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https://www.readbyqxmd.com/read/28923845/high-sensitivity-cardiac-troponin-i-as-a-gatekeeper-for-coronary-computed-tomography-angiography-and-stress-testing-in-patients-with-acute-chest-pain
#1
Maros Ferencik, Thomas Mayrhofer, Michael T Lu, Pamela K Woodard, Quynh A Truong, W Frank Peacock, Fabian Bamberg, Benjamin C Sun, Jerome L Fleg, John T Nagurney, James E Udelson, Wolfgang Koenig, James L Januzzi, Udo Hoffmann
BACKGROUND: Most patients presenting to the emergency department (ED) with suspected acute coronary syndrome (ACS) undergo noninvasive cardiac testing with a low diagnostic yield. We determined whether a combination of high-sensitivity cardiac troponin I (hs-cTnI) and cardiovascular risk factors might improve selection of patients for cardiac testing. METHODS: We included patients from the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) I and II trials who presented to the ED with acute chest pain and were referred for cardiac testing...
September 18, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28921899/stimulus-induced-conformational-transformation-of-cyclic-peptide-for-selective-cell-targeting-on-off-gatekeeper-of-mesoporous-nanocarrier
#2
Jeonghun Lee, Eun-Taex Oh, Jaehun Song, Ha Gyeong Kim, Heon Joo Park, Chulhee Kim
The αvβ3 integrin is upregulated on many cancer cells. We designed a dual functional cyclic peptide gatekeeper with a capability of stimuli-responsive conformational transformation which could serve as a selective cell targeting on-off gatekeeper for mesoporous nanocarriers. The advantage of employing the motif of stimuli-induced conformational transformation of cyclic peptides is that they could be utilized not only as an on-off gatekeeper for the triggered release of cargo drugs but also as a targeting ligand of the carriers to desired cells with their respective binding receptors...
September 17, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28919207/phospho-regulation-of-soma-to-axon-transcytosis-of-neurotrophin-receptors
#3
Naoya Yamashita, Rajshri Joshi, Sheng Zhang, Zhong-Yin Zhang, Rejji Kuruvilla
Axonal targeting of signaling receptors is essential for neuronal responses to extracellular cues. Here, we report that retrograde signaling by target-derived nerve growth factor (NGF) is necessary for soma-to-axon transcytosis of TrkA receptors in sympathetic neurons, and we define the molecular underpinnings of this positive feedback regulation that enhances neuronal sensitivity to trophic factors. Activated TrkA receptors are retrogradely transported in signaling endosomes from distal axons to cell bodies, where they are inserted on soma surfaces and promote phosphorylation of resident naive receptors, resulting in their internalization...
September 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28915613/alternative-promotion-and-suppression-of-metastasis-by-jnk2-governed-by-its-phosphorylation
#4
Sike Hu, Xiaoli Dong, Wenjuan Gao, Dwayne Stupack, Yanhua Liu, Rong Xiang, Na Li
Fos-related antigen 1 (Fra1) has been proposed as a gatekeeper of the mesenchymal-epithelial transition to epithelial-mesenchymal transition. Here, we showed that de-phosphorylated JNK2 increased the expression of Fra1 by promoting the expression of c-Jun and Jun-B. Conversely, phosphorylated JNK2 suppressed its expression via enhancing the ubiquitination of c-Jun and Jun-B. These data provided insights into the regulatory mechanism of JNK2 on the expression of Fra1. Our study thus demonstrated that the conversion of JNK2 from its phosphorylation to de-phosphorylation status promoted the switch of breast cancer cells from mesenchymal-epithelial transition to epithelial-mesenchymal transition...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903659/sage-on-the-stage-women-s-representation-at-an-academic-conference
#5
Camille S Johnson, Pamela K Smith, Chunlei Wang
Who presents at conferences matters. Presenting research benefits speakers, and presenters shape the conclusions audiences draw about who can succeed in a field. This is particularly important for members of historically underrepresented or disadvantaged groups, such as women. We investigated gender representation over a 13-year period among speakers at the largest social and personality psychology conference. On average, women were underrepresented as speakers, though this effect diminished over time. Chairs appeared to serve as gatekeepers: In symposia chaired by women, almost half of the invited speakers were women, whereas in symposia chaired by men, it was a third...
April 2017: Personality & Social Psychology Bulletin
https://www.readbyqxmd.com/read/28894364/epcam-aptamer-functionalized-polydopamine-coated-mesoporous-silica-nanoparticles-loaded-with-dm1-for-targeted-therapy-in-colorectal-cancer
#6
Yang Li, Yanhong Duo, Shiyun Bao, Lisheng He, Kai Ling, Jinfeng Luo, Yue Zhang, Hao Huang, Han Zhang, Xiaofang Yu
DM1, a maytansine derivative, is a highly potential cytotoxic agent but with severe side effects; therefore, its application in clinical cancer therapy is limited. Here, in order to mitigate this intrinsic drawback of DM1, we developed mesoporous silica nanoparticles (MSNs) loaded with DM1 and surface-decorated with hydrochloride dopamine (PDA), polyethylene glycol (PEG), and epithelial cell adhesion molecule (EpCAM) aptamer (APt) for the targeted treatment of colorectal cancer (CRC). In this system, the PDA coating could be used as pH-sensitive gatekeepers to control the release of DM1 from MSNs in response to the pH stimulus and EpCAM APt-guided active targeting enables the increased delivery of DM1 to CRC as well as a reduction in toxicity and side effects by minimizing the exposure of normal tissues to DM1...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28887966/core-shell-structured-polypyrrole-mesoporous-sio2-nanocomposite-capped-with-graphene-quantum-dots-as-gatekeeper-for-irradiation-controlled-release-of-methotrexate
#7
Xiaolin Liu, Dan Shou, Chuanxiang Chen, Huihui Mao, Yong Kong, Yongxin Tao
A core-shell structured nanocomposite of polypyrrole/mesoporous SiO2 (PPy/mSiO2) is rationally designed as the nanocarrier for methotrexate (MTX), a chemotherapeutic drug for cancer treatment. Graphene quantum dots (GQDs) are introduced to the outer surface of PPy/mSiO2, and it functions as a gatekeeper for the loaded MTX through the formation of H-bonds with the functionalized mSiO2. In the proposed nanocarrier for MTX, the mesopores in mSiO2 are beneficial for the accommodation of MTX, resulting in enhanced encapsulation capacity of the nanocarrier; on the other hand, PPy can effectively convert the near-infrared (NIR) light to heat...
December 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28887504/macrophages-unlock-progression-of-breast-cancer-cells-experiencing-matrigel-segregation-in-transplantation-models
#8
Misa Ogura, Victoria L Bridgeman, Ilaria Malanchi
Basement membrane matrix proteins, such as matrigel, are able to improve the efficiency of tumour transplantation. This assay represents the gold standard to measure tumour initiation potential in vivo of a limited number of cancer cells. However, in culture conditions, matrigel directly signals to cancer cells altering their phenotype. We here investigate how matrigel influences the tumour reconstitution dynamics of breast cancer cells in vivo. This is particularly relevant in the setting of limiting dilution assay where cells are transplanted in a relatively high amount of Matrigel...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28885951/providers-perspectives-on-barriers-and-facilitators-to-connecting-women-veterans-to-alcohol-related-care-from-primary-care
#9
Traci H Abraham, Eleanor T Lewis, Michael A Cucciare
BACKGROUND: Unhealthy drinking is relatively common among women U.S. military Veterans. Primary care is often the setting where patients first come into contact with the health care system, and providers in this setting play a critical role in connecting unhealthy drinkers to appropriate care. Little is known about primary care providers' perspectives on factors that affect whether women Veterans presenting to primary care with unhealthy drinking connect to alcohol-related care. Understanding factors that affect whether patients connect to alcohol-related care may improve providers' ability to support women Veterans with unhealthy drinking get needed care...
September 2017: Military Medicine
https://www.readbyqxmd.com/read/28880149/dual-function-of-the-pi3k-akt-mtorc1-axis-in-myelination-of-the-peripheral-nervous-system
#10
Gianluca Figlia, Camilla Norrmén, Jorge A Pereira, Daniel Gerber, Ueli Suter
Myelination is a biosynthetically demanding process in which mTORC1, the gatekeeper of anabolism, occupies a privileged regulatory position. We have shown previously that loss of mTORC1 function in Schwann cells (SCs) hampers myelination. Here, we genetically disrupted key inhibitory components upstream of mTORC1, TSC1 or PTEN, in mouse SC development, adult homeostasis, and nerve injury. Surprisingly, the resulting mTORC1 hyperactivity led to markedly delayed onset of both developmental myelination and remyelination after injury...
September 7, 2017: ELife
https://www.readbyqxmd.com/read/28880093/quantification-of-transporter-and-receptor-proteins-in-dog-brain-capillaries-and-choroid-plexus-relevance-for-the-distribution-in-brain-and-csf-of-selected-bcrp-and-p-gp-substrates
#11
Clemens Braun, Atsushi Sakamoto, Holger Fuchs, Naoki Ishiguro, Shinobu Suzuki, Yunhai Cui, Klaus Klinder, Michitoshi Watanabe, Tetsuya Terasaki, Achim Sauer
Transporters at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) play a pivotal role as gatekeepers for efflux or uptake of endogenous and exogenous molecules. The protein expression of a number of them has already been determined in the brains of rodents, non-human primates and humans using quantitative targeted absolute proteomics (QTAP). The dog is an important animal model for drug discovery and development, especially for safety evaluations. The purpose of the present study is to clarify the relevance of the transporter protein expression for drug distribution in the dog brain and CSF...
September 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28874658/liver-x-receptors-constrain-tumor-development-and-metastasis-dissemination-in-pten-deficient-prostate-cancer
#12
Anthony Alioui, Julie Dufour, Valerio Leoni, Anke Loregger, Martina Moeton, Luigi Iuliano, Chiara Zerbinati, Amandine Septier, Pierre Val, Allan Fouache, Vincenzo Russo, David H Volle, Jean-Marc A Lobaccaro, Noam Zelcer, Silvère Baron
Advanced prostate cancer (PCa) is a clinical challenge as no curative therapeutic is available. In this context, a better understanding of metastasis and resistance mechanisms in PCa is an important issue. As phosphatase and tensin homolog (PTEN) loss is the most common genetic lesion in such cancer, we investigate human data sets for mechanisms that can constrain cancer evolution in this setting. Here we report a liver X receptor (LXR) signature, which tightly correlates with PTEN loss, in PCa. Accordingly, the LXR pathway is deregulated in prostate carcinomas in Pten-null mice...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28874410/identification-and-characterization-of-the-major-porin-of-desulfovibrio-vulgaris-hildenborough
#13
L Zeng, E Wooton, D A Stahl, P J Walian
Due in large part to their ability to facilitate the diffusion of a diverse range of solutes across the outer membrane (OM) of Gram-negative bacteria, the porins represent one of the most prominent and important bacterial membrane protein superfamilies. Notably, for the Gram-negative bacterium Desulfovibrio vulgaris Hildenborough (DvH), a model organism for studies of sulfate-reducing bacteria, no porins have been identified or proposed in its annotated genome. Results from initial biochemical studies suggested that the product of gene DVU0799, one of the most abundant proteins of the DvH OM and purified as a homotrimeric complex, was a strong porin candidate...
September 5, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28871841/men-and-suicide-prevention-a-scoping-review
#14
Sophia Struszczyk, Paul Michael Galdas, Paul Alexander Tiffin
BACKGROUND: Male suicide rates are higher than their female counterparts in almost every country around the world. Several developed countries have attempted to implement suicide prevention programmes, but few have specifically targeted men. AIMS: To identify what is currently known about suicide prevention strategies, programmes, and interventions of relevance to men. METHOD: A scoping review guided by Arksey and O'Malley's five-stage framework...
September 5, 2017: Journal of Mental Health
https://www.readbyqxmd.com/read/28868023/next-generation-sequencing-in-order-to-better-characterize-a-brca-variant-of-uncertain-significance
#15
Steven Sorscher, Shakti Ramkissoon
BRCA germline mutations are the most common predisposing factor in familial breast-ovarian cancer syndrome families. However, many screened patients are identified as harboring BRCA variants of uncertain significance (VUS), rather than carrying deleterious germline mutations [Calo et al.: Cancers 2010; 2:1644-1660]. While such VUSs are typically reclassified as benign polymorphisms, this may occur years after the VUS is first identified [Murray et al.: Genet Med 2011; 13; 998-1005]. Loss of heterozygosity (LOH) of BRCA is nearly always the gatekeeper event in inherited BRCA-related breast cancer and LOH of BRCA is rare in sporadic cancers [Osorio et al...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28857232/hepatic-ppar%C3%AE-coactivator-1%C3%AE-drives-mitochondrial-and-anabolic-signatures-that-contribute-to-hepatocellular-carcinoma-progression
#16
Elena Piccinin, Claudia Peres, Elena Bellafante, Simon Ducheix, Claudio Pinto, Gaetano Villani, Antonio Moschetta
The peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1β (PGC-1 β) coactivator is a master regulator of mitochondrial biogenesis and oxidative metabolism as well as of antioxidant defense. Specifically in the liver PGC-1β also promotes de novo lipogenesis, thus sustaining cellular anabolic processes. Given the relevant pathogenic role of mitochondrial and fatty acid metabolism in hepatocarcinoma (HCC), here we pointed to PGC-1β as a putative novel transcriptional player in the development and progression of HCC...
August 31, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28854593/gynaecologists-and-industry-ain-t-no-sunshine
#17
Cynthia M Farquhar, Paolo Vercellini, Jane Marjoribanks
The field of reproductive medicine is known for its innovations, and where there is innovation there is marketing and engagement with the doctors who are potential prescribers and users of those innovations. Financial connections between drug and device manufacturers with doctors have been extensively debated over the past decade. On one hand, relationships between doctors and industry could be considered synergistic by allowing the development of improved treatments. On the other hand, payment (and other benefits) from industry to doctors may subtly shift the main objective of the collaboration from patients' health to mutual benefits for both doctors and industry...
August 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28853575/structure-guided-development-of-covalent-and-mutant-selective-pyrazolopyrimidines-to-target-t790m-drug-resistance-in-epidermal-growth-factor-receptor
#18
Julian Engel, Steven Smith, Jonas Lategahn, Hannah L Tumbrink, Lisa Goebel, Christian Becker, Elisabeth Hennes, Marina Keul, Anke Unger, Heiko Müller, Matthias Baumann, Carsten Schultz-Fademrecht, Georgia Günther, Jan G Hengstler, Daniel Rauh
Reversible epidermal growth factor receptor (EGFR) inhibitors prompt a beneficial clinical response in non-small cell lung cancer patients who harbor activating mutations in EGFR. However, resistance mutations, particularly the gatekeeper mutation T790M, limit this efficacy. Here, we describe a structure-guided development of a series of covalent and mutant-selective EGFR inhibitors that effectively target the T790M mutant. The pyrazolopyrimidine-based core differs structurally from that of aminopyrimidine-based third-generation EGFR inhibitors and therefore constitutes a new set of inhibitors that target this mechanism of drug resistance...
September 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28851477/strategies-for-public-health-initiatives-targeting-dairy-consumption-in-young-children-a-qualitative-formative-investigation-of-parent-perceptions
#19
Mary E Jung, Jessica E Bourne, Andrea Buchholz, Kathleen A Martin Ginis
OBJECTIVE: Dairy products contain essential nutrients to ensure healthy growth and bone development in children. However, a significant proportion of children in developed countries fail to consume the daily recommended intake of dairy products. Parents are the gatekeepers of familial nutritional intake and represent a potential vehicle through which to increase dairy consumption in children. As such, formative research was conducted to gain insight into parents' perceived barriers to and benefits of purchasing and consuming dairy products and to develop innovative message content that could be utilized in future public health campaigns...
August 30, 2017: Public Health Nutrition
https://www.readbyqxmd.com/read/28851364/-always-paracetamol-they-give-them-paracetamol-for-everything-a-qualitative-study-examining-eastern-european-migrants-experiences-of-the-uk-health-service
#20
Hannah Madden, Jane Harris, Christian Blickem, Rebecca Harrison, Hannah Timpson
BACKGROUND: The enlargement of the European Union since 2004 has led to an increase in the number of Eastern European migrants living in the UK. The health of this group is under-researched though some mixed evidence shows they are at higher risk of certain physical health conditions such as heart attacks, strokes, HIV and alcohol use and have poorer mental health. This is compounded by poor or insecure housing, low pay, isolation and prejudice. We aimed to understand the health needs and health service experiences of the Eastern European population in a town in Northern England...
August 29, 2017: BMC Health Services Research
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