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https://www.readbyqxmd.com/read/28822012/mtor-co-targeting-strategies-for-head-and-neck-cancer-therapy
#1
Zhiyong Wang, Juan Callejas Valera, Xuefeng Zhao, Qianming Chen, J Silvio Gutkind
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression...
August 18, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28815048/society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-bladder-carcinoma
#2
Ashish M Kamat, Joaquim Bellmunt, Matthew D Galsky, Badrinath R Konety, Donald L Lamm, David Langham, Cheryl T Lee, Matthew I Milowsky, Michael A O'Donnell, Peter H O'Donnell, Daniel P Petrylak, Padmanee Sharma, Eila C Skinner, Guru Sonpavde, John A Taylor, Prasanth Abraham, Jonathan E Rosenberg
The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Guérin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urologic best-practice guidelines and consensus reports have been developed and strengthened based on data on the timing, dose, and duration of therapy from randomized clinical trials, as well as by critical evaluation of criteria for progression...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28813182/impact-of-selection-bias-on-treatment-effect-size-estimates-in-randomized-trials-of-oral-health-interventions-a-meta-epidemiological-study
#3
H Saltaji, S Armijo-Olivo, G G Cummings, M Amin, B R da Costa, C Flores-Mir
Emerging evidence suggests that design flaws of randomized controlled trials can result in over- or underestimation of the treatment effect size (ES). The objective of this study was to examine associations between treatment ES estimates and adequacy of sequence generation, allocation concealment, and baseline comparability among a sample of oral health randomized controlled trials. For our analysis, we selected all meta-analyses that included a minimum of 5 oral health randomized controlled trials and used continuous outcomes...
August 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28810973/the-influence-of-combat-experience-on-psychologically-healthy-soldiers-attentiveness-to-environmental-threats
#4
Bethany Ranes, Chris P Long, Stephanie Traynham, Amanda Hayes
INTRODUCTION: In contrast to previous research that has primarily examined how psychological disorders (e.g., post-traumatic stress disorder [PTSD], anxiety) are affected by and affect individuals' threat perceptions, this study examines the relationship between combat experience and threat-monitoring in psychologically healthy Soldiers. Existing research has established how prolonged or intense experiences with war-related stressors can lead individuals to undergo an unconscious fear-conditioning process that affects the circuitry of the prefrontal cortex, hippocampus, amygdala, and anterior cingulate cortex regions of the brain...
July 2017: Military Medicine
https://www.readbyqxmd.com/read/28810061/single-dose-pharmacokinetics-of-co-crystal-of-tramadol-celecoxib-results-of-a-4-way-randomized-open-label-phase-i-clinical-trial-in-healthy-subjects
#5
Sebastián Videla, Mounia Lahjou, Anna Vaqué, Mariano Sust, Mercedes Encabo, Lluis Soler, Artur Sans, Eric Sicard, Neus Gascón, Gregorio Encina, Carlos Plata-Salamán
AIM: Co-Crystal of Tramadol-Celecoxib (CTC) is a novel co-crystal molecule containing two active pharmaceutical ingredients (APIs) under development by Esteve (E-58425) and Mundipharma Research (MR308). This Phase I study compared single-dose pharmacokinetics (PK) of CTC with those of the individual reference products (immediate-release [IR] tramadol and celecoxib) alone and in open combination. METHODS: Healthy adults aged 18-55 years were orally administered four treatments under fasted conditions (separated by 7-day wash-out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment-1); 100 mg IR tramadol (Treatment-2); 100 mg celecoxib (Treatment-3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment-4)...
August 15, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28807536/effectiveness-of-household-lockable-pesticide-storage-to-reduce-pesticide-self-poisoning-in-rural-asia-a-community-based-cluster-randomised-controlled-trial
#6
Melissa Pearson, Chris Metcalfe, Shaluka Jayamanne, David Gunnell, Manjula Weerasinghe, Ravi Pieris, Chamil Priyadarshana, Duleeka W Knipe, Keith Hawton, Andrew H Dawson, Palitha Bandara, Dhammika deSilva, Indika Gawarammana, Michael Eddleston, Flemming Konradsen
BACKGROUND: Agricultural pesticide self-poisoning is a major public health problem in rural Asia. The use of safer household pesticide storage has been promoted to prevent deaths, but there is no evidence of effectiveness. We aimed to test the effectiveness of lockable household containers for prevention of pesticide self-poisoning. METHODS: We did a community-based, cluster-randomised controlled trial in a rural area of North Central Province, Sri Lanka. Clusters of households were randomly assigned (1:1), with a sequence computer-generated by a minimisation process, to intervention or usual practice (control) groups...
August 11, 2017: Lancet
https://www.readbyqxmd.com/read/28807024/society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-bladder-carcinoma
#7
Ashish M Kamat, Joaquim Bellmunt, Matthew D Galsky, Badrinath R Konety, Donald L Lamm, David Langham, Cheryl T Lee, Matthew I Milowsky, Michael A O'Donnell, Peter H O'Donnell, Daniel P Petrylak, Padmanee Sharma, Eila C Skinner, Guru Sonpavde, John A Taylor, Prasanth Abraham, Jonathan E Rosenberg
The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Guérin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urologic best-practice guidelines and consensus reports have been developed and strengthened based on data on the timing, dose, and duration of therapy from randomized clinical trials, as well as by critical evaluation of criteria for progression...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806961/molecular-analysis-demonstrates-high-prevalence-of-chloroquine-resistance-but-no-evidence-of-artemisinin-resistance-in-plasmodium-falciparum-in-the-chittagong-hill-tracts-of-bangladesh
#8
Mohammad Shafiul Alam, Benedikt Ley, Maisha Khair Nima, Fatema Tuj Johora, Mohammad Enayet Hossain, Kamala Thriemer, Sarah Auburn, Jutta Marfurt, Ric N Price, Wasif A Khan
BACKGROUND: Artemisinin resistance is present in the Greater Mekong region and poses a significant threat for current anti-malarial treatment guidelines in Bangladesh. The aim of this molecular study was to assess the current status of drug resistance in the Chittagong Hill Tracts of Bangladesh near the Myanmar border. METHODS: Samples were obtained from patients enrolled into a Clinical Trial (NCT02389374) conducted in Alikadam, Bandarban between August 2014 and January 2015...
August 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28797232/prognostic-significance-of-braf-and-nras-mutations-in-melanoma-a-german-study-from-routine-care
#9
Markus V Heppt, Timo Siepmann, Jutta Engel, Gabriele Schubert-Fritschle, Renate Eckel, Laura Mirlach, Thomas Kirchner, Andreas Jung, Anja Gesierich, Thomas Ruzicka, Michael J Flaig, Carola Berking
BACKGROUND: Hotspot mutations of the oncogenes BRAF and NRAS are the most common genetic alterations in cutaneous melanoma. Specific inhibitors of BRAF and MEK have shown significant survival benefits in large phase III trials. However, the prognostic significance of BRAF and NRAS mutations outside of clinical trials remains unclear. METHODS: The mutational status of BRAF (exon 15) and NRAS (exon 2 and 3) was determined in melanoma samples of 217 patients with pyrosequencing and Sanger sequencing...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28792417/vibrio-tapetis-from-wrasse-used-for-ectoparasite-bio-control-in-salmon-farming-phylogenetic-analysis-and-serotyping
#10
Snorre Gulla, Anita Rønneseth, Henning Sørum, Øyvind Vågnes, Sabela Balboa, Jesús L Romalde, Duncan J Colquhoun
So-called 'cleaner fish', including various wrasse (Labridae) species, have become increasingly popular in Norwegian salmon farming in recent years for biocontrol of the salmon louse Lepeophtheirus salmonis. Cleaner fish mortalities in salmon farms are, however, often high. Various bacterial agents are frequently associated with episodes of increased cleaner fish mortality, and Vibrio tapetis is regularly cultured from diseased wrasse. In the present study, we investigated the genetic relationships among 54 V...
August 9, 2017: Diseases of Aquatic Organisms
https://www.readbyqxmd.com/read/28783467/the-physiological-effects-of-concurrent-strength-and-endurance-training-sequence-a-systematic-review-and-meta-analysis
#11
Zsolt Murlasits, Zsuzsanna Kneffel, Lukman Thalib
We conducted a systematic literature review and meta-analysis to assess the chronic effects of the sequence of concurrent strength and endurance training on selected important physiological and performance parameters, namely lower body 1 repetition maximum (1RM) and maximal aerobic capacity (VO2max/peak). Based on predetermined eligibility criteria, chronic effect trials, comparing strength-endurance (SE) with endurance-strength (ES) training sequence in the same session were included. Data on effect sizes, sample size and SD as well other related study characteristics were extracted...
August 7, 2017: Journal of Sports Sciences
https://www.readbyqxmd.com/read/28780976/prospective-clinical-integration-of-an-amplicon-based-next-generation-sequencing-method-to-select-advanced-non-small-cell-lung-cancer-patients-for-genotype-tailored-treatments
#12
Jon Zugazagoitia, Daniel Rueda, Nuria Carrizo, Ana Belen Enguita, David Gómez-Sánchez, Asunción Díaz-Serrano, Elisabeth Jiménez, Antonio Mérida, Rosa Calero, Ricardo Lujan, Eduardo De Miguel, Pablo Gámez, Vicente Díaz-Hellín, Juan Antonio Nuñez, Lara Iglesias, Irene Ferrer, Luis Paz-Ares, Santiago Ponce-Aix
INTRODUCTION: A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm. PATIENTS AND METHODS: After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs...
June 23, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28776571/expanded-molecular-profiling-of-myxofibrosarcoma-reveals-potentially-actionable-targets
#13
Ellen Heitzer, Sandra Sunitsch, Magdalena M Gilg, Birgit Lohberger, Beate Rinner, Karl Kashofer, Nicole Stündl, Peter Ulz, Joanna Szkandera, Andreas Leithner, Bernadette Liegl-Atzwanger
Myxofibrosarcomas are morphologically heterogeneous soft tissue sarcomas lacking a specific immunohistochemical expression profile and recurrent genetic changes. The study was designed to gain further insights into the molecular landscape of myxofibrosarcomas by targeted re-sequencing of known cancer driver hotspot mutations and the analysis of genomewide somatic copy number alterations. A well-defined group of myxofibrosarcomas, including myxofibrosarcomas G1 (n=6), myxofibrosarcomas G3 (n=7), myxofibrosarcomas with morphologically heterogeneous and independently selectable G1 and G3 areas within a tumor (n=8), and myxofibrosarcomas G3 with subsequent tumor recurrence (n=1) or metastatic disease (n=3) were evaluated...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28775390/isolation-characterization-and-selection-of-indigenous-bradyrhizobium-strains-with-outstanding-symbiotic-performance-to-increase-soybean-yields-in-mozambique
#14
Amaral Machaculeha Chibeba, Stephen Kyei-Boahen, Maria de Fátima Guimarães, Marco Antonio Nogueira, Mariangela Hungria
Soybean inoculation with effective rhizobial strains makes unnecessary the use of N-fertilizers in the tropics. A frequently reported problem is the failure of the inoculant strains to overcome the competition imposed by indigenous rhizobial populations. The screening of indigenous rhizobia, already adapted to local conditions, searching for highly effective strains for use as inoculants represents a promising strategy in overcoming inoculation failure. The objective of this study was to isolate and characterize indigenous rhizobia and to identify strains that hold potential to be included in inoculant formulations for soybean production, with both promiscuous and non-promiscuous soybean cultivars, in Mozambican agro-climatic conditions...
August 1, 2017: Agriculture, Ecosystems & Environment
https://www.readbyqxmd.com/read/28767002/employment-status-five-years-after-a-randomised-controlled-trial-comparing-multidisciplinary-and-brief-intervention-in-employees-on-sick-leave-due-to-low-back-pain
#15
Pernille Pedersen, Claus Vinther Nielsen, Ole Kudsk Jensen, Chris Jensen, Merete Labriola
AIMS: To evaluate differences in employment status, during a five-year follow-up period in patients on sick leave due to low back pain who had participated in a trial comparing a brief and a multidisciplinary intervention. METHODS: From 2004 to 2008, 535 patients were referred to the Spine Centre at the Regional Hospital in Silkeborg if they had been on sick leave for 3-16 weeks due to low back pain. All patients underwent a clinical examination by a rehabilitation physician and a physiotherapist, and were randomised to either the brief intervention or the multidisciplinary intervention...
August 1, 2017: Scandinavian Journal of Public Health
https://www.readbyqxmd.com/read/28758927/transcriptome-profiling-in-human-diseases-new-advances-and-perspectives
#16
REVIEW
Amelia Casamassimi, Antonio Federico, Monica Rienzo, Sabrina Esposito, Alfredo Ciccodicola
In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level...
July 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28757034/microbial-community-sequencing-analysis-of-the-calf-eye-microbiota-and-relationship-to-infectious-bovine-keratoconjunctivitis
#17
J N Cullen, A Lithio, A S Seetharam, Y Zheng, G Li, D Nettleton, A M O'Connor
Infectious bovine keratoconjunctivitis (IBK) is an important production limiting disease in cattle. Moraxella bovis has historically been considered the primary causal agent; however, vaccines have not been consistently shown as effective in controlling disease incidence. The purpose of this study was to examine the bacterial community of calf eyes prior to disease onset using high-throughput sequencing of 16S ribosomal RNA and determine if it was associated with IBK occurrence. The study was designed as a case-control nested within a randomized controlled trial (RCT)...
August 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28754491/recombinant-human-c1-esterase-inhibitor-for-prophylaxis-of-hereditary-angio-oedema-a-phase-2-multicentre-randomised-double-blind-placebo-controlled-crossover-trial
#18
Marc A Riedl, Vesna Grivcheva-Panovska, Dumitru Moldovan, James Baker, William H Yang, Bruno M Giannetti, Avner Reshef, Sladjana Andrejevic, Richard F Lockey, Roman Hakl, Shmuel Kivity, Joseph R Harper, Anurag Relan, Marco Cicardi
BACKGROUND: Hereditary angio-oedema is a recurrent, oedematous disorder caused by deficiency of functional C1 inhibitor. Infusions of plasma-derived C1 esterase inhibitor deter attacks of hereditary angio-oedema, but the prophylactic effect of recombinant human C1 esterase inhibitor has not been rigorously studied. We aimed to assess the efficacy of recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema. METHODS: We conducted this phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial at ten centres in Canada, the Czech Republic, Israel, Italy, Macedonia, Romania, Serbia, and the USA...
July 25, 2017: Lancet
https://www.readbyqxmd.com/read/28753842/molecular-and-genomic-profiling-to-identify-actionable-targets-in-chromophobe-renal-cell-cancer
#19
Philip Abbosh, Srinath Sundararajan, Sherri Z Millis, Adam Hauben, Sandeep Reddy, Daniel M Geynisman, Robert Uzzo
Metastatic chromophobe renal cell cancer (chRCC) is a rare subtype of RCC with no standard treatment. We performed molecular profiling of 12 chRCC cases to identify alterations predictive of response to therapy. Tests included immunohistochemistry assays, fluorescence in situ hybridization, and next-generation sequencing. Analysis identified c-KIT overexpression in 6/9 (67%) samples analyzed, and loss of protein expression of RRM1 and MGMT in 11/12 (92%) and of PTEN in 7/12 samples (58%). Mutations of TP53, PTEN, APC, and VHL genes were identified...
January 23, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28751267/detrusor-contraction-during-rapid-bladder-filling-caused-by-cold-or-warm-water-a-randomized-controlled-double-blind-trial
#20
Marko Kozomara, Ulrich Mehnert, Burkhardt Seifert, Thomas M Kessler
PURPOSE: We investigated if the detrusor contraction during rapid bladder filling is provoked by cold or warm water. PATIENTS & METHODS: Patients suffering from neurogenic lower urinary tract dysfunction (NLUTD) were included into this randomized controlled double-blind trial. At the end of standard urodynamic investigation, the patients received 2 fillings of the bladder using a 4°C (ice water test, IWT) or 36°C (warm water test, WWT) saline solution with a speed of 100 mL/min...
July 24, 2017: Journal of Urology
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