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Clinical approach

Gustav Burström, Christian Buerger, Jurgen Hoppenbrouwers, Rami Nachabe, Cristian Lorenz, Drazenko Babic, Robert Homan, John M Racadio, Michael Grass, Oscar Persson, Erik Edström, Adrian Elmi Terander
OBJECTIVEThe goal of this study was to develop and validate a system for automatic segmentation of the spine, pedicle identification, and screw path suggestion for use with an intraoperative 3D surgical navigation system.METHODSCone-beam CT (CBCT) images of the spines of 21 cadavers were obtained. An automated model-based approach was used for segmentation. Using machine learning methodology, the algorithm was trained and validated on the image data sets. For measuring accuracy, surface area errors of the automatic segmentation were compared to the manually outlined reference surface on CBCT...
March 22, 2019: Journal of Neurosurgery. Spine
Anneli Peolsson, Håkan Löfgren, Åsa Dedering, Birgitta Öberg, Peter Zsigmond, Henrik Hedevik, Johanna Wibault
OBJECTIVEInformation about postoperative rehabilitation for cervical radiculopathy (CR) is scarce. The aim of this study was to investigate the additional benefits of structured postoperative rehabilitation (SPT), which was performed in all patients, compared with a pragmatic standard postoperative approach (SA), in which rehabilitation was used as needed and patients sought physiotherapy on their own without a referral, in patients with MRI evidence of disc herniation and concomitant clinical signs who underwent surgery for CR...
March 22, 2019: Journal of Neurosurgery. Spine
Rachel S Lee, Luxi Zhang, Adeline Berger, Mitchell G Lawrence, Jiangning Song, Birunthi Niranjan, Rebecca G Davies, Natalie L Lister, Shahneen K Sandhu, Mark A Rubin, Gail P Risbridger, Renea A Taylor, David S Rickman, Lisa G Horvath, Roger J Daly
Approximately 50% of prostate cancers harbor the TMPRSS2:ERG fusion, resulting in elevated expression of the ERG transcription factor. Despite the identification of this subclass of prostate cancers, no personalized therapeutic strategies have achieved clinical implementation. Kinases are attractive therapeutic targets as signaling networks are commonly perturbed in cancers. The impact of elevated ERG expression on kinase signaling networks in prostate cancer has not been investigated. Resolution of this issue may identify novel therapeutic approaches for ERG-positive prostate cancers...
March 19, 2019: Neoplasia: An International Journal for Oncology Research
Ying-Ju Lin, Wen-Miin Liang, Chao-Jung Chen, Hsinyi Tsang, Jian-Shiun Chiou, Xiang Liu, Chi-Fung Cheng, Ting-Hsu Lin, Chiu-Chu Liao, Shao-Mei Huang, Jianxin Chen, Fuu-Jen Tsai, Te-Mao Li
BACKGROUND: Chinese herbal medicines (CHMs) are a resource of natural compounds (ingredients) and their potential chemical derivatives with anticancer properties, some of which are already in clinical use. Bei-Mu (BM), Jie-Geng (JG), and Mai-Men-Dong-Tang (MMDT) are important CHMs prescribed for patients with lung cancer that have improved the survival rate. HYPOTHESIS/PURPOSE: The aim of this study was to systemically investigate the mechanisms of action of these CHM products in lung cancer cells...
March 13, 2019: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Nicole S Bryce, Edna C Hardeman, Peter W Gunning, John G Lock
The actin cytoskeleton is dysregulated in cancer, yet this critical cellular machinery has not translated as a druggable clinical target due to cardio-toxic side-effects. Many actin regulators are also considered undruggable, being structural proteins lacking clear functional sites suitable for targeted drug design. In this review, we discuss opportunities and challenges associated with drugging the actin cytoskeleton through its structural regulators, taking tropomyosins as a target example. In particular, we highlight emerging data acquisition and analysis trends driving phenotypic, imaging-based compound screening...
March 19, 2019: Current Opinion in Chemical Biology
Carmen Oi Kwan Law, Chuan Huang, Qing Pan, Joseph Lee, Qin Hao, Ting-Fung Chan, Norman Wai Sing Lo, Irene Ling Ang, Alex Koon, Margaret Ip, Edwin Chan, Terrence Chi Kong Lau
Bacteria with multiple drug resistance (MDR) have become a global issue worldwide, and hundreds of thousands of people's lives are threatened every year. The emergence of novel MDR strains and insufficient development of new antimicrobial agents are the major reasons that limit the choice of antibiotics for the treatment of bacterial infection. Thus, preserving the clinical value of current antibiotics could be one of the effective approaches to resolve this problem. Here we identified numerous novel small RNAs that were downregulated in the MDR clinical isolates of Pseudomonas aeruginosa (P...
February 22, 2019: Molecular Therapy. Nucleic Acids
Bruce Ng, Tanesha Cash-Mason, Yi Wang, Jessica Seitzer, Julja Burchard, Duncan Brown, Vadim Dudkin, Joseph Davide, Vasant Jadhav, Laura Sepp-Lorenzino, Pedro J Cejas
Clinical application of siRNA-based therapeutics outside of the liver has been hindered by the inefficient delivery of siRNA effector molecules into extra-hepatic organs and cells of interest. To understand the parameters that enable RNAi activity in vivo, it is necessary to develop a systematic approach to identify which cells within a tissue are permissive to oligonucleotide internalization and activity. In the present study, we evaluate the distribution and activity within the lung of chemically stabilized siRNA to characterize cell-type tropism and structure-activity relationship...
February 26, 2019: Molecular Therapy. Nucleic Acids
Philip P Chamberlain
Targeted protein degradation offers considerable promise for the discovery of new therapeutics. In Cell Chemical Biology, Brand et al. (2019) identify selective degraders of CDK6 derived from clinically approved CDK4/6 inhibitors. This approach offers the possibility of a differentiated therapeutic profile with potential to treat acute myeloid leukemia.
March 21, 2019: Cell Chemical Biology
Tuuli Lappalainen, Alexandra J Scott, Margot Brandt, Ira M Hall
Affordable genome sequencing technologies promise to revolutionize the field of human genetics by enabling comprehensive studies that interrogate all classes of genome variation, genome-wide, across the entire allele frequency spectrum. Ongoing projects worldwide are sequencing many thousands-and soon millions-of human genomes as part of various gene mapping studies, biobanking efforts, and clinical programs. However, while genome sequencing data production has become routine, genome analysis and interpretation remain challenging endeavors with many limitations and caveats...
March 21, 2019: Cell
Alberto J Espay, Jeffrey M Hausdorff, Álvaro Sánchez-Ferro, Jochen Klucken, Aristide Merola, Paolo Bonato, Serene S Paul, Fay B Horak, Joaquin A Vizcarra, Tiago A Mestre, Ralf Reilmann, Alice Nieuwboer, E Ray Dorsey, Lynn Rochester, Bastiaan R Bloem, Walter Maetzler
Obtaining reliable longitudinal information about everyday functioning from individuals with Parkinson's disease (PD) in natural environments is critical for clinical care and research. Despite advances in mobile health technologies, the implementation of digital outcome measures is hindered by a lack of consensus on the type and scope of measures, the most appropriate approach for data capture (eg, in clinic or at home), and the extraction of timely information that meets the needs of patients, clinicians, caregivers, and health care regulators...
March 22, 2019: Movement Disorders: Official Journal of the Movement Disorder Society
Steven Cohen, Christopher Gilmore, Leonardo Kapural, Steven Hanling, Anthony Plunkett, Meredith McGee, Joseph Boggs
Chronic low back pain represents one of the most common sources of disability and a significant healthcare burden for the U.S. military. Present treatments for chronic back pain are often ineffective, poorly tolerated, invasive, destructive, and/or associated with complications and lead to the progression to invasive surgical procedures. There have been multiple calls for the development of a minimally invasive system that is effective without the risks or complications of existing surgical therapies, which could prevent the need for surgery and the recurrence of pain...
March 1, 2019: Military Medicine
Matthew S Mesley, Kathryn Edelman, Jane Sharpless, Allison Borrasso, Julia B Billigen, Ross Puffer, Dana Williams, Steven Benso, Ava M Puccio, Walt Schneider, Ryan Soose, Sue Beers, Anthony Kontos, Michael Collins, David O Okonkwo
BACKGROUND: Targeted Evaluation Action and Monitoring of Traumatic Brain Injury (TEAM-TBI) is a monitored, multiple interventional research identifying clinical profiles and assigns individualized, evidence-based treatment program. The objective of the current study was to assess overall participant satisfaction of the multi-disciplinary care team and approach. METHODS: Between 2014 and 2017, 90 participants completed the 4-day TEAM-TBI clinical intake evaluation resulting in individualized treatment recommendations followed by a six-month intervention phase follow-up...
March 1, 2019: Military Medicine
Michael R Lewin-Smith, Stacy L Strausborger, H Marie Jenkins, Natalya Merezhinskaya, Paul A Latkany, Robert A Mazzoli, Marcus H Colyer, Michael J Mines
BACKGROUND: The Military Health System recognizes the importance of analyzing "foreign bodies" removed from US service members through several policy documents. This activity focuses on detecting potentially toxic metals. Intra-ocular "foreign bodies" (IOFBs) represent a small, clinically important subset. The development of ocular metallosis with iron and copper fragments is a specific local reaction to IOFBs. The results of the compositional analysis of removed IOFBs can influence clinical management decisions aimed at optimizing the preservation of sight...
March 1, 2019: Military Medicine
Tanisha L Hammill, Elizabeth McKenna, Quintin Hecht, Kari Buchanan, Nina Pryor
OBJECTIVE: Information is summarized from the overall body of published literature regarding ototoxic chemicals encountered outside of clinical exposures, largely in occupational settings. While summarizing the most common non-pharmaceutical ototoxins, this review provides clinically relevant information and recommendations such that hearing health professionals may adopt a more comprehensive and appropriate diagnostic case history, test battery, documentation scheme, and education delivery...
March 1, 2019: Military Medicine
Laveta Stewart, Faraz Shaikh, William Bradley, Dan Lu, Dana M Blyth, Joseph L Petfield, Timothy J Whitman, Margot Krauss, Lauren Greenberg, David R Tribble
We examined risk factors for combat-related extremity wound infections (CEWI) among U.S. military patients injured in Iraq and Afghanistan (2009-2012). Patients with ≥1 combat-related, open extremity wound admitted to a participating U.S. hospital (≤7 days postinjury) were retrospectively assessed. The population was classified based upon most severe injury (amputation, open fracture without amputation, or open soft-tissue injury defined as non-fracture/non-amputation wounds). Among 1271 eligible patients, 395 (31%) patients had ≥1 amputation, 457 (36%) had open fractures, and 419 (33%) had open soft-tissue wounds as their most severe injury, respectively...
March 1, 2019: Military Medicine
Cortney M Schoonover, Stephen L Turner, Yvette Woods, Enrique Smith-Forbes, Daniel I Rhon
Low back pain (LBP) is a common condition suffered by military personnel. Psychosocial factors play a role in LBP prognosis and can be addressed with self-management tools. This study's purpose was to (1) describe clinical changes in psychosocial factors of LBP following a self-management intervention and (2) explore the LBP experience of military trainees. Ten participants in Initial Entry Training (IET) were included in this mixed methods study. A self-management intervention of exercises and psychosocial education was provided...
March 1, 2019: Military Medicine
Igor Kaidashev, Liudmyla G Savchenko, Nataliia I Digtiar, Liudmyla G Selikhova, Elvira I Kaidasheva, Oksana A Shlykova, Liudmyla E Vesnina
INTRODUCTION: Liraglutide (L) is the analogue of human glucagon-like peptide 1 which stimulates glucose-dependent insulin secretion and can modify a level of inflammatory biomarkers. L can influence NF-kB inflammatory cascade, but the mechanisms of anti-inflammatory activities of L remain to be determined. In animal models L influenced an activity of Sirtuin 1(SIRT1). Moreover, recent evidences strongly suggest that SIRT1 up-regulation may serve as a potent therapeutic approach against development and progression of diabetic complications ...
January 1, 2019: Romanian Journal of Internal Medicine
Amod Tilak, Smita Shenoy, Muralidhar Varma, Asha Kamath, Amruta Tripathy, Ravi Sori, Kavitha Saravu
Introduction There is a dearth of studies assessing the efficacy and immunological improvement in patients started on antiretroviral therapy (ART) in India. This study was undertaken to assess the 2-year treatment outcomes in HIV-positive patients initiated on ART in a tertiary-care hospital. Methods After approval from the Institutional Ethics Committee, adult HIV-positive patients from a tertiary-care hospital, initiated on ART between January 2013 and February 2015, were included in the study. Data on clinical and immunological parameters were obtained from medical case records over a period of 2 years after initiation of therapy...
March 22, 2019: Journal of Basic and Clinical Physiology and Pharmacology
Gary J Doherty, Michele Petruzzelli, Emma Beddowes, Saif S Ahmad, Carlos Caldas, Richard J Gilbertson
The complexity of human cancer underlies its devastating clinical consequences. Drugs designed to target the genetic alterations that drive cancer have improved the outcome for many patients, but not the majority of them. Here, we review the genomic landscape of cancer, how genomic data can provide much more than a sum of its parts, and the approaches developed to identify and validate genomic alterations with potential therapeutic value. We highlight notable successes and pitfalls in predicting the value of potential therapeutic targets and discuss the use of multi-omic data to better understand cancer dependencies and drug sensitivity...
March 22, 2019: Annual Review of Biochemistry
Maria Reinecke, Benjamin Ruprecht, Sandra Poser, Svenja Wiechmann, Mathias Wilhelm, Stephanie Heinzlmeir, Bernhard Kuster, Guillaume Médard
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) have proven valuable for the elucidation of a compound's target profile under close-to-physiological conditions and often revealing potentially synergistic or toxic off-targets. Current Kinobeads enrich more than 300 native protein kinases from cell lines or tissues but do not systematically cover phosphatidylinositol 3-kinases (PI3Ks) and phosphatidylinositol 3-kinase-related kinases (PIKKs). Some PIKKs and PI3Ks show aberrant activation in many human diseases and are indeed validated drug targets...
March 22, 2019: ACS Chemical Biology
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