

Analysis of the use of the IAEA rapid method of 89Sr and 90Sr in milk for environmental monitoring

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): M. Herranz, R. Idoeta, S. Rozas, F. Legarda
Rapid methods that are used during nuclear accidents or incident situations must first be implemented and validated in radioactivity measurement laboratories, so they can be ready to provide quick answers to governments, regulatory organizations and people in such situations. As these accident situations are rare and the methods are thus not frequently used, the best way to achieve this is to use the same methods for both routine environmental monitoring and rapid or emergency situations. Before this can be done, however, an analysis of the conditions under which a rapid method could be effectively used in routine situations should be carried out.This work analyses the performance of the rapid method for the simultaneous determination of ⁸⁹Sr and ⁹⁰Sr in milk, published by the IAEA, and compares it with another, more conventional method used for routine environmental purposes.Through numerical calculations and considering different ⁸⁹Sr and ⁹⁰Sr activities, we also conducted a study to obtain the optimum values for determination parameters – such as sample mass, counting times, time lapse between measurements and background counting times – that will allow the use of the IAEA rapid method as a routine environmental one.



http://ift.tt/2smhDkd

Radiocesium decontamination of a riverside in Fukushima, Japan

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): Tatsuhiro Nishikiori, Satoshi Suzuki
Extensive decontamination measures have been implemented in the area affected by the Fukushima Dai-ichi nuclear disaster. Typical decontamination measures, such as removing topsoil of several centimeters in depth, are not suitable for rivers where contaminated sediments have been deposited. A decontamination measure was tested that considered the spatial distribution of radiocesium at the lower part of a tributary of the Abukuma River in Fukushima. The radiocesium distribution in the flood channel was vertically and horizontally highly heterogeneous. In some parts, the activity concentration was high (>10 kBq/kg for ¹³⁷Cs) even at depths of 25 cm in the sediment. This may be due to plant growth in the flood channel favoring the deposition of sediment with high activity concentration. On the basis of the radiocesium distribution, the flood channel sediment was removed to a depth of 15–35 cm, which accumulated the most radiocesium (>3.0 kBq/kg for the sum of ¹³⁴Cs and ¹³⁷Cs). The upper 5 cm of soil was removed from the dike slopes. The river bed was not decontaminated because the activity concentration was low (<1 kBq/kg) in the river bed sediment and because the water shields gamma rays emitted from the sediment. The test decontamination measure reduced the air dose rate by a factor of approximately two, demonstrating the effectiveness of our measures. Annual external doses were calculated for when this part of the dike and the flood channel is used for commuting to school and outdoor education. The doses during the activities at the test site accounted for only 1–2% of the value during daily life in the surrounding area, indicating that radiation exposure during riverside activities is limited.



http://ift.tt/2rpkfsw

On the Receiving End of Autonomy and Law

http://ift.tt/2shEIDV

Patient‐Driven Second Opinions in Oncology: A Systematic Review

AbstractBackground.Although patient‐driven second opinions are increasingly sought in oncology, the desirability of this trend remains unknown. Therefore, this systematic review assesses evidence on the motivation for and frequency of requests for second opinions and examines how they evolve and their consequences for oncological practice.Materials and Methods.Relevant databases were sought using the terms "cancer," "second opinion," and "self‐initiated." Included were peer‐reviewed articles that reported on patient‐initiated second opinions within oncology. Selection, data extraction, and quality assessment were performed and discussed by two researchers.Results.Of the 25 included studies, the methodological designs were qualitative (n = 4), mixed (n = 1), or quantitative (n = 20). Study quality was rated high for 10 studies, moderate for eight, and low for seven studies. Reported rates of second opinion seeking ranged from 1%–88%. Higher education was most consistently related to seeking a second opinion. Patients' primary motivations were a perceived need for certainty or confirmation, a lack of trust, dissatisfaction with communication, and/or a need for more (personalized) information. Reported rates of diagnostic or therapeutic discrepancies between the first and second opinions ranged from 2%–51%.Discussion.Additional studies are required to further examine the medical, practical, and psychological consequences of second opinions for patients and oncologists. Future studies could compare the potential advantages and disadvantages of second opinion seeking, and might offer guidance to patients and physicians to better facilitate the second opinion process. Some practical recommendations are provided for oncologists to optimally discuss and conduct second opinions with their patients.Implications for Practice.Although cancer patients increasingly seek a second opinion, the benefits of this process remain unclear. Results of this systematic review suggest that the available studies on this topic are highly variable in both methodology and quality. Moreover, reported rates for a second opinion (1%–88%) as well as for disagreement between the first and second opinion (2%–51%) range widely. The primary motivations of patients are a need for certainty, lack of trust, dissatisfaction with communication, and/or a need for more (personalized) information. Additional research should evaluate how unnecessary second opinions might be avoided. Practical suggestions are provided for oncologists to optimize second opinions.

http://ift.tt/2tfm90c

Psychosocial and Aesthetic Advantages of Reconstruction after Prophylactic Mastectomy: A Quality of Life and Aesthetic Analysis

J reconstr Microsurg
DOI: 10.1055/s-0037-1602785

Background Proper patient counseling regarding reconstruction after prophylactic mastectomy (PM) requires greater understanding of quality of life (QoL) and aesthetic outcomes. Our study evaluates these end points using the validated BREAST-Q and Garbay system. Methods We performed a retrospective chart review of 1,254 mastectomy patients (July 2008 through July 2012). Of those with completed preoperative BREAST-Q and reconstruction with a minimum of 6-month follow-up, 18 underwent bilateral PM (BPM), 36 underwent contralateral PM (CPM), and 30 matched controls were selected who underwent unilateral therapeutic mastectomy (TM) with contralateral symmetry procedure. Preoperative and 6-month postreconstruction BREAST-Q scores were compared within and between groups. Subsequently, aesthetic evaluation of 21 of a group of randomly selected reconstructions (7 TM, 7 CPM, and 7 BPM) was performed by 14 plastic surgery researchers. Potential correlations between aesthetic evaluations and QoL outcomes were examined. Results Demographic characteristics, preoperative satisfaction scores, and postoperative morbidity rates were similar among all three groups. Although reconstruction after BPM was associated with improved aesthetic outcomes (p < 0.001), a significant postoperative increase in satisfaction with breasts was noted only in the TM group (p = 0.006). CPM was associated with improved psychosocial well-being (p = 0.039) in our study. No further significant differences were noted. Conclusion Although BPM with reconstruction is associated with higher aesthetic outcomes compared with CPM or TM, QoL is not significantly increased. Reconstruction after CPM, but not BPM, is associated with increased psychosocial well-being. These valuable findings should be taken into account during preoperative counseling regarding elective PMs.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2s4TcF0

The innovative concept of three-dimensional hybrid receptor modeling

Publication date: September 2017
Source:Atmospheric Environment, Volume 164
Author(s): A. Stojić, S. Stanišić Stojić
The aim of this study was to improve the current understanding of air pollution transport processes at regional and long-range scale. For this purpose, three-dimensional (3D) potential source contribution function and concentration weighted trajectory models, as well as new hybrid receptor model, concentration weighted boundary layer (CWBL), which uses a two-dimensional grid and a planetary boundary layer height as a frame of reference, are presented. The refined approach to hybrid receptor modeling has two advantages. At first, it considers whether each trajectory endpoint meets the inclusion criteria based on planetary boundary layer height, which is expected to provide a more realistic representation of the spatial distribution of emission sources and pollutant transport pathways. Secondly, it includes pollutant time series preprocessing to make hybrid receptor models more applicable for suburban and urban locations. The 3D hybrid receptor models presented herein are designed to identify altitude distribution of potential sources, whereas CWBL can be used for analyzing the vertical distribution of pollutant concentrations along the transport pathway.



http://ift.tt/2s4zr0m

Simulated nutrient dissolution of Asian aerosols in various atmospheric waters: Potential links to marine primary productivity

Publication date: September 2017
Source:Atmospheric Environment, Volume 164
Author(s): Lingyan Wang, Yanfeng Bi, Guosen Zhang, Sumei Liu, Jing Zhang, Zhaomeng Xu, Jingling Ren, Guiling Zhang
To probe the bioavailability and environmental mobility of aerosol nutrient elements (N, P, Si) in atmospheric water (rainwater, cloud and fog droplets), ten total suspended particulate (TSP) samples were collected at Fulong Mountain, Qingdao from prevailing air mass trajectory sources during four seasons. Then, a high time-resolution leaching experiment with simulated non-acidic atmospheric water (non-AAW, Milli-Q water, pH 5.5) and subsequently acidic atmospheric water (AAW, hydrochloric acid solution, pH 2) was performed. We found that regardless of the season or source, a monotonous decreasing pattern was observed in the dissolution of N, P and Si compounds in aerosols reacted with non-AAW, and the accumulated dissolved curves of P and Si fit a first-order kinetic model. No additional NO3⁻ + NO2⁻ dissolved out, while a small amount of NH4⁺ in Asian dust (AD) samples was released in AAW. The similar dissolution behaviour of P and Si from non-AAW to AAW can be explained by the Transition State Theory. The sources of aerosols related to various minerals were the natural reasons that affected the amounts of bioavailable phosphorus and silicon in aerosols (i.e., solubility), which can be explained by the dissolution rate constant of P and Si in non-AAW with lower values in mineral aerosols. The acid/particle ratio and particle/liquid ratio also have a large effect on the solubility of P and Si, which was implied by Pearson correlation analysis. Acid processing of aerosols may have great significance for marine areas with limited P and Si and post-acidification release increases of 1.1–10-fold for phosphorus and 1.2–29-fold for silicon. The decreasing mole ratio of P and Si in AAW indicates the possibility of shifting from a Si-limit to a P-limit in aerosols in the ocean, which promotes the growth of diatoms prior to other algal species.



http://ift.tt/2rkj6at

Effects of industrial and agricultural waste amendment on soil greenhouse gas production in a paddy field in Southeastern China

Publication date: September 2017
Source:Atmospheric Environment, Volume 164
Author(s): Weiqi Wang, Suvadip Neogi, Derrick Y.F. Lai, Congsheng Zeng, Chun Wang, Dongping Zeng
Controlling the production and subsequent emissions of greenhouse gases (GHGs) from paddy fields is crucial to minimize the climatic impacts arising from crop production. The application of chemical or biological amendments is one possible way to limit the production of GHGs in paddy soils. Yet, few existing studies have examined the impacts of applying fertilizers originated from industrial and agricultural wastes on soil GHG production and its governing factors in subtropical paddy fields. In this study, we examined the effects of various agricultural and industrial amendments, including biochar, steel slag, shell slag, gypsum slag, and slag-derived silicate and calcium fertilizers, on the production potential of GHGs in an early paddy field in southeast China. The mean CO2 production rates from soils amended with steel slag as well as silicate and calcium fertilizers were significantly higher than those of the controls by 13.4% and 18.6%, respectively (P < 0.05). Mean soil CH4 production rates from the plots amended with steel slag, biochar, shell slag, and gypsum slag were significantly lower than those of the controls by 42.5%, 36.1%, 60.8%, and 61.8%, respectively (P < 0.05). Meanwhile, we found no significant difference in mean soil N2O production rates between the control and any of the treatments (P > 0.05). Overall, the soil production rate of CO2 was positively correlated with that of CH4 (P < 0.05), but negatively correlated with that of N2O (P < 0.05). When compared to the controls, the ratio of soil CO2:CH4 production increased significantly in the plots receiving biochar, and silicate and calcium fertilizer amendments (P < 0.05), while that of CO2:N2O production increased significantly only in the biochar-amended plots. Soil CH4:N2O production ratio decreased significantly in the plots amended with steel slag and gypsum slag, as compared to the controls (P < 0.05). Our results suggest that the application of biochar, shell slag and gypsum slag would help reduce greenhouse gas production and mitigate climate change impacts of rice cultivation, largely attributable to the reduction in methanogenesis.



http://ift.tt/2rkZfrN

Topographically-controlled site conditions drive vegetation pattern on inland dunes in Poland

Publication date: July 2017
Source:Acta Oecologica, Volume 82
Author(s): Piotr Sewerniak, Michał Jankowski
The inland dunes of Central Europe are commonly overplanted by Scots pine (Pinus sylvestris) monocultures in which the primary occurrence of the natural vegetation pattern is obliterated. We hypothesize that on naturally revegetated inland dunes the pattern is clear and driven by topographically-controlled site conditions. To test this hypothesis, we addressed the following research questions: (1) Does topography drive vegetation patterns on inland dunes and if so, what are main differences between vegetation in varying relief positions? (2) To what extent does topography involve the variability of microclimates and of soil properties, and how does the topographically-induced differentiation of these site conditions control vegetation patterns? We conducted interdisciplinary studies (applying floristic, pedological and microclimatic research techniques) on a naturally revegetated inland dune area situated on a military artillery training ground near Toruń, northern Poland. We investigated vegetation patterns with reference to three topographical position variants (north-facing slopes, south-facing slopes, and intra-dune depressions). We found distinct differences in vegetation characteristics covering the aforementioned topographical positions. This primarily concerned species composition of ground vegetation: Calluna vulgaris was dominant species on north-facing slopes, Corynephorus canescens on south-facing slopes, while Calamagrostis epigejos in intra-dune depressions. In comparison to dune slopes, the depressions were characterized by much higher biodiversity of vascular plant species. This followed the most favorable soil conditions for the existence of plants (higher moisture and nutrient pools) occurring in low topographical positions. However, tree succession was most advanced not in depressions, where the competitive impact of tall grasses on seedlings was recognized, but on north-facing slopes. Based on our results, we formulated some suggestions, which could be useful for both practical foresters to increase biodiversity of ecosystems and for practices that work on the fixation of dunes by restoring vegetation.



http://ift.tt/2svgczz

Effects of temporally biased watering on the nitrogen response of Chenopodium album

Publication date: July 2017
Source:Acta Oecologica, Volume 82
Author(s): Toshihiko Kinugasa, Yumi Hozumi
Plant growth responses to an increasing N deposition are stimulated by an increase in annual precipitation, but such a stimulation has not always been found. We hypothesized that the effect of precipitation on plant N responses can change with temporally biased precipitation: a plant N response will be suppressed when precipitation is lower in the late growing period because larger plants are more susceptible to water limitations. We grew Chenopodium album under a high and low N application level with three watering patterns while maintaining the total supplied watering amount during the experimental period: constant watering, low watering in the first period and high watering in the latter period, and high watering in the first period and low watering in the latter period. The watering pattern did not affect plant dry mass under low N conditions. The plant dry mass under high N conditions was reduced by low watering in the first period, but the reduction was fully compensated in the subsequent high watering period by the stimulation of photosynthesis. Low watering following high watering under high N conditions did not suppress plant growth, but partial leaf wilting was observed at the end of the experimental period. Finally, at the end of the experiment, the response of plant dry mass to N was not different among the watering patterns. We concluded that a plant's response to increasing N deposition could be affected by temporally biased precipitation, depending on the scale of the precipitation bias and the ability of the plant to compensate or mitigate growth inhibition due to a water deficit. Precipitation deficits later in the growing period may be more detrimental to plant growth and can reduce plant responses to an increasing N deposition.



http://ift.tt/2rcgwzk

Distress and everyday problems in Dutch mothers and fathers of young adolescents with Down syndrome

Publication date: August 2017
Source:Research in Developmental Disabilities, Volume 67
Author(s): Jan Pieter Marchal, Hedy A. van Oers, Heleen Maurice-Stam, Martha A. Grootenhuis, A.S. Paul van Trotsenburg, Lotte Haverman
BackgroundTo provide targeted support to parents of children with DS, knowledge of their distress and everyday problems is crucial. For this purpose, psychosocial screening instruments can be a valuable addition to routine clinical practice.AimsTo determine differences on a psychosocial screener concerning distress and everyday problems in parents of young adolescents (YAs) with DS versus control parents and in mothers of YAs with DS versus fathers.Methods and proceduresWe compared outcomes of the Distress Thermometer for Parents in 76 mothers and 44 fathers of 11–13-year-olds with DS versus 64 mothers and 52 fathers of age-matched children without DS (comparing mothers and fathers separately). Additionally, we compared mothers and fathers within 34 parent couples of YAs with DS.Outcomes and resultsClinical distress was not more frequent than in control parents. Mothers further did not report more everyday problems and only differed from their controls on one problem domain and some problem items. Fathers, however, reported more problems than their controls across most domains and wished to talk to a professional about their situation more frequently. Outcomes in mothers and fathers within parent couples did not differ significantly.Conclusions and implicationsThis is one of few studies to report on the use of psychosocial screening instruments in parents of children with DS. Our results suggested that attention for fathers of YAs with DS is required. Psychosocial screening instruments that inquire about specific problems and the wish for referral can play an important role in achieving this.



http://ift.tt/2smASdF

JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin

Abstract

Purpose

Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells.

Methods

The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species.

Results

We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production.

Conclusions

JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

http://ift.tt/2s4Dwl1

Your help changes the future of thyroid disease – Make a spring donation to the ATA!

This spring, we would like to extend a note of thanks to all the Friends of the American Thyroid Association (ATA.) We are grateful that you have chosen to be part of the ATA community.

It is our mission and privilege to provide reliable thyroid education and awareness information, patient care resources, and research grants to help you and all those patients and families who seek answers, information, and guidance on thyroid conditions and treatments. Read more

The post Your help changes the future of thyroid disease – Make a spring donation to the ATA! appeared first on American Thyroid Association.

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A case of cystic type intraductal papillary neoplasm of the bile duct diagnosed by SpyGlass DS, a novel peroral cholangioscopy

Publication date: Available online 12 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Takeshi Kuwada, Masahiro Shiokawa, Norimitsu Uza, Yuzo Kodama




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The G-BHQ synergistic effect: Improved double quenching molecular beacons based on guanine and Black Hole Quencher for sensitive simultaneous detection of two DNAs

Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Dongshan Xiang, Fengquan Li, Chenyi Wu, Boan Shi, Kun Zhai
We designed two double quenching molecular beacons (MBs) with simple structure based on guanine (G base) and Black Hole Quencher (BHQ), and developed a new analytical method for sensitive simultaneous detection of two DNAs by synchronous fluorescence analysis. In this analytical method, carboxyl fluorescein (FAM) and tetramethyl-6-carboxyrhodamine (TAMRA) were respectively selected as fluorophore of two MBs, Black Hole Quencher 1 (BHQ-1) and Black Hole Quencher 2 (BHQ-2) were respectively selected as organic quencher, and three continuous nucleotides with G base were connected to organic quencher (BHQ-1 and BHQ-2). In the presence of target DNAs, the two MBs hybridize with the corresponding target DNAs, the fluorophores are separated from organic quenchers and G bases, leading to recovery of fluorescence of FAM and TAMRA. Under a certain conditions, the fluorescence intensities of FAM and TAMRA all exhibited good linear dependence on their concentration of target DNAs (T1 and T2) in the range from 4 × 10⁻¹⁰ to 4 × 10⁻⁸molL⁻¹ (M). The detection limit (3σ, n = 13) of T1 was 3 × 10⁻¹⁰M and that of T2 was 2×10⁻¹⁰M, respectively. Compared with the existing analysis methods for multiplex DNA with MBs, this proposed method based on double quenching MBs is not only low fluorescence background, short analytical time and low detection cost, but also easy synthesis and good stability of MB probes.

Graphical abstract

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Application of headspace and direct immersion solid-phase microextraction in the analysis of organothiophosphates related to the Chemical Weapons Convention from water and complex matrices

Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Marc André Althoff, Andreas Bertsch, Manfred Metzulat, Thomas M. Klapötke, Konstantin L. Karaghiosoff
The successful application of headspace (HS) and direct immersion (DI) solid phase microextraction (SPME) for the unambiguous identification and characterization of a series of toxic thiophosphate esters, such as Amiton (I), from aqueous phases and complex matrices (e.g. grass and foliage) has been demonstrated. A Thermo Scientific gas chromatograph (GC) – tandem mass spectrometer (MS/MS) system with a TriPlus RSH® autosampler and a SPME tool was used to investigate the effect of different parameters that influence the extraction efficiency: e.g. pH of the sample matrix and extraction temperature.The developed methods were employed for the detection of several Amiton derivatives (Schedule II of the CWC) that are structurally closely related to each other; some of which are new and have not been reported in literature previously. In addition, a novel DI SPME method from complex matrices for the analysis of organophosphates related to the CWC was developed. The studies clearly show that DI SPME for complex matrices is superior to HS extraction and can potentially be applied to other related compounds controlled under the CWC.

Graphical abstract

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Impaired body perception in developmental prosopagnosia

Publication date: August 2017
Source:Cortex, Volume 93
Author(s): Federica Biotti, Katie L.H. Gray, Richard Cook
Developmental prosopagnosia (DP) is a lifelong neurodevelopmental disorder associated with difficulties recognising and discriminating faces. In some cases, the perceptual deficits seen in DP appear to be face-specific. However, DP is known to be a heterogeneous condition, and many cases undoubtedly exhibit impaired perception of other complex objects. There are several well-documented parallels between body and face perception; for example, faces and bodies are both thought to recruit holistic analysis and engage similar regions of visual cortex. In light of these similarities, individuals who exhibit face perception deficits, possibly due to impaired holistic processing or aberrant white matter connectivity, might also show co-occurring deficits of body perception. The present study therefore sought to investigate body perception in DP using a sensitive delayed match-to-sample task and a sizeable group of DPs. To determine whether body perception deficits, where observed, co-vary with wider object recognition deficits, observers' face and body matching ability was compared with performance in a car matching condition. Relative to age-matched controls, the DP sample exhibited impaired body matching accuracy at the group level, and several members of the sample were impaired at the single-case level. Consistent with previous reports of wider object recognition difficulties, a number of the DPs also showed evidence of impaired car recognition.



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Simplified split-bolus intravenous contrast injection technique for pediatric abdominal CT

Publication date: Available online 12 June 2017
Source:Clinical Imaging
Author(s): Yong Hee Kim, Myung-Joon Kim, Hyun Joo Shin, Haesung Yoon, Mi-Jung Lee
PurposeTo investigate pediatric abdominal CT using a simplified split-bolus (Split group) contrast injection compared with a single bolus (Control group).MethodsRadiation dose, image quality and diagnostic accuracy were compared.ResultsSplit group demonstrated lower effective dose (2.46 vs. 2.85mSv, p=0.002) and noise levels in aorta, liver and portal vein (p<0.001). There was one false-negative case of portal vein obliteration in the Split group.ConclusionsA simple method of split-bolus intravenous contrast injection technique can provide adequate and homogeneous enhancement in pediatric abdominal CT.



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Βeta-catenin N-terminal domain: An enigmatic region prone to cancer causing mutations

Publication date: July–September 2017
Source:Mutation Research/Reviews in Mutation Research, Volume 773
Author(s): Mohd Saleem Dar, Paramjeet Singh, Riyaz A. Mir, Mohd Jamal Dar
The Wnt/β-catenin is a highly conserved signaling pathway involved in cell fate decisions during various stages of development. Dysregulation of canonical Wnt/β-catenin signaling has been associated with various diseases including cancer. β-Catenin, the central component of canonical Wnt signaling pathway, is a multi-functional protein playing both structural and signaling roles. β-Catenin is composed of three distinct domains: N-terminal domain, C-terminal domain and a central armadillo repeat domain. N-terminal domain of β-catenin harbours almost all of the cancer causing mutations, thus deciphering its critical structural and functional roles offers great potential in cancer detection and therapy. Here, in this review, we have collected information from pharmacological analysis, bio-physical and structural studies, molecular modeling, in-vivo and in-vitro assays, and transgenic animal experiments employing various N-terminal domain variants of β-catenin to discuss the interaction of β-catenin with its binding partners that specifically interact with this domain and the implications of these interactions on signaling, cell fate determination, and in tumorigenesis. A thorough understanding of interactions between β-catenin and its binding partners will enable us to more effectively understand how β-catenin switches between its multiple roles, and will lead to the development of specific assays for the identification of small molecules as chemotherapeutic agents to treat diseases, including cancer and neurological disorders, where Wnt/β-catenin signaling is dysregulated.



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Patient Outcomes With STEMI Caused by Aneurysmal Coronary Artery Disease and Treated With Primary PCI

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Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure

AbstractBackground

The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF).

Objectives

This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo.

Methods

The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization.

Results

A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001).

Conclusions

Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm.

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Traditional Chinese Medicine for Cardiovascular Disease: Evidence and Potential Mechanisms

Abstract

Traditional Chinese medicine (TCM) has more than 2,000 years of history and has gained widespread clinical applications. However, the explicit role of TCM in preventing and treating cardiovascular disease remains unclear due to a lack of sound scientific evidence. Currently available randomized controlled trials on TCM are flawed, with small sample sizes and diverse outcomes, making it difficult to draw definite conclusions about the actual benefits and harms of TCM. Here, we systematically assessed the efficacy and safety of TCM for cardiovascular disease, as well as the pharmacological effects of active TCM ingredients on the cardiovascular system and potential mechanisms. Results indicate that TCM might be used as a complementary and alternative approach to the primary and secondary prevention of cardiovascular disease. However, further rigorously designed randomized controlled trials are warranted to assess the effect of TCM on long-term hard endpoints in patients with cardiovascular disease.

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How to Use Beta-Blockers in Heart Failure With Reduced Ejection Fraction and Atrial Fibrillation

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RAS Fingerprint

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Antithrombotic Therapy and First Myocardial Infarction in Patients With Atrial Fibrillation

AbstractBackground

Patients with atrial fibrillation (AF) have increased risk of thromboembolic events such as stroke and myocardial infarction (MI). Although it has been established that the efficacy of anticoagulation is superior to that of antiplatelet agents for stroke prophylaxis in AF, the optimal antithrombotic treatment remains uncertain for primary protection against MI.

Objectives

The authors investigated the incidence of first-time MI in patients with AF according to antithrombotic treatment and estimated the risk of stroke and bleeding.

Methods

Subjects with first-time AF diagnosed from 1997 to 2012 without history of coronary artery disease were identified using Danish nationwide administrative registries. Subjects were divided into time varying exposure groups according to antithrombotic treatment. The relative risks of outcomes were estimated by Poisson regression models.

Results

A total of 71,959 patients (median 75 years of age; females: 47%). At baseline, 37,539 patients (52%) were treated with vitamin K antagonist (VKA) monotherapy, 25,458 (35%) with acetylsalicylic acid (ASA) monotherapy and 8,962 (13%) with dual-therapy (VKA + ASA). The incidence of MI was 3% (n = 2,275). Relative to the VKA-treated group, the associated risk of MI was significantly higher for ASA (incidence rate ratio [IRR]: 1.54; 95% confidence interval [CI]: 1.40 to 1.68) and dual-therapy (IRR: 1.22; 95% CI: 1.06 to 1.40). The bleeding risk was significantly higher for dual-therapy (IRR: 1.93; 95% CI: 1.81 to 2.07). The risk of stroke relative to that of VKA therapy was significantly higher for both ASA (IRR: 2.00; 95% CI: 1.88 to 2.12) and dual-therapy (IRR: 1.30; 95% CI: 1.18 to 1.43).

Conclusions

VKA monotherapy in patients with AF was associated with a lower risk of first-time MI and stroke than ASA monotherapy. Combination of ASA and VKA therapy was not associated with a lower risk of MI but was associated with increased bleeding risk.

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2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant): A Report of the ACC Competency Management Committee

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Preventing Myocardial Infarction in Patients With Atrial Fibrillation: Another Piece of the Puzzle

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Reply: Directly Observed Therapy: A Possible Tool to Tackle Medication Nonadherence in the CVD Epidemic

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Outcomes of PCI in Relation to Procedural Characteristics and Operator Volumes in the United States

AbstractBackground

Professional guidelines have reduced the recommended minimum number to an average of 50 percutaneous coronary intervention (PCI) procedures performed annually by each operator. Operator volume patterns and associated outcomes since this change are unknown.

Objectives

The authors describe herein PCI operator procedure volumes; characteristics of low-, intermediate-, and high-volume operators; and the relationship between operator volume and clinical outcomes in a large, contemporary, nationwide sample.

Methods

Using data from the National Cardiovascular Data Registry collected between July 1, 2009, and March 31, 2015, we examined operator annual PCI volume. We divided operators into low- (<50 PCIs per year), intermediate- (50 to 100 PCIs per year), and high- (>100 PCIs per year) volume groups, and determined the adjusted association between annual PCI volume and in-hospital outcomes, including mortality.

Results

The median annual number of procedures performed per operator was 59; 44% of operators performed <50 PCI procedures per year. Low-volume operators more frequently performed emergency and primary PCI procedures and practiced at hospitals with lower annual PCI volumes. Unadjusted in-hospital mortality was 1.86% for low-volume operators, 1.73% for intermediate-volume operators, and 1.48% for high-volume operators. The adjusted risk of in-hospital mortality was higher for PCI procedures performed by low- and intermediate-volume operators compared with those performed by high-volume operators (adjusted odds ratio: 1.16 for low versus high; adjusted odds ratio: 1.05 for intermediate vs. high volume) as was the risk for new dialysis post PCI. No volume relationship was observed for post-PCI bleeding.

Conclusions

Many PCI operators in the United States are performing fewer than the recommended number of PCI procedures annually. Although absolute risk differences are small and may be partially explained by unmeasured differences in case mix between operators, there remains an inverse relationship between PCI operator volume and in-hospital mortality that persisted in risk-adjusted analyses.

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JACC Instructions for Authors

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PCI Volume Benchmarks: Still Adequate for Quality Assessment in 2017?

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Cardiovascular Disease in Incarcerated Populations

Abstract

Currently, 2.2 million individuals are incarcerated, and more than 11 million have been released from U.S. correctional facilities. Individuals with a history of incarceration are more likely to be of racial and ethnic minority populations, poor, and have higher rates of cardiovascular risk factors, especially smoking and hypertension. Cardiovascular disease is a leading cause of death among incarcerated individuals, and those recently released have a higher risk of being hospitalized and dying of cardiovascular disease compared with the general population, even after accounting for differences in racial identity and socioeconomic status. In this review, the authors: 1) present information on the cardiovascular health of justice-involved populations, and unique prevention and care conditions in correctional facilities; 2) identify knowledge gaps; and 3) propose promising areas for research to improve the cardiovascular health of this population. An Executive Summary of a National Heart, Lung, and Blood Institute workshop on this topic is available.

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Protein-Losing Enteropathy in Patients With Congenital Heart Disease

AbstractBackground

Protein-losing enteropathy (PLE), characterized by loss of proteins in the intestine, is a devastating complication in patients with congenital heart disease. The cause of PLE is unknown, but lymphatic involvement has been suspected.

Objectives

The authors evaluated the use of lymphangiographic imaging and liver lymphatic embolization as a treatment for PLE.

Methods

This was a single-center, retrospective review of imaging and interventions used in 8 consecutive patients with liver lymphatic embolization and congenital heart disease with elevated central venous pressure complicated by PLE.

Results

Liver lymphangiography was performed in 8 patients (5 males, 3 females; median age, 21 years), 7 of whom demonstrated leakage of liver lymph into the duodenum through abnormal hepatoduodenal lymphatic communications. This was confirmed by duodenoscopy with simultaneous injection of isosulfan blue dye into the liver lymphatics in 6 of 7 patients. Liver lymphatic embolization with ethiodized oil in 2 patients resulted in a temporary increase in albumin blood level and symptom improvement in 1 patient, but was complicated by duodenal bleeding in both patients. Of the remaining 6 patients, liver lymphatic embolization with n-butyl cyanoacrylate glue resulted in sustained improvement of the serum albumin level and symptoms in 3 patients, temporary improvement in 2 patients, and no change in 1 patient with median follow-up of 135 days (range, 84 to 1,005 days).

Conclusions

The authors demonstrated liver lymph leakage as a cause of PLE in patients with congenital heart disease and elevated central venous pressure. Lymphatic embolization led to improved albumin levels and relief of symptoms. Further experience with the technique is needed to determine long-term outcome of this procedure.

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Changing Demographics: A New Approach to Global Health Care Due to the Aging Population

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Once More Unto the Breach: A New Treatment Paradigm for Protein-Losing Enteropathy

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Lafora Disease Is an Inherited Metabolic Cardiomyopathy

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Association of Triglyceride-Related Genetic Variants With Mitral Annular Calcification

AbstractBackground

Mitral annular calcium (MAC), commonly identified by cardiac imaging, is associated with cardiovascular events and predisposes to the development of clinically important mitral valve regurgitation and mitral valve stenosis. However, its biological determinants remain largely unknown.

Objectives

The authors sought to evaluate whether a genetic predisposition to elevations in plasma lipids is associated with the presence of MAC.

Methods

The authors used 3 separate Mendelian randomization techniques to evaluate the associations of lipid genetic risk scores (GRS) with MAC in 3 large patient cohorts: the Framingham Health Study, MESA (Multiethnic European Study of Atherosclerosis), and the AGE-RS (Age, Gene/Environment Susceptibility-Reykjavik Study). The authors provided cross-ethnicity replication in the MESA Hispanic-American participants.

Results

MAC was present in 1,149 participants (20.4%). In pooled analyses across all 3 cohorts, a triglyceride GRS was significantly associated with the presence of MAC (odds ratio [OR] per triglyceride GRS unit: 1.73; 95% confidence interval [CI]: 1.24 to 2.41; p = 0.0013). Neither low- nor high-density lipoprotein cholesterol GRS was significantly associated with MAC. Results were consistent in cross-ethnicity analyses among the MESA Hispanic-Americans cohort (OR per triglyceride GRS unit: 2.04; 95% CI: 1.03 to 4.03; p = 0.04). In joint meta-analysis across all included cohorts, the triglyceride GRS was associated with MAC (OR per triglyceride GRS unit: 1.79; 95% CI: 1.32 to 2.41; p = 0.0001). The results were robust to several sensitivity analyses that limit both known and unknown forms of genetic pleiotropy.

Conclusions

Genetic predisposition to elevated triglyceride levels was associated with the presence of MAC, a risk factor for clinically significant mitral valve disease, suggesting a causal association. Whether reducing triglyceride levels can lower the incidence of clinically significant mitral valve disease requires further study.

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Directly Observed Therapy: A Possible Tool to Tackle Medication Nonadherence in the CVD Epidemic

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Genetics and Valve Calcification

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Data on analysis of coronary atherosclerosis on computed tomography and 18F-sodium fluoride positron emission tomography

Publication date: Available online 12 June 2017
Source:Data in Brief
Author(s): Toshiro Kitagawa, Hideya Yamamoto, Shinya Toshimitsu, Ko Sasaki, Atsuhiro Senoo, Yumiko Kubo, Fuminari Tatsugami, Kazuo Awai, Yutaka Hirokawa, Yasuki Kihara
This article contains the data showing illustrative examples of plaque classification on coronary computed tomography angiography (CCTA) and measurement of ¹⁸F-sodium fluoride (¹⁸F-NaF) uptake in coronary atherosclerotic lesions on positron emission tomography (PET). We divided the lesions into one of three plaque types on CCTA (calcified plaque, non-calcified plaque, partially calcified plaque). Focal ¹⁸F-NaF uptake of each lesion was quantified using maximum tissue-to-background ratio. This article also provides a representative case with a non-calcified coronary plaque detected on CCTA and identified on ¹⁸F-NaF PET/non-contrast computed tomography based on a location of a vessel branch as a landmark. These complement the data reported by Kitagawa et al. [1].



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Quality assurance of the PREOPANC trial (2012-003181-40) for preoperative radiochemotherapy in pancreatic cancer

Abstract

Background

The Dutch Pancreatic Cancer Group initiated the national, multicentre, controlled PREOPANC trial, randomising between preoperative radiochemotherapy and direct explorative laparotomy for patients with (borderline) resectable pancreatic cancer. The aim of this dummy run is to evaluate compliance with the radiotherapy protocol of this trial, and the quality of delineation and radiation plans.

Methods

Eleven radiation oncology departments open for accrual of patients in the PREOPANC trial were provided with all necessary information of a selected 'dummy' patient. Each institute was asked to delineate the target volumes, including gross tumour volume, internal gross tumour volume (iGTV), internal clinical target volume, and planning target volume. The institutions were also asked to provide a radiation treatment plan in accordance with the PREOPANC trial protocol.

Results

The range of the iGTV was 19.3–77.2 cm³ with a mean iGTV of 41.5 cm³ (standard deviation 14.8 cm³). Nine institutions made a treatment plan using an arc technique for treatment delivery, one an intensity modulated technique and one a 3-field conformal technique. All institutions reached the prescribed target coverage, without exceeding the organs at risk constraints. The institution with the 3‑field conformal technique was advised to use a more sophisticated technique (e. g. volumetric modulated arc therapy) to reduce the dose to the spinal cord.

Conclusion

All institutions showed acceptable deviations from the PREOPANC trial protocol and achieved an acceptable quality of delineation and radiation technique. All institutions were allowed to continue participation in the PREOPANC trial.

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Editorial Board

Publication date: August 2017
Source:Microbiological Research, Volume 201





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Using Force to Punch Holes: Mechanics of Contractile Nanomachines

Publication date: Available online 12 June 2017
Source:Trends in Cell Biology
Author(s): Maximilian Brackmann, Sergey Nazarov, Jing Wang, Marek Basler
Using physical force to translocate macromolecules across a membrane has the advantage of being a universal solution independent of the properties of the target membrane. However, physically punching a stiff membrane is not a trivial task and three things are necessary for success: a sharp tip, a source of energy, and the ability to strongly bind to the target. In this review we describe the basic mechanism of membrane puncturing by contractile nanomachines with a focus on the T4 phage, R-type pyocin, and the bacterial Type VI secretion system (T6SS) based on recent studies of the structures and dynamics of their assembly.



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Surface water mitigates the anti-metamorphic effects of elevated perchlorate concentrations in New Mexico spadefoot toad larvae ( Spea multiplicata )

Abstract

Perchlorate (ClO₄⁻) has potential to negatively impact amphibian populations by inhibiting thyroid hormone production, and thus metamorphosis in developing larvae. However, variability exists in species sensitivity, and there is evidence suggesting that natural surface waters can mitigate the anti-metamorphic potential of perchlorate. New Mexico spadefoot toad tadpoles, Spea multiplicata, were exposed to natural surface waters spiked with nominal concentrations of 0, 1000, 1350, 1710, 3000, 5110, and 8000 μg/L perchlorate ion for up to 42 days. No consistent dose-response trends were observed in mortality, rate of metamorphosis, Gosner stage, mass, or length. This study suggests that perchlorate exposure to concentrations as high as 8000 μg/L in natural surface waters does not result in adverse effects on New Mexico spadefoot tadpoles and emphasizes the importance of using site-specific conditions and species when evaluating ecological risks in perchlorate-impacted areas.

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Ozone risk assessment for an Alpine larch forest in two vegetative seasons with different approaches: comparison of POD 1 and AOT40

Abstract

The upper vegetation belts like larch forests are supposed to be under great pressure because of climate change in the next decades. For this reason, the evaluation of the risks due to abiotic stressors like ozone is a key step. Two different approaches were used here: mapping AOT40 index by means of passive samplers and direct measurements of ozone deposition.

Measurements of ozone fluxes using the eddy-correlation technique were carried out for the first time over a larch forest in Paspardo (I) at 1750 m a.s.l. Two field campaigns were run: the first one in 2010 from July to October and the second one in the following year from June to September. Vertical exchange of ozone, energy, and momentum were measured on a tower platform at 26 m above ground level to study fluxes dynamics over this ecosystem. Since the tower was located on a gentle slope, an "ad hoc" methodology was developed to minimize the effects of the terrain inclination. The larch forest uptake was estimated by means of a two-layer model to separate the understorey uptake from the larch one. Even if the total ozone fluxes were generally high, up to 30–40 nmol O₃ m⁻² s⁻¹ in both years, the stomatal uptake by the larch forest was relatively low (around 15% of the total deposition).

Ozone risk was assessed considering the POD₁ received by the larch forest and the exposure index AOT40 estimated with both local data and data from the map obtained by the passive samplers monitoring.

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A Nationwide Study of Stereotactic Radiosurgery in a Newly Diagnosed Spine Metastasis Population

Background: Stereotactic radiosurgery (SRS), a technique that is emerging as a new treatment option, has been reported to be an effective, noninvasive treatment for spine metastasis patients. Objective: This nationwide study aimed to understand the current state of SRS for spine metastasis. Methods: Patients in this study were first diagnosed with a metastatic spine tumor between 1 July and 31 December 2011. One group (the SRS group) received SRS at least once within 1 year of diagnosis and the other (the non-SRS group) did not receive SRS. We analyzed the characteristics, medication, and survival of each group. Results: In 628 new patients, there were no significant differences between groups regarding gender, age, type of health insurance, and comorbidities. There were significant differences with regard to the medical costs (USD 23,276 vs. 18,458; p = 0.001) and the duration of hospital stay (101.3 vs. 86.5 days; p = 0.023). Median survival was significantly longer in the SRS group (p = 0.003). Conclusions: There was no significant pretreatment baseline demographic difference between the SRS and the non-SRS group. There was a tendency for greater use of medication in the SRS group. Patients with a longer overall survival tended to be those who underwent SRS treatment.
Stereotact Funct Neurosurg 2017;95:189-196

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Aberrant Expression of FLI-1 in Melanoma

Abstract

FLI-1 (Friend leukemia integration site 1) nuclear transcription factor has been proposed as a suitable tool in the differential diagnosis of small round cell sarcomas. It has also been described as nuclear marker of endothelial differentiation. Expression of FLI-1 has been demonstrated in Ewing's sarcoma/ primitive neuroectodermal tumor (ES/PNET) and vascular neoplasms. In the present study, we describe two cases of metastatic melanoma with small round blue cell morphology that showed strong nuclear expression of FLI-1. Because of the small round blue cell morphology and negative immunohistochemical staining for pan-melanocytic cocktail (HMB45, anti MART1 and anti-tyrosinase) and SOX10 in both cases, FLI-1 immunostaining was requested as part of the tumors workup. FLI-1 was strongly positive in both cases. Ultimately, both cases were established as being metastatic melanoma. Dermatopathologists should be aware that melanoma can be strongly positive for FLI-1 and not to mistake these cases for ES/PNET or vascular lesions, especially in those cases with unusual morphology.

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ULTRASTRUCTURAL ASPECTS OF PRIMARY ANETODERMA

Abstract

Anetoderma (anetos, Greek for slack) [1], also known as macular atrophy, is a rare elastolytic disorder characterized by circumscribed areas of flaccid skin due to focal loss of dermal elastic tissue, resulting in normochromic or erythematous papules and plaques with a wrinkled and atrophic surface.

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Apical extrusion of debris during the preparation of oval root canals: a comparative study between a full-sequence SAF system and a rotary file system supplemented by XP-endo finisher file

Abstract

Objectives

The purpose of this study was to assess the amount of apically extruded debris during the preparation of oval canals with either a rotary file system supplemented by the XP-endo Finisher file or a full-sequence self-adjusting file (SAF) system.

Materials and methods

Sixty mandibular incisors were randomly assigned to two groups: group A: stage 1—glide path preparation with Pre-SAF instruments. Stage 2—cleaning and shaping with SAF. Group B: stage 1—glide path preparation with ProGlider file. Stage 2—cleaning and shaping with ProTaper Next system. Stage 3—Final cleaning with XP-endo Finisher file. The debris extruded during each of the stages was collected, and the debris weights were compared between the groups and between the stages within the groups using t tests with a significance level set at P < 0.05.

Results

The complete procedure for group B resulted in significantly more extruded debris compared to group A. There was no significant difference between the stages in group A, while there was a significant difference between stage 2 and stages 1 and 3 in group B, but no significant difference between stages 1 and 3.

Conclusions

Both instrumentation protocols resulted in extruded debris. Rotary file followed by XP-endo Finisher file extruded significantly more debris than a full-sequence SAF system. Each stage, in either procedure, had its own contribution to the extrusion of debris.

Clinical relevance

Final preparation with XP-endo Finisher file contributes to the total amount of extruded debris, but the clinical relevance of the relative difference in the amount of apically extruded debris remains unclear.

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Insulin Resistance and Metformin Use on Volume of Benign Thyroid Nodules

Conditions:   Thyroid Nodule;   Insulin Resistance
Interventions:   Drug: Metformin;   Drug: Placebo
Sponsor:   Hospital Universitário Clementino Fraga Filho
Recruiting - verified June 2017

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Effect of Pre-warming on Perioperative Hypothermia During HoLEPunder Spinal Anesthesia

Condition:   Hypothermia
Interventions:   Other: pre-warming;   Other: no warming
Sponsor:   Hallym University Kangnam Sacred Heart Hospital
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Daily-level associations between PTSD and cannabis use among young sexual minority women

Publication date: November 2017
Source:Addictive Behaviors, Volume 74
Author(s): Emily R. Dworkin, Debra Kaysen, Michele Bedard-Gilligan, Isaac C. Rhew, Christine M. Lee
IntroductionSexual minority women have elevated trauma exposure and prevalence of posttraumatic stress disorder (PTSD) compared to heterosexual women and they are also more likely to use cannabis, although no research has examined relationships between PTSD and cannabis use in this population. Daily-level methodologies are necessary to examine proximal associations between PTSD and use.MethodsThis study included 90 trauma-exposed young adult women who identified as sexual minorities (34.4% identified as lesbian and 48.9% identified as bisexual) and evaluated daily-level associations between their PTSD symptoms and cannabis use. Participants were assessed at two measurement waves, one year apart, each consisting of 14 consecutive daily assessments.ResultsCannabis use occurred on 22.8% of the days. Results from generalized linear mixed effects models showed that a person's mean level of PTSD symptom severity across days was strongly associated with same-day likelihood of cannabis use (OR=2.67 for 1 SD increase in PTSD score; p<0.001). However, daily deviation from one's average PTSD score was not associated with cannabis use on the same day.ConclusionsFindings suggest that PTSD severity may confer general risk for cannabis use, rather than being a state-dependent risk factor.



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Electrodermal responses during appetitive conditioning are sensitive to contingency instruction ambiguity

Publication date: Available online 12 June 2017
Source:International Journal of Psychophysiology
Author(s): Karolien van den Akker, Chantal Nederkoorn, Anita Jansen
Studies on human appetitive conditioning using food rewards can benefit from including psychophysiological outcome measures. The present study tested whether the skin conductance response can function as a measure of differential responding in an appetitive conditioning paradigm including an acquisition and extinction phase, and examined which time window during a trial is most sensitive to conditioning effects. As a secondary aim, the effects of ambiguous vs. non-ambiguous contingency instructions on conditioned responses (skin conductance responses, US expectancies, chocolate desires, and CS evaluations) were assessed. Results indicated differential skin conductance responses in an anticipatory time window and during unexpected omission of the US in early extinction. Interestingly however, anticipatory responses were only found for participants who received ambiguous contingency instructions – possibly indicating a call for additional processing resources in response to the ambiguous CS+. Further, ambiguous instructions slowed the extinction of US expectancies but did not influence chocolate desires and CS evaluations. It is concluded that skin conductance can function as a sensitive measure of differential responding in appetitive conditioning, though its sensitivity might depend on the specific task context.



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