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clinical and translational

Žana Kralj, Milenka Dedić, Anđela Kovačević, Mario Malički, Jelena Dedić, Marina Pelivan, Dubravka Vuković, Carrie Fisher, Rachel L Kember, John Nurnberger, Maja Bućan, Dolores Britvić
OBJECTIVE: To test the validity and reliability of the Diagnostic Interview for Genetic Studies (DIGS) in patients with mental illness in Croatia. MATERIALS AND METHODS: Following translation, back-translation, and pilot testing, the Croatian version of DIGS (CRO-DIGS) was administered to a total of 150 inpatients and outpatients diagnosed at the Clinical Hospital in Split with bipolar and major depressive disorder (n=56), schizophrenia and schizoaffective disorder (n=62), and alcohol dependence or use disorders (n=32)...
October 21, 2016: Psychiatric Genetics
Famke Aeffner, Nathan T Martin, Mirza Peljto, Joshua C Black, Justin K Major, Maryam Jangani, Michael O Ports, Joseph S Krueger, G David Young
Tissue image analysis (tIA) is emerging as a powerful tool for quantifying biomarker expression and distribution in complex diseases and tissues. Pancreatic ductal adenocarcinoma (PDAC) develops in a highly complex and heterogeneous tissue environment and, generally, has a very poor prognosis. Early detection of PDAC is confounded by limited knowledge of the pre-neoplastic disease stages and limited methods to quantitatively assess disease heterogeneity. We sought to develop a tIA approach to assess the most common PDAC precursor lesions, pancreatic intraepithelial neoplasia (PanIN), in tissues from Kras(LSL-G12D/+); Trp53(LSL-R172H/+); Pdx-Cre (KPC) mice, a validated model of PDAC development...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Mathieu Pecqueux, Isabell Liebetrau, Wiebke Werft, Hendrik Dienemann, Thomas Muley, Joachim Pfannschmidt, Benjamin Müssle, Nuh Rahbari, Sebastian Schölch, Markus W Büchler, Jürgen Weitz, Christoph Reissfelder, Christoph Kahlert
MicroRNAs are small non-coding RNAs with a length of 18-25 nucleotides. They can regulate tumor invasion and metastasis by changing the expression and translation of their target mRNAs. Their expression is substantially altered in colorectal cancer cells as well as in the adjacent tumor-associated stroma. Both of these compartments have a mutual influence on tumor progression. In the development of metastases, cancer cells initially interact with the host tissue. Therefore, compartment-specific expression signatures of these three locations-tumor, associated stroma, and host tissue-can provide new insights into the complex tumor biology of colorectal cancer...
October 21, 2016: International Journal of Molecular Sciences
Şermin Yalın Sapmaz, Dilek Ergin, Nesrin Şen Celasin, Handan Özek Erkuran, Duygu Karaarslan, Siğnem Öztekin, Bengisu Uzel Tanrıverdi, Ertuğrul Köroğlu, Ömer Aydemir
The goal of this study was to assess the validity and reliability of the Turkish version of the DSM-5 Dissociative Symptoms Severity Scale-Child Form. The scale was prepared by translating and then back translating the DSM-5 Dissociative Symptoms Severity Scale. The study groups included one group of 30 patients diagnosed with posttraumatic stress disorder who were treated in a child and adolescent psychiatry unit and a second group of 83 healthy volunteers from middle and high schools in the community. For assessment, the Adolescent Dissociative Experiences Scale (ADES) was used in addition to the DSM-5 Dissociative Symptoms Severity Scale...
October 24, 2016: Journal of Trauma & Dissociation
Belinda Goodenough, Richard Fleming, Michael Young, Kim Burns, Cindy Jones, Fallon Forbes
Providing information about latest research via educational sessions to health professionals caring for people with dementia may be insufficient to drive change. This project explored self-reported impacts on practice change of adding information about knowledge translation (KT) to a national dementia education program. Six national workshop days were held. Each provided the option of participating in a Principles of KT and innovation implementation seminar in addition to a clinical topic update (sexualities and dementia, or managing behavioural and psychological symptoms of dementia)...
October 24, 2016: Gerontology & Geriatrics Education
Martijn S Visser, Myrthe Dieleman, Stijn Klijn, Reinier Timman, Mats Lundström, Jan J V Busschbach, Nicolaas J Reus
PURPOSE: The Catquest-9SF questionnaire is a unidimensional, reliable, valid and short patient-reported outcome measure for quantifying benefits in visual functioning from cataract surgery. Our aim was to develop a formal Dutch translation, calculate norm scores, assess its validity and test-retest reliability and provide an easy way for use in clinical practice. METHODS: Translation of the questionnaire was performed according to guidelines of the International Society for Pharmacoeconomics and Outcomes Research...
October 24, 2016: Acta Ophthalmologica
Paolo Cifani, Alex Kentsis
Given superior analytical features, mass spectrometry proteomics is well suited for the basic investigation and clinical diagnosis of human disease. Modern mass spectrometry enables detailed functional characterization of the pathogenic biochemical processes, as achieved by accurate and comprehensive quantification of proteins and their regulatory chemical modifications. Here, we describe how high-accuracy mass spectrometry in combination with high-resolution chromatographic separations can be leveraged to meet these analytical requirements in a mechanism-focused manner...
October 24, 2016: Proteomics
Andrew J Massey
Clinical development of Chk1 inhibitors is currently focussed on evaluating activity as monotherapy and as potentiators of chemotherapy. To aid translation of pre-clinical studies, we sought to understand the effects of the tumour growth environment on Chk1 signalling and sensitivity to small molecule Chk1 inhibition. Spheroid culture altered Chk1 signalling to a more xenograft like state but decreased sensitivity to Chk1 inhibition. Growth in low serum did not alter DDR signalling but increased the sensitivity of A2058 and U2OS tumour cells to Chk1 inhibition...
October 24, 2016: Scientific Reports
Lulu Xie, Hongyi Kang, Maiken Nedergaard
BACKGROUND: Stroke is one of the leading causes of death and disability worldwide. As a consequence, several excellent rodent models have been developed to gain insight into the pathophysiology of stroke and testing the efficacy of neuroprotective interventions. However, one potential problem is that albeit roughly 80% of strokes occur in awake patients, all existing murine stroke models employ anesthesia. Moreover, epidemiological studies have shown that stroke injury is more severe in the minority of patients that suffer stroke while asleep...
2016: Journal of Nature and Science
Neil M D'Souza, Penny Fang, Jennifer Logan, Jinzhong Yang, Wen Jiang, Jing Li
Malignancies of the central nervous system (CNS), particularly glioblastoma and brain metastases from a variety of disease sites, are difficult to treat despite advances in multimodality approaches consisting of surgery, chemotherapy, and radiation therapy (RT). Recent successes of immunotherapeutic strategies including immune checkpoint blockade (ICB) via anti-PD-1 and anti-CTLA-4 antibodies against aggressive cancers, such as melanoma, non-small cell lung cancer, and renal cell carcinoma, have presented an exciting opportunity to translate these strategies for CNS malignancies...
2016: Frontiers in Oncology
Bo Wang, Shannon J Walsh, Muhammad W Saif
5-Fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents in solid tumors, including colon, gastric and breast cancers. The pharmacogenetic syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency leading to severe toxicity after administration of 5-flourouracil (5-FU) and capecitabine has been well-recognized. However, the data about the association of the target enzyme, thymidylate synthase (TYMS) with the toxicity of these agents is limited. A 50-year-old Caucasian woman with T2N2M0 Stage IIIB squamous cell rectal cancer after local surgical excision initiated 5-FU therapy with mitomycin-C and radiation therapy in the adjuvant setting...
September 21, 2016: Curēus
Ilyas Singeç, Anton Simeonov
Pluripotent stem cell research has made extraordinary progress over the last decade. The robustness of nuclear reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has created entirely novel opportunities for drug discovery and personalized regenerative medicine. Patient- and disease-specific iPSCs can be expanded indefinitely and differentiated into relevant cell types of different organ systems. As the utilization of iPSCs is becoming a key enabling technology across various scientific disciplines, there are still important challenges that need to be addressed...
2016: Drug Target Review
John Slattery, Derrick F MacFabe, Richard E Frye
Recent studies have highlighted the fact that the enteric microbiome, the trillions of microbes that inhabit the human digestive tract, has a significant effect on health and disease. Methods for manipulating the enteric microbiome, particularly through probiotics and microbial ecosystem transplantation, have undergone some study in clinical trials. We review some of the evidence for microbiome alteration in relation to childhood disease and discuss the clinical trials that have examined the manipulation of the microbiome in an effort to prevent or treat childhood disease with a primary focus on probiotics, prebiotics, and/or synbiotics (ie, probiotics + prebiotics)...
2016: Clinical Medicine Insights. Pediatrics
C Gustavo De Moraes, Jeffrey M Liebmann, Leonard A Levin
Glaucomatous visual field progression has both personal and societal costs and therefore has a serious impact on quality of life. At the present time, intraocular pressure (IOP) is considered to be the most important modifiable risk factor for glaucoma onset and progression. Reduction of IOP has been repeatedly demonstrated to be an effective intervention across the spectrum of glaucoma, regardless of subtype or disease stage. In the setting of approval of IOP-lowering therapies, it is expected that effects on IOP will translate into benefits in long-term patient-reported outcomes...
October 20, 2016: Progress in Retinal and Eye Research
Nicola J Stagg, Ben-Quan Shen, Flavia Brunstein, Chunze Li, Amrita V Kamath, Fiona Zhong, Melissa Schutten, Bernard M Fine
Antibody drug conjugates (ADC) consist of potent cytotoxic drugs conjugated to antibodies via chemical linkers, which enables specific targeting of tumor cells while reducing systemic exposure to the cytotoxic drug and improving the therapeutic window. The valine citrulline monomethyl auristatin E (vcMMAE, conventional linker-drug) ADC platform has shown promising clinical activity in several cancers, but peripheral neuropathy (PN) is a frequent adverse event leading to treatment discontinuation and dose reduction...
October 20, 2016: Regulatory Toxicology and Pharmacology: RTP
Bryan J Mathis, Taixing Cui
There has been a continued interest in translational research focused on both natural products and manipulation of functional groups on these compounds to create novel derivatives with higher desired activities. Oleanolic acid, a component of traditional Chinese medicine used in hepatitis therapy, was modified by chemical processes to form 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO). This modification increased anti-inflammatory activity significantly and additional functional groups on the CDDO backbone have shown promise in treating conditions ranging from kidney disease to obesity to diabetes...
2016: Advances in Experimental Medicine and Biology
Pierre-Henri Conze, Vincent Noblet, François Rousseau, Fabrice Heitz, Vito de Blasi, Riccardo Memeo, Patrick Pessaux
PURPOSE: Toward an efficient clinical management of hepatocellular carcinoma (HCC), we propose a classification framework dedicated to tumor necrosis rate estimation from dynamic contrast-enhanced CT scans. Based on machine learning, it requires weak interaction efforts to segment healthy, active and necrotic liver tissues. METHODS: Our contributions are two-fold. First, we apply random forest (RF) on supervoxels using multi-phase supervoxel-based features that discriminate tissues based on their dynamic in response to contrast agent injection...
October 22, 2016: International Journal of Computer Assisted Radiology and Surgery
Sihem Ait-Oudhia, Donald E Mager
Cancer is a complex disease that is characterized by an uncontrolled growth and spread of abnormal cells. Drug development in oncology is particularly challenging and is associated with one of the highest attrition rates of compounds despite substantial investments in resources. Pharmacokinetic and pharmacodynamic (PK/PD) modeling seeks to couple experimental data with mathematical models to provide key insights into factors controlling cytotoxic effects of chemotherapeutics and cancer progression. PK/PD modeling of anti-cancer compounds is equally challenging, partly based on the complexity of biological and pharmacological systems...
October 22, 2016: Journal of Pharmacokinetics and Pharmacodynamics
Andrés F Henao-Martínez, Kathryn Colborn, Gabriel Parra-Henao
Chagas disease is a complex tropical parasitic infection. It affects a significant portion of the population in Latin America, especially in areas of poverty and poor access to health care. It also affects immigrants in high-income countries who lack access to health care due to their legal status. Millions of people are at risk of contracting the disease, and approximately 30 % of chronically infected patients will develop cardiomyopathy. The cost of caring for patients that have been infected is substantial...
October 22, 2016: Parasitology Research
Judy Craft, Martin Christensen, Shannon Bakon, Lisa Wirihana
BACKGROUND: Nursing students' ability to learn, integrate and apply bioscience knowledge to their clinical practice remains a concern. OBJECTIVES: To evaluate the implementation, influence, and student perspective of a team-teaching workshop to integrate bioscience theory with clinical nursing practice. DESIGN: The team-teaching workshop was offered prior to commencement of the university semester as a refresher course at an Australian university...
October 18, 2016: Nurse Education Today
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