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https://www.readbyqxmd.com/read/28441582/synthesis-and-antiproteasomal-activity-of-novel-o-benzyl-salicylamide-based-inhibitors-built-from-leucine-and-phenylalanine
#1
Radek Jorda, Jan Dušek, Eva Řezníčková, Karel Pauk, Pratibha P Magar, Aleš Imramovský, Vladimír Kryštof
Inhibition of protein degradation is one of strategies for suppression of uncontrolled proliferation of cancer cells. Proteolytic degradation in cells is mainly ensured by proteasome and its inhibition by bortezomib showed benefit in clinical use for the treatment of multiple myeloma. We report here the library of antiproteasomal O-benzyl salicylamides built from leucine and phenylalanine. Prepared compounds displayed antiproliferative activity on K562, CEM and U266 cancer cell lines, ranging from high micromolar to submicromolar GI50 values...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28441357/investigation-of-the-anti-leishmania-leishmania-infantum-activity-of-some-natural-sesquiterpene-lactones
#2
Imke F Wulsten, Thais A Costa-Silva, Juliana T Mesquita, Marta L Lima, Mariana K Galuppo, Noemi N Taniwaki, Samanta E T Borborema, Fernando B Da Costa, Thomas J Schmidt, Andre G Tempone
Leishmaniases are neglected infectious diseases caused by parasites of the 'protozoan' genus Leishmania. Depending on the parasite species, different clinical forms are known as cutaneous, muco-cutaneous, and the visceral leishmaniasis (VL). VL is particularly fatal and the therapy presents limitations. In the search for new anti-leishmanial hit compounds, seven natural sesquiterpene lactones were evaluated against promastigotes and intracellular amastigotes of Leishmania (Leishmania) infantum, a pathogen causing VL...
April 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28441074/assessing-lebanese-bilingual-children-the-use-of-cross-linguistic-lexical-tasks-in-lebanese-arabic
#3
Christel Khoury Aouad Saliby, Christophe Dos Santos, Edith Kouba Hreich, Camille Messarra
Since norms for vocabulary acquisition in Lebanese bilingual children (L1: Lebanese, L2: French and/or English) do not yet exist, clinical assessment based on normative data and using appropriate tools remains difficult for speech and language therapists. The current study focuses on exploring and comparing lexical performances of typically developing Lebanese bilingual children (32 Bi-TD, aged 5;7 to 6;9) and those with specific language impairment (10 Bi-SLI, aged 5;9 to 7;10), using cross-linguistic lexical tasks (LITMUS-CLT, COST Action IS0804, 2011) in Lebanese Arabic language (CLT-LB), specific to the Lebanese context...
April 25, 2017: Clinical Linguistics & Phonetics
https://www.readbyqxmd.com/read/28440983/-detection-of-cardiovascular-risk-in-healthcare-workers-on-the-basis-of-who-jnc-7-atp-iii-criteria
#4
Roma Rubí Rodríguez-Reyes, José Eduardo Navarro-Zarza, Tania Leticia Tello-Divicino, Isela Parra-Rojas, Oscar Zaragoza-García, Iris Paola Guzmán-Guzmán
BACKGROUND: Anthropometric and blood pressure measurements are significant parameters in the assessment of cardiovascular risk (CVR). The aim was to establish the distribution of clinical-anthropometric parameters in health care workers according to the criteria established by WHO/JNC 7/ATP III. METHODS: Observational, cross-sectional study in 350 workers of a general hospital. Definitions of anthropometric alterations were made considering the criteria established by WHO and the Asian ATP III, while altered blood pressure was defined by criteria JNC 7 and ATP III...
May 2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28440963/clinical-sequencing-using-a-next-generation-sequencing-based-multiplex-gene-assay-in-patients-with-advanced-solid-tumors
#5
Tadayuki Kou, Masashi Kanai, Yoshihiro Yamamoto, Mayumi Kamada, Masahiko Nakatsui, Tomohiro Sakuma, Hiroaki Mochizuki, Akinori Hiroshima, Aiko Sugiyama, Eijiro Nakamura, Hidehiko Miyake, Sachiko Minamiguchi, Kyoichi Takaori, Shigemi Matsumoto, Hironori Haga, Hiroshi Seno, Shinji Kosugi, Yasushi Okuno, Manabu Muto
Advances in next-generation sequencing (NGS) technologies have enabled physicians to test for genomic alterations in multiple cancer-related genes at once in daily clinical practice. In April 2015, we introduced clinical sequencing using an NGS-based multiplex gene assay (OncoPrime(™) ) certified by the Clinical Laboratory Improvement Amendment. This assay covers the entire coding regions of 215 genes and the rearrangement of 17 frequently rearranged genes with clinical relevance in human cancers. The principal indications for the assay were cancers of unknown primary site, rare tumors, and any solid tumors that were refractory to standard chemotherapy...
April 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28440743/targeting-underlying-biologic-mechanisms-in-selecting-adjunctive-therapies-to-improve-periodontal-treatment-in-smokers-a-commentary
#6
Maria L Geisinger, Nicolaas C Geurs, Dorothy Ogdon, Michael S Reddy
Despite well-established evidence that cigarette smoking is the largest modifiable risk factor for periodontal disease and has many deleterious health effects, the treatment of periodontal disease in smokers remains a challenge of periodontal therapy. A recent meta-analysis revealed that the adjunctive use of local delivery of antimicrobials, but not systemic antibiotic usage, with nonsurgical periodontal therapy resulted in an improvement in clinical periodontal parameters. Further evaluation of the current literature reveals that host modulation therapy may also result in a clinical benefit in smokers...
April 25, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28440204/apixaban-metabolism-pharmacologic-properties-and-drug-interaction
#7
Peter Kubisz, Lucia Stanciakova, Miroslava Dobrotova, Matej Samos, Marian Mokan, Jan Stasko
BACKGROUND: Apixaban is an oral, potent, highly selective, reversible and direct inhibitor of activated coagulation factor X, that is the end point of the intrinsic and extrinsic coagulation pathway. Additionally, apixaban has the capacity to indirectly inhibit thrombin-induced platelet aggregation. This new oral anticoagulant represents an immediate-release form of peroral drug with quick dissolution, linear pharmacokinetics, good bioavailability and rapid onset and offset of action...
April 24, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28440199/anti-hyperglycemic-agents-for-the-treatment-of-type-2-diabetes-mellitus-role-in-cardioprotection-during-the-last-decade
#8
Duygu Kocyigit, Kadri Murat Gurses, Muhammed Ulvi Yalcin, Lale Tokgozoglu
Type 2 diabetic patients are known to have a tendency to develop cardiovascular (CV) disease (CVD), and related unfavourable outcomes such as heart failure, myocardial infarction (MI), cerebrovascular events (eg. stroke), and related mortality. Long- term clinical trials have revealed contradictory findings regarding the relationship between glycemic control and CV benefits due to variations in the key characteristics of the study population. During the last decade, number of pharmacological agents used for glucose- lowering in the treatment of type 2 diabetes mellitus (T2DM) has increased owing to the introduction of dipeptidyl peptidase- IV (DPP- IV) inhibitors, glucagon- like peptide- 1 (GLP- 1) receptor agonists, and sodium-glucose co-transporter 2 (SGLT- 2) inhibitors...
April 23, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28440009/sodium-glucose-co-transporter-2-inhibitors-for-type-2-diabetes-mellitus-an-overview-for-the-primary-care-physician
#9
REVIEW
Paresh Dandona, Ajay Chaudhuri
AIMS: Sodium-glucose co-transporter type 2 (SGLT2) inhibitors are a new class of anti-hyperglycaemic agents in type 2 diabetes mellitus (T2DM). This review examines their mechanism of action and provides an overview of safety and efficacy from the main studies of SGLT2 inhibitors marketed in the United States and Europe, namely, canagliflozin, dapagliflozin and empagliflozin. METHODS: We searched the PubMed database to identify relevant publications on the mechanism of action of SGLT2 inhibitors and clinical trial reports...
April 24, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28439950/protein-disulfide-isomerase-inhibition-synergistically-enhances-the-efficacy-of-sorafenib-for-hepatocellular-carcinoma
#10
Jae-Kyung Won, Su Jong Yu, Chae Young Hwang, Sung-Hwan Cho, Sang-Min Park, Kwangsoo Kim, Won-Mook Choi, Hyeki Cho, Eun Ju Cho, Jeong-Hoon Lee, Kyung Bun Lee, Yoon Jun Kim, Kyung-Suk Suh, Ja-June Jang, Chung Yong Kim, Jung-Hwan Yoon, Kwang-Hyun Cho
Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients' survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28439798/the-changing-landscape-of-genetic-testing-for-inherited-breast-cancer-predisposition
#11
REVIEW
Anosheh Afghahi, Allison W Kurian
The advent of multiple-gene germline panel testing has led to significant advances in hereditary breast and ovarian cancer risk assessment. These include guideline-specific cancer risk management recommendations for patients and their families, such as screening with breast magnetic resonance imaging and risk-reducing surgeries, which have the potential to reduce substantially the morbidity and mortality associated with a hereditary cancer predisposition. However, controversy remains about the clinical validity and actionability of genetic testing in a broader patient population...
May 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28439755/what-do-key-stakeholders-think-about-hiv-self-testing-in-canada-results-from-a-cross-sectional-survey
#12
N Pant Pai, M Smallwood, D Gulati, N Lapczak, A Musten, C Gaydos, C Johnston, M Steben, T Wong, N Engel, J Kim
Human immunodeficiency virus (HIV) self-testing presents an empowering alternative to facility-based testing for reaching undiagnosed HIV infected individuals, but is not currently available in Canada. We surveyed stakeholders (clinical providers, public health professionals, researchers) engaged in HIV testing initiatives nationwide to identify the concerns, opportunities and challenges to implementing HIV self-testing in Canada. An online cross-sectional survey was disseminated by the Canadian Institutes of Health Research Centre for REACH 2...
April 24, 2017: AIDS and Behavior
https://www.readbyqxmd.com/read/28439495/immunotherapies-in-sarcoma-updates-and-future-perspectives
#13
REVIEW
Marwan Ghosn, Elie El Rassy, Hampig Raphael Kourie
Sarcomas are malignant tumors that are characterized by a wide diversity of subtypes with various cytogenetic profiles. Despite major treatment breakthroughs, standard treatment modalities combining chemotherapy, radiotherapy, and surgery failed to improve overall survival. Therefore, high expectations are foreseen with immunotherapy upon its maturation and better understanding of its mechanism of action. This paper presents a targeted review of the published data and ongoing clinical trials in immunotherapies of sarcomas, mainly adoptive cell therapies, cancer vaccines and immune checkpoint inhibitors...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28439376/-back-to-bedside-residents-and-fellows-perspectives-on-finding-meaning-in-work
#14
Dustin M Hipp, Kristy L Rialon, Kathryn Nevel, Anai N Kothari, Lcdr Dinchen A Jardine
BACKGROUND: Physician burnout is common and associated with significant consequences for physicians and patients. One mechanism to combat burnout is to enhance meaning in work. OBJECTIVE: To provide a trainee perspective on how meaning in work can be enhanced in the clinical learning environment through individual, program, and institutional efforts. METHODS: "Back to Bedside" resulted from an appreciative inquiry exercise by 37 resident and fellow members of the ACGME's Council of Review Committee Residents (CRCR), which was guided by the memoir When Breath Becomes Air by Paul Kalanithi...
April 2017: Journal of Graduate Medical Education
https://www.readbyqxmd.com/read/28439022/structure-of-a-protective-epitope-of-group-b-streptococcus-type-iii-capsular-polysaccharide
#15
Filippo Carboni, Roberto Adamo, Monica Fabbrini, Riccardo De Ricco, Vittorio Cattaneo, Barbara Brogioni, Daniele Veggi, Vittoria Pinto, Irene Passalacqua, Davide Oldrini, Rino Rappuoli, Enrico Malito, Immaculada Y Ros Margarit, Francesco Berti
Despite substantial progress in the prevention of group B Streptococcus (GBS) disease with the introduction of intrapartum antibiotic prophylaxis, this pathogen remains a leading cause of neonatal infection. Capsular polysaccharide conjugate vaccines have been tested in phase I/II clinical studies, showing promise for further development. Mapping of epitopes recognized by protective antibodies is crucial for understanding the mechanism of action of vaccines and for enabling antigen design. In this study, we report the structure of the epitope recognized by a monoclonal antibody with opsonophagocytic activity and representative of the protective response against type III GBS polysaccharide...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438838/allosteric-mechanism-of-action-of-the-therapeutic-anti-ige-antibody-omalizumab
#16
Anna M Davies, Elizabeth G Allan, Anthony H Keeble, Jean Delgado, Benjamin P Cossins, Alkistis N Mitropoulou, Marie O Y Pang, Tom Ceska, Andrew J Beavil, Graham Craggs, Marta Westwood, Alistair J Henry, James M McDonnell, Brian J Sutton
Immunoglobulin E and its interactions with receptors FcϵRI and CD23 play a central role in allergic disease. Omalizumab, a clinically-approved therapeutic antibody, inhibits the interaction between IgE and FcϵRI, preventing mast cell and basophil activation, and blocks IgE binding to CD23 on B cells and antigen-presenting cells. We solved the crystal structure of the complex between an omalizumab-derived Fab and IgE-Fc, with one Fab bound to each Cϵ3 domain. Free IgE-Fc adopts an acutely bent structure, but in the complex it is only partially bent, with large-scale conformational changes in the Cϵ3 domains that inhibit the interaction with FcϵRI...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438745/management-of-chronic-pain-using-complementary-and-integrative-medicine
#17
REVIEW
Lucy Chen, Andreas Michalsen
Complementary and integrative medicine (CIM) encompasses both Western-style medicine and complementary health approaches as a new combined approach to treat a variety of clinical conditions. Chronic pain is the leading indication for use of CIM, and about 33% of adults and 12% of children in the US have used it in this context. Although advances have been made in treatments for chronic pain, it remains inadequately controlled for many people. Adverse effects and complications of analgesic drugs, such as addiction, kidney failure, and gastrointestinal bleeding, also limit their use...
April 24, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28438353/the-role-of-vitamin-d-in-the-immune-system-as-a-pro-survival-molecule
#18
REVIEW
Salvatore Chirumbolo, Geir Bjørklund, Andrea Sboarina, Antonio Vella
PURPOSE: Vitamin D is a fascinating and attractive molecule that has gained particular attention in medicine in recent years. Its immunomodulatory and anti-inflammatory potential might resemble the activity of many nature-derived molecules (eg, flavonoids), but its role in biology was selected during a long evolutionary pathway to dampen the damaging effect of cell stress response and of the immune reaction. In this sense, this molecule can be considered an ancient hormone that serves, in its primary role, as a pro-survival agent...
April 21, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28438284/intradiscal-o2o3-rationale-injection-technique-short-and-long-term-outcomes-for-the-treatment-of-low-back-pain-due-to-disc-herniation
#19
REVIEW
Francesco Giurazza, Gianluigi Guarnieri, Kieran J Murphy, Mario Muto
The management of low back pain should always start with a conservative approach; however, when it fails, intervention is required and at that moment the most appropriate choice remains unclear. Before invasive surgery, minimally invasive techniques can be adopted. In European trials and in a trans-Canadian clinical trial 03 ozone has been used successfully. In total over 50,000 patients have been treated safely. Ozone is a gas normally present in the atmosphere with potent oxidizing power; it has been used for percutaneous intradiscal injection combined with oxygen (O2O3) at very low concentrations for 15 years in Europe...
May 2017: Canadian Association of Radiologists Journal, Journal L'Association Canadienne des Radiologistes
https://www.readbyqxmd.com/read/28437604/antiplasmodial-mode-of-action-of-pantothenamides-pantothenate-kinase-serves-as-a-metabolic-activator-not-as-a-target
#20
Marianne de Villiers, Christina Spry, Cristiano Joao Macuamule, Leanne Barnard, Gordon Wells, Kevin J Saliba, Erick Strauss
N-substituted pantothenamides (PanAms) are pantothenate analogues with up to nanomolar potency against blood-stage Plasmodium falciparum (the most virulent species responsible for malaria). Although these compounds are known to target coenzyme A (CoA) biosynthesis and/or utilization, their exact mode of action (MoA) is still unknown. Importantly, PanAms that retain the natural β-alanine moiety are more potent than other variants, consistent with the involvement of processes that are selective for pantothenate (the precursor of CoA) or its derivatives...
April 24, 2017: ACS Infectious Diseases
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