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Marianne Goodman, David Banthin, Nicholas J Blair, Kathryn A Mascitelli, Jaime Wilsnack, Jennifer Chen, Julie W Messenger, M Mercedes Perez-Rodriguez, Joseph Triebwasser, Harold W Koenigsberg, Raymond R Goetz, Erin A Hazlett, Antonia S New
OBJECTIVE: Despite advances in suicide prevention implemented throughout the US Department of Veterans Affairs (VA) including the hiring of Suicide Prevention Coordinators (SPCs) at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services, suicide by veterans remains a critical problem affecting 20 veterans daily. Few empirically based treatment strategies for suicide prevention for postdeployment military personnel exist. This study aimed to test whether dialectical behavior therapy (DBT), one of the few psychosocial treatments with proven efficacy in diminishing suicidal behavior in individuals with personality disorder, can be applied to veterans irrespective of personality diagnosis...
October 25, 2016: Journal of Clinical Psychiatry
Alessandra Gasior, Giulia Brisighelli, Karen Diefenbach, Victoria Alison Lane, Carlos Reck, Richard J Wood, Marc Levitt
Introduction Functional constipation is a common problem in children. It usually can be managed with laxatives but a small subset of patients develop intolerable cramps and need to be temporarily treated with enemas. The senior author has previously reported: 1) open sigmoid resection as a surgical option, but this did not sufficiently reduce the laxative need, then 2) a transanal approach (with resection of rectosigmoid), but this led to a high rate of soiling due to extensive stretching of the anal canal and loss of the rectal reservoir...
October 25, 2016: European Journal of Pediatric Surgery
Ramnath Subbaraman, Ruvandhi R Nathavitharana, Srinath Satyanarayana, Madhukar Pai, Beena E Thomas, Vineet K Chadha, Kiran Rade, Soumya Swaminathan, Kenneth H Mayer
BACKGROUND: India has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world's "missing" patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The "cascade of care" is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions. METHODS AND FINDINGS: The care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India's TB patients...
October 2016: PLoS Medicine
Rein M G J Houben, Peter J Dodd
BACKGROUND: The existing estimate of the global burden of latent TB infection (LTBI) as "one-third" of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI. METHODS AND FINDINGS: We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014...
October 2016: PLoS Medicine
Joanne Elizabeth Hegarty, Jane Elizabeth Harding, Gregory David Gamble, Caroline Anne Crowther, Richard Edlin, Jane Marie Alsweiler
BACKGROUND: Neonatal hypoglycaemia is common, affecting up to 15% of newborns, and can cause brain damage. Currently, there are no strategies, beyond early feeding, to prevent neonatal hypoglycaemia. Our aim was to determine a dose of 40% oral dextrose gel that will prevent neonatal hypoglycaemia in newborn babies at risk. METHODS AND FINDINGS: We conducted a randomised, double-blind, placebo-controlled dose-finding trial of buccal dextrose gel to prevent neonatal hypoglycaemia at two hospitals in New Zealand...
October 2016: PLoS Medicine
Mehrdad Namdari, Ali Eatemadi
Heart valves are currently under thorough investigation in tissue engineering (TE) research. Mechanical and biological heart valve prostheses which are recently used have several shortcomings. While allogenic and xenogenic biological prostheses are related to graft rejection, degeneration and thrombosis, resulting in a high rate of reoperation. Mechanical prostheses on the other hand are based on metallic, carbon, and polymeric components, and require continuous treatment with anticoagulant, which result in adverse reactions, e...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jay N Lozier, Mark T Kloos, Elizabeth P Merricks, Nathaly Lemoine, Margaret H Whitford, Robin A Raymer, Dwight A Bellinger, Timothy C Nichols
Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons...
2016: Comparative Medicine
Dian Su, Carl K Ng, Mehraban Khosraviani, Shang-Fan Yu, Ely Cosino, Surinder Kaur, Keyang Xu
Affinity capture liquid chromatography-mass spectrometry (LC-MS) intact antibody assay has been widely used for direct drug-to-antibody ratio (DAR) and catabolite characterization of antibody-drug conjugates (ADCs). However, the intact mass spectra of new ADCs, which incorporate new types of linkers and/or payloads other than maytansines and auristatins, are more complex than those examined previously. The current method has showed some limitations in elucidating certain structural modifications. Herein, we report an alternative analytical approach for ADCs, such as THIOMABTM antibody-drug conjugates (TDCs), where the linker-drugs are site-specifically conjugated in the Fab region...
October 25, 2016: Analytical Chemistry
Magdalena Zaborowska, Jonatan Tillander, Rickard Brånemark, Lars Hagberg, Peter Thomsen, Margarita Trobos
Staphylococci and enterococci account for most deep infections associated with bone-anchored percutaneous implants for amputation treatment. Implant-associated infections are difficult to treat; therefore, it is important to investigate if these infections have a biofilm origin and to determine the biofilm antimicrobial susceptibility to improve treatment strategies. The aims were: (i) to test a novel combination of the Calgary biofilm device and a custom-made susceptibility MIC plate (Sensititre(®) ), (ii) to determine the biofilm formation and antimicrobial resistance in clinical isolates causing implant-associated osteomyelitis, and (iii) to describe the associated clinical outcome...
October 25, 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Wan-Ju Lee, Leslie Briars, Todd A Lee, Gregory S Calip, Katie J Suda, Glen T Schumock
OBJECTIVE: To characterize the use of tumor necrosis factor-alpha inhibitors (TNFI) in children with juvenile idiopathic arthritis (JIA) and young adults with rheumatoid arthritis (RA). METHODS: Patients with incident JIA or RA were identified using the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. The incident diagnosis was defined as no prior claims with a JIA/RA code and no JIA/RA medications recorded during the previous 6 months...
October 25, 2016: Pharmacotherapy
Marília Silveira de Almeida Campos, Lorena Rocha Ayres, Manuela Roque Siane Morelo, Fabiana Angelo Marques, Leonardo Régis Leira Pereira
Several newer antiepileptic drugs (AEDs) have been introduced into clinical practice, offering choices for individualizing the treatment of epilepsy since AEDs have different efficacy and tolerability profiles. In particular, questions exist regarding which AEDs are the best options for the monotherapy of focal epilepsy. Is carbamazepine (CBZ), which is considered the standard treatment for focal epilepsy, still the best option for monotherapy of focal epilepsy, despite the emergence of new AEDs? In this systematic review, we compared the relative tolerability of all available AEDs for monotherapy of all types of epilepsy as well as their efficacy in the monotherapy of focal epilepsy...
October 25, 2016: Pharmacotherapy
L Hepburn, D J Hijnen, B R Sellman, T Mustelin, M A Sleeman, R D May, I Strickland
Atopic dermatitis (AD) is a complex, chronic inflammatory skin disorder affecting more than 10% of UK children and is a major cause of occupation-related disability. A subset of patients, particularly those with severe AD, are persistently colonised with Staphylococcus aureus (S. aureus) and exacerbation of disease is commonly associated with this bacterium by virtue of increased inflammation and allergic sensitisation, aggravated by skin barrier defects. Understanding the complex biology of S. aureus is an important factor when developing new drugs to combat infection...
October 25, 2016: British Journal of Dermatology
Michael J Mitchell, Catherine Metzler-Guillemain, Toure Aminata, Charles Coutton, Christophe Arnoult, Pierre F Ray
Azoospermia, defined by the absence of sperm in the ejaculate, is estimated to affect up to 1% of men in the general population. Assisted reproductive technologies have revolutionized the treatment of infertility, and some azoospermic men, those with a post-meiotic defect, can conceive following the use of viable spermatoza recovered from testicular or epididymal biopsies. Although male infertility is a multifactorial disease, it is believed that genetic factors are predominant in the etiology of azoospermia and severe oligozoospermia...
October 25, 2016: Clinical Genetics
Zheng Zhang, Hannah A Ledford, Seojin Park, Wenying Wang, Sassan Rafizadeh, Hyo Jeong Kim, Wilson Xu, Ling Lu, Victor C Lau, Anne A Knowlton, Xiao-Dong Zhang, Ebenezer N Yamoah, Nipavan Chiamvimonvat
The normal function of ion channels depends critically on the precise subcellular localization and the number of channel proteins on the cell surface membrane. Small-conductance, Ca(2+) -activated K(+) channels (SK, KCa 2) are expressed in human atrial myocytes and responsible for shaping atrial action potentials. Understanding the mechanisms of SK channel trafficking may provide new insights into the regulation controlling the repolarization of atrial myocytes. We have previously demonstrated that the C and N termini of SK2 channels interact with actin-binding proteins, α-actinin2 and filamin A, respectively...
October 25, 2016: Journal of Physiology
Susanna Wallerstedt
Medical and scientific assessments as the basis for prioritization and resource allocation for new drug treatment - experiences from five years of systematic workIn this study, the process for introduction of new drug treatment in Region Västra Götaland (second largest region in Sweden encompassing 1.6 million inhabitants, 17% of all inhabitants in Sweden) is described. A working group, consisting of persons with relevant expertise and declared conflicts of interest, contributes with medical and scientific assessments as the basis for prioritization and resource allocation...
October 18, 2016: Läkartidningen
Jan Liliemark, Lars Lööf, Gustaf Befrits, Stefan Back, Lars Sandman
The County Council's board for new therapies (the NT Council) provides recommendations on the use of new drugs based on the ethical platform of priorities, founded by the Swedish parliament. The Council has formulated a policy that interprets the parliamentary ethical platform and operationalize its need and solidarity principle and cost effectiveness principle in four dimensions. The NT Council weighs the health economic evaluation of the drug and the four dimensions: the severity of the condition, the rarity of the condition, the effect size and the data reliability to determine the willingness to pay level and whether the platform allows a recommendation for using of the drug...
October 18, 2016: Läkartidningen
Wei Zhao, Xiaohui Zhang, Jia Liu, Bei Sun, Hua Tang, Hong Zhang
Metformin was demonstrated to have effects on breast cancer, and microRNA-27a (miR-27a) is a prognostic marker for breast cancer progression and patient survival. AMPKα2 was found to be a suppressor in breast cancer MCF-7 cells. Therefore, the present study aimed to explain this phenomenon in regards to the relationship between microRNAs (miRNAs) and their target genes and to predict how AMPKα2 may be a downstream target gene of miR-27a, thus exploring the new mechanism of metformin in the treatment of breast cancer regarding miRNAs...
October 24, 2016: Oncology Reports
Hong-Xia Cui, Honglan Wang, Yuchun Wang, Juan Song, Hua Tian, Chunhui Xia, Yetong Shen
Changes in the carbohydrate structure on the surface of tumor cells is an important feature of cancer metastasis. The specific role of sialic acids in the glycoconjugate terminal has not yet been clearly elucidated in these processes. Previously, we reported that α2,3-sialic acid residues in breast cancer are associated with metastatic potential. The α2,3-sialyltransferase ST3Gal III, which adds α2,3-sialic acids to glycoproteins, is overexpressed in various tumors, and enzyme activity is correlated with tumor metastasis, yet its mechanistic role has not been fully evaluated...
October 18, 2016: Oncology Reports
Hiroko Kitahara, Mariko Hirai, Koroku Kato, George Bou-Gharios, Hiroyuki Nakamura, Shuichi Kawashiri
Inhibition of epidermal growth factor receptor (EGFR) signalling has emerged as a new treatment strategy for oral squamous cell carcinoma (OSCC). Previously, we found that loss of EGFR expression in OSCC was associated with epithelial-mesenchymal transition (EMT), and may have functional implications with regard to resistance to cetuximab, a monoclonal anti-EGFR antibody. Eribulin (a microtubule inhibitor) reportedly renders breast cancer less aggressive, and less likely to metastasise, by triggering mesenchymal‑to‑epithelial (MET) transition...
October 21, 2016: Oncology Reports
Eva Vidomanova, Peter Racay, Ivana Pilchova, Erika Halasova, Jozef Hatok
Glioblastoma (GB) is the most frequent and biologically the most aggressive primary brain tumor in adults. Standard treatment for newly diagnosed GB consists of surgical resection, radiotherapy and chemotherapy. Resistance to therapy is a major obstacle, even with optimal treatment with a survival median of only 12-15 months. The heterogeneity and treatment response of GB makes this tumor type a challenging area of research. The aim of our study was to study the response of normal human astrocyte (HA) and human GB (T98G) cell lines to apoptosis inhibitors in vitro...
October 21, 2016: Oncology Reports
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