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Abdulkadir Kocak, Ismail Erol, Muslum Yildiz, Hatice Can
Developing small compound based drugs targeting the β-secretase (BACE) enzyme is one of the most promising strategies in treatment of the Alzheimer's disease. As the enzyme shows the activity based on the acid-base reaction at a very narrow pH range, the protonation state of aspartic acids with the residue number 32 and 228 (Asp32 and Asp228), which forms the active site dyad, along with the protonation state of the ligand (substrate or inhibitor) play very critical role in interactions between the ligand and enzyme...
October 17, 2016: Journal of Molecular Graphics & Modelling
Philippe Glorennec, Jean-Paul Lucas, Anne-Camille Mercat, Alain-Claude Roudot, Barbara Le Bot
Children are exposed to toxic metals and metalloids via their diet and environment. Our objective was to assess the aggregate chronic exposure of children aged 3-6years, living in France, to As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V present in diet, tap water, air, soil and floor dust in the years 2007-2009. Dietary data came from the French Total Diet Study, while concentrations in residential tap water, soil and indoor floor dust came from the 'Plomb-Habitat' nationwide representative survey on children's lead exposure at home...
October 19, 2016: Environment International
A N Stephens, C A Bishop, S Liu, M Fitzharris
BACKGROUND: Alcohol contributes to approximately 30% of all serious crashes. While the majority of drivers acknowledge the risks associated with drink-driving, a significant proportion of the population continue to engage in this behaviour. Attitudes towards drink-driving as well as personal alcohol consumption patterns are likely to underpin a driver's decision to drink-drive. These associations were explored in the current study. METHODS: A large (N=2994) cross-sectional online survey of a representative sample of drivers in Australia was conducted...
October 19, 2016: Accident; Analysis and Prevention
Ruca Maass, Christian A Kloeckner, Bengt Lindstrøm, Monica Lillefjell
Neighborhood social capital has repeatedly been linked to favorable health-outcomes and life satisfaction. However, it has been questioned whether it's impact on health has been over-rated. We aim to investigate relationships between neighborhood social capital and self-rated health (SRH) and life satisfaction (LS) respectively, both directly and indirectly mediated via Sense of Coherence and self-esteem. Based on a cross-sectional population-survey (N=865) in a medium size Norwegian municipality, we specified a structural equation model (SEM) including the above-listed variables, while controlling for gender, age, education, income, and employment status...
October 19, 2016: Health & Place
Påvel G Lindberg, Maxime Térémetz, Sylvain Charron, Oussama Kebir, Agathe Saby, Narjes Bendjemaa, Stéphanie Lion, Benoît Crépon, Raphaël Gaillard, Catherine Oppenheim, Marie-Odile Krebs, Isabelle Amado
Inhibition is considered a key mechanism in schizophrenia. Short-latency intracortical inhibition (SICI) in the motor cortex is reduced in schizophrenia and is considered to reflect locally deficient γ-aminobutyric acid (GABA)-ergic modulation. However, it remains unclear how SICI is modulated during motor inhibition and how it relates to neural processing in other cortical areas. Here we studied motor inhibition Stop signal task (SST) in stabilized patients with schizophrenia (N = 28), healthy siblings (N = 21) and healthy controls (n = 31) matched in general cognitive status and educational level...
September 30, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
K Holstein, A Batorova, M Carvalho, K Fijnvandraat, P Holme, K Kavakli, T Lambert, A Rocino, V Jiménez-Yuste, J Astermark
INTRODUCTION: Inhibitor development in people with haemophilia is a serious complication that may require intensive and costly interventions. The goal of inhibitor management should be permanent inhibitor eradication through immune tolerance induction (ITI), but well-designed studies are lacking and the management of patients is therefore defined by the experience and views of the clinician. OBJECTIVES: To explore the current clinical practice and outcome of ITI therapy in Europe and how this may have changed over the last decade, as well as to provide consensus recommendations to guide clinicians in their clinical practice...
October 15, 2016: Thrombosis Research
Dewei Zhao, Frank Witte, Faqiang Lu, Jiali Wang, Junlei Li, Ling Qin
As a new generation of medical metallic material, magnesium (Mg) and its alloys with or without surface coating have attracted a great deal of attention due to its biodegradability and potential for avoiding a removal operation after the implant has fulfilled its function for surgical fixation of injured musculoskeletal tissues. Although a few clinical cases on Mg-based orthopaedic implants were reported more than a century ago, it was not until recently that clinical trials using these implants with improved physicochemical properties were carried out in Germany, China and Korea for bone fracture fixation...
October 11, 2016: Biomaterials
BanuPriya Sridharan, Amy D Laflin, Michael A Holtz, Donna M Pacicca, Nicholas K Wischmeier, Michael S Detamore
To date, many osteochondral regenerative approaches have utilized varied combinations of biocompatible materials and cells to engineer cartilage. Even in cell-based approaches, to date, no study has utilized stem cell aggregates alone for regenerating articular cartilage. Thus, the purpose of this study was to evaluate the performance of a novel stem cell-based aggregate approach in a fibrin carrier to regenerate osteochondral defects in the Sprague-Dawley rat trochlear groove model. Two different densities of rat bone marrow mesenchymal stem cell (rBMSC) aggregates were fabricated by the hanging drop technique...
October 22, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Henry Maia Peixoto, Marcelo Augusto Mota Brito, Gustavo Adolfo Sierra Romero, Wuelton Marcelo Monteiro, Marcus Vinícius Guimarães de Lacerda, Maria Regina Fernandes de Oliveira
OBJECTIVE: The aim of this study was to estimate the incremental budget impact (IBI) of a rapid diagnostic test to detect G6PDd in male patients infected with Plasmodium vivax in the Brazilian Amazon, as compared to the routine protocol recommended in Brazil which does not include G6PDd testing. METHODS: The budget impact analysis was performed from the perspective of the Brazilian health system, in the Brazilian Amazon for the years 2013, 2014 and 2015. The analysis used a decision model to compare two scenarios: the first consisting of the routine recommended in Brazil which does not include prior diagnosis of dG6PD, and the second based on the use of RDT CareStart(™) G6PD (CS-G6PD) in all male subjects diagnosed with vivax malaria...
October 22, 2016: Tropical Medicine & International Health: TM & IH
Letícia Couto Garcia, Danilo Bandini Ribeiro, Fabio de Oliveira Roque, Jose Manuel Ochoa-Quintero, William F Laurance
In November 2015, a large mine-tailing dam owned by Samarco Corporation collapsed in Brazil, generating a massive wave of toxic mud that spread down the Doce River, killing 19 people and affecting biodiversity across hundreds of kilometers of river, riparian lands, and Atlantic coast. Besides the disaster's serious human and socioeconomic tolls, we estimate the regional loss of environmental services to be ~US$5.21 billion/year. Although our estimate is conservative, it is still six times higher than the fine imposed on Samarco by Brazilian environmental authorities...
October 22, 2016: Ecological Applications: a Publication of the Ecological Society of America
Rory J McCrimmon
Despite the introduction of newer technologies and improved insulin formulations, recurrent hypoglycaemia continues to affect the lives of many people with Type 1 and Type 2 diabetes. Developing strategies or therapies designed to prevent or minimize hypoglycaemia risk is of utmost importance to help individuals safely achieve glycaemic targets. Novel, educational or behavioural approaches need to be based on a clear understanding of the mechanisms underpinning both the detection of hypoglycaemia and why repeated exposure to hypoglycaemia leads to the development of a clinical syndrome referred to as impaired awareness of hypoglycaemia...
October 22, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Agnieszka Fiszer, Marianna E Ellison-Klimontowicz, Wlodzimierz J Krzyzosiak
Polyglutamine (polyQ) diseases comprise a group of nine genetic disorders that are caused by the expansion of the CAG triplet repeat, which encodes glutamine, in unrelated single genes. Various oligonucleotide (ON)-based therapeutic approaches have been considered for polyQ diseases. The very attractive CAG repeat-targeting strategy offers selective silencing of the mutant allele by directly targeting the mutation site. CAG repeat-targeting miRNA-like siRNAs have been shown to specifically inhibit the mutant gene expression, and their characteristic feature is the formation of mismatches in their interactions with the target site...
October 21, 2016: Acta Biochimica Polonica
Anika Wranke, Beatriz Calle Serrano, Benjamin Heidrich, Janina Kirschner, Birgit Bremer, Patrick Lehmann, Svenja Hardtke, Katja Deterding, Kerstin Port, Max Westphal, Michael P Manns, Markus Cornberg, Heiner Wedemeyer
BACKGROUND: Hepatitis delta is the most severe form of viral hepatitis. Pegylated interferon alfa (PEG- IFNα) is effective in only 25-30% of patients and is associated with frequent side effects. The aim of this study was to analyze the clinical long-term outcome of hepatitis delta in relation to different antiviral treatment strategies. METHODS: We studied 136 anti-HDV-positive patients who were followed for at least 6 months in a retrospective single-center cohort (mean time of follow up 5...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jeannine Coburn, Jamie Harris, Alexander D Zakharov, Jennifer Poirier, Naohiko Ikegaki, Andre Kajdacsy-Balla, Monika Pilichowska, Alexander V Lyubimov, Hiroyuki Shimada, David L Kaplan, Bill Chiu
Neuroblastoma is the most common extracranial childhood solid tumor. Treatment of high risk tumors require intense multi-cycle chemotherapies, resulting in short- and long-term toxicities. Here we present treatment of an orthotopic neuroblastoma mouse model, with silk fibroin materials loaded with vincristine, doxorubicin, or the combination as a intratumoral, sustained release system. The materials, loaded with vincristine with or without doxorubicin, significantly decreased neuroblastoma tumor growth compared to materials loaded without drug or doxorubicin only as well as intravenous (IV) drug treatment...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
T Akhvlediani, N Akhvlediani, T Kuchuloria
Health care associated infections are the most frequent adverse event accompanying healthcare delivery worldwide. Of these, respiratory tract infections, including ventilator-associated pneumonia (VAP), have been recognized as the most common infections in acute hospitals. Sparse anecdotal and epidemiologic data from intensive care units (ICU) and infectious diseases physicians, as well as several publications in this field, suggest that the etiology of VAP in Georgia is most likely Klebsiella pneumoniae. This review article discusses the challenges of infection control in the Georgian health care system, with a focus on VAP...
September 2016: Georgian Medical News
T Kuchuloria, T Akhvlediani, N Akhvlediani
This root cause analysis concerns the conflict in the Eastern Ukraine and its impact on healthcare delivery in the context of treating internally displaced persons (IDPs). Inadequate treatment of tuberculosis (TB) was selected as a major topic for intervention planning in conflict areas in Ukraine. With respect to treating TB among IDPs, rapid diagnosis and adequate nutrition and shelter are important components of care and disease control. The DOT, supported by trained primary healthcare providers equipped with rapid MDR TB diagnostic capacities, need to provide appropriate shelter and nutrition to IDPs...
September 2016: Georgian Medical News
E Vashakidze, I Mikadze, E Pachkoria
Hepatitis C virus is responsible for the majority of persistent viral infections of the liver, chronic hepatitis, liver cirrhosis and/ or hepatocellular carcinoma. Two strategies are important to curtailing the rising prevalence of disease: efficient diagnosis of acute hepatitis and identification of the likely mode of transmission. The aim of this study was to identify the clinical and epidemiological hallmarks of acute hepatitis C. During 2013-2015, 31 patients were hospitalized with a diagnosis of acute C hepatitis...
September 2016: Georgian Medical News
Katsuhiko Hirota, Hiromichi Yumoto, Bayarmagnai Sapaar, Takashi Matsuo, Tetsuo Ichikawa, Yoichiro Miyake
Candida albicans is commonly found as a member of the human microflora and a major human opportunistic fungal pathogen. A perturbation of the microbiome can lead to infectious diseases caused by various microorganisms, including C. albicans. Moreover, the interactions between C. albicans and bacteria are considered to play critical roles in human health. The major biological feature of C. albicans, which impacts human health, resides in its ability to form biofilms. In particular, the extracellular matrix (ECM) of Candida biofilm plays a multifaceted role and therefore may be considered as a highly attractive target to combat biofilm-related infectious diseases...
October 21, 2016: Journal of Applied Microbiology
Sainath S Kasar, Kiran R Marathe, Amey J Bhide, Abhijeet P Herwade, Ashok P Giri, Vijay L Maheshwari, Pankaj K Pawar
BACKGROUND: Identification and characterization of plant defensive molecules enrich our resources to design crop protection strategies. In particular, plant derived proteinaceous inhibitor(s) of insect digestive enzymes appear to be a safe, sustainable and attractive option. RESULTS: A glycoprotein having non-competitive α-amylase inhibitory activity with molecular weight 8.3 kDa was isolated and purified from seeds of Withania somnifera (WSAI). Its mass spectrometry analysis revealed 59% sequence coverage with Wrightide II type α-AI from Wrightia religiosa...
October 22, 2016: Pest Management Science
D Donegan, N Singh Ospina, R Rodriguez-Gutierrez, Z Al-Hilli, G B Thompson, B L Clarke, W F Young
BACKGROUND: In patients with multiple endocrine neoplasia type 1 (MEN-1), pancreaticoduodenal (PD) neuroendocrine tumors (NETs) are associated with early mortality, yet, the best treatment strategy, remains uncertain. AIM: To assess patient important outcomes (mortality and metastasis) of PD NETs and predictors of outcomes in patients with MEN-1. METHODS: Retrospective cohort of patients with MEN-1 who attended the Mayo Clinic, Rochester, MN from 1997-2014...
October 21, 2016: Clinical Endocrinology
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