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https://www.readbyqxmd.com/read/29679667/systemic-delivery-of-bace1-sirna-through-neuron-targeted-nanocomplexes-for-treatment-of-alzheimer-s-disease
#1
Pengzhen Wang, Xiaoyao Zheng, Qian Guo, Peng Yang, Xiaoying Pang, Kang Qian, Wei Lu, Qizhi Zhang, Xinguo Jiang
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme to cleave the amyloid precursor protein to develop Alzheimer's disease (AD). Reducing BACE1 expression in central neuron through RNA interference technology shows great promise to overcome AD. However, to obtain an efficient and neurons-specific delivery of siRNA against BACE1 through systemic administration remains challenging. Here, we design and prepare siRNA nano-carriers based on PEGylated poly(2-(N,N-dimethylamino) ethyl methacrylate) (PEG-PDMAEMA) modified with both the CGN peptide for blood-brain barrier (BBB) penetration and the Tet1 peptide for neuron-specific binding...
April 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29677526/anti-inflammatory-effects-of-4-o-methyl-benzenesulfonyl-benzoxazolone-mbb-in-vivo-and-in-vitro-as-a-novel-nsaids-lead-compound
#2
Li Tang, Jie-Ran Luo, Dai-Tian Li, Rui Ge, Yun-Long Ma, Fei Xu, Tai-Gang Liang, Shu-Rong Ban, Qing-Shan Li
BACKGROUND: Great attention has been paid to the development of novel anti-inflammatory drugs to overcome the adverse reactions of traditional drugs. Recently, a new compound 4-o-methyl-benzenesulfonyl benzoxazolone (MBB) we have prepared attracted our attention for its promising anti-inflammatory activity and low toxicity. The present study aimed to further investigate the anti-inflammatory effects of MBB both in vivo and in vitro in order to determine its potential as a novel NSAIDs lead compound...
December 15, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29669470/web-based-rehabilitation-interventions-for-people-with-rheumatoid-arthritis-a-systematic-review
#3
Cynthia Srikesavan, Catherine Bryer, Usama Ali, Esther Williamson
Background Rehabilitation approaches for people with rheumatoid arthritis include joint protection, exercises and self-management strategies. Health interventions delivered via the web have the potential to improve access to health services overcoming time constraints, physical limitations, and socioeconomic and geographic barriers. The objective of this review is to determine the effects of web-based rehabilitation interventions in adults with rheumatoid arthritis. Methods Randomised controlled trials that compared web-based rehabilitation interventions with usual care, waiting list, no treatment or another web-based intervention in adults with rheumatoid arthritis were included...
January 1, 2018: Journal of Telemedicine and Telecare
https://www.readbyqxmd.com/read/29665040/discovery-characterization-and-clinical-utility-of-prostaglandin-agonists-for-the-treatment-of-glaucoma
#4
REVIEW
Peter G Klimko, Najam A Sharif
Topical ophthalmic formulations of analogs of the endogenous arachidonic acid cyclooxygenase metabolite, prostaglandin F2α (PGF2α ), are the standard of care for treating the blinding disease glaucoma. These are the most potent and efficacious medical therapies for lowering intraocular pressure (IOP), the most important identified risk factor for disease progression. They have few side-effects and offer the convenience of once-a-day dosing. It was initially believed that endogenous PGs raised IOP and caused substantial ocular surface adverse effects...
April 17, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29658921/site-directed-immobilization-of-bone-morphogenetic-protein-2-to-solid-surfaces-by-click-chemistry
#5
Claudia Siverino, Barbara Tabisz, Tessa Lühmann, Lorenz Meinel, Thomas Müller, Heike Walles, Joachim Nickel
Different therapeutic strategies for the treatment of non-healing long bone defects have been intensively investigated. Currently used treatments present several limitations that have led to the use of biomaterials in combination with osteogenic growth factors, such as bone morphogenetic proteins (BMPs). Commonly used absorption or encapsulation methods require supra-physiological amounts of BMP2, typically resulting in a so-called initial burst release effect that provokes several severe adverse side effects...
March 29, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29655877/endocrine-and-haemodynamic-changes-in-resistant-hypertension-and-blood-pressure-responses-to-spironolactone-or-amiloride-the-pathway-2-mechanisms-substudies
#6
Bryan Williams, Thomas M MacDonald, Steve V Morant, David J Webb, Peter Sever, Gordon T McInnes, Ian Ford, J Kennedy Cruickshank, Mark J Caulfield, Sandosh Padmanabhan, Isla S Mackenzie, Jackie Salsbury, Morris J Brown
BACKGROUND: In the PATHWAY-2 study of resistant hypertension, spironolactone reduced blood pressure substantially more than conventional antihypertensive drugs. We did three substudies to assess the mechanisms underlying this superiority and the pathogenesis of resistant hypertension. METHODS: PATHWAY-2 was a randomised, double-blind crossover trial done at 14 UK primary and secondary care sites in 314 patients with resistant hypertension. Patients were given 12 weeks of once daily treatment with each of placebo, spironolactone 25-50 mg, bisoprolol 5-10 mg, and doxazosin 4-8 mg and the change in home systolic blood pressure was assessed as the primary outcome...
April 11, 2018: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29642900/cisplatin-based-therapy-the-role-of-the-mitogen-activated-protein-kinase-signaling-pathway
#7
REVIEW
Iman W Achkar, Nabeel Abdulrahman, Hend Al-Sulaiti, Jensa Mariam Joseph, Shahab Uddin, Fatima Mraiche
Cisplatin is a widely used chemotherapeutic agent for treatment of various cancers. However, treatment with cisplatin is associated with drug resistance and several adverse side effects such as nephrotoxicity, reduced immunity towards infections and hearing loss. A Combination of cisplatin with other drugs is an approach to overcome drug resistance and reduce toxicity. The combination therapy also results in increased sensitivity of cisplatin towards cancer cells. The mitogen activated protein kinase (MAPK) pathway in the cell, consisting of extracellular signal regulated kinase, c-Jun N-terminal kinase, p38 kinases, and downstream mediator p90 ribosomal s6 kinase (RSK); is responsible for the regulation of various cellular events including cell survival, cell proliferation, cell cycle progression, cell migration and protein translation...
April 11, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29623257/immune-dysregulation-in-cancer-patients-undergoing-immune-checkpoint-inhibitor-treatment-and-potential-predictive-strategies-for-future-clinical-practice
#8
REVIEW
Ronald Anderson, Bernardo L Rapoport
Realization of the full potential of immune checkpoint inhibitor-targeted onco-immunotherapy is largely dependent on overcoming the obstacles presented by the resistance of some cancers, as well as on reducing the high frequency of immune-related adverse events (IRAEs) associated with this type of immunotherapy. With the exception of combining therapeutic monoclonal antibodies, which target different types of immune checkpoint inhibitory molecules, progress in respect of improving therapeutic efficacy has been somewhat limited to date...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29623171/bioresorbable-coronary-scaffolds-deployment-tips-and-tricks-and-the-future-of-the-technology
#9
REVIEW
J Ribamar Costa, Alexandre Abizaid
Bioresorbable scaffolds (BRS) were developed as an alternative to drug-eluting stents (DES) to facilitate vessel restoration and reduce the risk of future adverse events. However, recent meta-analyses and "real-world" registries have raised some concern about the safety of this novel technology, especially due to an increased risk of thrombosis within the first weeks of scaffold implantation. These devices appear to be less forgiving to poor implantation strategies when compared to contemporary DES...
January 2018: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/29621751/skin-barrier-restoration-and-moisturization-using-horse-oil-loaded-dissolving-microneedle-patches
#10
Chisong Lee, Younghyon Andrew Eom, Huisuk Yang, Mingyu Jang, Sang Uk Jung, Ye Oak Park, Si Eun Lee, Hyungil Jung
BACKGROUND: Horse oil (HO) has skin barrier restoration and skin-moisturizing effects. Although cream formulations have been used widely and safely, their limited penetration through the stratum corneum is a major obstacle to maximizing the cosmetic efficacy of HO. Therefore, we aimed to encapsulate HO in a cosmetic dissolving microneedle (DMN) for efficient transdermal delivery. METHODS: To overcome these limitations of skin permeation, HO-loaded DMN (HO-DMN) patches were developed and evaluated for their efficacy and safety using in vitro and clinical studies...
April 5, 2018: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/29621421/role-of-bulk-and-nanosized-sio-2-to-overcome-salt-stress-during-fenugreek-germination-trigonella-foenum-graceum-l
#11
Reihane Ivani, Seyed Hossein Sanaei Nejad, Bijan Ghahraman, Ali Reza Astaraei, Hassan Feizi
The effects of bulk and Nanosized SiO2 on seed germination and seedling growth indices of fenugreek under salinity stress were studied in the College of Agriculture, Ferdowsi University of Mashhad, Iran, in 2013. The experimental treatments included four levels of salinity stress (0, 50, 100 and 150 mM), two concentrations of bulk (50 and 100 ppm), two concentrations of nanosized SiO2 (50 and 100 ppm), and control (without any SiO2 types). Seedling growth attributes significantly improved when bulk and nanosized SiO2 concentrations applied singly or with different levels of salt stress...
April 5, 2018: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29618498/impact-of-thiopurines-on-the-natural-history-and-surgical-outcome-of-ulcerative-colitis-a-cohort-study
#12
Carl Eriksson, Sara Rundquist, Yang Cao, Scott Montgomery, Jonas Halfvarson
OBJECTIVE: Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation. DESIGN: Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included...
April 4, 2018: Gut
https://www.readbyqxmd.com/read/29617777/adolescent-wound-care-self-efficacy-and-practices-after-voluntary-medical-male-circumcision-a-multicountry-assessment
#13
Webster Mavhu, Karin Hatzold, Kim H Dam, Michelle R Kaufman, Eshan U Patel, Lynn M Van Lith, Catherine Kahabuka, Arik V Marcell, Lusanda Mahlasela, Emmanuel Njeuhmeli, Kim Seifert Ahanda, Getrude Ncube, Gissenge Lija, Collen Bonnecwe, Aaron A R Tobian
Background: Adolescent boys (aged 10-19 years) constitute the majority of voluntary medical male circumcision (VMMC) clients in sub-Saharan Africa. They are at higher risk of postoperative infections compared to adults. We explored adolescents' wound-care knowledge, self-efficacy, and practices after VMMC to inform strategies for reducing the risks of infectious complications postoperatively. Methods: Quantitative and qualitative data were collected in South Africa, Tanzania, and Zimbabwe between June 2015 to September 2016...
April 3, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29615158/reduction-in-central-line-associated-bloodstream-infections-in-a-nicu-practical-lessons-for-its-achievement-and-sustainability
#14
Judith A Hawes, Kyong-Soon Lee
Central venous catheters are commonly used for the provision of parenteral nutrition and medications for critically ill neonates in the NICU. However, central line-associated bloodstream infections (CLABSIs) are a major complication associated with their use and remain an important cause of nosocomial sepsis in NICUs. Central line-associated bloodstream infection has shifted from being an expected routine complication of central line use to an adverse event now evaluated as a critical event with the goal of identifying root causes so future CLABSI events are prevented...
March 1, 2018: Neonatal Network: NN
https://www.readbyqxmd.com/read/29603022/cytotoxic-effects-to-mouse-and-human-gingival-fibroblasts-of-a-nanohybrid-ormocer-versus-dimethacrylate-based-composites
#15
Andrea Schubert, Christopher Ziegler, Andrea Bernhard, Ralf Bürgers, Nicolai Miosge
OBJECTIVES: Tooth-colored composites have emerged as a standard restorative material in caries therapy and have largely replaced materials such as silver amalgam or glass ionomer cements. In addition to their superior esthetics and desirable mechanical properties, composites also comprise negative characteristics, such as wear, shrinkage, and an adverse biocompatibility. Modifications of classic resin-based dental composites have been developed to overcome these shortcomings. For example, ormocers are innovative inorganic-organic hybrid polymers that form a siloxane network modified by the incorporation of organic groups...
March 30, 2018: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29596646/new-single-capsule-of-bismuth-metronidazole-and-tetracycline-given-with-omeprazole-versus-quadruple-therapy-consisting-of-bismuth-omeprazole-amoxicillin-and-clarithromycin-for-eradication-of-helicobacter-pylori-in-duodenal-ulcer-patients-a-chinese-prospective
#16
Yong Xie, Xiaolin Pan, Yan Li, Huahong Wang, Yiqi Du, Jianming Xu, Jiangbin Wang, Zhirong Zeng, Ye Chen, Guoxin Zhang, Kaichun Wu, Dongsheng Liu, Nonghua Lv
Objectives: To assess the efficacy and safety of omeprazole given with the new single capsule of bismuth, metronidazole and tetracycline (OBMT) compared with quadruple treatment consisting of omeprazole, bismuth, amoxicillin and clarithromycin (OBAC) for Helicobacter pylori eradication in duodenal ulcer patients. Methods: This single-blind, randomized multicentre trial was conducted in 10 tertiary hospitals in China between January 2013 and April 2014. Patients were randomized to receive 10 days of OBMT therapy or 10 days of OBAC therapy...
March 27, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29596095/dexamethasone-as-an-adjuvant-for-caudal-blockade-in-pediatric-surgical-patients-a-systematic-review-and-meta-analysis
#17
Matthew A Chong, Daniel J Szoke, Nicolas M Berbenetz, Cheng Lin
BACKGROUND: Caudal block is commonly used to provide postoperative analgesia after pediatric surgery in the lower abdomen. Typically administered as a single-shot technique, 1 limitation of this block is the short duration of analgesia. To overcome this, dexamethasone has been used as an adjuvant to prolong block duration. However, there are concerns about steroid-related morbidity and the optimal route of dexamethasone administration (eg, caudal or intravenous) is unknown. METHODS: We conducted a systematic review and random-effects meta-analysis of randomized controlled trials recruiting pediatric surgical patients receiving a caudal block for surgical anesthesia or postoperative analgesia...
March 27, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29592839/high-resolution-mass-spectrometry-based-methodologies-for-identification-of-etravirine-bioactivation-to-reactive-metabolites-in-vitro-and-in-vivo-approaches
#18
Ana L A Godinho, Inês L Martins, João Nunes, Catarina Charneira, Jorge Grilo, Diogo M Silva, Sofia A Pereira, Karina Soto, M Conceição Oliveira, M Matilde Marques, Cristina C Jacob, Alexandra M M Antunes
Drug bioactivation to reactive metabolites capable of covalent adduct formation with bionucleophiles is a major cause of drug-induced adverse reactions. Therefore, elucidation of reactive metabolites is essential to unravel the toxicity mechanisms induced by drugs and thereby identify patient subgroups at higher risk. Etravirine (ETR) was the first second-generation Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) to be approved, as a therapeutic option for HIV-infected patients who developed resistance to the first-generation NNRTIs...
March 25, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29587793/thriving-in-scrubs-a-qualitative-study-of-resident-resilience
#19
Abigail Ford Winkel, Anne West Honart, Annie Robinson, Aubrie-Ann Jones, Allison Squires
BACKGROUND: Physician well-being impacts both doctors and patients. In light of high rates of physician burnout, enhancing resilience is a priority. To inform effective interventions, educators need to understand how resilience develops during residency. METHODS: A qualitative study using grounded theory examined the lived experience of resilience in residents. A cohort of obstetrics and gynecology residents were selected as a purposive, intensity sample.. Eighteen residents in all years of training participated in semi-structured interviews...
March 27, 2018: Reproductive Health
https://www.readbyqxmd.com/read/29579254/the-tendril-plot-a-novel-visual-summary-of-the-incidence-significance-and-temporal-aspects-of-adverse-events-in-clinical-trials
#20
Martin Karpefors, James Weatherall
Background: In contrast to efficacy, safety hypotheses of clinical trials are not always pre-specified, and therefore, the safety interpretation work of a trial tends to be more exploratory, often reactive, and the analysis more statistically and graphically challenging. Methods: We introduce a new means of visualizing the adverse event data across an entire clinical trial. Results: The approach overcomes some of the current limitations of adverse event analysis and streamlines the way safety data can be explored, interpreted and analyzed...
March 21, 2018: Journal of the American Medical Informatics Association: JAMIA
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