BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Spatially Enhanced Differential RNA Methylation Analysis from Affinity-Based Sequencing Data with Hidden Markov Model Sun, 02 Aug 2015 14:09:30 +0000 With the development of new sequencing technology, the entire N6-methyl-adenosine (m6A) RNA methylome can now be unbiased profiled with methylated RNA immune-precipitation sequencing technique (MeRIP-Seq), making it possible to detect differential methylation states of RNA between two conditions, for example, between normal and cancerous tissue. However, as an affinity-based method, MeRIP-Seq has yet provided base-pair resolution; that is, a single methylation site determined from MeRIP-Seq data can in practice contain multiple RNA methylation residuals, some of which can be regulated by different enzymes and thus differentially methylated between two conditions. Since existing peak-based methods could not effectively differentiate multiple methylation residuals located within a single methylation site, we propose a hidden Markov model (HMM) based approach to address this issue. Specifically, the detected RNA methylation site is further divided into multiple adjacent small bins and then scanned with higher resolution using a hidden Markov model to model the dependency between spatially adjacent bins for improved accuracy. We tested the proposed algorithm on both simulated data and real data. Result suggests that the proposed algorithm clearly outperforms existing peak-based approach on simulated systems and detects differential methylation regions with higher statistical significance on real dataset. Yu-Chen Zhang, Shao-Wu Zhang, Lian Liu, Hui Liu, Lin Zhang, Xiaodong Cui, Yufei Huang, and Jia Meng Copyright © 2015 Yu-Chen Zhang et al. All rights reserved. Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet Sun, 02 Aug 2015 14:03:54 +0000 In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group), a diet with 35% fat (HF group), or a high-fat diet supplemented with 2.5% krill oil (HF+KO group). The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism. Alessandra Ferramosca, Annalea Conte, and Vincenzo Zara Copyright © 2015 Alessandra Ferramosca et al. All rights reserved. The Role of Cardiolipin in Cardiovascular Health Sun, 02 Aug 2015 13:50:37 +0000 Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria. The importance of CL in cardiovascular health is underscored by the life-threatening genetic disorder Barth syndrome (BTHS), which manifests clinically as cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the gene encoding tafazzin, the transacylase that carries out the second CL remodeling step. In addition to BTHS, CL is linked to other cardiovascular diseases (CVDs), including cardiomyopathy, atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and Tangier disease. The link between CL and CVD may possibly be explained by the physiological roles of CL in pathways that are cardioprotective, including mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein kinase (MAPK) pathways. In this review, we focus on the role of CL in the pathogenesis of CVD as well as the molecular mechanisms that may link CL functions to cardiovascular health. Zheni Shen, Cunqi Ye, Keanna McCain, and Miriam L. Greenberg Copyright © 2015 Zheni Shen et al. All rights reserved. Green Tea Increases the Concentration of Total Mercury in the Blood of Rats following an Oral Fish Tissue Bolus Sun, 02 Aug 2015 13:40:25 +0000 Fish has many health benefits but is also the most common source of methylmercury. The bioavailability of methylmercury in fish may be affected by other meal components. In this study, the effect of green tea on the bioavailability of methylmercury from an oral bolus of fish muscle tissue was studied in rats and compared to a water treated control group and a group treated with meso-2,3-dimercaptosuccinic acid (DMSA), a compound used medically to chelate mercury. Rats were given a single oral dose of fish tissue via gavage and one of the treatments. Rats were given access to food for 3 h at 12 h intervals. They were dosed with each of the treatments with each meal. Blood samples were collected for 95 hours. Green tea significantly increased the concentration of total mercury in blood relative to the control, whereas DMSA significantly decreased it. In addition, feeding caused a slight increase in blood mercury for several meals following the initial dose. Elsa M. Janle, Helene Freiser, Christopher Manganais, Tzu-Ying Chen, Bruce A. Craig, and Charles R. Santerre Copyright © 2015 Elsa M. Janle et al. All rights reserved. Evaluation of Ricinus communis L. for the Phytoremediation of Polluted Soil with Organochlorine Pesticides Sun, 02 Aug 2015 13:38:40 +0000 Phytoremediation is an attractive alternative to conventional treatments of soil due to advantages such as low cost, large application areas, and the possibility of in situ treatment. This study presents the assessment of phytoremediation processes conducted under controlled experimental conditions to evaluate the ability of Ricinus communis L., tropical plant species, to promote the degradation of 15 persistent organic pollutants (POPs), in a 66-day period. The contaminants tested were hexachlorocyclohexane (HCH), DDT, heptachlor, aldrin, and others. Measurements made in rhizosphere soil indicate that the roots of the studied species reduce the concentration of pesticides. Results obtained during this study indicated that the higher the hydrophobicity of the organic compound and its molecular interaction with soil or root matrix the greater its tendency to concentrate in root tissues and the research showed the following trend: HCHs < diclofop-methyl < chlorpyrifos < methoxychlor < heptachlor epoxide < endrin < o,p′-DDE < heptachlor < dieldrin < aldrin < o,p′-DDT < p,p′-DDT by increasing order of log values. The experimental results confirm the importance of vegetation in removing pollutants, obtaining remediation from 25% to 70%, and demonstrated that Ricinus communis L. can be used for the phytoremediation of such compounds. Sandra Regina Rissato, Mário Sergio Galhiane, João Roberto Fernandes, Marli Gerenutti, Homero Marques Gomes, Renata Ribeiro, and Marcos Vinícius de Almeida Copyright © 2015 Sandra Regina Rissato et al. All rights reserved. Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer’s Disease Sun, 02 Aug 2015 13:32:40 +0000 Alzheimer’s disease (AD) is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD) and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA) levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia. J. Thomas, C. J. Thomas, J. Radcliffe, and C. Itsiopoulos Copyright © 2015 J. Thomas et al. All rights reserved. Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes Sun, 02 Aug 2015 13:31:30 +0000 Dichloroacetate (DCA) is a water purification byproduct that is known to be hepatotoxic and hepatocarcinogenic and to induce peripheral neuropathy and damage macrophages. This study characterizes the effects of the haloacetate on lung cells by exposing rat alveolar type II (L2) cells to 0–24 mM DCA for 6–24 hours. Increasing DCA concentration and the combination of increasing DCA concentration plus longer exposures decrease measures of cellular health. Length of exposure has no effect on oxidative stress biomarkers, glutathione, SOD, or CAT. Increasing DCA concentration alone does not affect total glutathione or its redox ratio but does increase activity in the SOD/CAT oxidative stress defense pathway. These data suggest that alveolar type II cells rely on SOD and CAT more than glutathione to combat DCA-induced stress. Alexis Valauri-Orton, Frizzi Bschorer, and Karen K. Bernd Copyright © 2015 Alexis Valauri-Orton et al. All rights reserved. Moderate Dietary Supplementation with Omega-3 Fatty Acids Does Not Impact Plasma Von Willebrand Factor Profile in Mildly Hypertensive Subjects Sun, 02 Aug 2015 13:23:39 +0000 Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have blood pressure lowering and antithrombotic effects, which may benefit hypertensive patients. Increased plasma concentration of von Willebrand factor (vWF), a procoagulant glycoprotein, has been identified in patients with severe hypertension, with some, but not all studies showing an increase with mild hypertension. In this study, we determined the plasma concentration, multimer distribution, and collagen binding activity of vWF in subjects with mild hypertension and determined whether these parameters might improve after dietary supplementation with moderate amounts of LC n-3 PUFAs. Hypertensive and normotensive subjects were randomized to 12-week treatment with LC n-3 PUFAs (2.52 g/day) or placebo (canola oil). Home blood pressure measurements were recorded daily, and blood samples were collected every 3 weeks. LC n-3 PUFAs increased the n-3 index to cardioprotective levels (>8%). Plasma concentration, multimer distribution, and collagen binding activity of vWF were not reduced by LC n-3 PUFA treatment. We conclude that, at the concentration and duration used in this study, benefits of LC n-3 PUFAs in subjects with mild hypertension are not associated with a direct effect on vWF concentration or function. This trial is registered with the Australian New Zealand Clinical Trials Registry ACTRN12610000713099. Corinna S. Bürgin-Maunder, Peter R. Brooks, Deborah Hitchen-Holmes, and Fraser D. Russell Copyright © 2015 Corinna S. Bürgin-Maunder et al. All rights reserved. Air Pollution by Hydrothermal Volcanism and Human Pulmonary Function Sun, 02 Aug 2015 12:59:13 +0000 The aim of this study was to assess whether chronic exposure to volcanogenic air pollution by hydrothermal soil diffuse degassing is associated with respiratory defects in humans. This study was carried in the archipelago of the Azores, an area with active volcanism located in the Atlantic Ocean where Eurasian, African, and American lithospheric plates meet. A cross-sectional study was performed on a study group of 146 individuals inhabiting an area where volcanic activity is marked by active fumarolic fields and soil degassing (hydrothermal area) and a reference group of 359 individuals inhabiting an area without these secondary manifestations of volcanism (nonhydrothermal area). Odds ratio (OR) and 95% confidence intervals (CIs) were adjusted for age, gender, fatigue, asthma, and smoking. The OR for restrictive defects and for exacerbation of obstructive defects (COPD) in the hydrothermal area was 4.4 (95% CI 1.78–10.69) and 3.2 (95% CI 1.82–5.58), respectively. Increased prevalence of restrictions and all COPD severity ranks (mild, moderate, and severe) was observed in the population from the hydrothermal area. These findings may assist health officials in advising and keeping up with these populations to prevent and minimize the risk of respiratory diseases. Diana Linhares, Patrícia Ventura Garcia, Fátima Viveiros, Teresa Ferreira, and Armindo dos Santos Rodrigues Copyright © 2015 Diana Linhares et al. All rights reserved. Omega-3 PUFAs Lower the Propensity for Arachidonic Acid Cascade Overreactions Sun, 02 Aug 2015 12:55:54 +0000 A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic window which is widened by n-3 nutrients. The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions. Recognizing the factors that predispose the cascade to an unwanted overactivity gives a rational approach for arranging beneficial interactions between the n-3 and n-6 essential nutrients that are initial components of the cascade. Much detailed evidence for harmful cascade actions was collected by pharmaceutical companies as they developed drugs to decrease those actions. A remaining challenge is to understand the factors that predispose the cascade toward unwanted outcomes and create the need for therapeutic interventions. Such understanding involves recognizing the similar dynamics for dietary n-3 and n-6 nutrients in forming the immediate precursors of the cascade plus the more vigorous actions of the n-6 precursor, arachidonic acid, in forming potent mediators that amplify unwanted cascade outcomes. Tools have been developed to aid deliberate day-to-day quantitative management of the propensity for cascade overactivity in ways that can decrease the need for drug treatments. Bill Lands Copyright © 2015 Bill Lands. All rights reserved. ω-3 PUFAs and Resveratrol Differently Modulate Acute and Chronic Inflammatory Processes Sun, 02 Aug 2015 12:37:18 +0000 -3 PUFAs and polyphenols have multiple effects on inflammation in vivo and in vitro. The effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and resveratrol (RV) were investigated in LPS-stimulated peripheral blood leukocytes (PBLs) (i.e., acute inflammation) and IL-1 activated human chondrocytes (i.e., chronic inflammation). Inflammatory mediators including chemokines, cytokines, interleukins, and PGE2 were measured by multiplex analysis and gene expression was quantified by RT-PCR. In PBLs, RV decreased the secretion of PGE2, CCL5/RANTES, and CXCL8/IL-8 but increased IL-1, IL-6, and IL-10. In contrast to RV, -3 PUFAs augmented the production of PGE2 and CXCL8/IL-8. EPA and DHA similarly affected the pattern of inflammatory mediators. Combination of RV and -3 PUFAs exerted synergistic effects on CCL5/RANTES and had additive effects on IL-6 or CXCL8/IL-8. Both -3 PUFAs and RV reduced catabolic gene expression (e.g., MMPs, ADAMTS-4, IL-1, and IL-6) in activated chondrocytes. The data suggest that -3 PUFAs and RV differ in the regulation of acute inflammation of peripheral blood leukocytes but have common properties in modulating features related to chronic inflammation of chondrocytes. Joseph Schwager, Nathalie Richard, Christoph Riegger, and Norman Salem Jr. Copyright © 2015 Joseph Schwager et al. All rights reserved. Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall Sun, 02 Aug 2015 12:29:47 +0000 Omega-3 polyunsaturated fatty acids (n-3 PUFA) consumption is associated with reduced cardiovascular disease risk. Increasing evidence demonstrating a beneficial effect of n-3 PUFA on arterial wall properties is progressively emerging. We reviewed the recent available evidence for the cardiovascular effects of n-3 PUFA focusing on structural and functional properties of the vascular wall. In experimental studies and clinical trials n-3 PUFA have shown the ability to improve arterial hemodynamics by reducing arterial stiffness, thus explaining some of its cardioprotective properties. Recent studies suggest beneficial effects of n-3 PUFA on endothelial activation, which are likely to improve vascular function. Several molecular, cellular, and physiological pathways influenced by n-3 PUFA can affect arterial wall properties and therefore interfere with the atherosclerotic process. Although the relative weight of different physiological and molecular mechanisms and the dose-response on arterial wall properties have yet to be determined, n-3 PUFA have the potential to beneficially impact arterial wall remodeling and cardiovascular outcomes by targeting arterial wall stiffening and endothelial dysfunction. Michela Zanetti, Andrea Grillo, Pasquale Losurdo, Emiliano Panizon, Filippo Mearelli, Luigi Cattin, Rocco Barazzoni, and Renzo Carretta Copyright © 2015 Michela Zanetti et al. All rights reserved. Omega-3 Polyunsaturated Fatty Acids: The Way Forward in Times of Mixed Evidence Sun, 02 Aug 2015 12:22:15 +0000 Almost forty years ago, it was first hypothesized that an increased dietary intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert protective effects against several pathologies. Decades of intense preclinical investigation have supported this hypothesis in a variety of model systems. Several clinical cardiovascular studies demonstrated the beneficial health effects of omega-3 PUFA, leading medical institutions worldwide to publish recommendations for their increased intake. However, particularly in recent years, contradictory results have been obtained in human studies focusing on cardiovascular disease and the clinical evidence in other diseases, particularly chronic inflammatory and neoplastic diseases, was never established to a degree that led to clear approval of treatment with omega-3 PUFA. Recent data not in line with the previous findings have sparked a debate on the health efficacy of omega-3 PUFA and the usefulness of increasing their intake for the prevention of a number of pathologies. In this review, we aim to examine the controversies on the possible use of these fatty acids as preventive/curative tools against the development of cardiovascular, metabolic, and inflammatory diseases, as well as several kinds of cancer. Karsten H. Weylandt, Simona Serini, Yong Q. Chen, Hui-Min Su, Kyu Lim, Achille Cittadini, and Gabriella Calviello Copyright © 2015 Karsten H. Weylandt et al. All rights reserved. The Omega-3 Fatty Acid Docosahexaenoic Acid Modulates Inflammatory Mediator Release in Human Alveolar Cells Exposed to Bronchoalveolar Lavage Fluid of ARDS Patients Sun, 02 Aug 2015 12:20:32 +0000 Background. This study investigated whether the 1 : 2 ω-3/ω-6 ratio may reduce proinflammatory response in human alveolar cells (A549) exposed to an ex vivo inflammatory stimulus (bronchoalveolar lavage fluid (BALF) of acute respiratory distress syndrome (ARDS) patients). Methods. We exposed A549 cells to the BALF collected from 12 ARDS patients. After 18 hours, fatty acids (FA) were added as docosahexaenoic acid (DHA, ω-3) and arachidonic acid (AA, ω-6) in two ratios (1 : 2 or 1 : 7). 24 hours later, in culture supernatants were evaluated cytokines (TNF-α, IL-6, IL-8, and IL-10) and prostaglandins (PGE2 and PGE3) release. The FA percentage content in A549 membrane phospholipids, content of COX-2, level of PPARγ, and NF-κB binding activity were determined. Results. The 1 : 2 DHA/AA ratio reversed the baseline predominance of ω-6 over ω-3 in the cell membranes (P < 0.001). The proinflammatory cytokine release was reduced by the 1 : 2 ratio (P < 0.01 to <0.001) but was increased by the 1 : 7 ratio (P < 0.01). The 1 : 2 ratio reduced COX-2 and PGE2 (P < 0.001) as well as NF-κB translocation into the nucleus (P < 0.01), while it increased activation of PPARγ and IL-10 release (P < 0.001). Conclusion. This study demonstrated that shifting the FA supply from ω-6 to ω-3 decreased proinflammatory mediator release in human alveolar cells exposed to BALF of ARDS patients. Paolo Cotogni, Antonella Trombetta, Giuliana Muzio, Marina Maggiora, and Rosa Angela Canuto Copyright © 2015 Paolo Cotogni et al. All rights reserved. Patient-Specific CT-Based Instrumentation versus Conventional Instrumentation in Total Knee Arthroplasty: A Prospective Randomized Controlled Study on Clinical Outcomes and In-Hospital Data Sun, 02 Aug 2015 11:38:06 +0000 Total knee arthroplasty (TKA) is a frequently performed procedure in orthopaedic surgery. Recently, patient-specific instrumentation was introduced to facilitate correct positioning of implants. The aim of this study was to compare the early clinical results of TKA performed with patient-specific CT-based instrumentation and conventional technique. A prospective, randomized controlled trial on 112 patients was performed between January 2011 and December 2011. A group of 112 patients who met the inclusion and exclusion criteria were enrolled in this study and randomly assigned to an experimental or control group. The experimental group comprised 52 patients who received the Signature CT-based implant positioning system, and the control group consisted of 60 patients with conventional instrumentation. Clinical outcomes were evaluated with the KSS scale, WOMAC scale, and VAS scales to assess knee pain severity and patient satisfaction with the surgery. Specified in-hospital data were recorded. Patients were followed up for 12 months. At one year after surgery, there were no statistically significant differences between groups with respect to clinical outcomes and in-hospital data, including operative time, blood loss, hospital length of stay, intraoperative observations, and postoperative complications. Further high-quality investigations of various patient-specific systems and longer follow-up may be helpful in assessing their utility for TKA. Andrzej Kotela, Jacek Lorkowski, Marek Kucharzewski, Magdalena Wilk-Frańczuk, Zbigniew Śliwiński, Bogusław Frańczuk, Paweł   Łęgosz, and Ireneusz Kotela Copyright © 2015 Andrzej Kotela et al. All rights reserved. Corrigendum to “Evaluation of Candida Colonization and Specific Humoral Responses against Candida albicans in Patients with Atopic Dermatitis” Sun, 02 Aug 2015 11:25:04 +0000 Javad Ghaffari, Mehdi Taheri Sarvtin, Mohammad Taghi Hedayati, Zohreh Hajheydari, Jamshid Yazdani, and Tahereh Shokohi Copyright © 2015 Javad Ghaffari et al. All rights reserved. Three-Dimensional Modelling inside a Differential Pressure Laminar Flow Bioreactor Filled with Porous Media Sun, 02 Aug 2015 11:15:22 +0000 A three-dimensional computational fluid dynamics- (CFD-) model based on a differential pressure laminar flow bioreactor prototype was developed to further examine performance under changing culture conditions. Cell growth inside scaffolds was simulated by decreasing intrinsic permeability values and led to pressure build-up in the upper culture chamber. Pressure release by an integrated bypass system allowed continuation of culture. The specific shape of the bioreactor culture vessel supported a homogenous flow profile and mass flux at the scaffold level at various scaffold permeabilities. Experimental data showed an increase in oxygen concentration measured inside a collagen scaffold seeded with human mesenchymal stem cells when cultured in the perfusion bioreactor after 24 h compared to static culture in a Petri dish (dynamic: 11% O2 versus static: 3% O2). Computational fluid simulation can support design of bioreactor systems for tissue engineering application. Birgit Weyand, Meir Israelowitz, James Kramer, Christian Bodmer, Mariel Noehre, Sarah Strauss, Elmar Schmälzlin, Christoph Gille, Herbert P. von Schroeder, Kerstin Reimers, and Peter M. Vogt Copyright © 2015 Birgit Weyand et al. All rights reserved. Microbiological Analysis of Necrosols Collected from Urban Cemeteries in Poland Sun, 02 Aug 2015 08:59:51 +0000 Decomposition of organic matter is the primary function in the soil ecosystem, which involves bacteria and fungi. Soil microbial content depends on many factors, and secondary biological and chemical contaminations change and affect environmental feedback. Little work has been done to estimate the microbiological risk for cemetery employees and visitors. The potential risk of infection for people in the cemetery is primarily associated with injury and wound contamination during performing the work. The aim of this study was to analyze the microbiota of cemetery soil obtained from cemeteries and bacterial composition in selected soil layers encountered by gravediggers and cemetery caretakers. The most common bacterial pathogens were Enterococcus spp. (80.6%), Bacillus spp. (77.4%), and E. coli (45.1%). The fungi Penicillium spp. and Aspergillus spp. were isolated from 51% and 6.4% of samples, respectively. Other bacterial species were in the ground cemetery relatively sparse. Sampling depth was not correlated with bacterial growth (), but it was correlated with several differences in microbiota composition (superficial versus deep layer). Ireneusz Całkosiński, Katarzyna Płoneczka-Janeczko, Magda Ostapska, Krzysztof Dudek, Andrzej Gamian, and Krzysztof Rypuła Copyright © 2015 Ireneusz Całkosiński et al. All rights reserved. Corrigendum to “Short-Term Changes in Light Distortion in Orthokeratology Subjects” Sun, 02 Aug 2015 08:33:56 +0000 Elena Santolaria Sanz, Alejandro Cerviño, Antonio Queiros, Cesar Villa-Collar, Daniela Lopes-Ferreira, and Jose Manuel González-Méijome Copyright © 2015 Elena Santolaria Sanz et al. All rights reserved. All Three Rows of Outer Hair Cells Are Required for Cochlear Amplification Thu, 30 Jul 2015 17:29:53 +0000 In the mammalian auditory system, the three rows of outer hair cells (OHCs) located in the cochlea are thought to increase the displacement amplitude of the organ of Corti. This cochlear amplification is thought to contribute to the high sensitivity, wide dynamic range, and sharp frequency selectivity of the hearing system. Recent studies have shown that traumatic stimuli, such as noise exposure and ototoxic acid, cause functional loss of OHCs in one, two, or all three rows. However, the degree of decrease in cochlear amplification caused by such functional losses remains unclear. In the present study, a finite element model of a cross section of the gerbil cochlea was constructed. Then, to determine effects of the functional losses of OHCs on the cochlear amplification, changes in the displacement amplitude of the basilar membrane (BM) due to the functional losses of OHCs were calculated. Results showed that the displacement amplitude of the BM decreases significantly when a single row of OHCs lost its function, suggesting that all three rows of OHCs are required for cochlear amplification. Michio Murakoshi, Sho Suzuki, and Hiroshi Wada Copyright © 2015 Michio Murakoshi et al. All rights reserved. Mmu-miR-27a-5p-Dependent Upregulation of MCPIP1 Inhibits the Inflammatory Response in LPS-Induced RAW264.7 Macrophage Cells Thu, 30 Jul 2015 12:10:03 +0000 Lipopolysaccharide (LPS) stimulates macrophages to release proinflammatory cytokines. MicroRNAs (miRNAs) are short noncoding RNAs that are involved in inflammatory reaction. Our previously study identified the downregulated expression of mmu-miR-27a-5p in RAW267.4 cells treated with LPS. To dissect the mechanism that mmu-miR-27a-5p regulates target genes and affects proinflammatory cytokine secretion more clearly, based on previous bioinformatics prediction data, one of the potential target genes, MCPIP1 was observed to be upregulated with qRT-PCR and western blot. Luciferase reporter assays were performed to further confirm in silico prediction and determine that MCPIP1 is the target of mmu-miR-27-5p. The results suggested that mmu-miR-27a-5p directly targeted the 3′-UTR of MCPIP1 and the interaction between mmu-miR-27-5p and the 3′-UTR of MCPIP1 is sequence-specific. MCPIP1 overexpression decreased the secretion of IL-6, IL-1β, and IL-10 in macrophage cells stimulated with LPS. Our findings may provide the important information for the precise roles of mmu-miR-27a-5p in the macrophage inflammatory response to LPS stimulation in the future. Ying Cheng, Li Du, Hanwei Jiao, Huapei Zhu, Kailian Xu, Shiyu Guo, Qiaoyun Shi, Tianjing Zhao, Feng Pang, Xiaoxiao Jia, and Fengyang Wang Copyright © 2015 Ying Cheng et al. All rights reserved. Pulmonary Responses of Sprague-Dawley Rats in Single Inhalation Exposure to Graphene Oxide Nanomaterials Thu, 30 Jul 2015 12:01:33 +0000 Graphene is receiving increased attention due to its potential widespread applications in future. However, the health effects of graphene have not yet been well studied. Therefore, this study examined the pulmonary effects of graphene oxide using male Sprague-Dawley rats and a single 6-hour nose-only inhalation technique. Following the exposure, the rats were allowed to recover for 1 day, 7 days, or 14 days. A total of three groups were compared: control (fresh air), low concentration ( mg/m3), and high concentration ( mg/m3). The exposure to graphene oxide did not induce significant changes in the body weights, organ weights, and food consumption during the 14 days of recovery time. The microalbumin and lactate dehydrogenase levels in the bronchoalveolar lavage (BAL) fluid were not significantly changed due to the exposure. Similarly, total cell count, macrophages, polymorphonuclear leukocytes, and lymphocytes were not significantly altered in the BAL fluid. Plus, the histopathological examination of the rat lungs only showed an uptake of graphene oxide in the alveolar macrophages of the high-concentration group. Therefore, these results demonstrate that the single inhalation exposure to graphene oxide induce minimal toxic responses in rat lungs at the concentrations and time points used in the present study. Sung Gu Han, Jin Kwon Kim, Jae Hoon Shin, Joo Hwan Hwang, Jong Seong Lee, Tae-Gyu Kim, Ji Hyun Lee, Gun Ho Lee, Keun Soo Kim, Heon Sang Lee, Nam Woong Song, Kangho Ahn, and Il Je Yu Copyright © 2015 Sung Gu Han et al. All rights reserved. Heavy Metal Adsorption onto Kappaphycus sp. from Aqueous Solutions: The Use of Error Functions for Validation of Isotherm and Kinetics Models Thu, 30 Jul 2015 09:44:35 +0000 Biosorption process is a promising technology for the removal of heavy metals from industrial wastes and effluents using low-cost and effective biosorbents. In the present study, adsorption of Pb2+, Cu2+, Fe2+, and Zn2+ onto dried biomass of red seaweed Kappaphycus sp. was investigated as a function of pH, contact time, initial metal ion concentration, and temperature. The experimental data were evaluated by four isotherm models (Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich) and four kinetic models (pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion models). The adsorption process was feasible, spontaneous, and endothermic in nature. Functional groups in the biomass involved in metal adsorption process were revealed as carboxylic and sulfonic acids and sulfonate by Fourier transform infrared analysis. A total of nine error functions were applied to validate the models. We strongly suggest the analysis of error functions for validating adsorption isotherm and kinetic models using linear methods. The present work shows that the red seaweed Kappaphycus sp. can be used as a potentially low-cost biosorbent for the removal of heavy metal ions from aqueous solutions. Further study is warranted to evaluate its feasibility for the removal of heavy metals from the real environment. Md. Sayedur Rahman and Kathiresan V. Sathasivam Copyright © 2015 Md. Sayedur Rahman and Kathiresan V. Sathasivam. All rights reserved. Neuroinflammation and Neurodegeneration: Pinpointing Pathological and Pharmacological Targets Thu, 30 Jul 2015 07:56:23 +0000 Antonio Carlos Pinheiro de Oliveira, Eduardo Candelario-Jalil, Bernd L. Fiebich, Magda da Silva Santos, András Palotás, and Helton José dos Reis Copyright © 2015 Antonio Carlos Pinheiro de Oliveira et al. All rights reserved. Applications of Environmental Epidemiology in Addressing Public Health Challenges in East Asia Thu, 30 Jul 2015 07:53:14 +0000 Shih-Bin Su, Jamal H. Hashim, and Chong-huai Yan Copyright © 2015 Shih-Bin Su et al. All rights reserved. Advanced Computational Approaches for Medical Genetics and Genomics Thu, 30 Jul 2015 06:34:50 +0000 Zhi Wei, Xiao Chang, and Junwen Wang Copyright © 2015 Zhi Wei et al. All rights reserved. Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary Cultures Wed, 29 Jul 2015 13:16:23 +0000 To study cocaine’s toxic effects in vitro, we have used primary mesencephalic and striatal cultures from rat embryonic brain. Treatment with cocaine causes a dramatic increase in DNA fragmentation in both primary cultures. The toxicity induced by cocaine was paralleled with a concomitant decrease in the microtubule associated protein 2 (MAP2) and/or neuronal nucleus protein (NeuN) staining. We also observed in both cultures that the cell death caused by cocaine was induced by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper shows that cocaine causes apoptotic cell death and inhibition of the neurite prolongation in striatal and mesencephalic cell culture. These data suggest that if similar neuronal damage could be produced in the developing human brain, it could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following prenatal exposure to cocaine. Lucilia B. Lepsch, Cleopatra S. Planeta, and Critoforo Scavone Copyright © 2015 Lucilia B. Lepsch et al. All rights reserved. Neck Circumference as a Predictive Indicator of CKD for High Cardiovascular Risk Patients Wed, 29 Jul 2015 11:26:43 +0000 Background. Neck circumference (NC) is an anthropometric measure of obesity for upper subcutaneous adipose tissue distribution which is associated with cardiometabolic risk. This study investigated whether NC is associated with indicators of chronic kidney disease (CKD) for high cardiometabolic risk patients. Methods. A total of 177 consecutive patients who underwent the outpatient departments of cardiology were prospectively enrolled in the study. The patients were aged >20 years with normal renal function or with stages 1–4 CKD. A linear regression was performed using the Enter method to present an unadjusted , standardized coefficients, and standard error, and the Durbin-Watson test was used to assess residual independence. Results. Most anthropometric measurements from patients aged ≧65 were lower than those from patients aged <65, except for women’s waist circumference (WC) and waist hip ratio. Female NC obtained the highest values for 24 hr CCR, uric acid, microalbuminuria, hsCRP, triglycerides, and HDL compared to BMI, WC, and hip circumference. The significances of female NC with 24 hr CCR and uric acid were improved after adjusted age and serum creatinine. Conclusions. NC is associated with indicators of CKD for high cardiometabolic risk patients and can be routinely measured as easy as WC in the future. Ya-Fang Liu, Shih-Tai Chang, Wei-Shiang Lin, Jen-Te Hsu, Chang-Min Chung, Jung-Jung Chang, Kuo-Chun Hung, Kang-Hua Chen, Chi-Wen Chang, Fu-Chi Chen, Yun-Wen Shih, and Chi-Ming Chu Copyright © 2015 Ya-Fang Liu et al. All rights reserved. Intellectual Impairment in Patients with Newly Diagnosed HIV Infection in Southwestern Nigeria Wed, 29 Jul 2015 09:22:38 +0000 Neurocognitive impairment is a detrimental complication of HIV infection. Here, we characterized the intellectual performance of patients with newly diagnosed HIV infection in southwestern Nigeria. We conducted a prospective study at Owo Federal Medical Center by using the adapted Wechsler Adult Intelligence Scale (WAIS). The raw scores were converted to standardized scores (z-scores) and correlated with clinical and laboratory findings. Fifty-eight HIV positive patients were recruited; 72% were in WHO stages 3 and 4. We detected a high rate of intellectual impairment in HIV positive patients and controls (63.8% and 10%, resp.; ). HIV positive patients performed worse throughout the subtests of both verbal and performance intelligence quotients. Presence of opportunistic infections was associated with worse performance in the similarities and digit symbol tests and performance and full scale scores. Lower body weight correlated with poor performance in different WAIS subtests. The high rate of advanced disease stage warrants measures aimed at earlier diagnosis and treatment. Assessment of neurocognitive performance at diagnosis may offer the opportunity to improve functioning in daily life and counteract disease progression. Taofiki A. Sunmonu, Johann Sellner, Olubunmi A. Ogunrin, Frank A. Imarhiagbe, Morenikeji A. Komolafe, Olusegun T. Afolabi, Olayinka S. Ilesanmi, Fatai Olanrewaju, and Benedicta Y. Oladimeji Copyright © 2015 Taofiki A. Sunmonu et al. All rights reserved. The Effects of Dorsal Cortical Comminution on Radiographic Results following Percutaneous Pinning for Extra-Articular Colles’ Fracture Wed, 29 Jul 2015 08:53:25 +0000 A number of studies have demonstrated that dorsal cortical comminution (DCC) can predict redisplacement after nonoperative treatment of Colles’ fractures; however, the effects of a DCC defect on radiographic outcomes following percutaneous pinning for dorsally displaced extraarticular Colles’ fractures are unclear. We, therefore, performed a retrospective study on 85 patients who sustained such fractures treated with percutaneous pinning within 2006–2009. The main outcome measures included four radiographic parameters, including radial height, radial inclination, radial tilt, and ulnar variance. The radiological results showed that all fractures after percutaneous pinning followed the same time series changes and patterns of fracture collapse regardless of the presence of a DCC defect. The use of the pinning construct is to provide support for static loading but not for dynamic loading. Although the final radiographic outcomes were classified as acceptable in fractures with and without DCC, we recommend that a different approach in the management of displaced Colles’ fractures might be necessary in consideration of increasing patient expectations of health care. Po-Yao Chuang, Tien-Yu Yang, Shih-Hsun Shen, Yao-Hung Tsai, and Kuo-Chin Huang Copyright © 2015 Po-Yao Chuang et al. All rights reserved.