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https://www.readbyqxmd.com/read/29351570/joint-adolescent-adult-early-phase-clinical-trials-to-improve-access-to-new-drugs-for-adolescents-with-cancer-proposals-from-the-multi-stakeholder-platform-accelerate
#1
N Gaspar, L V Marshall, D Binner, R Herold, R Rousseau, P Blanc, R Capdeville, J Carleer, C Copland, Y Kerloeguen, K Norga, L Pacaud, M-A Sevaux, C Spadoni, J Sterba, F Ligas, T Taube, M Uttenreuther-Fischer, S Chioato, M A O'Connell, B Geoerger, J-Y Blay, J C Soria, S Kaye, B Wulff, L Brugières, G Vassal, A D J Pearson
The impressive progress recently observed in adult cancers through the introduction of new drugs has not yet been translated to adolescents between 12 and 17 years of age. Currently adolescents are grouped with children, so their access to new, effective drugs already available for adults is delayed because paediatric drug development starts late relative to adult programmes. Moreover, specific early phase trials designed exclusively for adolescents in rare diseases recruit poorly, even if conducted internationally...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29350780/an-evolutionary-concept-analysis-of-futility-in-healthcare
#2
Lauren Morata
AIM: To report a concept analysis of futility in healthcare. BACKGROUND: Each member of the healthcare team, the physician, the nurse, the patient, the family and all others involved perceive futility differently. The current evidence and knowledge in regard to futility in healthcare manifest a plethora of definitions, meanings and interpretations without consensus. DESIGN: Concept analysis. DATA SOURCES: Databases searched included Medline, Cumulative Index of Nursing and Allied Health Literature, Academic Search Premier, Cochrane Database of Systematic Reviews and PsycINFO...
January 19, 2018: Journal of Advanced Nursing
https://www.readbyqxmd.com/read/29350363/is-nighttime-laparoscopic-general-surgery-under-general-anesthesia-safe
#3
Ahmet Kemalettin Koltka, Mehmet İlhan, Achmet Ali, Ali Fuat Kaan Gök, Nükhet Sivrikoz, Teoman Hakan Yanar, Mustafa Kayıhan Günay, Cemalettin Ertekin
BACKGROUND: Fatigue and sleep deprivation can affect rational decision-making and motor skills, which can decrease medical performance and quality of patient care. The aim of the present study was to investigate the association between times of the day when laparoscopic general surgery under general anesthesia was performed and their adverse outcomes. METHODS: All laparoscopic cholecystectomies and appendectomies performed at the emergency surgery department of a tertiary university hospital from 01...
January 2018: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
https://www.readbyqxmd.com/read/29350231/tuning-the-sensitivity-of-lanthanide-activated-nir-nanothermometers-in-the-biological-windows
#4
P Cortelletti, A Skripka, C Facciotti, M Pedroni, G Caputo, N Pinna, M Quintanilla, A Benayas, F Vetrone, A Speghini
Lanthanide-activated SrF2 nanoparticles with a multishell architecture were investigated as optical thermometers in the biological windows. A ratiometric approach based on the relative changes in the intensities of different lanthanide (Nd3+ and Yb3+) NIR emissions was applied to investigate the thermometric properties of the nanoparticles. It was found that an appropriate doping with Er3+ ions can increase the thermometric properties of the Nd3+-Yb3+ coupled systems. In addition, a core containing Yb3+ and Tm3+ can generate light in the visible and UV regions upon near-infrared (NIR) laser excitation at 980 nm...
January 19, 2018: Nanoscale
https://www.readbyqxmd.com/read/29350183/integrated-biocircuits-engineering-functional-multicellular-circuits-and-devices
#5
Jordan Prox, Tory Smith, Chad Holl, Nick Chehade, Liang Guo
Novel in vitro platforms are currently revolutionizing the study and reconstruction of cellular circuitry to bypass the pertaining obstacles of data retrieval in vivo. While earlier approaches have provided great insights into culturing circuits in planar dissociated cell culture systems, the lack of full control over network activity and formation limits our understanding of their functionality. Thus, integrating various controllable parameters are required in creating a suitable microenvironment including cell patterning, highly-specified electrical and chemical stimuli, and rational circuit formation via logic functions...
January 19, 2018: Journal of Neural Engineering
https://www.readbyqxmd.com/read/29350179/risks-in-clinical-applications-of-scopolamine-butylbromide-injection
#6
Lei Zheng, Jing Yang, Chao Song
OBJECTIVE: To investigate and analyze the clinical application of scopolamine butylbromide injection and promote the rational use of the drug. MATERIALS AND METHODS: We classified and analyzed 3,695 cases of scopolamine butylbromide injection (effective cases only) collected over the period of January 2016 to July 2017, including details on gender, age, course of treatment, high-risk patients with other medications, adverse drug reactions, and drug combinations...
January 19, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29349856/self-responsibility-rationing-and-treatment-decision-making-managing-moral-narratives-alongside-fiscal-reality-in-the-obesity-surgery-clinic
#7
Amanda Owen-Smith, Joanna Coast, Jenny L Donovan
BACKGROUND: Addressing the prevalence of severe obesity and its concomitant morbidities is widely acknowledged as one of the most pressing global health priorities. Nevertheless, a paucity of effective interventions and universal pressure on health-care budgets means that access to obesity treatments is often limited. Although health-care rationing can be conceived as a socially constructed process, little is known about how decisions emerge within the context of face-to-face doctor-patient interactions...
January 19, 2018: Health Expectations: An International Journal of Public Participation in Health Care and Health Policy
https://www.readbyqxmd.com/read/29349841/novel-mof-derived-co-n-c-bifunctional-catalysts-for-highly-efficient-zn-air-batteries-and-water-splitting
#8
Mingdao Zhang, Quanbin Dai, Hegen Zheng, Mindong Chen, Liming Dai
Metal-organic frameworks (MOFs) and MOF-derived materials have recently attracted considerable interest as alternatives to noble-metal electrocatalysts. Herein, the rational design and synthesis of a new class of Co@N-C materials (C-MOF-C2-T) from a pair of enantiotopic chiral 3D MOFs by pyrolysis at temperature T is reported. The newly developed C-MOF-C2-900 with a unique 3D hierarchical rodlike structure, consisting of homogeneously distributed cobalt nanoparticles encapsulated by partially graphitized N-doped carbon rings along the rod length, exhibits higher electrocatalytic activities for oxygen reduction and oxygen evolution reactions (ORR and OER) than that of commercial Pt/C and RuO2 , respectively...
January 19, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29349753/expensive-care-resource-based-thresholds-for-potentially-inappropriate-treatment-in-intensive-care
#9
Dominic Wilkinson, Stavros Petrou, Julian Savulescu
In intensive care, disputes sometimes arise when patients or surrogates strongly desire treatment, yet health professionals regard it as potentially inappropriate. While professional guidelines confirm that physicians are not always obliged to provide requested treatment, determining when treatment would be inappropriate is extremely challenging. One potential reason for refusing to provide a desired and potentially beneficial treatment is because (within the setting of limited resources) this would harm other patients...
January 18, 2018: Monash Bioethics Review
https://www.readbyqxmd.com/read/29349597/drug-repurposing-screening-identifies-bortezomib-and-panobinostat-as-drugs-targeting-cancer-associated-fibroblasts-cafs-by-synergistic-induction-of-apoptosis
#10
Hak-Min Lee, Eunmyong Lee, So-Young Yeo, Sang Shin, Hyun-Kyu Park, Do-Hyun Nam, Seok-Hyung Kim
Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval...
January 18, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29349513/3d-qsar-study-of-steroidal-and-azaheterocyclic-human-aromatase-inhibitors-using-quantitative-profile-of-protein-ligand-interactions
#11
Sehan Lee, Mace G Barron
Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential target for endocrine disrupting chemicals as well as breast cancer therapy. In this work, 3D-QSAR combined with quantitative profile of protein-ligand interactions was employed in the identification and characterization of critical steric and electronic features of aromatase-inhibitor complexes and the estimation of their quantitative contribution to inhibition potency...
January 18, 2018: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29349464/boundary-induced-nucleation-control-a-theoretical-perspective
#12
Oleg Buller, Hong Wang, Wenchong Wang, Lifeng Chi, Andreas Heuer
The pre-patterning of a substrate to create energetically more attractive or repulsive regions allows one to generate a variety of structures in physical vapor deposition experiments. A particularly interesting structure is generated if the energetically attractive region forms a rectangular grid. For specific combinations of the particle flux, the substrate temperature and the lattice size it is possible to generate exactly one cluster per cell, giving rise to nucleation control. Here, we show that the experimental observations of nucleation control can be very well understood from a theoretical perspective...
January 19, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29349458/trends-in-adsorption-of-electrocatalytic-water-splitting-intermediates-on-cubic-abo3-oxides
#13
Joseph H Montoya, Andrew D Doyle, Jens K Nørskov, Aleksandra Vojvodic
The reactivity of solid oxide surfaces towards adsorption of oxygen and hydrogen is a key metric for the design of new catalysts for electrochemical water splitting. In this paper, we report on trends in the adsorption energy of different adsorbed intermediates derived from the oxidation and reduction of water for ternary ABO3 oxides in the cubic perovskite structure. Our findings support a previously reported trend that rationalizes the observed lower bound in oxygen evolution (OER) overpotentials from correlations in OH* and OOH* adsorption energies...
January 19, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29349292/membrane-insertion-of-and-membrane-potential-sensing-by-semiconductor-voltage-nanosensors-feasibility-demonstration
#14
Kyoungwon Park, Yung Kuo, Volodymyr Shvadchak, Antonino Ingargiola, Xinghong Dai, Lawrence Hsiung, Wookyeom Kim, Hong Zhou, Peng Zou, Alex J Levine, Jack Li, Shimon Weiss
We developed membrane voltage nanosensors that are based on inorganic semiconductor nanoparticles. We provide here a feasibility study for their utilization. We use a rationally designed peptide to functionalize the nanosensors, imparting them with the ability to self-insert into a lipid membrane with a desired orientation. Once inserted, these nanosensors could sense membrane potential via the quantum confined Stark effect, with a single-particle sensitivity. With further improvements, these nanosensors could potentially be used for simultaneous recording of action potentials from multiple neurons in a large field of view over a long duration and for recording electrical signals on the nanoscale, such as across one synapse...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29348627/chikungunya-virus-nsp1-interacts-directly-with-nsp2-and-modulates-its-atpase-activity
#15
Sameer Kumar, Abhishek Kumar, Prabhudutta Mamidi, Atul Tiwari, Sriram Kumar, Animamalar Mayavannan, Sagarika Mudulli, Ajit Kumar Singh, Bharat Bhusan Subudhi, Soma Chattopadhyay
Chikungunya virus (CHIKV) is a mosquito-borne virus, which has created an alarming threat in the world due to unavailability of vaccine and antiviral compounds. The CHIKV nsP2 contains ATPase, RTPase, helicase and protease activities, whereas, nsP1 is a viral capping enzyme. In alphaviruses, the four non-structural proteins form the replication complex in the cytoplasm and this study characterizes the interaction between CHIKV nsP1 and nsP2. It was observed that, both the proteins co-localize in the cytoplasm and interact in the CHIKV infected cells by confocal microscopy and immunoprecipitation assay...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348439/dual-suppression-of-inner-and-outer-mitochondrial-membrane-functions-augments-apoptotic-responses-to-oncogenic-mapk-inhibition
#16
Madhavika N Serasinghe, Jesse D Gelles, Kent Li, Lauren Zhao, Franco Abbate, Marie Syku, Jarvier N Mohammed, Brateil Badal, Cuahutlehuanitzin A Rangel, Kyle L Hoehn, Julide Tok Celebi, Jerry Edward Chipuk
Mitogen-activated protein kinase (MAPK) pathway inhibitors show promise in treating melanoma, but are unsuccessful in achieving long-term remission. Concordant with clinical data, BRAFV600E melanoma cells eliminate glycolysis upon inhibition of BRAFV600E or MEK with the targeted therapies Vemurafenib or Trametinib, respectively. Consequently, exposure to these therapies reprograms cellular metabolism to increase mitochondrial respiration and restrain cell death commitment. As the inner mitochondrial membrane (IMM) is sub-organellar site of oxidative phosphorylation (OXPHOS), and the outer mitochondrial membrane (OMM) is the major site of anti-apoptotic BCL-2 protein function, we hypothesized that suppressing these critical mitochondrial membrane functions would be a rational approach to maximize the pro-apoptotic effect of MAPK inhibition...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348271/intratumoral-payload-concentration-correlates-with-the-activity-of-antibody-drug-conjugates
#17
Donglu Zhang, Shang-Fan Yu, S Cyrus Khojasteh, Yong Ma, Thomas H Pillow, Jack D Sadowsky, Dian Su, Katherine R Kozak, Keyang Xu, Andrew G Polson, Peter Dragovich, Cornelis Eca Hop
Antibody-drug conjugates (ADCs) have become important scaffolds for targeted cancer therapies. However, ADC exposure - response correlation is not well characterized. We demonstrated that intratumor payload exposures correlated well with the corresponding efficacies of several disulfide-linked ADCs bearing an DNA alkylating agent, pyrrolo[2,1-c][1,4]benzodiazepine-dimer (PBD), in HER2-expressing xenograft models. The correlation suggests that a threshold concentration of intratumor payload is required to support sustained efficacy and an ADC can deliver an excessive level of payload to tumors that does not enhance efficacy ('Plateau' effect)...
January 18, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29348071/a-focused-fragment-library-targeting-the-antibiotic-resistance-enzyme-oxacillinase-48-synthesis-structural-evaluation-and-inhibitor-design
#18
Sundus Akhter, Bjarte Aarmo Lund, Aya Ismael, Manuel Langer, Johan Isaksson, Tony Christopeit, Hanna-Kirsti S Leiros, Annette Bayer
β-Lactam antibiotics are of utmost importance when treating bacterial infections in the medical community. However, currently their utility is threatened by the emergence and spread of β-lactam resistance. The most prevalent resistance mechanism to β-lactam antibiotics is expression of β-lactamase enzymes. One way to overcome resistance caused by β-lactamases, is the development of β-lactamase inhibitors and today several β-lactamase inhibitors e.g. avibactam, are approved in the clinic. Our focus is the oxacillinase-48 (OXA-48), an enzyme reported to spread rapidly across the world and commonly identified in Escherichia coli and Klebsiella pneumoniae...
December 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29348070/rational-approach-to-highly-potent-and-selective-apoptosis-signal-regulating-kinase-1-ask1-inhibitors
#19
Frank Lovering, Paul Morgan, Christophe Allais, Ann Aulabaugh, Joanne Brodfuehrer, Jeanne Chang, Jotham Coe, WeiDong Ding, Heather Dowty, Margaret Fleming, Richard Frisbie, Julia Guzova, David Hepworth, Jayasankar Jasti, Steve Kortum, Ravi Kurumbail, Shashi Mohan, Nikolaos Papaioannou, Joseph W Strohbach, Fabien Vincent, Katherine Lee, Christoph W Zapf
Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases...
December 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29347954/a-reverse-vaccinology-approach-to-the-identification-and-characterization-of-ctenocephalides-felis-candidate-protective-antigens-for-the-control-of-cat-flea-infestations
#20
Marinela Contreras, Margarita Villar, Sara Artigas-Jerónimo, Lidiia Kornieieva, Sergіі Mуtrofanov, José de la Fuente
BACKGROUND: Despite the abundance of the domestic cat flea, Ctenocephalides felis (Bouché, 1835) and disease risks associated with them, flea control is difficult and requires the development of new control interventions such as vaccines. In this study, a reverse vaccinology approach was designed to achieve a rational selection of cat flea candidate protective antigens. METHODS: Based on transcriptomics and proteomics data from unfed adult fleas it was possible to select more specific candidate protective antigens based on highly represented and functionally relevant proteins present in the predicted exoproteome...
January 18, 2018: Parasites & Vectors
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