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Sebastian Klaus, Alexander Meschnig, Ernst von Kardorff
OBJEKTIVES: Using qualitative-hermeneutical methods with a focus on biographical (risk-) constellations for conditions of success or failure of return to work - and therefore on the efficiency and sustainability of employment participation benefits - the study accompanies participants during a time span of 2 years after their vocational retraining on their way back into the first labor market. METHODS: The study applies a mixed method design which combines 30 episodical-narrative interviews of participating rehabilitants alongside with a questionnaire survey of a total of 214 participants and 19 interviews of scientists and vocational retraining experts...
June 2018: Die Rehabilitation
Jan Heimeshoff, Constanze Merz, Marcel Ricklefs, Felix Kirchhoff, Axel Haverich, Christoph Bara, Christian Kühn
BACKGROUND:  A wearable cardioverter-defibrillator (WCD) can terminate ventricular fibrillation and ventricular tachycardias via electrical shock and thus give transient protection from sudden cardiac death. We investigated its role after cardiac surgery. METHODS:  We retrospectively analyzed all patients who were discharged with a WCD from cardiac surgery department. The WCD was prescribed for patients with a left ventricular ejection fraction (LVEF) of ≤35% or an explanted implantable cardioverter-defibrillator (ICD)...
June 20, 2018: Thoracic and Cardiovascular Surgeon
Rukeya Sawut, Nijat Kasim, Balati Maihemuti, Li Hu, Abdugheni Abliz, Abdusalam Abdujappar, Miradil Kurban
The objective of this study was to investigate heavy metal contamination in four major vegetable bases and determine the health risks of residents in the vicinity of the highly urbanized city Urumqi in Xinjiang, China. In this paper, we determined the contents of six heavy metals (i.e., As, Zn, Cd, Cr, Hg, and Pb) in surface soil and groundwater to evaluate the levels of heavy metal pollution and human health risks using the pollution index (PI), the Nemerow integrated pollution index (NIPI), the ecological risk factor (Ei r ), risk index (RI) and the health risk assessment model...
June 17, 2018: Science of the Total Environment
Amy Christensen, Christian J Pike
Alzheimer's disease (AD) pathogenesis is a multifactorial process that involves numerous pathways within the central nervous system. Thus, interventions that interact with several disease-related pathways may offer an increased opportunity for successful prevention and treatment of AD. Translocator protein 18 kD (TSPO) is a mitochondrial protein that is associated with regulation of many cellular processes including inflammation, steroid synthesis, apoptosis, and mitochondrial respiration. Although TSPO ligands have been shown to be protective in several neurodegenerative paradigms, little work has been done to assess their potential as treatments for AD...
June 17, 2018: Neuroscience Letters
Guohua Lv, Ashutosh Kumar, Yun Huang, David Eliezer
Fibrillar α-synuclein (AS) is the major component of Lewy bodies, the pathological hallmark of Parkinson's disease. Using solid-state nuclear magnetic resonance (ssNMR), we previously reported a structural characterization of mouse AS (mAS) fibrils and found that the secondary structure of the mAS fibrils is highly similar to a form of human AS (hAS) fibrils. Recently, a three-dimensional structure of these same hAS fibrils was determined by ssNMR and scanning transmission electron microscopy. Using medium- and long-range distance restraints obtained from ssNMR spectra, we found that the single protofilament structure of mAS fibrils is also similar to that of the hAS fibrils...
June 19, 2018: Biophysical Journal
Harsha Mysore Rajagopal, Srikanta Belagihalli Manjegowda, Chandraprakash Serkad, Shylaja Mallaiah Dharmesh
Antiulcer potency of structurally defined low molecular weight modified pectin from turmeric (MTrPP) including inhibitory effects on H. pylori has been demonstrated previously by us. Given that ulcer is a disorder characterized by inflammatory responses leading to initiation, aggravation and perpetuation of disease conditions, the present study aims to understand the possible anti-inflammatory mechanisms through which MTrPP delivered antiulcer effects. Rats triggered with early phase gastric inflammation (LPS) followed by ulcer induction (swim-stress) were pretreated with MTrPP (150 mg/kg b...
June 17, 2018: International Journal of Biological Macromolecules
Penelope R Brock, Rudolf Maibach, Margaret Childs, Kaukab Rajput, Derek Roebuck, Michael J Sullivan, Véronique Laithier, Milind Ronghe, Patrizia Dall'Igna, Eiso Hiyama, Bénédicte Brichard, Jane Skeen, M Elena Mateos, Michael Capra, Arun A Rangaswami, Marc Ansari, Catherine Rechnitzer, Gareth J Veal, Anna Covezzoli, Laurence Brugières, Giorgio Perilongo, Piotr Czauderna, Bruce Morland, Edward A Neuwelt
Background Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival. Methods We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses...
June 21, 2018: New England Journal of Medicine
Siu Ling Wong, Denisa D Wagner
Peptidylarginine deiminase 4 (PAD4) is a nuclear citrullinating enzyme that is critically involved in the release of decondensed chromatin from neutrophils as neutrophil extracellular traps (NETs). NETs, together with fibrin, are implicated in host defense against pathogens; however, the formation of NETs (NETosis) has injurious effects that may outweigh their protective role. For example, PAD4 activity produces citrullinated neoantigens that promote autoimmune diseases, such as rheumatoid arthritis, to which PAD4 is genetically linked and where NETosis is prominent...
June 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yongjian Wang, Palma Rico-Lastres, Ainhoa Lezamiz, Marc Mora, Carles Solsona, Guillaume Stirnemann, Sergi Garcia-Manyes
Understanding the molecular mechanisms governing protein-nucleic acid interactions is fundamental to many nuclear processes. However, how nucleic acid binding affects the conformation and dynamics of the substrate protein remains poorly understood. Here we use a combination of single molecule force spectroscopy AFM and biochemical assays to show that the binding of TG-rich ssDNA triggers a mechanical switch in the RRM1 domain of TDP-43, toggling between an entropic spring devoid of mechanical stability and a shock absorber bound-form that resists unfolding forces of 40 pN...
June 20, 2018: Journal of Physical Chemistry Letters
Mary C Tolcher, Sherif A Shazly, Alireza A Shamshirsaz, William E Whitehead, Jimmy Espinoza, Alex C Vidaeff, Michael A Belfort, Ahmed A Nassr
BACKGROUND: Controversy exists regarding the optimal mode of delivery for fetuses with open neural tube defects. OBJECTIVE: To compare neurological outcomes among infants with open neural tube defects who underwent vaginal compared to caesarean delivery. SEARCH STRATEGY: Electronic databases MEDLINE, EMBASE, Scopus, and Clinicaltrials. gov were searched from inception to November 2017. SELECTION CRITERIA: Eligible studies included observational or randomised studies comparing vaginal and caesarean delivery in pregnancies with fetal open neural tube defects who did not undergo prenatal repair...
June 20, 2018: BJOG: An International Journal of Obstetrics and Gynaecology
Anne-Floor W Pouwer, Roel D M Mus, Joanna IntHout, Ate G J van der Zee, Johan Bulten, Leon F A G Massuger, Joanne A de Hullu
OBJECTIVE: To determine the efficacy of the addition of an ultrasound of the groins in routine follow-up of patients with vulvar squamous cell carcinoma (SCC) after a negative sentinel lymph node (SLN). DESIGN: Prospective single center study. SETTING: A tertiary expert oncology center for the treatment of vulvar cancer. POPULATION: All vulvar SCC patients with a negative SLN, treated between 2006 and 2014. METHODS: We prospectively collected data of 139 vulvar SCC patients treated with a SLN procedure...
June 20, 2018: BJOG: An International Journal of Obstetrics and Gynaecology
Yuan Xu, Yi-Fan Han, Bing Ye, Yin-Long Zhang, Jian-Da Dong, Shao-Jun Zhu, Jiong Chen
Chemotherapy is one of the most effective forms of cancer treatment. It has been widely used in the treatment of various malignant tumors. In order to investigate molecular mechanisms responsible for the chemoresistance of anaplastic thyroid cancer (ATC), we established the doxorubicin (Dox) resistance of human ATC SW1736 and 8305C cells and named them SW1736/Dox and 8305C/Dox, respectively. We evaluated the expression of various micro-RNAs (miRNAs) between control and Dox-resistant ATC cells and found that the expression of miR-27b-3p was significantly increased in Dox-resistant ATC cells...
June 20, 2018: Basic & Clinical Pharmacology & Toxicology
Jennifer Unger, Keshet Ronen, Trevor Perrier, Brian DeRenzi, Jennifer Slyker, Alison Drake, Dyphna Mogaka, John Kinuthia, Grace John-Stewart
OBJECTIVE: To assess the effect of short message service (SMS) communication on facility delivery, exclusive breastfeeding (EBF) and contraceptive use. DESIGN: MOBILE WACH WAS A 3-ARM UNBLINDED INDIVIDUALLY RANDOMISED CONTROLLED TRIAL: SETTING: A public sector maternal child health (MCH) clinic in Nairobi, Kenya. POPULATION: Three hundred women attending antenatal care were randomised, 100 to each arm, and followed for 24 weeks postpartum...
June 20, 2018: BJOG: An International Journal of Obstetrics and Gynaecology
Agnieszka Maszewska, Marta Zygmunt, Iwona Grzejdziak, Antoni Różalski
AIMS: Catheter-associated urinary tract infections (CAUTI) caused by Proteus mirabilis are very difficult to treat due to the ability of biofilm formation and drug resistance of these bacteria. The aim of this study was to assess the anti-biofilm activity of phages and develop phage cocktail to combat biofilm of P. mirabilis strains. METHODS AND RESULTS: Planktonic forms and biofilms of 50 tested uropathogenic P. mirabilis strains showed different sensitivity to 13 phages used...
June 20, 2018: Journal of Applied Microbiology
Adaobi Okonkwo, Joy Mitra, Gavin S Johnson, Li Li, Wan Mohaiza Dashwood, Muralidhar Hegde, Chen Yue, Roderick H Dashwood, Praveen Rajendran
SCOPE: DNA repair inhibitors have broad clinical applications in tumor types with DNA repair defects, including colorectal cancer. Structural analogs of the anticancer agent sulforaphane (SFN) were investigated as modifiers of histone deacetylase (HDAC) and histone acetyltransferase (HAT) activity, and for effects on DNA damage/repair pertinent to human colorectal cancer. METHODS AND RESULTS: In the polyposis in rat colon (Pirc) model, single oral administration of SFN and structurally-related long-chain isothiocyanates (ITCs) decreased HDAC3 expression and increased pH2AX levels markedly in adenomatous colon polyps, extending our prior observations on HDAC3 inhibition/turnover in cell-based assays...
June 20, 2018: Molecular Nutrition & Food Research
Paulo R L Machado, Camila S Ribeiro, Jaqueline França-Costa, Mayra E F Dourado, Cristiana T Trinconi, Jenicer K U Yokoyama-Yasunaka, Hayna Malta-Santos, Valéria M Borges, Edgar M Carvalho, Silvia R B Uliana
OBJECTIVES: There is a clear need for new strategies of leishmaniasis treatment. This work was conducted to evaluate the efficacy of the co-administration of tamoxifen and meglumine antimoniate (SbV ) in a phase II pilot clinical trial in localized cutaneous leishmaniasis patients. METHODS: A randomized controlled pilot clinical trial was conducted to evaluate the efficacy and safety of oral (40 mg/day for 20 days) or topical tamoxifen (0.1% tamoxifen citrate for 20 days) combined with meglumine antimoniate (20 mg SbV /kg/day for 20 days) versus a standard SbV protocol (20 mg/kg/day for 20 days) for the treatment of cutaneous leishmaniasis...
June 20, 2018: Tropical Medicine & International Health: TM & IH
Ingus Perkons, Iveta Pugajeva, Vadims Bartkevics
An analytical method based on liquid chromatography with quadrupole time-of-flight mass spectrometry has been developed for the simultaneous determination of six aminoglycoside antibiotics in honey. The sample pretreatment included extraction with aqueous trichloroacetic acid followed by solid-phase extraction on Strata-X polymeric reversed phase cartridges. Liquid chromatography separation was performed on an Obelisc R zwitterionic type mixed-mode column. An ionBooster™ heated electrospray source was used and showed enhanced ionization efficiency in comparison to a conventional electrospray source...
June 20, 2018: Journal of Separation Science
Marja-Leena Linne
Neuroinformatics is an area of science that aims to integrate neuroscience data and develop modern computational tools to increase our understanding of the functions of the nervous system in health and disease. Neuroinformatics tools include, among others, databases for storing and sharing data, repositories for managing documents and source code, and software tools for analysing, modelling and simulating signals and images. This MiniReview aims to present the state-of-the-art in neuroinformatics and computational in silico modelling of neurobiological processes and neuroscientific phenomena as well as to discuss the use of in silico models in neurotoxicology research...
June 20, 2018: Basic & Clinical Pharmacology & Toxicology
D Lanz, P Moore, J Daru
Debates about emergency research consent are especially pertinent to the obstetric setting. While there is an opportunity to approach women antenatally, this is not always appropriate: advance consent for conditions with an incidence of less than 1 in 10 is seen as potentially inducing unnecessary anxiety (RCOG Clinical Governance Advice 6a, February 2016). In our experience of patient and public involvement work (Moss et al, BJOG 2016;124:362-365) and of recruitment processes in the SALVO trial (Khan et al...
June 20, 2018: BJOG: An International Journal of Obstetrics and Gynaecology
Josephina A N Meester, Maja Sukalo, Kim C Schröder, Denny Schanze, Gareth Baynam, Guntram Borck, Nuria C Bramswig, Duygu Duman, Brigitte Gilbert-Dussardier, Muriel Holder-Espinasse, Peter Itin, Diana S Johnson, Shelagh Joss, Hannele Koillinen, Fiona McKenzie, Jenny Morton, Heike Nelle, Willie Reardon, Claudia Roll, Mustafa A Salih, Ravi Savarirayan, Ingrid Scurr, Miranda Splitt, Elizabeth Thompson, Hannah Titheradge, Colm P Travers, Lionel Van Maldergem, Margo Whiteford, Dagmar Wieczorek, Geert Vandeweyer, Richard Trembath, Lut Van Laer, Bart L Loeys, Martin Zenker, Laura Southgate, Wim Wuyts
Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts is currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort...
June 20, 2018: Human Mutation
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