BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Indirect Manganese Removal by Stenotrophomonas sp. and Lysinibacillus sp. Isolated from Brazilian Mine Water Tue, 01 Dec 2015 12:56:46 +0000 Manganese is a contaminant in the wastewaters produced by Brazilian mining operations, and the removal of the metal is notoriously difficult because of the high stability of the Mn(II) ion in aqueous solutions. To explore a biological approach for removing excessive amounts of aqueous Mn(II), we investigated the potential of Mn(II) oxidation by both consortium and bacterial isolates from a Brazilian manganese mine. A bacterial consortium was able to remove 99.7% of the Mn(II). A phylogenetic analysis of isolates demonstrated that the predominant microorganisms were members of Stenotrophomonas, Bacillus, and Lysinibacillus genera. Mn(II) removal rates between 58.5% and 70.9% were observed for Bacillus sp. and Stenotrophomonas sp. while the Lysinibacillus isolate 13P removes 82.7%. The catalytic oxidation of Mn(II) mediated by multicopper oxidase was not properly detected; however, in all of the experiments, a significant increase in the pH of the culture medium was detected. No aggregates inside the cells grown for a week were found by electronic microscopy. Nevertheless, an energy-dispersive X-ray spectroscopy of the isolates revealed the presence of manganese in Stenotrophomonas sp. and Lysinibacillus sp. grown in K medium. These results suggest that members of Stenotrophomonas and Lysinibacillus genera were able to remove Mn(II) by a nonenzymatic pathway. Natália Rocha Barboza, Soraya Sander Amorim, Pricila Almeida Santos, Flávia Donária Reis, Mônica Mendes Cordeiro, Renata Guerra-Sá, and Versiane Albis Leão Copyright © 2015 Natália Rocha Barboza et al. All rights reserved. Motor Functional Evaluation from Physiology and Biomechanics to Clinical and Training Application Tue, 01 Dec 2015 12:13:21 +0000 Jullia Maria D’Andréa Greve, Angelica Castilho Alonso, Luiz Mochizuki, Paulo R. Lucareli, Chandramouli Krishnan, and Richard Baker Copyright © 2015 Jullia Maria D’Andréa Greve et al. All rights reserved. Growth Inhibition and Membrane Permeabilization of Candida lusitaniae Using Varied Pulse Shape Electroporation Tue, 01 Dec 2015 12:03:03 +0000 Candida lusitaniae is an opportunistic yeast pathogen, which can readily develop resistance to antifungal compounds and result in a complex long-term treatment. The efficient treatment is difficult since structure and metabolic properties of the fungal cells are similar to those of eukaryotic host. One of the potential methods to improve the inhibition rate or the cell permeability to inhibitors is the application of electroporation. In this work we investigated the dynamics of the growth inhibition and membrane permeabilization of C. lusitaniae by utilizing the various pulse shape and duration electric field pulses. Our results indicated that single electroporation procedure using 8 kV/cm electric field may result in up to % inhibition rate. Also it has been experimentally shown that the electroporation pulse shape may influence the inhibitory effect; however, the amplitude of the electric field and the pulse energy remain the most important parameters for definition of the treatment outcome. The dynamics of the cell membrane permeabilization in the 2–8 kV/cm electric field were overviewed. V. Novickij, A. Grainys, E. Lastauskienė, R. Kananavičiūtė, D. Pamedytytė, A. Zinkevičienė, L. Kalėdienė, J. Novickij, A. Paškevičius, and J. Švedienė Copyright © 2015 V. Novickij et al. All rights reserved. Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation Tue, 01 Dec 2015 10:39:51 +0000 A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved. Liang Liu, Chao Gao, Ping Yao, and Zhiyong Gong Copyright © 2015 Liang Liu et al. All rights reserved. Antiangiogenic and Neurogenic Activities of Sleeping Beauty-Mediated PEDF-Transfected RPE Cells In Vitro and In Vivo Tue, 01 Dec 2015 06:45:24 +0000 Pigment epithelium-derived factor (PEDF) is a potent multifunctional protein that inhibits angiogenesis and has neurogenic and neuroprotective properties. Since the wet form of age-related macular degeneration is characterized by choroidal neovascularization (CNV), PEDF would be an ideal candidate to inhibit CNV and support retinal pigment epithelial (RPE) cells. However, its short half-life has precluded its clinical use. To deliver PEDF to the subretinal space, we transfected RPE cells with the PEDF gene using the Sleeping Beauty transposon system. Transfected cells expressed and secreted biologically active recombinant PEDF (rPEDF). In cultures of human umbilical vein endothelial cells, rPEDF reduced VEGF-induced cumulative sprouting by ≥47%, decreased migration by 77%, and increased rate of apoptosis at least 3.4 times. rPEDF induced neurite outgrowth in neuroblastoma cells and protected ganglion and photoreceptor cells in organotypic retinal cultures. In a rat model of CNV, subretinal transplantation of PEDF-transfected cells led to a reduction of the CNV area by 48% 14 days after transplantation and decreased clinical significant lesions by 55% and 40% after 7 and 14 days, respectively. We showed that transplantation of pigment epithelial cells overexpressing PEDF can restore a permissive subretinal environment for RPE and photoreceptor maintenance, while inhibiting choroidal blood vessel growth. Sandra Johnen, Yassin Djalali-Talab, Olga Kazanskaya, Theresa Möller, Nina Harmening, Martina Kropp, Zsuzsanna Izsvák, Peter Walter, and Gabriele Thumann Copyright © 2015 Sandra Johnen et al. All rights reserved. Impact of Clinical Pharmacy Services on KAP and QOL in Cancer Patients: A Single-Center Experience Mon, 30 Nov 2015 15:19:55 +0000 This study was to evaluate the efficacy of pharmaceutical intervention (PI) on chemotherapy knowledge-attitude-practice (KAP) and quality of life (QOL) in cancer patients. A prospective, randomized, controlled study was carried out at Oncology Ward in a tertiary hospital affiliated to Southern Medical University, China. Eligible patient was randomly assigned to pharmaceutical intervention (PI) group or control group. Each patient in PI group was given information booklets and was given 30 min face-to-face medication education and psychological counseling by clinical pharmacists, 2 sessions per week for 2 months. Patients in control group only received conventional treatment. All participants were asked to complete a structured Chemotherapy KAP Questionnaire and QOL Questionnaire at pre- and poststudy time. A total of 149 cancer patients (77 in PI group and 72 in control group) completed the study. The baseline scores of KAP and QOL in 2 groups were similar. At the end of study, only knowledge score was significantly increased; meanwhile no difference existed for attitude, practice, and QOL scores in control group; both KAP scores and QOL score were significantly increased in PI group. As for the between-group comparison, both KAP scores and QOL score in PI group were significantly higher than those in control group. In conclusion, pharmaceutical intervention has a positive role in increasing chemotherapy-related knowledge, improving patients’ positive emotions, dealing with chemotherapy adverse reactions, and improving the quality of life of patients. Yan Wang, Huimin Wu, and Feng Xu Copyright © 2015 Yan Wang et al. All rights reserved. CRISPR/CAS9-Mediated Genome Editing of miRNA-155 Inhibits Proinflammatory Cytokine Production by RAW264.7 Cells Mon, 30 Nov 2015 13:59:29 +0000 MicroRNA 155 (miR-155) is a key proinflammatory regulator in clinical and experimental rheumatoid arthritis (RA). Here we generated a miR-155 genome knockout (GKO) RAW264.7 macrophage cell line using the clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (CAS9) technology. While upregulating the Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1), the miR-155 GKO line is severely impaired in producing proinflammatory cytokines but slightly increased in osteoclastogenesis upon treatment with receptor activator of nuclear factor-B ligand (RANKL). Taken together, our results suggest that genome editing of miR-155 holds the potential as a therapeutic strategy in RA. Weixia Jing, Xuewu Zhang, Wenyan Sun, Xiujuan Hou, Zhongqiang Yao, and Yuelan Zhu Copyright © 2015 Weixia Jing et al. All rights reserved. Decorin: A Growth Factor Antagonist for Tumor Growth Inhibition Mon, 30 Nov 2015 13:51:10 +0000 Decorin (DCN) is the best characterized member of the extracellular small leucine-rich proteoglycan family present in connective tissues, typically in association with or “decorating” collagen fibrils. It has substantial interest to clinical medicine owing to its antifibrotic, anti-inflammatory, and anticancer effects. Studies on DCN knockout mice have established that a lack of DCN is permissive for tumor development and it is regarded as a tumor suppressor gene. A reduced expression or a total disappearance of DCN has been reported to take place in various forms of human cancers during tumor progression. Furthermore, when used as a therapeutic molecule, DCN has been shown to inhibit tumor progression and metastases in experimental cancer models. DCN affects the biology of various types of cancer by targeting a number of crucial signaling molecules involved in cell growth, survival, metastasis, and angiogenesis. The active sites for the neutralization of different growth factors all reside in different parts of the DCN molecule. An emerging concept that multiple proteases, especially those produced by inflammatory cells, are capable of cleaving DCN suggests that native DCN could be inactivated in a number of pathological inflammatory conditions. In this paper, we review the role of DCN in cancer. Tero A. H. Järvinen and Stuart Prince Copyright © 2015 Tero A. H. Järvinen and Stuart Prince. All rights reserved. Kidney Injury Molecule-1 and Cardiovascular Diseases: From Basic Science to Clinical Practice Mon, 30 Nov 2015 13:30:51 +0000 Despite the recent findings concerning pathogenesis and novel therapeutic strategies, cardiovascular disease (CVD) still stays the leading cause of morbidity and mortality in patients with renal dysfunction, especially acute kidney injury (AKI). Early detection of patients with impaired renal function with cardiovascular risk may help ensure more aggressive treatment and improve clinical outcome. Kidney injury molecule-1 (KIM-1) is a new, promising marker of kidney damage which is currently the focus of countless studies worldwide. Some recent animal and human studies established KIM-1 as an important marker of acute tubular necrosis (ATN) and reliable predictor of development and prognosis of AKI. Food and Drug Administration (FDA) in USA acclaimed KIM-1 as an AKI biomarker for preclinical drug development. Recent data suggest the importance of monitoring of KIM-1 for early diagnosis and clinical course not only in patients with various forms of AKI and other renal diseases but also in patients with cardiorenal syndrome, heart failure, cardiopulmonary bypass, cardiothoracic surgical interventions in the pediatric emergency setting, and so forth. The aim of this review article is to summarize the literature data concerning KIM-1 as a potential novel marker in the early diagnosis and prediction of clinical outcome of certain cardiovascular diseases. Branislava Medić, Branislav Rovčanin, Gordana Basta Jovanović, Sanja Radojević-Škodrić, and Milica Prostran Copyright © 2015 Branislava Medić et al. All rights reserved. Safety Evaluation of the Coagulase-Negative Staphylococci Microbiota of Salami: Superantigenic Toxin Production and Antimicrobial Resistance Mon, 30 Nov 2015 13:08:47 +0000 The risks of contracting staphylococci food poisoning by the consumption of improperly manufactured salami and the possibility of this food being reservoirs for antibiotic resistance were evaluated. Nineteen coagulase-negative staphylococci (CNS) strains were found in commercial and artisanal salami. The species in commercial salami were S. saprophyticus, S. sciuri, S. xylosus, and S. carnosus. Artisanal salami showed S. succinus, S. epidermidis, and S. hominis but no S. carnosus. Phylogenetic analyses grouped the strains into three major staphylococcal species groups, comprised of 4 refined clusters with similarities superior to 90%. Fifteen strains harbored multiple enterotoxin genes, with high incidence of seb/sec and sea, 57% and 50%, respectively, intermediate incidence of sed/seh/selm and sei/seln/tst-H, 33% and 27%, correspondingly, and low incidence of see/selj/selo and seg, of respectively 13% and 1%. Real time RT-PCR and enzyme-linked-immunosorbent assays confirmed the enterotoxigenicity of the strains, which expressed and produced enterotoxins in vitro. The CNS strains showed multiresistance to several antimicrobials of therapeutic importance in both human and veterinarian medicine, such as β-lactams, vancomycin, and linezolid. The effective control of undue staphylococci in fermented meat products should be adopted to prevent or limit the risk of food poisoning and the spread of antimicrobial-resistant strains. Raquel Soares Casaes Nunes, Eduardo Mere Del Aguila, and Vânia Margaret Flosi Paschoalin Copyright © 2015 Raquel Soares Casaes Nunes et al. All rights reserved. Histamine Induces Alzheimer’s Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures Mon, 30 Nov 2015 11:46:39 +0000 Among the top ten causes of death in the United States, Alzheimer’s disease (AD) is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO) cultures is reported. For the first time, we have demonstrated that the MBO cultures exhibit increased blood brain barrier (BBB) permeability as shown by IgG leakage into the brain parenchyma, astrocyte activation as evidenced by increased expression of glial fibrillary acidic protein (GFAP), and neuronal damage-response as suggested by increased vimentin-positive neurons occur upon histamine treatment. Identical responses—a breakdown of the BBB, astrocyte activation, and neuronal expression of vimentin—were then demonstrated in brains from AD patients compared to age-matched controls, consistent with other reports. Thus, the histamine-treated MBO culture system may provide a valuable tool in combating AD. Jonathan C. Sedeyn, Hao Wu, Reilly D. Hobbs, Eli C. Levin, Robert G. Nagele, and Venkat Venkataraman Copyright © 2015 Jonathan C. Sedeyn et al. All rights reserved. Inhibition of ACE Retards Tau Hyperphosphorylation and Signs of Neuronal Degeneration in Aged Rats Subjected to Chronic Mild Stress Mon, 30 Nov 2015 11:24:28 +0000 With increasing life expectancy, Alzheimer’s disease (AD) and other types of age-associated dementia are on the rise worldwide. Treatment approaches for dementia are insufficient and novel therapies are not readily available. In this context repurposing of established drugs appears attractive. A well-established class of cardiovascular drugs, which targets the angiotensin II system, is such a candidate, which currently undergoes a paradigm shift with regard to the potential benefit for treatment of neurodegenerative symptoms. In search for additional evidence, we subjected aged rats to chronic unpredictable mild stress, which is known to enhance the development of AD-related neuropathological features. We report here that four weeks of chronic mild stress induced a strong upregulation of the hippocampal angiotensin-converting enzyme (Ace) at gene expression and protein level. Concomitantly, tau protein hyperphosphorylation developed. Signs of neurodegeneration were detected by the significant downregulation of neuronal structure proteins such as microtubule-associated protein 2 (Map2) and synuclein-gamma (Sncg). Ace was involved in neurodegenerative symptoms because treatment with the brain-penetrating ACE inhibitor, captopril, retarded tau hyperphosphorylation and signs of neurodegeneration. Moreover, ACE inhibitor treatment could counteract glutamate neurotoxicity by preventing the downregulation of glutamate decarboxylase 2 (Gad2). Taken together, ACE inhibition targets neurodegeneration triggered by environmental stress. Said AbdAlla, Ahmed el Hakim, Ahmed Abdelbaset, Yasser Elfaramawy, and Ursula Quitterer Copyright © 2015 Said AbdAlla et al. All rights reserved. Antifatigue Activity of Liquid Cultured Tricholoma matsutake Mycelium Partially via Regulation of Antioxidant Pathway in Mouse Mon, 30 Nov 2015 07:59:56 +0000 Tricholoma matsutake has been popular as food and biopharmaceutical materials in Asian countries for its various pharmacological activities. The present study aims to analyze the antifatigue effects on enhancing exercise performance of Tricholoma matsutake fruit body (ABM) and liquid cultured mycelia (TM) in mouse model. Two-week Tricholoma matsutake treatment significantly enhances the exercise performance in weight-loaded swimming, rotating rod, and forced running test. In TM- and ABM-treated mice, some factors were observed at 60 min after swimming compared with nontreated mice, such as the increased levels of adenosine triphosphate (ATP), antioxidative enzymes, and glycogen and the reduced levels of malondialdehyde and reactive oxygen species in muscle, liver, and/or serum. Further data obtained from western blot show that CM and ABM have strongly enhanced the activation of 5′-AMP-activated protein kinase (AMPK), and the expressions of peroxisome proliferator have activated receptor γ coactivator-1α (PGC-1α) and phosphofructokinase-1 (PFK-1) in liver. Our data suggest that both Tricholoma matsutake fruit body and liquid cultured mycelia possess antifatigue effects related to AMPK-linked antioxidative pathway. The information uncovered in our study may serve as a valuable resource for further identification and provide experimental evidence for clinical trials of Tricholoma matsutake as an effective agent against fatigue related diseases. Quan Li, Yanzhen Wang, Guangsheng Cai, Fange Kong, Xiaohan Wang, Yang Liu, Chuanbin Yang, Di Wang, and Lirong Teng Copyright © 2015 Quan Li et al. All rights reserved. Transmission of Information in Neoplasia by Extracellular Vesicles Mon, 30 Nov 2015 07:23:49 +0000 Aurelio Lorico, Denis Corbeil, John M. Pawelek, and Riccardo Alessandro Copyright © 2015 Aurelio Lorico et al. All rights reserved. Corrigendum to “Strategy for the Management of Macular Edema in Retinal Vein Occlusion: The European VitreoRetinal Society Macular Edema Study” Mon, 30 Nov 2015 06:54:00 +0000 Ron A. Adelman, Aaron J. Parnes, Silvia Bopp, Ihab Saad Othman, Didier Ducournau, and EVRS Macular Edema Study Group Copyright © 2015 Ron A. Adelman et al. All rights reserved. QT Interval Variability Index and QT Interval Duration in Different Sleep Stages: Analysis of Polysomnographic Recordings in Nonapneic Male Patients Sun, 29 Nov 2015 13:58:40 +0000 The aim of the study was to determine whether different sleep stages, especially REM sleep, affect QT interval duration and variability in male patients without obstructive sleep apnea (OSA). Polysomnographic recordings of 30 patients were analyzed. Beat-to-beat QT interval variability was calculated using QTV index (QTVI) formula. For QTc interval calculation, in addition to Bazett’s formula, linear and parabolic heart rate correction formulas with two separate α values were used. QTVI and QTc values were calculated as means of 2 awake, 3 NREM, and 3 REM sleep episodes; the duration of each episode was 300 sec. Mean QTVI values were not statistically different between sleep stages. Therefore, elevated QTVI values found in patients with OSA cannot be interpreted as physiological sympathetic impact during REM sleep and should be considered as a risk factor for potentially life-threatening ventricular arrhythmias. The absence of difference of the mean QTc interval values between NREM and REM stages seems to confirm our conclusion that sympathetic surges during REM stage do not induce repolarization variability. In patients without notable structural and electrical remodeling of myocardium, physiological elevation in sympathetic activity during REM sleep remains subthreshold concerning clinically significant increase of myocardial electrical instability. Moonika Viigimae, Deniss Karai, Peeter Pirn, Kristjan Pilt, Kalju Meigas, and Jyri Kaik Copyright © 2015 Moonika Viigimae et al. All rights reserved. Perinatal Health Statistics as the Basis for Perinatal Quality Assessment in Croatia Sun, 29 Nov 2015 13:04:17 +0000 Context. Perinatal mortality indicators are considered the most important measures of perinatal outcome. The indicators reliability depends on births and deaths reporting and recording. Many publications focus on perinatal deaths underreporting and misclassification, disabling proper international comparisons. Objective. Description of perinatal health care quality assessment key indicators in Croatia. Methods. Retrospective review of reports from all maternities from 2001 to 2014. Results. According to reporting criteria for birth weight ≥500 g, perinatal mortality (PNM) was reduced by 31%, fetal mortality (FM) by 32%, and early neonatal mortality (ENM) by 29%. According to reporting criteria for ≥1000 g, PNM was reduced by 43%, FM by 36%, and ENM by 54%. PNM in ≥22 weeks’ (wks) gestational age (GA) was reduced by 28%, FM by 30%, and ENM by 26%. The proportion of FM at 32–36 wks GA and at term was the highest between all GA subgroups, as opposed to ENM with the highest proportion in 22–27 wks GA. Through the period, the maternal mortality ratio varied from 2.4 to 14.3/100,000 live births. The process indicators have been increased in number by more than half since 2001, the caesarean deliveries from 11.9% in 2001 to 19.6% in 2014. Conclusions. The comprehensive perinatal health monitoring represents the basis for the perinatal quality assessment. Urelija Rodin, Boris Filipović-Grčić, Josip Đelmiš, Tatjana Glivetić, Josip Juras, Željka Mustapić, and Ruža Grizelj Copyright © 2015 Urelija Rodin et al. All rights reserved. Dopamine D2 Receptor Is Involved in Alleviation of Type II Collagen-Induced Arthritis in Mice Sun, 29 Nov 2015 12:30:01 +0000 Human and murine lymphocytes express dopamine (DA) D2-like receptors including DRD2, DRD3, and DRD4. However, their roles in rheumatoid arthritis (RA) are less clear. Here we showed that lymphocyte DRD2 activation alleviates both imbalance of T-helper (Th)17/T-regulatory (Treg) cells and inflamed symptoms in a mouse arthritis model of RA. Collagen-induced arthritis (CIA) was prepared by intradermal injection of chicken collagen type II (CII) in tail base of DBA/1 mice or Drd2−/− C57BL/6 mice. D2-like receptor agonist quinpirole downregulated expression of proinflammatory Th17-related cytokines interleukin- (IL-) 17 and IL-22 but further upregulated expression of anti-inflammatory Treg-related cytokines transforming growth factor- (TGF-) β and IL-10 in lymphocytes in vitro and in ankle joints in vivo in CIA mice. Quinpirole intraperitoneal administration reduced both clinical arthritis score and serum anti-CII IgG level in CIA mice. However, Drd2−/− CIA mice manifested more severe limb inflammation and higher serum anti-CII IgG level and further upregulated IL-17 and IL-22 expression and downregulated TGF-β and IL-10 expression than wild-type CIA mice. In contrast, Drd1−/− CIA mice did not alter limb inflammation or anti-CII IgG level compared with wild-type CIA mice. These results suggest that DRD2 activation is involved in alleviation of CIA symptoms by amelioration of Th17/Treg imbalance. Jian-Hua Lu, Yi-Qian Liu, Qiao-Wen Deng, Yu-Ping Peng, and Yi-Hua Qiu Copyright © 2015 Jian-Hua Lu et al. All rights reserved. Nonpharmacological Interventions to Reduce Behavioral and Psychological Symptoms of Dementia: A Systematic Review Sun, 29 Nov 2015 12:14:15 +0000 Introduction. Behavioral and psychological symptoms of dementia (BPSD) are defined as a group of symptoms of disturbed perceptive thought content, mood, or behavior that include agitation, depression, apathy, repetitive questioning, psychosis, aggression, sleep problems, and wandering. Care of patients with BPSD involves pharmacological and nonpharmacological interventions. We reviewed studies of nonpharmacological interventions published in the last 10 years. Methods. We performed a systematic review in Medline and Embase databases, in the last 10 years, until June 2015. Key words used were (1) non-pharmacological interventions, (2) behavioral symptoms, (3) psychological symptoms, and (4) dementia. Results. We included 20 studies published in this period. Among these studies, program activities were more frequent (five studies) and the symptoms more responsive to the interventions were agitation. Discussion. Studies are heterogeneous in many aspects, including size sample, intervention, and instruments of measures. Conclusion. Nonpharmacological interventions are able to provide positive results in reducing symptoms of BPSD. Most studies have shown that these interventions have important and significant efficacy. Alexandra Martini de Oliveira, Marcia Radanovic, Patrícia Cotting Homem de Mello, Patrícia Cardoso Buchain, Adriana Dias Barbosa Vizzotto, Diego L. Celestino, Florindo Stella, Catherine V. Piersol, and Orestes V. Forlenza Copyright © 2015 Alexandra Martini de Oliveira et al. All rights reserved. Oxidative Stress in Placenta: Health and Diseases Sun, 29 Nov 2015 11:59:06 +0000 During pregnancy, development of the placenta is interrelated with the oxygen concentration. Embryo development takes place in a low oxygen environment until the beginning of the second trimester when large amounts of oxygen are conveyed to meet the growth requirements. High metabolism and oxidative stress are common in the placenta. Reactive oxidative species sometimes harm placental development, but they are also reported to regulate gene transcription and downstream activities such as trophoblast proliferation, invasion, and angiogenesis. Autophagy and apoptosis are two crucial, interconnected processes in the placenta that are often influenced by oxidative stress. The proper interactions between them play an important role in placental homeostasis. However, an imbalance between the protective and destructive mechanisms of autophagy and apoptosis seems to be linked with pregnancy-related disorders such as miscarriage, preeclampsia, and intrauterine growth restriction. Thus, potential therapies to hold oxidative stress in leash, promote placentation, and avoid unwanted apoptosis are discussed. Fan Wu, Fu-Ju Tian, and Yi Lin Copyright © 2015 Fan Wu et al. All rights reserved. Effects of Bee Venom Injections at Acupoints on Neurologic Dysfunction Induced by Thoracolumbar Intervertebral Disc Disorders in Canines: A Randomized, Controlled Prospective Study Sun, 29 Nov 2015 11:30:58 +0000 Intervertebral disk disease (IVDD) is a major spine disorder in canines that causes neurological dysfunction, particularly in the thoracolumbar area. Analgesic and anti-inflammatory drugs are typically used to reduce nociceptive signals to decrease canine suffering. Bee venom (BV) has been reported to exert anti-inflammatory and analgesic effects. Injection of BV at acupoints has been widely used to treat clinical disorders including inflammation, pain, and arthritis. The current study was intended to determine whether BV injections at acupoints can enhance treatment of canine neurological dysfunction caused by IVDD. A single-blind controlled trial involving 40 adult canines with neurological dysfunction induced by IVDD subdivided into 2 groups was designed, and 36 canines finished the study. The myelopathy scoring system (MSS) grade and functional numeric scale (FNS) scores improved further after BV treatment than after control treatment. BV injection exerted a particularly strong effect on canines with moderate to severe IVDD and dramatically reduced clinical rehabilitation time. The results indicate that BV injections at acupoints are more effective at protecting canines from IVDD-induced neurological dysfunction and pain than is treatment alone. Li-Chuan Tsai, Yi-Wen Lin, and Ching-Liang Hsieh Copyright © 2015 Li-Chuan Tsai et al. All rights reserved. Alternatives to Transplantation in the Treatment of Heart Failure: New Diagnostic and Therapeutic Insights Sun, 29 Nov 2015 11:16:39 +0000 Francesco Nicolini, Massimo F. Piepoli, Giulio Agnetti, and Giuseppe Siniscalchi Copyright © 2015 Francesco Nicolini et al. All rights reserved. Comment on “Is There a Risk of Yellow Fever Virus Transmission in South Asian Countries with Hyperendemic Dengue?” Sun, 29 Nov 2015 11:04:15 +0000 John T. Cathey Copyright © 2015 John T. Cathey. All rights reserved. Anatomical Study of Intrahemispheric Association Fibers in the Brains of Capuchin Monkeys (Sapajus sp.) Sun, 29 Nov 2015 08:01:07 +0000 Previous studies suggest that the complexity of fiber connections in the brain plays a key role in the evolutionary process of the primate brain and behaviors. The patterns of brain fiber systems have been studied in detail in many nonhuman primates, but not in Sapajus sp. Behavioral studies indicated that Sapajus sp. (bearded capuchins) show highly cognitive behaviors such as tool use comparable to those in other nonhuman primates. To compare the brain fiber systems in capuchins with those in other nonhuman primates and humans, the intrahemispheric fibers systems in 24 cerebral hemispheres of Sapajus were dissected by a freezing-thawing procedure. Dissection of the hemispheres in lateral view indicated short arcuate fibers, uncinate fasciculus, and inferior longitudinal fasciculus, while that in a medial view indicated short arcuate fibers, the cingulum united with the superior longitudinal fasciculus, and inferior longitudinal fasciculus. The results showed that the fiber systems in Sapajus are comparable to those in rhesus and humans, except for a lack of independent superior longitudinal fasciculus and cingulum in Sapajus. Kellen Christina Malheiros Borges, Hisao Nishijo, Tales Alexandre Aversi-Ferreira, Jussara Rocha Ferreira, and Leonardo Ferreira Caixeta Copyright © 2015 Kellen Christina Malheiros Borges et al. All rights reserved. A Kinetic-Model-Based Approach to Identify Malfunctioning Components in Signal Transduction Pathways from Artificial Clinical Data Sun, 29 Nov 2015 07:30:56 +0000 Detection of malfunctioning reactions or molecules from clinical data is essential for disease treatments. In order to find an alternative to the existing oversimplistic mathematical models, a kinetic model is developed in this work to infer the malfunctioning reactions/molecules by quantifying the similarity between the clinical profile and the output profiles predicted from the model in which certain reactions/molecules malfunction. The new approach was tested in IL-6 and TNF-α/NF-κB signaling pathway, for four abnormal conditions including up/downregulation of single reaction rate constants and up/downregulation of single molecules. Since limited quantitative clinical data were available, the IL-6 ODE model was used to generate artificial clinical data for the abnormal steady-state value shown in two key molecules: nuclear STAT3 and SOCS3. Similarly, the TNF-α/NF-κB model was used to obtain the data in which abnormal oscillation dynamic was shown in the profile of NF-κB. The results show that the approach developed in this study was able to successfully identify the malfunctioning reactions and molecules from the clinical data. It was also found that this new approach was noise-robust and that it managed to reveal unique solution for the faulty components in a network. Xianhua Li, Nicholas Ribaudo, and Zuyi (Jacky) Huang Copyright © 2015 Xianhua Li et al. All rights reserved. Computer-Aided Decision Support for Melanoma Detection Applied on Melanocytic and Nonmelanocytic Skin Lesions: A Comparison of Two Systems Based on Automatic Analysis of Dermoscopic Images Thu, 26 Nov 2015 14:26:45 +0000 Commercially available clinical decision support systems (CDSSs) for skin cancer have been designed for the detection of melanoma only. Correct use of the systems requires expert knowledge, hampering their utility for nonexperts. Furthermore, there are no systems to detect other common skin cancer types, that is, nonmelanoma skin cancer (NMSC). As early diagnosis of skin cancer is essential, there is a need for a CDSS that is applicable to all types of skin lesions and is suitable for nonexperts. Nevus Doctor (ND) is a CDSS being developed by the authors. We here investigate ND’s ability to detect both melanoma and NMSC and the opportunities for improvement. An independent test set of dermoscopic images of 870 skin lesions, including 44 melanomas and 101 NMSCs, were analysed by ND. Its sensitivity to melanoma and NMSC was compared to that of Mole Expert (ME), a commercially available CDSS, using the same set of lesions. ND and ME had similar sensitivity to melanoma. For ND at 95% melanoma sensitivity, the NMSC sensitivity was 100%, and the specificity was 12%. The melanomas misclassified by ND at 95% sensitivity were correctly classified by ME, and vice versa. ND is able to detect NMSC without sacrificing melanoma sensitivity. Kajsa Møllersen, Herbert Kirchesch, Maciel Zortea, Thomas R. Schopf, Kristian Hindberg, and Fred Godtliebsen Copyright © 2015 Kajsa Møllersen et al. All rights reserved. Strong Public Health Recommendations from Weak Evidence? Lessons Learned in Developing Guidance on the Public Health Management of Meningococcal Disease Thu, 26 Nov 2015 13:58:49 +0000 The evidence underpinning public health policy is often of low quality, leading to inconsistencies in recommended interventions. One example is the divergence in national policies across Europe for managing contacts of invasive meningococcal disease. Aiming to develop consistent guidance at the European level, a group of experts reviewed the literature and formulated recommendations. The group defined eight priority research questions, searched the literature, and formulated recommendations using GRADE methodology. Five of the research questions are discussed in this paper. After taking into account quality of evidence, benefit, harm, value, preference, burden on patient of the intervention, and resource implications, we made four strong recommendations and five weak recommendations for intervention. Strong recommendations related not only to one question with very low quality of evidence as well as to two questions with moderate to high quality of evidence. The weak recommendations related to two questions with low and very low quality of evidence but also to one question with moderate quality of evidence. GRADE methodology ensures a transparent process and explicit recognition of additional factors that should be considered when making recommendations for policy. This approach can be usefully applied to many areas of public health policy where evidence quality is often low. Germaine Hanquet, Pawel Stefanoff, Wiebke Hellenbrand, Sigrid Heuberger, Pierluigi Lopalco, and James M. Stuart Copyright © 2015 Germaine Hanquet et al. All rights reserved. Minimal Invasive Percutaneous Osteosynthesis for Elderly Valgus Impacted Proximal Humeral Fractures with the PHILOS Thu, 26 Nov 2015 13:19:23 +0000 There is a growing concern about elderly valgus impacted proximal humeral fractures. The aim of this study was to evaluate the treatment and clinical outcomes following minimal invasive percutaneous plate osteosynthesis (MIPPO) with the proximal humeral internal locking system (PHILOS) for the treatment of elderly valgus impacted proximal humeral fracture. Between May 2008 and May 2012, 27 patients (average age 67.3, range 61–74) with valgus impacted proximal humeral fractures were enrolled in the study. The patients were treated with MIPPO using PHILOS-plate through the anterolateral delta-splitting approach. Rehabilitation exercises were done gradually. The NEER score and Constant-Murley score were used to evaluate shoulder function. All the patients were followed up by routine radiological imaging and clinical examination. There were 15 cases of II-part greater tuberosity fractures, 10 cases of III-part greater tuberosity fractures, and 2 cases of IV-part fractures according to the NEER classification. The surgery was successful in all patients with an average follow-up of 20.8 (range: 11–34) months. The fractures united in an average of 7.2 (6–14) weeks without implant loosening. According to NEER score, there were 17 excellent, 7 satisfactory, 2 unsatisfactory, and 1 poor. The mean Constant-Murley score was . No complication including axillary nerve damage, postoperative nerve or vessel damage, infections, DVT, or death was observed. In conclusion, the MIPPO technique with the PHILOS through the anterolateral delta-splitting approach seems to be a safe and easy treatment for elderly valgus impacted proximal humeral fractures. A case-control study and longer follow-up time are needed. Hang Chen, Xiaochuan Hu, Haochen Tang, Guoyong Yang, and Ming Xiang Copyright © 2015 Hang Chen et al. All rights reserved. Successful Cognitive Aging: Between Functional Decline and Failure of Compensatory Mechanisms Thu, 26 Nov 2015 13:17:26 +0000 Marc Verny, Emmanuel Moyse, and Slavica Krantic Copyright © 2015 Marc Verny et al. All rights reserved. Clinical and Etiological Characteristics of Atypical Hand-Foot-and-Mouth Disease in Children from Chongqing, China: A Retrospective Study Thu, 26 Nov 2015 12:56:30 +0000 Background. Hand-foot-and-mouth disease (HFMD) is a disease that had similar manifestations to chickenpox, impetigo, and measles, which is easy to misdiagnose and subsequently causes delayed therapy and subsequent epidemic. To date, no study has been conducted to report the clinical and epidemiological characteristics of atypical HFMD. Methods. 64 children with atypical HFMD out of 887 HFMD children were recruited, stool was collected, and viral VP1 was detected. Results. The atypical HFMD accounted for 7.2% of total HFMD in the same period (64/887) and there were two peaks in its prevalence in nonepidemic seasons. Ten children (15.6%) had manifestations of neurologic involvement, of whom 4 (6.3%) were diagnosed with severe HFMD and 1 with critically severe HFMD, but all recovered smoothly. Onychomadesis and desquamation were found in 14 patients (21.9%) and 15 patients (23.4%), respectively. The most common pathogen was coxsackievirus A6 (CV-A6) which accounted for 67.2%, followed by nontypable enterovirus (26.6%), enterovirus 71 (EV-A71) (4.7%), and coxsackievirus A16 (A16) (1.5%). Conclusions. Atypical HFMD has seasonal prevalence. The manifestations of neurologic involvement in atypical HFMD are mild and usually have a good prognosis. CV-A6 is a major pathogen causing atypical HFMD, but not a major pathogen in Chongqing, China. Xiang Yan, Zhen-Zhen Zhang, Zhen-Hua Yang, Chao-Min Zhu, Yun-Ge Hu, and Quan-Bo Liu Copyright © 2015 Xiang Yan et al. 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