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https://www.readbyqxmd.com/read/28343018/cus-as-a-gatekeeper-of-mesoporous-upconversion-nanoparticles-based-drug-controlled-release-system-for-tumor-targeted-multimodal-imaging-and-synergetic-chemo-thermotherapy
#1
Xiangjie Su, Feifei Zhao, Yuhui Wang, Xiaosa Yan, Shaona Jia, Bin Du
In this work, a tumor-targeted multifunctional mesoporous upconversion nanoparticle-based drug controlled release system was developed for UCL/MRI/PAT guided synergetic chemo- thermotherapy. Herein, the core-shell mesoporous upconversion nanoparticles served as drug carrier exhibiting higher upconversion luminescence emission intensity, with CuS as a gatekeeper through a cleavable disulfide bond under the influence of glutathione. CuS could not only prevent drug from early release during the delivery but also improve the delivery system function with the ability of photothermal therapy and photoacoustic tomography...
March 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28340906/veterans-treatment-courts-a-case-study-of-their-efficacy-for-veterans-needs
#2
John W Erickson
Veterans Treatment Courts (VTCs) were created to: (1) address issues unique to U.S. Military Veterans; and, (2) where possible, avoid punishing veterans for crimes that may have been committed as a direct result of their mental conditions (e.g., Posttraumatic Stress Disorder (PTSD) and/or Traumatic Brain Injury (TBI)). Little research has been undertaken to ascertain whether VTCs are accomplishing their intended goals. To that end, the present case study examined three operating VTCs in order to determine if they are meeting their objectives...
November 2016: International Journal of Law and Psychiatry
https://www.readbyqxmd.com/read/28340149/individual-and-regional-determinants-for-physical-therapy-utilization-in-germany-multilevel-analysis-of-national-survey-data
#3
Alexander Rommel, Lars Eric Kroll
Background: Physical therapy (PT) is included in many clinical guidelines and a commonly used health service. However, access to its benefits should not strongly depend on social or demographic factors. Objective: The present study used the Andersen model to explain to what extent PT utilization in Germany depends on factors beyond medical need. Methods: The German Health Interview and Examination Survey for Adults (DEGS, 2008-2011; target population, 18-79 years) is part of the German health-monitoring system...
March 9, 2017: Physical Therapy
https://www.readbyqxmd.com/read/28336274/characterization-molecular-docking-dynamics-simulation-and-metadynamics-of-kisspeptin-receptor-with-kisspeptin
#4
Mohd Ashraf Rather, Syed Hussain Basha, Irfan Ahmad Bhat, Niti Sharma, Priyanka Nandanpawar, Mohan Badhe, Gireesh-Babu P, Aparna Chaudhari, Jitendra Kumar Sundaray, Rupam Sharma
We report molecular characterization of the kisspeptin receptor (kiss1r), an essential gatekeeper for reproduction and onset of puberty in vertebrates. The full-length cDNA sequence of kiss1r is 1786bp which consist of 5' UTR (untranslated region) 261bp, 3' UTR of 424bp and open reading frame of 1101 encoding a putative protein of 366 amino acids. Basal tissue expression pattern of kiss1r mRNA revealed that it is mainly expressed in the brain and testis. We also report the structure of the kiss1r, along with plausible activation mechanism of this receptor by kisspeptin using computational modelling and dynamic simulation approach of multiple 100ns of timescale...
March 20, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28331001/quantitative-tyrosine-phosphoproteomics-of-egfr-tyrosine-kinase-inhibitor-treated-lung-adenocarcinoma-cells-reveals-potential-novel-biomarkers-of-therapeutic-response
#5
Xu Zhang, Tapan Maity, Manoj K Kashyap, Mukesh Bansal, Abhilash Venugopalan, Sahib Singh, Shivangi Awasthi, Arivusudar Marimuthu, Harrys Kishore Charles Jacob, Natalya Belkina, Stephanie Pitts, Constance M Cultraro, Shaojian Gao, Fatos Kirkali, Romi Biswas, Raghothama Chaerkady, Andrea Califano, Akhilesh Pandey, Udayan Guha
Mutations in the Epidermal growth factor receptor (EGFR) kinase domain, such as the L858R missense mutation and deletions spanning the conserved sequence 747LREA750, are sensitive to tyrosine kinase inhibitors (TKIs). The gatekeeper site residue mutation, T790M accounts for around 60% of acquired resistance to EGFR TKIs. The first generation EGFR TKIs, erlotinib and gefitinib, and the second generation inhibitor, afatinib are FDA approved for initial treatment of EGFR mutated lung adenocarcinoma. The predominant biomarker of EGFR TKI responsiveness is the presence of EGFR TKI-sensitizing mutations...
March 22, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28326863/use-of-patient-controlled-psychiatric-hospital-admissions-patients-perspective
#6
Trine Ellegaard, Vibeke Bliksted, Kirsten Lomborg, Mimi Mehlsen
BACKGROUND: By patient-controlled admission (PCA), psychiatric patients with a PCA contract can initiate a brief admission without a health professional gatekeeper. However, research regarding use of PCA is scarce. AIMS: In this Danish multi-centre study, motives for and satisfaction with PCA were explored. METHODS: During a 1-year period, patients from 11 Danish mental health units evaluated PCA using a questionnaire developed for the purpose...
March 22, 2017: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/28326609/bridging-the-gap-connecting-resident-assistants-and-suicidal-residents-through-gatekeeper-training
#7
Kate McLean, Martin A Swanbrow Becker
One hundred sixty-two resident assistants (RAs) at a large southeastern university were randomly assigned to attend either a specialized 1-hr training program in suicide prevention (intervention group) or a stress and time management skills training program (control group). The results failed to show the suicide prevention training program had any impact on RA intervention behaviors, resident help-seeking behaviors, or RA perceptions of resident distress and suicidality 4 months following training. Results are interpreted and discussed in relation to strengthening suicide prevention training programs on college campuses...
March 21, 2017: Suicide & Life-threatening Behavior
https://www.readbyqxmd.com/read/28325821/phosphorylation-of-the-exocyst-protein-exo84-by-tbk1-promotes-insulin-stimulated-glut4-trafficking
#8
Maeran Uhm, Merlijn Bazuine, Peng Zhao, Shian-Huey Chiang, Tingting Xiong, Sheelarani Karunanithi, Louise Chang, Alan R Saltiel
Insulin stimulates glucose uptake through the translocation of the glucose transporter GLUT4 to the plasma membrane. The exocyst complex tethers GLUT4-containing vesicles to the plasma membrane, a process that requires the binding of the G protein (heterotrimeric guanine nucleotide-binding protein) RalA to the exocyst complex. We report that upon activation of RalA, the protein kinase TBK1 phosphorylated the exocyst subunit Exo84. Knockdown of TBK1 blocked insulin-stimulated glucose uptake and GLUT4 translocation; knockout of TBK1 in adipocytes blocked insulin-stimulated glucose uptake; and ectopic overexpression of a kinase-inactive mutant of TBK1 reduced insulin-stimulated glucose uptake in 3T3-L1 adipocytes...
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28322916/prediction-and-reduction-of-the-aggregation-of-monoclonal-antibodies
#9
Rob van der Kant, Anne R Karow-Zwick, Joost Van Durme, Michaela Blech, Rodrigo Gallardo, Daniel Seeliger, Kerstin Aßfalg, Pieter Baatsen, Griet Compernolle, Ann Gils, Joey M Studts, Patrick Schulz, Patrick Garidel, Joost Schymkowitz, Frederic Rousseau
Protein aggregation remains a major area of focus in the production of monoclonal antibodies. Improving the intrinsic properties of antibodies can improve manufacturability, attrition rates, safety, formulation, titers, immunogenicity and solubility. Here, we explore the potential of predicting and reducing the aggregation propensity of monoclonal antibodies, based on the identification of aggregation-prone regions (APRs) and their contribution to the thermodynamic stability of the protein. Although APRs are thought to occur in the antigen binding region to drive hydrophobic binding with antigen, we were able to rationally design variants that display a marked decrease in aggregation propensity while retaining antigen binding through the introduction of artificial aggregation gatekeeper residues...
March 17, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28322586/the-neonatal-methylome-as-a-gatekeeper-in-the-trajectory-to-childhood-asthma
#10
Avery DeVries, Donata Vercelli
Asthma is a heterogeneous group of conditions that typically begin in early life and result in recurrent, reversible bronchial obstruction. The role played by epigenetic mechanisms in the pathogenesis of childhood asthma is understood only in part. Here we discuss asthma epigenetics within a developmental perspective based on our recent demonstration that the epigenetic trajectory to childhood asthma begins at birth. We next discuss how this trajectory may be affected by prenatal environmental exposures. Finally, we examine in vitro studies that model the impact of asthma-associated exposures on the epigenome...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28320949/discovery-of-scmr-as-a-global-regulator-of-secondary-metabolism-and-virulence-in-burkholderia-thailandensis-e264
#11
Dainan Mao, Leah B Bushin, Kyuho Moon, Yihan Wu, Mohammad R Seyedsayamdost
Bacteria produce a diverse array of secondary metabolites that have been invaluable in the clinic and in research. These metabolites are synthesized by dedicated biosynthetic gene clusters (BGCs), which assemble architecturally complex molecules from simple building blocks. The majority of BGCs in a given bacterium are not expressed under normal laboratory growth conditions, and our understanding of how they are silenced is in its infancy. Here, we have addressed this question in the Gram-negative model bacterium Burkholderia thailandensis E264 using genetic, transcriptomic, metabolomic, and chemical approaches...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320636/the-significance-of-equivocal-exercise-treadmill-ecg-for-intermediate-risk-chest-pain-assessment-insight-from-coronary-ct-angiography-data
#12
Gary T E Lau, Henry Wei, Jo Wickham, Andrew C Y To
BACKGROUND: Exercise treadmill test (ETT) is commonly the first-line investigation in troponin-negative chest pain patients. Inconclusive results are common and often lead to repeated functional testings. Coronary computed tomographic angiography (CCTA) has excellent negative predictive value for coronary artery disease detection and may play an important role in their diagnostic workup. We aim to analyse ETT and CCTA findings to understand their modern roles in intermediate risk chest pain population with inconclusive ETT...
March 1, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28318346/use-of-patient-controlled-psychiatric-hospital-admissions-mental-health-professionals-perspective
#13
Trine Ellegaard, Mimi Mehlsen, Kirsten Lomborg, Vibeke Bliksted
BACKGROUND: In a patient-controlled admission (PCA) programme, the decision about hospital admission is made solely by the patient, with no gatekeeper function allocated to the mental health professionals (MHPs). Current knowledge about how MHPs experience and evaluate PCA is sparse. AIMS: This Danish multi-centre study examined the MHP assessment of the PCA programme in daily clinical practice, and compared PCA evaluations made by MHPs and patients. METHODS: A questionnaire was developed and a survey conducted over the course of a year at all Danish mental health units included in the PCA programme...
March 20, 2017: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/28316330/the-microbiota-of-the-respiratory-tract-gatekeeper-to-respiratory-health
#14
REVIEW
Wing Ho Man, Wouter A A de Steenhuijsen Piters, Debby Bogaert
The respiratory tract is a complex organ system that is responsible for the exchange of oxygen and carbon dioxide. The human respiratory tract spans from the nostrils to the lung alveoli and is inhabited by niche-specific communities of bacteria. The microbiota of the respiratory tract probably acts as a gatekeeper that provides resistance to colonization by respiratory pathogens. The respiratory microbiota might also be involved in the maturation and maintenance of homeostasis of respiratory physiology and immunity...
March 20, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28302726/the-rna-binding-protein-tristetraprolin-ttp-is-a-critical-negative-regulator-of-the-nlrp3-inflammasome
#15
Moritz Haneklaus, John D O'Neil, Andrew R Clark, Seth L Masters, Luke A J O'Neill
The NLRP3 inflammasome is a central regulator of inflammation in many common diseases, including atherosclerosis and Type 2 diabetes, driving the production of pro-inflammatory mediators such as IL-1β and IL-18. Due to its function as an inflammatory gatekeeper, expression and activation of NLRP3 need to be tightly regulated. In this study, we highlight novel post-transcriptional mechanisms that can modulate NLRP3 expression. We have identified the RNA-binding protein Tristetraprolin (TTP) as a negative regulator of NLRP3 in human macrophages...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28294393/the-new-msc-mscs-as-pericytes-are-sentinels-and-gatekeepers
#16
REVIEW
Arnold I Caplan
Human Mesenchymal Stem Cells, hMSCs, were first named over 25 years ago with the "stem cell" nomenclature derived from the fact that we and others could cause these cells to differentiate into a number of different mesodermal phenotypes in cell culture. The capacity to form skeletal tissue in vitro encouraged the use of hMSCs for the fabrication of tissue engineered skeletal repair tissue with subsequent transplantation to in vivo sites. With the current realization that MSCs are derived from perivascular cells, pericytes, and the immunomodulatory and trophic capabilities of MSCs in both in vitro and in vivo test systems, a complete re-evaluation of the role and functions of MSCs in the body was required...
March 15, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28287730/discovery-of-n-3r-4r-4-fluoro-1-6-3-methoxy-1-methyl-1h-pyrazol-4-yl-amino-9-methyl-9h-purin-2-yl-pyrrolidine-3-yl-acrylamide-pf-06747775-through-structure-based-drug-design-a-high-affinity-irreversible-inhibitor-targeting-oncogenic-egfr-mutants-with-selectivity
#17
Simon Planken, Douglas Carl Behenna, Sajiv K Nair, Theodore Otto Johnson, Asako Nagata, Chau Almaden, Simon Bailey, T Eric Ballard, Louise Bernier, Hengmiao Cheng, Sujin Cho-Schultz, Deepak Dalvie, Judith G Deal, Dac M Dinh, Martin P Edwards, Rose Ann Ferre, Ketan S Gajiwala, Michelle D Hemkens, Robert S Kania, John C Kath, Jean Matthews, Brion W Murray, Sherry Niessen, Suvi T M Orr, Mason Pairish, Neal W Sach, Hong Shen, Manli Shi, James Solowiej, Khanh Tran, Elaine Tseng, Paolo Vicini, Yuli Wang, Scott L Weinrich, Ru Zhou, Michael Zientek, Longqing Liu, Yiqin Luo, Shuibo Xin, Chengyi Zhang, Jennifer Anne Lafontaine
Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR-mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGFR mutations account for approximately 50% of relapses, the most common being the gatekeeper T790M substitution that renders existing therapies ineffective. The discovery of PF-06459988 (1), an irreversible pyrrolopyrimidine inhibitor of EGFR T790M mutants was recently disclosed1...
March 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28284363/-evaluation-of-family-doctor-centred-health-care-in-germany-based-on-aok-rheinland-hamburg-claims-data
#18
Mike Klora, Jan Zeidler, Melanie May, Nils Raabe, J-Matthias Graf von der Schulenburg
BACKGROUND: Health insurance funds in Germany are obliged to offer family doctor-centred health care models (Hausarztzentrierte Versorgung, "HzV"). The participation is voluntary for the insured persons. Participants agree to utilise outpatient specialist care only if their family doctor or general practitioner ("gatekeeper") refers them to a specialist. The aim of this programme is to both strengthen the role of general practitioners and to avoid unnecessary specialist visits and double examinations...
February 2017: Zeitschrift Für Evidenz, Fortbildung und Qualität Im Gesundheitswesen
https://www.readbyqxmd.com/read/28284191/a-feasibility-study-with-process-evaluation-of-a-preschool-intervention-to-improve-child-and-family-lifestyle-behaviours
#19
Lorraine McSweeney, Vera Araújo-Soares, Tim Rapley, Ashley Adamson
BACKGROUND: Around a fifth of children starting school in England are now overweight/obese. There is a paucity of interventions with the aim of obesity prevention in preschool-age children in the UK. Previous research has demonstrated some positive results in changing specific health behaviours, however, positive trends in overall obesity rates are lacking. Preschool settings may provide valuable opportunities to access children and their families not only for promoting healthy lifestyles, but also to develop and evaluate behaviour-change interventions...
March 11, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28283392/addictions-neuroclinical-assessment-a-reverse-translational-approach
#20
REVIEW
Laura E Kwako, Reza Momenan, Erica N Grodin, Raye Z Litten, David Goldman
Incentive salience, negative emotionality, and executive function are functional domains that are etiologic in the initiation and progression of addictive disorders, having been implicated in humans with addictive disorders and in animal models of addictions. Measures of these three neuroscience-based functional domains can capture much of the effects of inheritance and early exposures that lead to trait vulnerability shared across different addictive disorders. For specific addictive disorders, these measures can be supplemented by agent specific measures such as those that access pharmacodynamic and pharmacokinetic variation attributable to agent-specific gatekeeper molecules including receptors and drug-metabolizing enzymes...
March 7, 2017: Neuropharmacology
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