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https://www.readbyqxmd.com/read/27914364/structure-based-exploration-and-exploitation-of-the-s4-subsite-of-norovirus-3cl-protease-in-the-design-of-potent-and-permeable-inhibitors
#1
Anushka C Galasiti Kankanamalage, Yunjeong Kim, Athri D Rathnayake, Vishnu C Damalanka, Pathum M Weerawarna, Sean T Doyle, Amer F Alsoudi, D M Padmasankha Dissanayake, Gerald H Lushington, Nurjahan Mehzabeen, Kevin P Battaile, Scott Lovell, Kyeong-Ok Chang, William C Groutas
Human noroviruses are the primary cause of epidemic and sporadic acute gastroenteritis. The worldwide high morbidity and mortality associated with norovirus infections, particularly among the elderly, immunocompromised patients and children, constitute a serious public health concern. There are currently no approved human vaccines or norovirus-specific small-molecule therapeutics or prophylactics. Norovirus 3CL protease has recently emerged as a potential therapeutic target for the development of anti-norovirus agents...
November 14, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27914218/disruptive-influences-on-research-in-academic-pathology-departments-proposed-changes-to-the-common-rule-governing-informed-consent-for-research-use-of-biospecimens-and-to-rules-governing-return-of-research-results
#2
REVIEW
Mark E Sobel, Jennifer C Dreyfus
Academic pathology departments will be dramatically affected by proposed United States federal government regulatory initiatives. Pathology research will be substantially altered if proposed changes to the Common Rule (Code of Federal Regulations: Protection of Human Subjects title 45 CFR 46) and regulations governing the return of individual research results are approved and finalized, even more so now that the Precision Medicine initiative has been launched. Together, these changes are disruptive influences on academic pathology research as we know it, straining limited resources and compromising advances in diagnostic and academic pathology...
November 30, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27914201/shear-wave-ultrasound-elastographic-evaluation-of-the-rotator-cuff-tendon
#3
Stephanie W Hou, Alexander N Merkle, James S Babb, Robert McCabe, Soterios Gyftopoulos, Ronald S Adler
OBJECTIVES: (1) Assess the association between the B-mode morphologic appearance and elasticity in the rotator cuff tendon using shear wave elastography (SWE). (2) Assess the association between SWE and symptoms. METHODS: Institutional Review Board approval and informed consent were obtained. A retrospective review identified 21 studies in 19 eligible patients for whom SWE was performed during routine sonographic evaluations for shoulder pain. Evaluations were compared with 55 studies from 16 asymptomatic volunteers and 6 patients with asymptomatic contralateral shoulders...
December 3, 2016: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/27914041/paliperidone-loaded-nanolipomer-system-for-sustained-delivery-and-enhanced-intestinal-permeation-superiority-to-polymeric-and-solid-lipid-nanoparticles
#4
Hala Mahmoud Helal, Sana Mohamed Mortada, Marwa Ahmed Sallam
Paliperidone (PPD) is the most recent second-generation atypical antipsychotic approved for the treatment of schizophrenia. An immediate release dose causes extrapyramidal side effects. In this work, a novel nanolipomer carrier system for PPD with enhanced intestinal permeability and sustained release properties has been developed and optimized. PPD was successfully encapsulated into a lipomer consisting of a specific combination of biocompatible materials including poly-ε-caprolactone as a polymeric core, Lipoid S75, and Gelucire® 50/13 as a lipid shell and polyvinyl alcohol as a stabilizing agent...
December 2, 2016: AAPS PharmSciTech
https://www.readbyqxmd.com/read/27913999/the-role-of-her2-egfr-and-other-receptor-tyrosine-kinases-in-breast-cancer
#5
Jennifer L Hsu, Mien-Chie Hung
Breast cancer affects approximately 1 in 8 women, and it is estimated that over 246,660 women in the USA will be diagnosed with breast cancer in 2016. Breast cancer mortality has decline over the last two decades due to early detection and improved treatment. Over the last few years, there is mounting evidence to demonstrate the prominent role of receptor tyrosine kinases (RTKs) in tumor initiation and progression, and targeted therapies against the RTKs have been developed, evaluated in clinical trials, and approved for many cancer types, including breast cancer...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913776/necitumumab-for-the-treatment-of-squamous-cell-non-small-cell-lung-cancer
#6
Jessica K Brinkmeyer, Donald C Moore
Non-small cell lung cancer is the most common form of lung cancer, accounting for about 85% of all cases and is further subdivided into adenocarcinoma, squamous cell, and large cell carcinoma. Necitumumab (Portrazza™, Eli Lilly and Company) is an anti-epidermal growth factor receptor monoclonal antibody approved for the first-line treatment of squamous cell non-small cell lung cancer in combination with cisplatin and gemcitabine. The safety and efficacy of necitumumab has been evaluated in two-phase III clinical trials, one demonstrating a lack of efficacy in non-squamous non-small cell lung cancer and another demonstrating improvement in overall survival and progression-free survival in squamous cell non-small cell lung cancer...
December 2, 2016: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/27913762/aspen-felanpe-clinical-guidelines-nutrition-support-of-adult-patients-with-enterocutaneous-fistula
#7
Vanessa J Kumpf, Jose Eduardo de Aguilar-Nascimento, Jose Ignacio Diaz-Pizarro Graf, Amber M Hall, Liam McKeever, Ezra Steiger, Marion F Winkler, Charlene W Compher
BACKGROUND: The management of patients with enterocutaneous fistula (ECF) requires an interdisciplinary approach and poses a significant challenge to physicians, wound/stoma care specialists, dietitians, pharmacists, and other nutrition clinicians. Guidelines for optimizing nutrition status in these patients are often vague, based on limited and dated clinical studies, and typically rely on individual institutional or clinician experience. Specific nutrient requirements, appropriate route of feeding, role of immune-enhancing formulas, and use of somatostatin analogues in the management of patients with ECF are not well defined...
December 2, 2016: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27913692/factors-motivating-hpv-vaccine-uptake-among-vaccinated-and-nonvaccinated-hispanic-young-adult-women
#8
Dionne P Stephens, Hod Tamir, Tami L Thomas
INTRODUCTION: To identify factors influencing human papillomavirus (HPV) vaccination up taking decision making among vaccinated and nonvaccinated Hispanic college women. PARTICIPANTS: Hispanic young women between the ages of 18 and 24 years (N = 49). In total, 26 had not received the HPV vaccine, and 23 had started/completed the vaccine series. METHOD: Participants registered for the study via a psychology research pool at a large public university in the southeast United States after institutional review board approval...
December 2016: Hispanic Health Care International: the Official Journal of the National Association of Hispanic Nurses
https://www.readbyqxmd.com/read/27913567/drug-repositioning-screens-identify-triamterene-as-a-selective-drug-for-the-treatment-of-dna-mismatch-repair-deficient-cells
#9
Delphine Guillotin, Philip Austin, Rumena Begum, Marta O Freitas, Ashirwad Merve, Tim Brend, Susan C Short, Silvia Marino, Sarah A Martin
PURPOSE: The DNA Mismatch repair (MMR) pathway is required for the maintenance of genome stability. Unsurprisingly, mutations in MMR genes occur in a wide range of different cancers. Studies thus far have largely focused on specific tumor types or MMR mutations, however it is becoming increasingly clear that a therapy targeting MMR-deficiency in general would be clinically very beneficial. EXPERIMENTAL DESIGN: Based on a drug-repositioning approach, we screened a large panel of cell lines with various MMR deficiencies from a range of different tumor types with a compound drug library of previously approved drugs...
December 2, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27913561/hospitals-and-patients-working-in-unity-how-r-u-protocol-for-a-prospective-feasibility-study-of-telephone-peer-support-to-improve-older-patients-quality-of-life-after-emergency-department-discharge
#10
Judy A Lowthian, Alyse Lennox, Andrea Curtis, Jeremy Dale, Colette Browning, De Villiers Smit, Gillian Wilson, Debra O'Brien, Cate Rosewarne, Lee Boyd, Cath Garner, Peter Cameron
INTRODUCTION: Older people presenting to an emergency department (ED) have a higher likelihood of social isolation, loneliness and depression; which are all associated with negative health outcomes and increased health service use, including higher rates of ED attendance. The HOW R U? study aims to ascertain the feasibility and acceptability of a postdischarge telephone support programme for older ED patients following discharge. The intervention, which aims to improve quality of life, will be delivered by hospital-based volunteers...
December 2, 2016: BMJ Open
https://www.readbyqxmd.com/read/27913559/physical-activity-as-intervention-for-age-related-loss-of-muscle-mass-and-function-protocol-for-a-randomised-controlled-trial-the-lisa-study
#11
Christian Skou Eriksen, Ellen Garde, Nina Linde Reislev, Cathrine Lawaetz Wimmelmann, Theresa Bieler, Andreas Kraag Ziegler, Anne Theil Gylling, Kasper Juel Dideriksen, Hartwig Roman Siebner, Erik Lykke Mortensen, Michael Kjaer
INTRODUCTION: Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown...
December 2, 2016: BMJ Open
https://www.readbyqxmd.com/read/27913542/new-therapies-for-hemophilia
#12
Steven W Pipe
Individuals with severe hemophilia have benefitted from 5 decades of advances that have led to widespread availability of safe and efficacious factors VIII and IX, a multidisciplinary integrated care model through a network of specialized hemophilia treatment centers, and aggressive introduction of prophylactic replacement therapy to prevent bleeding and preserve joint health. Yet, there are remaining challenges and treatment gaps which have prevented complete abrogation of all joint bleeding, and progressive joint deterioration may continue in some affected individuals over the course of a lifetime...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913539/prevention-of-central-nervous-system-sequelae-in-sickle-cell-disease-without-evidence-from-randomized-controlled-trials-the-case-for-a-team-based-learning-collaborative
#13
Michael R DeBaun, Allison A King
Since 1998, the National Institutes of Health has funded 5 randomized controlled trials (RCTs) for primary and secondary prevention of strokes in children with sickle cell anemia (SCA). In a systematic fashion, these trials have significantly advanced the care of children with SCA. In the absence of an RCT, clinicians are often compelled to make decisions at the bedside, based on experience, observational studies, and principles of hematology. We will provide an initial example that describes how a team-based, learning collaborative developed a multisite standard care protocol with a low budget (<$10 000 per year) to overcome the intrinsic limitations of advancing the care of neurologic complications in sickle cell disease (SCD)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913523/advances-and-practical-use-of-monoclonal-antibodies-in-multiple-myeloma-therapy
#14
Hans C Lee, Donna M Weber
The use of proteasome inhibitors and immunomodulatory agents in the treatment of myeloma have resulted in significant improvements in patient outcomes over the last decade. Although these agents now form the backbone of current myeloma treatment regimens both in the frontline and in a relapsed setting, drug resistance remains an inevitable challenge that most patients will encounter during their disease course. Hence, new treatment strategies continue to be explored, and the recent regulatory approvals of the monoclonal antibodies (mAbs) daratumumab (DARA) and elotuzumab (ELO), which target the plasma cell surface proteins CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), respectively, have heralded the long-awaited era of antibody-based approaches in the treatment of myeloma...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913521/sequencing-of-nontransplant-treatments-in-multiple-myeloma-patients-with-active-disease
#15
Andrew J Yee, Noopur S Raje
The approval of several different classes of drugs in recent years has resulted in a dramatic expansion of treatment options for multiple myeloma patients, improving both survival and quality of life. Lenalidomide and bortezomib are now core components of treatment both at time of diagnosis and at relapse. Next-generation immunomodulatory drugs, like pomalidomide, and newer proteasome inhibitors like carfilzomib and ixazomib are available for use at relapse. Drugs with novel mechanisms of action such as the histone deacetylase inhibitor panobinostat and the monoclonal antibodies targeting SLAMF7 (elotuzumab) and CD38 (daratumumab) are significant steps forward...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913518/treatment-options-for-patients-with-myelodysplastic-syndromes-after-hypomethylating-agent-failure
#16
Hetty E Carraway
The treatment of patients with myelodysplastic syndromes (MDSs) has hinged primarily on supportive care (ie, blood transfusions, colony stimulating agents, iron chelation, etc.) and the US Food and Drug Administration-approved agents, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For patients no longer benefitting from these agents, there is a paucity of effective therapies. The challenges at this time include our limited understanding of the mechanisms of resistance to these therapies and the variables employed to select next best therapies for patients based on: (1) their performance status and medical comorbidities; (2) the molecular feature(s) of their MDS; (3) the prior treatments they have received; and (4) the long-term goal(s)/possibilities for their future treatment (ie, transplant vs no transplant)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913517/treatment-of-low-risk-myelodysplastic-syndromes
#17
Valeria Santini
The majority of myelodysplastic syndrome (MDS) patients belong to the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R) lower-risk categories. Their precise diagnostics and prognostic stratification is often a challenge, but may ensure the optimization of therapy. The availability of diverse treatment options has significantly improved the quality of life and survival of this group of patients. Anemia is the most relevant cytopenia in terms of frequency and symptoms in lower-risk MDS, and may be treated successfully with erythropoietic stimulating agents, provided a careful selection is performed on the basis of IPSS-R, endogenous erythropoietin levels, and transfusion independence...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913502/mrd-in-aml-does-it-already-guide-therapy-decision-making
#18
Gert Ossenkoppele, Gerrit Jan Schuurhuis
Prognostic factors determined at diagnosis are predictive for outcome whereas achievement of morphological complete remission (CR) is still an important end point during treatment. Residual disease after therapy may reflect the sum of all diagnosis and postdiagnosis resistance mechanisms/factors; its measurement could hypothetically be very instrumental for guiding treatment. The possibility of defining residual disease (minimal residual disease [MRD]) far below the level of 5% blast cells is changing the landscape of risk classification...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913472/novel-agents-in-chronic-lymphocytic-leukemia
#19
Nicole Lamanna, Susan O'Brien
The advent of novel small-molecule inhibitors has transformed the treatment approaches for patients with chronic lymphocytic leukemia (CLL). These therapies are becoming increasingly used in patients with relapsed disease, patients with 17p deletion, and, as of recently, also in the frontline setting for previously untreated patients with CLL. Moreover, many of these are oral therapies that are significantly less myelosuppressive than chemoimmunotherapy. However, these agents have their own set of unique toxicities with which providers must gain familiarity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913471/sequencing-of-chronic-lymphocytic-leukemia-therapies
#20
Jacqueline C Barrientos
It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in frontline, relapsed, refractory, and high-risk disease. Traditionally, frontline management of CLL has been a combination of chemotherapy (fludarabine, cyclophosphamide, bendamustine, or chlorambucil) with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab). The current landscape is rapidly evolving with the advent of therapies that demonstrate selective inhibition of important pathways necessary for CLL proliferation and survival...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
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