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base excess approach

Dov Lichtenberg, Ilya Pinchuk, Daniela Weber
The commonly used term "oxidative stress" (OS) is intuitively defined as an excess of pro-oxidative compounds, over antioxidants. The redox status is homeostatically controlled because on one hand, pro-oxidants are essential for normal body function, whereas, on the other hand, pro-oxidants (and OS) are associated with many diseases due to the risk of oxidative damage. One reason "to monitor the OS" is to identify people under OS and treat people under high OS by antioxidants, because it is believed that people under OS benefit from antioxidant supplementation more than others...
March 15, 2018: BioFactors
Filip Boratyński, Ewa Szczepańska, Aleksandra Grudniewska, Bartłomiej Skalny, Teresa Olejniczak
In this study, solid-state fermentation (SSF) was proposed as an alternative approach to obtain optically pure forms of one of the most common aroma compounds, whisky lactone. Filamentous fungi were used for enantioselective hydrolysis of a racemate of trans and cis whisky lactones, utilizing rapeseed cake as a growth medium. Among the tested fungi, Fusarium oxysporum AM13 and Papularia rosea AM17 were chosen for further studies. Various process parameters, including temperature, moisture content of solid media, and substrate concentration were optimized to maximize the efficiency of the kinetic resolution process...
March 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
P Cordero, J Li, J A Oben
Obesity is the pandemic of the 21st century. Obesity comorbidities, including hypertension, dyslipidaemia and glucose intolerance define metabolic syndrome, which increases mortality risk and decreases the quality of life. Compared with lifestyles (diet and physical activity) and pharmacological interventions, bariatric surgery is by far the most effective treatment for obesity and its comorbidities. This minimally invasive surgical treatment is based on an increase of satiety (by hormonal regulation and decreasing stomach volume) or a decrease in nutrient retention (gastric and/or intestinal resection)...
December 2017: Journal of the Royal College of Physicians of Edinburgh
Guangxin Chen, Juxiong Liu, Liqiang Jiang, Xin Ran, Dewei He, Yuhang Li, Bingxu Huang, Wei Wang, Dianfeng Liu, Shoupeng Fu
Neuroinflammation, characterized marked by microglial activation, plays a very important role in the pathogenesis of Parkinson's disease (PD). Upon activation, pro-inflammatory mediators are produced by microglia, triggering excessive inflammatory responses and ultimately damaging dopaminergic neurons. Therefore, the identification of agents that inhibit neuroinflammation may be an effective approach for developing novel treatments for PD. In this study, we sought to investigate whether peiminine protects dopaminergic neurons by inhibiting neuroinflammation...
March 12, 2018: International Journal of Molecular Sciences
David F Driscoll
The incidence of antimicrobial resistance (AMR) worldwide is increasing as the pipeline for the development of new chemotherapeutic entities is decreasing. Clearly, overexposure to antibiotics, including excessive dosing, is a key factor that fuels AMR. In fact, most of the new antibacterial agents under development are derivatives of existing classes of antibiotics. Novel approaches involving unique antimicrobial combinations, targets, and/or delivery systems are under intense investigation. An innovative combination of active pharmaceutical ingredients (APIs) consisting of antimicrobial drug(s), krill-oil-based phospholipids, and omega-3 fatty acid triglycerides, that may extend the therapeutic viability of currently effective antibiotics, at least until new chemical entities are introduced, is described...
March 10, 2018: Antibiotics
Xavier Bosch, Carmen Sanclemente-Ansó, Ona Escoda, Esther Monclús, Jonathan Franco-Vanegas, Pedro Moreno, Mar Guerra-García, Neus Guasch, Alfons López-Soto
BACKGROUND: Mainly because of the diversity of clinical presentations, diagnostic delays in lymphoma can be excessive. The time spent in primary care before referral to the specialist may be relatively short compared with the interval between hospital appointment and diagnosis. Although studies have examined the diagnostic intervals and referral patterns of patients with lymphoma, the time to diagnosis of outpatient compared to inpatient settings and the costs incurred are unknown. METHODS: We performed a retrospective study at two academic hospitals to evaluate the time to diagnosis and associated costs of hospital-based outpatient diagnostic clinics or conventional hospitalization in four representative lymphoma subtypes...
March 12, 2018: BMC Cancer
Ashraf Brik, Roman Meledin, Sachitanand Mali, Oded Kleifeld
We report a general and novel semisynthetic strategy for the preparation of ubiquitinated protein activity based probes applying sequential dehydroalanine formation on expressed proteins. We applied this approach to construct physiologically and therapeutically relevant ubiquitinated α-globin probe, which was used for the enrichment and proteomic identification of α-globin modulating deubiquitinases. We found USP15 as a potential deubiquitinase, modulating α-globin, which excess aggravates beta-thalassemia symptoms...
March 12, 2018: Angewandte Chemie
Shaghayegh Dezvarei, Hiroki Onoda, Osami Shoji, Yoshihito Watanabe, Stephen G Bell
The wild-type cytochrome P450 (CYP) monooxygenase enzyme CYP102A1 (P450Bm3) has low activity for cycloalkane oxidation. The oxidation of these substrates by variants of this enzyme in combination with perfluorinated decoy molecules (PFCs) was investigated to improve productivity. The use of rate accelerating variants, which have mutations located outside of the substrate binding pocket as well as an active site variant of CYP102A1 (A74G/F87V/L188Q) all enhanced cycloalkane oxidation (C5 to C10). The addition of the decoy molecules to the wild-type and the rate accelerating mutants of CYP102A1 boosted the substrate oxidation rates even further...
March 4, 2018: Journal of Inorganic Biochemistry
Paul C Norris, Charles N Serhan
Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels...
March 7, 2018: Biochemical and Biophysical Research Communications
Vincent Taschereau-Dumouchel, Aurelio Cortese, Toshinori Chiba, J D Knotts, Mitsuo Kawato, Hakwan Lau
Can "hardwired" physiological fear responses (e.g., for spiders and snakes) be reprogramed unconsciously in the human brain? Currently, exposure therapy is among the most effective treatments for anxiety disorders, but this intervention is subjectively aversive to patients, causing many to drop out of treatment prematurely. Here we introduce a method to bypass the subjective unpleasantness in conscious exposure, by directly pairing monetary reward with unconscious occurrences of decoded representations of naturally feared animals in the brain...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Andrew D Nguyen, Thi A Nguyen, Jiasheng Zhang, Swathi Devireddy, Ping Zhou, Anna M Karydas, Xialian Xu, Bruce L Miller, Frank Rigo, Shawn M Ferguson, Eric J Huang, Tobias C Walther, Robert V Farese
Frontotemporal dementia (FTD) is the most common neurodegenerative disorder in individuals under age 60 and has no treatment or cure. Because many cases of FTD result from GRN nonsense mutations, an animal model for this type of mutation is highly desirable for understanding pathogenesis and testing therapies. Here, we generated and characterized Grn R493X knockin mice, which model the most common human GRN mutation, a premature stop codon at arginine 493 (R493X). Homozygous Grn R493X mice have markedly reduced Grn mRNA levels, lack detectable progranulin protein, and phenocopy Grn knockout mice, with CNS microgliosis, cytoplasmic TDP-43 accumulation, reduced synaptic density, lipofuscinosis, hyperinflammatory macrophages, excessive grooming behavior, and reduced survival...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Rimante Ronto, Jason Hy Wu, Gitanjali M Singh
Non-communicable diseases (NCD) have increased dramatically in developed and developing countries. Unhealthy diet is one of the major factors contributing to NCD development. Recent evidence has identified deterioration in aspects of dietary quality across many world regions, including low- and middle-income countries (LMIC). Most burdens of disease attributable to poor diet can be prevented or delayed as they occur prematurely. Therefore, it is important to identify and target unhealthy dietary behaviours in order to have the greatest impact...
March 6, 2018: Public Health Nutrition
Colin P West, Liselotte N Dyrbye, Tait D Shanafelt
Physician burnout, a work-related syndrome involving emotional exhaustion, depersonalization, and a sense of reduced personal accomplishment, is prevalent internationally. Rates of burnout symptoms that have been associated with adverse effects on patients, the health care workforce, costs, and physician health exceed 50% in studies of both physicians-in-training and practicing physicians. This problem represents a public health crisis with negative impacts on individual physicians, patients, and health care organizations and systems...
March 5, 2018: Journal of Internal Medicine
Igor I Titov, Pavel S Vorozheykin
BACKGROUND: MicroRNAs proceeds through the different canonical and non-canonical pathways; the most frequent of the non-canonical ones is the splicing-dependent biogenesis of mirtrons. We compare the mirtrons and non-mirtrons of human and mouse to explore how their maturation appears in the precursor structure around the miRNA. RESULTS: We found the coherence of the overhang lengths what indicates the dependence between the cleavage sites. To explain this dependence we suggest the 2-lever model of the Dicer structure that couples the imprecisions in Drosha and Dicer...
February 9, 2018: BMC Genomics
Anne Martin, Josephine N Booth, Yvonne Laird, John Sproule, John J Reilly, David H Saunders
BACKGROUND: The global prevalence of childhood and adolescent obesity is high. Lifestyle changes towards a healthy diet, increased physical activity and reduced sedentary activities are recommended to prevent and treat obesity. Evidence suggests that changing these health behaviours can benefit cognitive function and school achievement in children and adolescents in general. There are various theoretical mechanisms that suggest that children and adolescents with excessive body fat may benefit particularly from these interventions...
March 2, 2018: Cochrane Database of Systematic Reviews
Iris Lucas, Michel Cotsaftis, Cyrille Bertelle
This paper introduces an original mathematical description for describing agents' decision-making process in the case of problems affected by both individual and collective behaviors in systems characterized by nonlinear, path dependent, and self-organizing interactions. An application to artificial financial markets is proposed by designing a multi-agent system based on the proposed formalization. In this application, agents' decision-making process is based on fuzzy logic rules and the price dynamics is purely deterministic according to the basic matching rules of a central order book...
February 2018: Chaos
Adamasco Cupisti, Csaba P Kovesdy, Claudia D'Alessandro, Kamyar Kalantar-Zadeh
Whereas the adequate intake of potassium is relatively high in healthy adults, i.e., 4.7 g per day, a dietary potassium restriction of usually less than 3 g per day is recommended in the management of patients with reduced kidney function, especially those who tend to develop hyperkalaemia including patients who are treated with angiotensin pathway modulators. Most potassium-rich foods are considered heart-healthy nutrients with high fibre, high anti-oxidant vitamins and high alkali content such as fresh fruits and vegetables; hence, the main challenge of dietary potassium management is to maintain high fibre intake and a low net fixed-acid load, because constipation and metabolic acidosis are per se major risk factors for hyperkalaemia...
February 25, 2018: Nutrients
Nadia Minian, Wayne K deRuiter, Mathangee Lingam, Tricia Corrin, Rosa Dragonetti, Heather Manson, Valerie H Taylor, Laurie Zawertailo, Arezoo Ebnahmady, Osnat C Melamed, Terri Rodak, Margaret Hahn, Peter Selby
BACKGROUND: Health behaviors directly impact the health of individuals, and populations. Since individuals tend to engage in multiple unhealthy behaviors such as smoking, excessive alcohol use, physical inactivity, and eating an unhealthy diet simultaneously, many large community-based interventions have been implemented to reduce the burden of disease through the modification of multiple health behaviors. Smoking cessation can be particularly challenging as the odds of becoming dependent on nicotine increase with every unhealthy behavior a smoker exhibits...
March 1, 2018: Systematic Reviews
Paul Wijnker, Vasco Sequeira, Diederik Kuster, Jolanda van der Velden
SIGNIFICANCE: Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease characterized by left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. Disease onset occurs between 20 and 50 years of age, thus affecting patients in the prime of their life. HCM is caused by mutations in sarcomere proteins, the contractile building blocks of the heart. Despite increased knowledge of causal mutations, the exact path from genetic defect leading to cardiomyopathy is complex and involves additional disease hits...
February 28, 2018: Antioxidants & Redox Signaling
María Teresa García-Valverde, Maria Rosende, Rafael Lucena, Soledad Cárdenas, Manuel Miró
Mesofluidic Lab-on-a-Valve (LOV) platforms have been proven suitable to accommodate automatic micro-solid-phase extraction approaches (µSPE) with on-chip handling of micrometer bead materials in a fully disposable mode to prevent sample cross-contamination and pressure drop effects. The efficiency of the extraction process notably depends upon the sorptive capacity of the material because the sorbent mass is usually down to 10 mg in LOV devices. Nanomaterials, capitalizing upon their enhanced surface to volume ratio and diversity of potential chemical moieties, are appealing alternates to microbead sorbents...
March 1, 2018: Analytical Chemistry
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