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https://www.readbyqxmd.com/read/28927262/autophagy-is-pro-senescence-when-seen-in-close-up-but-anti-senescence-in-long-shot
#1
Yoojin Kwon, Ji Wook Kim, Jo Ae Jeoung, Mi-Sung Kim, Chanhee Kang
When mammalian cells and animals face a variety of internal or external stresses, they need to make homeostatic changes so as to cope with various stresses. To this end, mammalian cells are equipped with two critical stress responses, autophagy and cellular senescence. Autophagy and cellular senescence share a number of stimuli including telomere shortening, DNA damage, oncogenic stress and oxidative stress, suggesting their intimate relationship. Autophagy is originally thought to suppress cellular senescence by removing damaged macromolecules or organelles, yet recent studies also indicated that autophagy promotes cellular senescence by facilitating the synthesis of senescence-associated secretory proteins...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28926384/effect-of-surgeon-and-hospital-volume-on-morbidity-and-mortality-after-hip-fracture
#2
Kanu Okike, Priscilla H Chan, Elizabeth W Paxton
BACKGROUND: Prior studies have examined the relationship between surgeon and hospital volumes and outcome following hip fracture surgical procedures, but the results have been inconclusive. The purpose of this study was to assess the hip fracture volume-outcome relationship by analyzing data from a large, managed care registry. METHODS: The Kaiser Permanente Hip Fracture Registry prospectively records information on surgically treated hip fractures within the managed health-care system...
September 20, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/28926114/diabetes-mediated-myelopoiesis-and-the-relationship-to-cardiovascular-risk
#3
REVIEW
Tessa J Barrett, Andrew J Murphy, Ira J Goldberg, Edward A Fisher
Diabetes is the greatest risk factor for the development of cardiovascular disease, which, in turn, is the most prevalent cause of mortality and morbidity in diabetics. These patients have elevations in inflammatory monocytes, a factor consistently reported to drive the development of atherosclerosis. In preclinical models of both type 1 and type 2 diabetes, studies have demonstrated that the increased production and activation of monocytes is driven by enhanced myelopoiesis, promoted by factors, including hyperglycemia, impaired cholesterol efflux, and inflammasome activation, that affect the proliferation of bone marrow precursor cells...
August 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28923872/exposure-response-relationships-for-isavuconazole-in-patients-with-invasive-aspergillosis-and-other-filamentous-fungi
#4
Amit V Desai, Laura L Kovanda, William W Hope, David Andes, Johan W Mouton, Donna L Kowalski, Robert W Townsend, Salim Mujais, Peter L Bonate
Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and other filamentous fungi from the SECURE trial. Two hundred and thirty one patients who received the clinical dosing regimen and had exposure parameters were included in this analysis...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923870/associations-between-voriconazole-therapeutic-drug-monitoring-toxicity-and-outcome-in-liver-transplant-patients-an-observational-study
#5
Zahra Hashemizadeh, Parisa Badiee, Seyed Ali Malekhoseini, Hadi Raeisi Shahraki, Bita Geramizadeh, Hashem Montaseri
The aim of this study was to investigate the variability of voriconazole plasma level and its relationship with clinical outcomes and adverse events, among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included and voriconazole trough levels were quantified by the validated high-performance liquid chromatography method. Cytochrome P450 genotypes of CYP2C19 were evaluated in allograft liver tissues. A total of 832 voriconazole trough levels from 104 patients were measured...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923762/translating-basic-research-into-clinical-practice-vitamin-d-in-asthma-mechanisms-of-action-and-considerations-for-clinical-trials
#6
REVIEW
Paul E Pfeffer, Catherine M Hawrylowicz
There is increasing interest in the therapeutic utility of vitamin D in asthma, supported by a significant body of evidence on epidemiological associations between vitamin D insufficiency and worse asthma control. In support of a causal relationship, vitamin D beneficially modulates diverse immunological pathways in heterogeneous asthma endotypes, regulating the actions of lymphocytes, mast cells, antigen-presenting cells and structural cells to dampen excessive inflammatory responses. Allergic asthma is characterised by a failure of immune tolerance, and development of pathological responses to inhaled aeroallergens, and vitamin D has been extensively shown to support immune regulation...
September 15, 2017: Chest
https://www.readbyqxmd.com/read/28923290/use-of-adult-sensory-panel-to-study-individual-differences-in-the-palatability-of-a-pediatric-hiv-treatment-drug
#7
Julie A Mennella, Phoebe S Mathew, Elizabeth D Lowenthal
PURPOSE: The recommended first-line treatment for young children infected with HIV includes the liquid formulation of the co-formulated protease inhibitors lopinavir/ritonavir (Kaletra(®) [Abbott Laboratories, Chicago, Illinois]). Clinical reports indicate that some children readily accept the taste of Kaletra, whereas others strongly reject it, which can deter therapeutic adherence and outcomes. METHODS: As a proof-of-concept approach, a sensory panel of genotyped adults was used to document the range of individual differences in the taste and palatability (hedonics) of the liquid formulation of Kaletra and other taste stimuli, including common excipients...
September 15, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28923160/applying-the-neurodynamics-of-emotional-circular-causalities-in-psychosocial-and-cognitive-therapy-using-multi-sensory-environments-an-orbde-case-study-analysis
#8
Janice Ryan
This exploratory, evidence-based practice research study focuses on presenting a plausible mesoscopic brain dynamics hypothesis for the benefits of treating clients with psychosocial and cognitive challenges using a mindful therapeutic approach and multi-sensory environments. After an extensive neuroscientific review of the therapeutic benefits of mindfulness, a multi-sensory environment is presented as a window of therapeutic opportunity to more quickly and efficiently facilitate the neurobiological experience of becoming more mindful or conscious of self and environment...
October 2017: Nonlinear Dynamics, Psychology, and Life Sciences
https://www.readbyqxmd.com/read/28923059/osteoglycin-promotes-meningioma-development-through-downregulation-of-nf2-and-activation-of-mtor-signaling
#9
Yu Mei, Ziming Du, Changchen Hu, Noah F Greenwald, Malak Abedalthagafi, Nathalie Y R Agar, Gavin P Dunn, Wenya Linda Bi, Sandro Santagata, Ian F Dunn
BACKGROUND: Meningiomas are the most common primary intracranial tumors in adults. While a majority of meningiomas are slow growing neoplasms that may cured by surgical resection, a subset demonstrates more aggressive behavior and insidiously recurs despite surgery and radiation, without effective alternative treatment options. Elucidation of critical mitogenic pathways in meningioma oncogenesis may offer new therapeutic strategies. We performed an integrated genomic and molecular analysis to characterize the expression and function of osteoglycin (OGN) in meningiomas and explored possible therapeutic approaches for OGN-expressing meningiomas...
September 18, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28922720/1-25-oh-2d3-deficiency-increases-tm40d-tumor-growth-in-bone-and-accelerates-tumor-induced-bone-destruction-in-a-breast-cancer-bone-metastasis-model
#10
Guangping Lu, Jun Li, Jiahui Chu, Shidai Jin, Ziyi Fu, Dengshun Miao, Yongmei Yin
Breast cancer is one of the most common malignancies and bone is the commonest site of distant metastases. Evidences indicate that adequate supply of vitamin D will decrease the morbidity and mortality of breast cancer. However, the main role of vitamin D deficiency in breast cancer bone metastases remains unclear. In this study, the relationship between vitamin D and breast cancer bone metastases were evaluated. Results showed that 1,25(OH)2D3 can not only inhibit the proliferation, migration and invasion of breast cancer cell TM40D in vitro, but also attenuate the breast cancer cell TM40D-induced bone destruction in vivo, whose underlying mechanism was at least partially through decreasing the number of the osteoclasts...
September 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922553/programmable-nucleic-acid-based-polygons-with-controlled-neuroimmunomodulatory-properties-for-predictive-qsar-modeling
#11
Morgan Brittany Johnson, Justin R Halman, Emily Satterwhite, Alexey V Zakharov, My N Bui, Kheiria Benkato, Victoria Goldsworthy, Taejin Kim, Enping Hong, Marina A Dobrovolskaia, Emil F Khisamutdinov, Ian Marriott, Kirill A Afonin
In the past few years, the study of therapeutic RNA nanotechnology has expanded tremendously to encompass a large group of interdisciplinary sciences. It is now evident that rationally designed programmable RNA nanostructures offer unique advantages in addressing contemporary therapeutic challenges such as distinguishing target cell types and ameliorating disease. However, to maximize the therapeutic benefit of these nanostructures, it is essential to understand the immunostimulatory aptitude of such tools and identify potential complications...
September 18, 2017: Small
https://www.readbyqxmd.com/read/28922245/a-craniometric-analysis-of-cranial-base-and-cranial-vault-differences-in-patients-with-metopic-craniosynostosis
#12
Sanjay Naran, Daniel Mazzaferro, Ari Wes, Arastoo Vossough, Scott P Bartlett, Jesse A Taylor
PURPOSE: The effect of synostosis is not confined to the immediate vicinity of the suture. The authors hypothesized metopic craniosynostosis results in migration of lateral structures from midline, and differences in segmental volume of the cranial fossa. METHODS: A retrospective case-controlled cohort analysis of patients with nonsyndromic metopic craniosynostosis was performed. Craniometric angles, distances to landmarks from midline, cephalic index, and segmented volume ratios were calculated...
September 15, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28922161/comorbidity-analysis-between-alzheimer-s-disease-and-type-2-diabetes-mellitus-t2dm-based-on-shared-pathways-and-the-role-of-t2dm-drugs
#13
Reagon Karki, Alpha Tom Kodamullil, Martin Hofmann-Apitius
BACKGROUND: Various studies suggest a comorbid association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) indicating that there could be shared underlying pathophysiological mechanisms. OBJECTIVE: This study aims to systematically model relevant knowledge at the molecular level to find a mechanistic rationale explaining the existing comorbid association between AD and T2DM. METHOD: We have used a knowledge-based modeling approach to build two network models for AD and T2DM using Biological Expression Language (BEL), which is capable of capturing and representing causal and correlative relationships at both molecular and clinical levels from various knowledge resources...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922009/the-development-and-initial-validation-of-the-countertransference-management-scale
#14
Andrés E Pérez-Rojas, Beatriz Palma, Avantika Bhatia, John Jackson, Earta Norwood, Jeffrey A Hayes, Charles J Gelso
Countertransference is an important aspect of the therapeutic relationship that exists in therapies of all theoretical orientations, and depending on how it is managed, it can either help or hinder treatment. Management of countertransference has been measured almost exclusively with the Countertransference Factors Inventory (Van Wagoner, Gelso, Hayes, & Diemer, 1991) and its variations, all of which focus on 5 therapist qualities theorized to facilitate management: self-insight, conceptualizing ability, empathy, self-integration, and anxiety management...
September 2017: Psychotherapy
https://www.readbyqxmd.com/read/28921890/phase-ii-study-of-dabigatran-in-children-with-venous-thrombosis-pharmacokinetics-safety-and-tolerabilty
#15
J M L Halton, M Albisetti, B Biss, L Bomgaars, M Brueckmann, S Gropper, R Harper, F Huang, M Luciani, H Maas, I Tartakovsky, L G Mitchell
BACKGROUND: The current standard-of-care treatments for pediatric venous thromboembolism (VTE) have limitations. Dabigatran etexilate (DE), a direct thrombin inhibitor, may offer an alternative therapeutic option. OBJECTIVES: To assess the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of DE oral liquid formulation (OLF) in pediatric patients with VTE. PATIENTS/METHODS: Patients who had completed planned treatment with low-molecular-weight heparin or oral anticoagulants for VTE were enrolled in two age groups (2-<12 and 1-<2 years) and received DE OLF based on an age- and weight-adjusted nomogram...
September 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28921000/-hemodynamic-interplay-between-tricuspid-valve-and-right-ventricle
#16
REVIEW
C Edel, R Erbel, T Budde
The tricuspid valve and the right ventricle are hemodynamically closely related. Pathological changes of the valve or of the ventricle itself and also various diseases beyond that can result in a downward spiral of mutual interference, which is of prognostic importance for the patient. The development of a functional tricuspid regurgitation is of great importance. Especially with the help of 3D-echocardiography, more and more changes and mechanisms have been identified that are crucial in this process. This article provides a review of the relationship between the tricuspid valve and the right ventricle emphasizing the current knowledge of the causes, the pathophysiological concepts, the underlying structural changes and the therapeutic approaches based on this...
September 18, 2017: Herz
https://www.readbyqxmd.com/read/28919706/profile-of-pembrolizumab-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma-design-development-and-place-in-therapy
#17
REVIEW
Sulsal Haque, Mahender Yellu, Jaskirat Randhawa, Nooshin Hashemi-Sadraei
Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919509/molecular-and-macro-scale-analysis-of-enzyme-crosslinked-silk-hydrogels-for-rational-biomaterial-design
#18
Meghan McGill, Jeannine M Coburn, Benjamin P Partlow, Xuan Mu, David L Kaplan
Silk fibroin-based hydrogels have exciting applications in tissue engineering and therapeutic molecule delivery; however, their utility is dependent on their diffusive properties. The present study describes a molecular and macro-scale investigation of enzymatically-crosslinked silk fibroin hydrogels, and demonstrates that these systems have tunable crosslink density and diffusivity. We developed a liquid chromatography tandem mass spectroscopy (LC-MS/MS) method to assess the quantity and order of covalent tyrosine crosslinks in the hydrogels...
September 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28919308/alternative-splicing-in-cancers-from-aberrant-regulation-to-new-therapeutics
#19
REVIEW
Xiaowei Song, Zhenyu Zeng, Huanhuan Wei, Zefeng Wang
Alternative splicing is one of the most common mechanisms for gene regulation in humans, and plays a vital role to increase the complexity of functional proteins. In this article, we seek to provide a general review on the relationships between alternative splicing and tumorigenesis. We briefly introduce the basic rules for regulation of alternative splicing, and discuss recent advances on dynamic regulation of alternative splicing in cancers by highlighting the roles of a variety of RNA splicing factors in tumorigenesis...
September 14, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28919130/the-nuts-and-bolts-of-cognitive-remediation-exploring-how-different-training-components-relate-to-cognitive-and-functional-gains
#20
Matteo Cella, Til Wykes
BACKGROUND: Cognitive Remediation (CR) is an evidence based treatment targeting cognitive and functional difficulties in people with psychosis. Despite the large number of effectiveness studies, only limited evidence exists for the active ingredients of this therapy. This study begins to fill this gap by exploring the relationship between CR ingredients, including alliance with a therapist, and therapy outcomes. METHOD: This is a secondary analysis based on data from a published randomised controlled trial comparing CR+treatment-as-usual (TAU) to TAU alone...
September 14, 2017: Schizophrenia Research
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