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https://www.readbyqxmd.com/read/28432532/a-portable-battery-powered-microfluidic-impedance-cytometer-with-smartphone-readout-towards-personal-health-monitoring
#1
Niloy Talukder, Abbas Furniturewalla, Tuan Le, Matthew Chan, Shreyas Hirday, Xinnan Cao, Pengfei Xie, Zhongtian Lin, Azam Gholizadeh, Steve Orbine, Mehdi Javanmard
We present a portable system for personalized blood cell counting consisting of a microfluidic impedance cytometer and portable analog readout electronics, feeding into an analog-to-digital converter (ADC), and being transmitted via Bluetooth to a user-accessible mobile application. We fabricated a microfluidic impedance cytometer with a novel portable analog readout. The novel design of the analog readout, which consists of a lock-in-amplifier followed by a high-pass filter stage for subtraction of drift and DC offset, and a post-subtraction high gain stage, enables detection of particles and cells as small as 1 μm in diameter, despite using a low-end 8-bit ADC...
June 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28431145/long-term-effects-of-a-lifestyle-intervention-and-oral-glucosamine-sulphate-in-primary-care-on-incident-knee-oa-in-overweight-women
#2
Bastiaan C de Vos, Marieke L A Landsmeer, Marienke van Middelkoop, Edwin H G Oei, Marjolein Krul, Sita M A Bierma-Zeinstra, Jos Runhaar
Objectives.: The present study was designed to evaluate the effect of a lifestyle intervention aimed to reduce body weight and of oral glucosamine sulphate on the incidence of knee osteoarthritis (OA) after 6-7 years in a population of middle-aged, overweight women, without knee OA at baseline. Methods.: The Prevention of knee Osteoarthritis in Overweight Females study, ISRCTN42823086, was a randomized controlled trial with a 2 × 2 factorial design. Four hundred and seven women aged 50-60 years with a BMI of ⩾27 kg/m 2 and free of knee OA were randomized...
April 20, 2017: Rheumatology
https://www.readbyqxmd.com/read/28426554/barking-up-the-right-tree-advancing-our-understanding-and-treatment-of-lymphoma-with-a-spontaneous-canine-model
#3
Dania Villarnovo, Angela L McCleary-Wheeler, Kristy L Richards
PURPOSE OF REVIEW: Spontaneous lymphoma in pet dogs is increasingly recognized as an ideal model for studying the disease in humans and for developing new targeted therapeutics for patients. Increasing interest by funding agencies, the private sector, and multidisciplinary academic collaborations between different disciplines and sectors now enables large knowledge gaps to be addressed and provides additional proof-of-concept examples to showcase the significance of the canine model. RECENT FINDINGS: The current review addresses the rationale for a canine lymphoma model including the valuable role it can play in drug development, serving as a link between mouse xenograft models and human clinical trials and the infrastructure that is now in place to facilitate these studies...
April 19, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#4
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425073/molecular-therapy-of-primary-hyperoxaluria
#5
Cristina Martin-Higueras, Armando Torres, Eduardo Salido
During the last few decades, the molecular understanding of the mechanisms involved in primary hyperoxalurias (PHs) has set the stage for novel therapeutic approaches. The availability of PH mouse models has facilitated preclinical studies testing innovative treatments. PHs are autosomal recessive diseases where the enzymatic deficit plays a central pathogenic role. Thus, molecular therapies aimed at restoring such deficit or limiting the consequences of the metabolic derangement could be envisioned, keeping in mind the specific challenges posed by the cell-autonomous nature of the deficiency...
April 19, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28424071/imatinib-treatment-of-poor-prognosis-mesenchymal-type-primary-colon-cancer-a-proof-of-concept-study-in-the-preoperative-window-period-impacct
#6
I Ubink, H J Bloemendal, S G Elias, M A Brink, M P Schwartz, Y C W Holierhoek, P M Verheijen, A W Boerman, R H J Mathijssen, W W J de Leng, R A de Weger, W M U van Grevenstein, M Koopman, M P Lolkema, O Kranenburg, I H M Borel Rinkes
BACKGROUND: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cancer...
April 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28413945/body-machine-interface-enables-people-with-cervical-spinal-cord-injury-to-control-devices-with-available-body-movements-proof-of-concept
#7
Farnaz Abdollahi, Ali Farshchiansadegh, Camilla Pierella, Ismael Seáñez-González, Elias Thorp, Mei-Hua Lee, Rajiv Ranganathan, Jessica Pedersen, David Chen, Elliot Roth, Maura Casadio, Ferdinando Mussa-Ivaldi
This study tested the use of a customized body-machine interface (BoMI) for enhancing functional capabilities in persons with cervical spinal cord injury (cSCI). The interface allows people with cSCI to operate external devices by reorganizing their residual movements. This was a proof-of-concept phase 0 interventional nonrandomized clinical trial. Eight cSCI participants wore a custom-made garment with motion sensors placed on the shoulders. Signals derived from the sensors controlled a computer cursor. A standard algorithm extracted the combinations of sensor signals that best captured each participant's capacity for controlling a computer cursor...
May 2017: Neurorehabilitation and Neural Repair
https://www.readbyqxmd.com/read/28408243/erlotinib-and-bevacizumab-in-patients-with-advanced-non-small-cell-lung-cancer-and-activating-egfr-mutations-belief-an-international-multicentre-single-arm-phase-2-trial
#8
Rafael Rosell, Urania Dafni, Enriqueta Felip, Alessandra Curioni-Fontecedro, Oliver Gautschi, Solange Peters, Bartomeu Massutí, Ramon Palmero, Santiago Ponce Aix, Enric Carcereny, Martin Früh, Miklos Pless, Sanjay Popat, Athanasios Kotsakis, Sinead Cuffe, Paolo Bidoli, Adolfo Favaretto, Patrizia Froesch, Noemí Reguart, Javier Puente, Linda Coate, Fabrice Barlesi, Daniel Rauch, Michael Thomas, Carlos Camps, Jose Gómez-Codina, Margarita Majem, Rut Porta, Riyaz Shah, Emer Hanrahan, Roswitha Kammler, Barbara Ruepp, Manuela Rabaglio, Marie Kassapian, Niki Karachaliou, Rachel Tam, David S Shames, Miguel A Molina-Vila, Rolf A Stahel
BACKGROUND: The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation...
April 10, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28403229/correction-interferon-%C3%AE-1a-for-the-treatment-of-ebola-virus-disease-a-historically-controlled-single-arm-proof-of-concept-trial
#9
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0169255.].
2017: PloS One
https://www.readbyqxmd.com/read/28395759/a-multicenter-phase-ii-study-of-personalized-folfiri-cetuximab-for-safe-dose-intensification
#10
Michèle Boisdron-Celle, Jean Philippe Metges, Olivier Capitain, Antoine Adenis, Jean Luc Raoul, Thierry Lecomte, You Heng Lam, Roger Faroux, Claude Masliah, Anne Lise Poirier, Virginie Berger, Alain Morel, Erick Gamelin
We conducted a multicenter proof of concept phase II trial in patients with advanced colorectal cancer receiving FOLFIRI-cetuximab regimens to explore individual drug tailoring using pharmacogenetics and pharmacokinetics (PK) monitoring. Patients were stratified by their pharmacogenetic/phenotypic status: the irinotecan dose was adjusted according to the number of TA tandem repeats in the UGT1A1 promoter, while the 5-fluorouracil (5-FU) dose was initially adjusted according to dihydropyrimidine dehydrogenase (DPD) activity at initial screening (5-FU(ODPM Tox)) followed by PK-guided dose optimization (5-FU(ODPM Protocol))...
February 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28390737/treatment-of-vitiligo-with-the-topical-janus-kinase-inhibitor-ruxolitinib
#11
Brooke Rothstein, Deep Joshipura, Ami Saraiya, Rana Abdat, Huda Ashkar, Yana Turkowski, Vaneeta Sheth, Victor Huang, Shiu Chung Au, Courtney Kachuk, Nicole Dumont, Alice B Gottlieb, David Rosmarin
BACKGROUND: Existing therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. Topical Janus kinase inhibitors may offer a new therapeutic option for vitiligo. OBJECTIVE: We sought to assess the role of topical ruxolitinib 1.5% cream, a Janus kinase inhibitor, in vitiligo treatment. METHODS: This 20-week, open-label, proof-of-concept trial of twice-daily topical ruxolitinib 1.5% cream was conducted in 12 patients with a minimum of 1% affected body surface area of vitiligo...
April 5, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28389630/identification-of-small-molecule-inhibitors-of-the-aurora-a-tpx2-complex
#12
Italia Anna Asteriti, Frederick Daidone, Gianni Colotti, Serena Rinaldo, Patrizia Lavia, Giulia Guarguaglini, Alessandro Paiardini
Aurora kinases are a family of cell division regulators that govern the correct assembly of a bipolar mitotic spindle and the fidelity of chromosome segregation. Their overexpression is associated with genomic instability and aneuploidy, and is frequently observed in cancer. Accordingly, competitive inhibitors targeting Aurora kinase activity at the ATP-binding site are being investigated for therapeutic purposes. Despite promising pre-clinical data, these molecules display moderate effects in clinical trials and incomplete selectivity, either against distinct family members, or other kinases...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388861/hydrogen-sulfide-releasing-therapeutics-translation-to-the-clinic
#13
John L Wallace, David Vaughan, Michael Dicay, Wallace K MacNaughton, Gilberto DeNucci
SIGNIFICANCE: Shortly after the discovery of the role of hydrogen sulfide in many physiological and pathological processes, attempts were made to develop novel pharmaceuticals that may be of benefit for treatment or prevention of a wide range of disorders. The promise of hydrogen sulfide (H2S)-based therapeutics is now being demonstrated in clinical trials. Recent Advances: H2S-releasing drugs, such as SG1002 for cardiovascular disorders, and ATB-346 for arthritis, have progressed into clinical trials and have shown considerable promise...
April 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28387587/multiple-object-tracking-as-a-tool-for-parametrically-modulating-memory-reactivation
#14
Jordan Poppenk, Ken A Norman
Converging evidence supports the "nonmonotonic plasticity" hypothesis that, although complete retrieval may strengthen memories, partial retrieval weakens them. Yet, the classic experimental paradigms used to study effects of partial retrieval are not ideally suited to doing so, because they lack the parametric control needed to ensure that the memory is activated to the appropriate degree (i.e., that there is some retrieval but not enough to cause memory strengthening). Here, we present a novel procedure designed to accommodate this need...
April 7, 2017: Journal of Cognitive Neuroscience
https://www.readbyqxmd.com/read/28387543/effect-of-4-aminopyridine-on-genioglossus-muscle-activity-during-sleep-in-healthy-adults
#15
Luigi Taranto-Montemurro, Scott A Sands, Ali Azarbarzin, Melania Marques, Camila M de Melo, Bradley A Edwards, Danny J Eckert, Ludovico Messineo, David P White, Andrew Wellman
RATIONALE: The reduction in upper airway muscle activity from wakefulness to sleep plays a key role in the development of obstructive sleep apnea. Potassium (K+) channels have been recently identified as the downstream mechanisms through which hypoglossal motoneuron membrane excitability is reduced both in non-REM (NREM) and REM sleep. In animal models, the administration of 4-aminopyridine (4-AP), a voltage-gated K+ channel blocker, increased genioglossus activity during wakefulness and across all sleep stages...
April 7, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28383465/emerging-therapies-for-sensorineural-hearing-loss
#16
Matthew Gordon Crowson, Ronna Hertzano, Debara L Tucci
OBJECTIVE: To critically review and evaluate the proposed mechanisms and documented results of the therapeutics currently in active clinical drug trials for the treatment of sensorineural hearing loss. DATA SOURCES: US National Institutes of Health (NIH) Clinical Trials registry, MEDLINE/PubMed. STUDY SELECTION & DATA EXTRACTION: A review of the NIH Clinical Trials registry identified candidate hearing loss therapies, and supporting publications were acquired from MEDLINE/PubMed...
April 5, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28375741/isocitrate-dehydrogenase-mutation-and-r-2-hydroxyglutarate-from-basic-discovery-to-therapeutics-development
#17
Lenny Dang, Shin-San Michael Su
The identification of heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) in subsets of cancers, including secondary glioblastoma, acute myeloid leukemia, intrahepatic cholangiocarcinoma, and chondrosarcomas, led to intense discovery efforts to delineate the mutations' involvement in carcinogenesis and to develop therapeutics, which we review here. The three IDH isoforms nicotinamide adenine dinucleotide phosphate-dependent IDH1 and IDH2, and nicotinamide adenine dinucleotide-dependent IDH3) contribute to regulating the circuitry of central metabolism...
April 3, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28372596/a-proof-of-concept-investigation-into-ketamine-as-a-pharmacological-treatment-for-alcohol-dependence-study-protocol-for-a-randomised-controlled-trial
#18
Amy McAndrew, Will Lawn, Tobias Stevens, Lilla Porffy, Brigitta Brandner, Celia J A Morgan
BACKGROUND: Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group...
April 4, 2017: Trials
https://www.readbyqxmd.com/read/28370307/open-label-proof-of-concept-study-of-brexanolone-in-the-treatment-of-severe-postpartum-depression
#19
Stephen J Kanes, Helen Colquhoun, James Doherty, Shane Raines, Ethan Hoffmann, David R Rubinow, Samantha Meltzer-Brody
OBJECTIVE: Preclinical evidence indicates that rapid changes in levels of allopregnanolone, the predominant metabolite of progesterone, confer dramatic behavioral changes and may trigger postpartum depression (PPD) in some women. Considering the pathophysiology of PPD (i.e., triggered by reproductive steroids), the need for fast-acting, efficacious treatments and the negative consequences of untreated PPD, there is an increasing focus on developing PPD therapies. Brexanolone (USAN; formerly SAGE-547 Injection), a proprietary injectable allopregnanolone formulation, was evaluated as a treatment for severe PPD in a proof-of-concept, open-label study...
March 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28366166/a-path-to-precision-in-the-icu
#20
REVIEW
David M Maslove, Francois Lamontagne, John C Marshall, Daren K Heyland
Precision medicine is increasingly touted as a groundbreaking new paradigm in biomedicine. In the ICU, the complexity and ambiguity of critical illness syndromes have been identified as fundamental justifications for the adoption of a precision approach to research and practice. Inherently protean diseases states such as sepsis and acute respiratory distress syndrome have manifestations that are physiologically and anatomically diffuse, and that fluctuate over short periods of time. This leads to considerable heterogeneity among patients, and conditions in which a "one size fits all" approach to therapy can lead to widely divergent results...
April 3, 2017: Critical Care: the Official Journal of the Critical Care Forum
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