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https://www.readbyqxmd.com/read/27921043/metabolic-vascular-syndrome-new-insights-into-a-multidimensional-network-of-risk-factors-and-diseases
#1
REVIEW
Gerhard H Scholz, Markolf Hanefeld
BACKGROUND: Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases...
October 2016: Visceral Medicine
https://www.readbyqxmd.com/read/27920527/pharmacokinetics-and-safety-of-dts-108-a-human-oligopeptide-bound-to-sn-38-with-an-esterase-sensitive-cross-linker-in-patients-with-advanced-malignancies-a-phase-i-study
#2
Romain Coriat, Sandrine J Faivre, Olivier Mir, Chantal Dreyer, Stanislas Ropert, Mohammed Bouattour, Robert Desjardins, François Goldwasser, Eric Raymond
BACKGROUND: DTS-108 is a hydrosoluble prodrug, where the SN-38 moiety is covalently linked to a 20-amino acid vector peptide by a specific esterase-sensitive cross-linker, releasing 7-ethyl-10-hydroxycampthotecin (SN-38) by esterase bond cleavage. METHODS: The pharmacokinetics of DTS-108, adverse events graded according to NCI-CTCv3.1, dose-limiting toxicities at cycle 1, the maximum tolerated dose (MTD), and the recommended Phase II dose (RP2D) of intravenous DTS-108 (1-2 hours) every 2 weeks were evaluated in a first-in-human Phase I study in patients with advanced/metastatic carcinomas, according to an accelerated dose escalation design...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27919976/phase-i-study-of-triweekly-nab-paclitaxel-combined-with-s-1-in-patients-with-her2-negative-metastatic-breast-cancer
#3
Koichi Sakaguchi, Katsuhiko Nakatsukasa, Tetsuya Taguchi
AIM: We conducted a phase I study to determine the maximum tolerated dose (MTD) and recommended dose (RD) of triweekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and S-1 combination therapy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). PATIENTS AND METHODS: This study was carried out with a 3+3 dose escalation design; patients with HER2-negative MBC received nab-paclitaxel at 180-260 mg/m(2) on day 1 and S-1 at 65-80 mg/m(2) daily on days 1-14, repeated every 3 weeks...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919901/safety-and-pharmacokinetics-of-cd101-iv-a-novel-echinocandin-in-healthy-adults
#4
Taylor Sandison, Voon Ong, Jonathan Lee, Dirk Thye
CD101 IV is a novel echinocandin with distinctive pharmacokinetic properties that is being developed as a once-weekly treatment for candidemia and invasive candidiasis. CD101 has potent in vitro activity and in vivo efficacy against a broad range of Candida and Aspergillus species. The primary objective of two randomized, double-blind, placebo-controlled, dose-escalation studies in healthy adults was to determine the safety and tolerability of CD101 IV. Sequential cohorts of 8 subjects (n=6, active; n=2, placebo) were administered single (50, 100, 200, 400 mg) or multiple once-weekly (100 mg ×2, 200 mg ×2, 400 mg ×3) doses of CD101 IV infused over 1 hour...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919760/proton-therapy-present-and-future
#5
REVIEW
Radhe Mohan, David Grosshans
In principle, proton therapy offers a substantial clinical advantage over the conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow escalation of tumor doses, greater sparing of normal tissues, thus potentially improving local control and survival while at the same time reducing toxicity and improving quality of life. Protons, accelerated to therapeutic energies ranging from 70 to 250MeV, typically with a cyclotron or a synchrotron, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry...
December 2, 2016: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/27919738/long-term-ethanol-self-administration-induces-%C3%AE-fosb-in-male-and-female-adolescent-but-not-in-adult-wistar-rats
#6
Aranza Wille-Bille, Soledad de Olmos, Leonardo Marengo, Florencia Chiner, Ricardo Marcos Pautassi
Early-onset ethanol consumption predicts later development of alcohol use disorders. Age-related differences in reactivity to ethanol's effects may underlie this effect. Adolescent rats are more sensitive and less sensitive than adults to the appetitive and aversive behavioral effects of ethanol, respectively, and more sensitive to the neurotoxic effects of experimenter-administered binge doses of ethanol. However, less is known about age-related differences in the neural consequences of self-administered ethanol...
December 2, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27918901/clinical-utility-of-methicillin-resistant-staphylococcus-aureus-nasal-polymerase-chain-reaction-assay-in-critically-ill-patients-with-nosocomial-pneumonia
#7
Melanie N Smith, Michael J Erdman, Jason A Ferreira, Petra Aldridge, Christopher A Jankowski
PURPOSE: This study investigated the diagnostic performance characteristics of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) assay in critically ill patients with nosocomial pneumonia. MATERIALS AND METHODS: This retrospective, single-center study included adult patients admitted to an intensive care unit with suspected nosocomial pneumonia. Patients must have received an MRSA nasal PCR assay and respiratory culture within predetermined time intervals...
November 15, 2016: Journal of Critical Care
https://www.readbyqxmd.com/read/27918781/the-role-of-adjuvant-chemotherapy-in-surgically-managed-p16-positive-oropharyngeal-squamous-cell-carcinoma
#8
S Andrew Skillington, Dorina Kallogjeri, James S Lewis, Jay F Piccirillo
Importance: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has a favorable prognosis, and p16 immunohistochemistry is a surrogate marker of high-risk HPV infection and strong prognosticator. Given this favorable prognosis, treatment de-escalation for p16-positive OPSCC is now being considered with the goal of decreasing treatment-associated morbidity without compromising tumor control. The role of adjuvant chemotherapy in this setting is becoming increasingly unclear...
December 1, 2016: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/27917870/high-frequency-stimulation-of-the-subthalamic-nucleus-blocks-compulsive-like-re-escalation-of-heroin-taking-in-rats
#9
Carrie L Wade, Marsida Kallupi, Daniel O Hernandez, Emmanuel Breysse, Giordano de Guglielmo, Elena Crawford, George F Koob, Paul Schweitzer, Christelle Baunez, Olivier George
Opioid addiction, including addiction to heroin, has dramatically increased in the last decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction particularly in individuals who are resistant to traditional therapies. Here, we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction...
December 5, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27917735/top-1-of-inpatients-administered-antimicrobial-agents-comprising-50-of-expenditures-a-descriptive-study-and-opportunities-for-stewardship-intervention
#10
Jennifer Dela-Pena, Luiza Kerstenetzky, Lucas Schulz, Ron Kendall, Alexander Lepak, Barry Fox
OBJECTIVE To characterize the top 1% of inpatients who contributed to the 6-month antimicrobial budget in a tertiary, academic medical center and identify cost-effective intervention opportunities targeting high-cost antimicrobial utilization. DESIGN Retrospective cohort study. PATIENTS Top 1% of the antimicrobial budget from July 1 through December 31, 2014. METHODS Patients were identified through a pharmacy billing database. Baseline characteristics were collected through a retrospective medical chart review...
December 5, 2016: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/27917586/a-qualitative-perspectival-review-of-the-australian-and-new-zealand-urology-education-and-training-program
#11
Prem Rashid
INTRODUCTION: The Australian and New Zealand (ANZ) urology training program was assessed via a prospective, qualitative review to explore the challenges facing the delivery of high quality urological training now and into the future. AIM: To report the reflective considerations and opinions of leaders in the ANZ urological surgical training program. METHODS: Ethics approved semi-structured, template-based, qualitative interview techniques were employed to evaluate key aspects of the current urology training program...
December 5, 2016: BJU International
https://www.readbyqxmd.com/read/27917532/do-women-have-a-choice-care-providers-and-decision-makers-perspectives-on-barriers-to-access-of-health-services-for-birth-after-a-previous-cesarean
#12
Sarah Munro, Jude Kornelsen, Kitty Corbett, Elizabeth Wilcox, Nick Bansback, Patricia Janssen
BACKGROUND: Repeat cesarean delivery is the single largest contributor to the escalating cesarean rate worldwide. Approximately 80 percent of women with a past cesarean are candidates for vaginal birth after a cesarean (VBAC), but in Canada less than one-third plan VBAC. Emerging evidence suggests that these trends may be due in part to nonclinical factors, including care provider practice patterns and delays in access to surgical and anesthesia services. This study sought to explore maternity care providers' and decision makers' attitudes toward and experiences with providing and planning services for women with a previous cesarean...
December 5, 2016: Birth
https://www.readbyqxmd.com/read/27917453/phase-i-study-of-mrx34-a-liposomal-mir-34a-mimic-administered-twice-weekly-in-patients-with-advanced-solid-tumors
#13
Muhammad S Beg, Andrew J Brenner, Jasgit Sachdev, Mitesh Borad, Yoon-Koo Kang, Jay Stoudemire, Susan Smith, Andreas G Bader, Sinil Kim, David S Hong
Purpose Naturally occurring tumor suppressor microRNA-34a (miR-34a) downregulates the expression of >30 oncogenes across multiple oncogenic pathways, as well as genes involved in tumor immune evasion, but is lost or under-expressed in many malignancies. This first-in-human, phase I study assessed the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumors. Patients and Methods Adult patients with solid tumors refractory to standard treatment were enrolled in a standard 3 + 3 dose escalation trial...
December 5, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27916416/dosimetric-feasibility-of-ablative-dose-escalated-focal-monotherapy-with-mri-guided-high-dose-rate-hdr-brachytherapy-for-prostate-cancer
#14
Ali Hosni, Marco Carlone, Alexandra Rink, Cynthia Ménard, Peter Chung, Alejandro Berlin
PURPOSE: To determine the dosimetric feasibility of dose-escalated MRI-guided high-dose-rate brachytherapy (HDR-BT) focal monotherapy for prostate cancer (PCa). METHODS: In all patients, GTV was defined with mpMRI, and deformably registered onto post-catheter insertion planning MRI. PTV included the GTV plus 9mm craniocaudal and 5mm in every other direction. In discovery-cohort, plans were obtained for each PTV independently aiming to deliver ⩾16.5Gy/fraction (two fraction schedule) while respecting predefined organs-at-risk (OAR) constraints or halted when achieved equivalent single-dose plan (24Gy)...
December 1, 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27916408/safety-tolerability-and-immunogenicity-of-a-4-antigen-staphylococcus-aureus-vaccine-sa4ag-results-from-a-first-in-human-randomised-placebo-controlled-phase-1-2-study
#15
Robert W Frenck, C Buddy Creech, Eric A Sheldon, David J Seiden, Martin K Kankam, James Baber, Edward Zito, Robin Hubler, Joseph Eiden, Joseph M Severs, Shite Sebastian, Jasdeep Nanra, Kathrin U Jansen, William C Gruber, Annaliesa S Anderson, Douglas Girgenti
BACKGROUND: A prophylactic Staphylococcus aureus four-antigen vaccine (SA4Ag) is under development for prevention of invasive S. aureus disease. A preliminary S. aureus three-antigen vaccine (SA3Ag) was reformulated to include a novel manganese transporter protein (MntC or rP305A). This study describes the first-in-human dose-finding, safety, and immunogenicity results for SA4Ag. METHODS: In this double-blind, sponsor-unblind, placebo-controlled, phase 1/2 study, 454 healthy adults aged 18-64years were randomised to receive a single dose of one of three formulations of SA4Ag with escalating dose levels of rP305A or placebo...
December 1, 2016: Vaccine
https://www.readbyqxmd.com/read/27915075/building-the-case-for-a-novel-teleost-model-of-non-breeding-aggression-and-its-neuroendocrine-control
#16
Laura Quintana, Lucía Zubizarreta, Cecilia Jalabert, Gervasio Batista, Rossana Perrone, Ana Silva
In vertebrates, aggression has been traditionally associated with high levels of circulating androgens in breeding males. Nevertheless, the centrality of androgens as primary modulators of aggression is being reconsidered in at least in two particular cases: 1) territorial aggression outside the breeding season, and 2) aggression by females. We are developing the weakly electric fish, Gymnotus omarorum, as a novel, advantageous model system to address these two alternative forms of aggression. This species displays a short, escalated contest, after which a clear hierarchical status emerges...
November 30, 2016: Journal of Physiology, Paris
https://www.readbyqxmd.com/read/27914999/dual-therapy-for-refractory-overactive-bladder-in-children-a-prospective-open-label-study
#17
Fannie Morin, Anne-Sophie Blais, Geneviève Nadeau, Katherine Moore, Lucie Genois, Stéphane Bolduc
PURPOSE: Mirabegron (β3-adrenoreceptor agonist) is a new molecule with a distinct mechanism of action from antimuscarinics. Combination therapy with solifenacin was recently studied in adult population. Our objective was to evaluate the efficacy and safety of mirabegron as add-on therapy, to treat urinary incontinence in children with idiopathic OAB, refractory/intolerant to antimuscarinics. MATERIALS AND METHODS: A prospective off-label study using add-on regimens of mirabegron was conducted with pediatric patients presenting no symptom improvement under intensive behavioural and medical therapies and/or significant side effects (S/E) on antimuscarinic dose escalation...
November 30, 2016: Journal of Urology
https://www.readbyqxmd.com/read/27914629/cytoplasmic-fmr1-interacting-protein-2-is-a-major-genetic-factor-underlying-binge-eating
#18
Stacey L Kirkpatrick, Lisa R Goldberg, Neema Yazdani, R Keith Babbs, Jiayi Wu, Eric R Reed, David F Jenkins, Amanda F Bolgioni, Kelsey I Landaverde, Kimberly P Luttik, Karen S Mitchell, Vivek Kumar, W Evan Johnson, Megan K Mulligan, Pietro Cottone, Camron D Bryant
BACKGROUND: Eating disorders are lethal and heritable; however, the underlying genetic factors are unknown. Binge eating is a highly heritable trait associated with eating disorders that is comorbid with mood and substance use disorders. Therefore, understanding its genetic basis will inform therapeutic development that could improve several comorbid neuropsychiatric conditions. METHODS: We assessed binge eating in closely related C57BL/6 mouse substrains and in an F2 cross to identify quantitative trait loci associated with binge eating...
October 25, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27913497/response-adapted-frontline-therapy-for-hodgkin-lymphoma-are-we-there-yet
#19
Peter W M Johnson
Treating Hodgkin lymphoma by using chemotherapy with or without radiotherapy is highly successful, with substantially fewer deaths from lymphoma than from other causes in recent studies of both early-stage and advanced-stage disease. Long-term toxicity is a major consideration in this context, and recent trials have used functional imaging with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography early in the course of treatment (interim PET) to assess response and modulate subsequent therapy. In early-stage disease, this has allowed omission of consolidation radiotherapy after a good response to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, and trials have shown that this can be done without detriment to overall survival, despite a small increase in rates of recurrence of ∼5%...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912833/treatment-of-locally-advanced-non-small-cell-lung-cancer
#20
REVIEW
Kit Tam, Megan Daly, Karen Kelly
Locally advanced non-small cell lung cancer is a heterogeneous disease with typically poor outcomes. Select patients may benefit from the integration of surgery, whereas patients with bulky, multistation, or contralateral (N3) mediastinal involvement are managed with definitive chemoradiation. Attempts to improve outcomes through induction, consolidation, or maintenance chemotherapy or radiation dose escalation have not demonstrated a survival benefit. Current research efforts focus on the integration of novel systemic agents that exploit tumor-specific driver mutations, augment antitumor immune response, or enhance radiation sensitivity...
February 2017: Hematology/oncology Clinics of North America
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