BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . 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. All rights reserved. A New Approach Using Manganese-Enhanced MRI to Diagnose Acute Mesenteric Ischemia in a Rabbit Model: Initial Experience Thu, 26 Nov 2015 12:50:58 +0000 Purpose. Manganese-enhanced MRI (MEMRI) has been applied to a wide range of biological and disease research. The purpose of the study was to use MEMRI to diagnose the acute mesenteric ischemia (AMI). Methods. The institutional experimental animal ethics committee approved this study. To optimize the dose of Mn2+ infusion, a dose-dependent curve was obtained using Mn2+-enhanced T1 map MRI by an intravenous infusion 2.5–20 nmol/g body weight (BW) of 50 nmol/L MnCl2. The eighteen animals were divided into control, sham-operated, and AMI groups. AMI models were performed by ligating the superior mesenteric artery (SMA). T1 values were measured on T1 maps in regions of the small intestinal wall and relaxation rate (ΔR1) was calculated. Results. A nonlinear relationship between infused MnCl2 solution dose and increase in small intestinal wall ΔR1 was observed. Control animal exhibited significant Mn2+ clearance over time at the dose of 15 nmol/g BW. In the AMI model, ΔR1 values (0.95 ± 0.13) in the small intestinal wall were significantly lower than in control group (2.05 ± 0.19) after Mn2+ infusion (P < 0.01). Conclusion. The data suggest that MEMRI shows potential as a diagnostic technique that is directly sensitive to the poor or absent perfusion in AMI. Da-wei Zhao, Cheng Cheng, Lian-qin Kuang, Yu-long Zhang, Hai-yun Cheng, Jia-yan Min, and Yi Wang Copyright © 2015 Da-wei Zhao et al. All rights reserved. Quantitative Evaluation of Growth Plates around the Knees of Adolescent Soccer Players by Diffusion-Weighted Magnetic Resonance Imaging Thu, 26 Nov 2015 06:55:12 +0000 Purpose. To quantitatively evaluate growth plates around the knees in adolescent soccer players utilizing the diffusion-weighted MR imaging (DWI). Methods. The knees and adjacent growth plates of eleven 14-year-old male soccer players were evaluated by MRI before (end of season’s summer break) and after two months of intense soccer training. MRI evaluation was conducted in coronal plane by PD-FSE and DWI. All images were screened for any major pathological changes. Later, central growth plate surface area (CGPSA) was measured and the apparent diffusion coefficient (ADC) values were calculated in two most central coronal slices divided into four regions: distal femur medial (DFM), distal femur lateral (DFL), proximal tibia medial (PTM), and proximal tibia lateral (PTL). Results. No gross pathology was diagnosed on MRI. CGPSA was not significantly reduced: DFM 278 versus 272, DFL 265 versus 261, PTM 193 versus 192, and PTL 214 versus 210. ADC decrease was statistically significant only for PTM: DFM 1.27 versus 1.22, DFL 1.37 versus 1.34, PTM 1.13 versus 1.03 (), and PTL 1.28 versus 1.22. Conclusions. DWI measurements indicate increased cellularity in growth plates around knees in footballers most prominent in PTM after intense training. No detectable differences on a standard PD-FSE sequence were observed. Zmago Krajnc, Mitja Rupreht, and Matej Drobnič Copyright © 2015 Zmago Krajnc et al. All rights reserved. Design and Synthesis of a Novel Cationic Peptide with Potent and Broad-Spectrum Antimicrobial Activity Wed, 25 Nov 2015 12:29:16 +0000 Antibacterial and antifungal peptides have increasingly been used to combat the antibiotic-resistant microbes in recent years. KW-13, a novel cationic α-helical antibacterial peptide consisting of 13 amino acid residues, was designed and chemically synthesized. The peptide has a net charge of +6 with a total hydrophobic ratio of 38%. The antibacterial experiments revealed that KW-13 strongly inhibited the growth of human pathogenic bacteria with minimal inhibitory concentrations of 4 and 16 μg/mL for Staphylococcus epidermidis and Staphylococcus aureus, respectively, while the hemolytic assay showed that this peptide did not destroy human red blood cells in vitro. Scanning electron microscopy imaging of Escherichia coli confirmed that KW-13 can damage the membrane of bacterial cells. Thus, this peptide could be a potential candidate for the treatment of infectious diseases. Wen-Ping Liu, Ya-Hui Chen, Xin Ming, and Yi Kong Copyright © 2015 Wen-Ping Liu et al. All rights reserved. Rapamycin Protects from Type-I Peritoneal Membrane Failure Inhibiting the Angiogenesis, Lymphangiogenesis, and Endo-MT Wed, 25 Nov 2015 12:12:32 +0000 Preservation of peritoneal membrane (PM) is essential for long-term survival in peritoneal dialysis (PD). Continuous presence of PD fluids (PDF) in the peritoneal cavity generates chronic inflammation and promotes changes of the PM, such as fibrosis, angiogenesis, and lymphangiogenesis. Mesothelial-to-mesenchymal transition (MMT) and endothelial-to-mesenchymal transition (Endo-MT) seem to play a central role in this pathogenesis. We speculated that Rapamycin, a potent immunosuppressor, could be beneficial by regulating blood and lymphatic vessels proliferation. We demonstrate that mice undergoing a combined PD and Rapamycin treatment (PDF + Rapa group) presented a reduced PM thickness and lower number of submesothelial blood and lymphatic vessels, as well as decreased MMT and Endo-MT, comparing with their counterparts exposed to PD alone (PDF group). Peritoneal water transport in the PDF + Rapa group remained at control level, whereas PD effluent levels of VEGF, TGF-β, and TNF-α were lower than in the PDF group. Moreover, the treatment of mesothelial cells with Rapamycin in vitro significantly decreased VEGF synthesis and selectively inhibited the VEGF-C and VEGF-D release when compared with control cells. Thus, Rapamycin has a protective effect on PM in PD through an antifibrotic and antiproliferative effect on blood and lymphatic vessels. Moreover, it inhibits Endo-MT and, at least partially, MMT. Guadalupe Tirma González-Mateo, Anna Rita Aguirre, Jesús Loureiro, Hugo Abensur, Pilar Sandoval, José Antonio Sánchez-Tomero, Gloria del Peso, José Antonio Jiménez-Heffernan, Vicente Ruiz-Carpio, Rafael Selgas, Manuel López-Cabrera, Abelardo Aguilera, and Georgios Liappas Copyright © 2015 Guadalupe Tirma González-Mateo et al. All rights reserved. N-Acetylneuraminic Acid Supplementation Prevents High Fat Diet-Induced Insulin Resistance in Rats through Transcriptional and Nontranscriptional Mechanisms Wed, 25 Nov 2015 12:00:52 +0000 N-Acetylneuraminic acid (Neu5Ac) is a biomarker of cardiometabolic diseases. In the present study, we tested the hypothesis that dietary Neu5Ac may improve cardiometabolic indices. A high fat diet (HFD) + Neu5Ac (50 or 400 mg/kg BW/day) was fed to rats and compared with HFD + simvastatin (10 mg/kg BW/day) or HFD alone for 12 weeks. Weights and serum biochemicals (lipid profile, oral glucose tolerance test, leptin, adiponectin, and insulin) were measured, and mRNA levels of insulin signaling genes were determined. The results indicated that low and high doses of sialic acid (SA) improved metabolic indices, although only the oral glucose tolerance test, serum triglycerides, leptin, and adiponectin were significantly better than those in the HFD and HFD + simvastatin groups (). Furthermore, the results showed that only high-dose SA significantly affected the transcription of hepatic and adipose tissue insulin signaling genes. The data suggested that SA prevented HFD-induced insulin resistance in rats after 12 weeks of administration through nontranscriptionally mediated biochemical changes that may have differentially sialylated glycoprotein structures at a low dose. At higher doses, SA induced transcriptional regulation of insulin signaling genes. These effects suggest that low and high doses of SA may produce similar metabolic outcomes in relation to insulin sensitivity through multiple mechanisms. These findings are worth studying further. Zhang Yida, Mustapha Umar Imam, Maznah Ismail, Norsharina Ismail, Nur Hanisah Azmi, Waiteng Wong, Hadiza Altine Adamu, Nur Diyana Md Zamri, Aini Ideris, and Maizaton Atmadini Abdullah Copyright © 2015 Zhang Yida et al. All rights reserved. Wide Local Excision for Dermatofibrosarcoma Protuberans: A Single-Center Series of 90 Patients Wed, 25 Nov 2015 11:51:04 +0000 Background. Dermatofibrosarcoma protuberans (DFSP), a rare low-grade sarcoma of fibroblast origin, tends to extend in a finger-like fashion beyond macroscopic tumor margins. Therefore, incomplete removal and subsequent recurrence are common. This study aimed to determine the efficacy of wide local excision (WLE) for controlling local recurrence of DFSP. Methods. The medical records of 90 DFSP patients who received WLE at our hospital between June 1992 and January 2015 were retrospectively reviewed. WLE was conducted including a 3 cm (range, 1 to 5 cm) safety margin according to tumor size, location, and recurrence status. Clinical and tumor characteristics and surgical methods were evaluated for risk factor analysis and local recurrence-free survival. Results. DFSP occurred most often in patients in their 30s (30%) and on the trunk (51.1%). Five patients (5.5%) experienced local recurrence during the 43.4-month follow-up period. Recurrence was found at a mean of 10.8 months after WLE. Although no factors were significantly associated with recurrence, recurrences were more frequent in head and neck. Recurrence-free survival was 87% in 6 years and 77% in 7 years. Conclusions. WLE with adequate lateral and deep margins can effectively control local recurrence rate and is a simple and effective method to treat DFSP. Byung Jun Kim, Hyeonwoo Kim, Ung Sik Jin, Kyung Won Minn, and Hak Chang Copyright © 2015 Byung Jun Kim et al. All rights reserved. Association of Polymorphic Variants of miRNA Processing Genes with Larynx Cancer Risk in a Polish Population Wed, 25 Nov 2015 08:54:11 +0000 Laryngeal cancer (LC) is one of the most prevalent types of head and neck cancer. An increasing interest has been focused on the role of microRNA (miRNAs) in LC development. The study group consisted of 135 larynx cancer patients and 170 cancer-free individuals. Nine polymorphisms of pre-miRNA processing genes, DROSHA (rs6877842), DGCR8 (rs3757, rs417309, and rs1640299), RAN (rs14035), XPO5 (rs11077), DICER1 (rs13078 and rs3742330) and TARBP2 (rs784567), were performed by TaqMan SNP Genotyping Assay. It was found that the frequency of the GT and the TT polymorphic variants of XPO5 gene were higher in LC patients than in controls ( and , resp.). In turn, the frequency of the CT genotype of RAN gene was higher in controls than in LC patients (). The TT and the AG of DICER1 gene ( for rs13078 and for rs3742330) as well as the AG and the GG genotypes of TARBP2 gene ( and , resp.) were associated with higher risk of LC occurrence. Our data suggested that polymorphisms of miRNA processing genes might be useful as predictive factors for the LC development. Ewa Osuch-Wojcikiewicz, Antoni Bruzgielewicz, Kazimierz Niemczyk, Olga Sieniawska-Buccella, Alicja Nowak, Anna Walczak, and Ireneusz Majsterek Copyright © 2015 Ewa Osuch-Wojcikiewicz et al. All rights reserved. Pauci-Immune Crescentic Glomerulonephritis: An ANCA-Associated Vasculitis Wed, 25 Nov 2015 07:35:34 +0000 Rapidly progressive glomerulonephritis (RPGN) is a syndrome signified by a precipitous loss of renal function, with features of glomerulonephritis including dysmorphic erythrocyturia and glomerular proteinuria. RPGN is associated with extensive crescent formation, and, thus, the clinical term RPGN is often used interchangeably with the pathologic term crescentic glomerulonephritis (CGN). From an immunopathologic standpoint, primary RPGN is divided into pauci-immune GN (PICG), anti-GBM GN, and immune complex GN. PICG, the most common etiology of primary RPGN, refers to a necrotizing glomerulonephritis with few or no immune deposits by immunofluorescence (IF) or electron microscopy (EM). In most patients, pauci-immune CGN is a component of a systemic small vessel vasculitis such as granulomatosis with polyangiitis (GPA). Approximately 90% of patients with PICG have circulating ANCA antibodies, leading to the nomenclature ANCA-associated vasculitis (AAV). Recent research has identified several other antibodies associated with PICG, which is now understood to be a complex spectrum of disease with considerable overlap in terms of clinical phenotype and outcomes. In addition, several genetic and environmental factors have recently been implicated in the pathogenesis of this disorder. With new prognostic classifications, enhanced understanding of immunopathologic mechanisms, and novel treatment paradigms, clinical and experimental interest in PICG remains high. Rafeel Syed, Amina Rehman, Gautam Valecha, and Suzanne El-Sayegh Copyright © 2015 Rafeel Syed et al. All rights reserved. Cofunctional Subpathways Were Regulated by Transcription Factor with Common Motif, Common Family, or Common Tissue Tue, 24 Nov 2015 14:10:30 +0000 Dissecting the characteristics of the transcription factor (TF) regulatory subpathway is helpful for understanding the TF underlying regulatory function in complex biological systems. To gain insight into the influence of TFs on their regulatory subpathways, we constructed a global TF-subpathways network (TSN) to analyze systematically the regulatory effect of common-motif, common-family, or common-tissue TFs on subpathways. We performed cluster analysis to show that the common-motif, common-family, or common-tissue TFs that regulated the same pathway classes tended to cluster together and contribute to the same biological function that led to disease initiation and progression. We analyzed the Jaccard coefficient to show that the functional consistency of subpathways regulated by the TF pairs with common motif, common family, or common tissue was significantly greater than the random TF pairs at the subpathway level, pathway level, and pathway class level. For example, HNF4A (hepatocyte nuclear factor 4, alpha) and NR1I3 (nuclear receptor subfamily 1, group I, member 3) were a pair of TFs with common motif, common family, and common tissue. They were involved in drug metabolism pathways and were liver-specific factors required for physiological transcription. In short, we inferred that the cofunctional subpathways were regulated by common-motif, common-family, or common-tissue TFs. Fei Su, Desi Shang, Yanjun Xu, Li Feng, Haixiu Yang, Baoquan Liu, Shengyang Su, Lina Chen, and Xia Li Copyright © 2015 Fei Su et al. All rights reserved. 3D Culture of MIN-6 Cells on Decellularized Pancreatic Scaffold: In Vitro and In Vivo Study Tue, 24 Nov 2015 12:36:06 +0000 Type 1 diabetes is an autoimmune disease which is due to the lack of β cells. The ideal therapy to cure the disease is pancreas transplantation, but its application is confined to a limited number of people due to the shortage of organ and the need for life-long immunosuppression. Regenerative medicine methods such as a tissue engineered pancreas seem to provide a useful method. In order to construct a microenvironment similar to the native pancreas that is suitable for not only cell growth but also cellular function exertion, a decellularized mouse pancreas was used as a natural 3D scaffold in this experiment. MIN-6 β cells were planted in the bioscaffold. The cell engraftment was verified by HE staining and SEM. Immunostaining procedures were performed to confirm the normal function of the engrafted cells. qRT-PCR demonstrated that insulin gene expression of the recellularized pancreas was upregulated compared with conventional plate-cultured cells. In vivo experiment was also accomplished to further evaluate the function of the recellularized bioscaffold and the result was inspiring. And beyond doubt this will bring new hope for type 1 diabetic patients. Di Wu, Jian Wan, Yan Huang, Yibing Guo, Tianxin Xu, Mingyan Zhu, Xiangjun Fan, Shajun Zhu, Changchun Ling, Xiaohong Li, Jingjing Lu, Hui Zhu, Pengcheng Zhou, Yuhua Lu, and Zhiwei Wang Copyright © 2015 Di Wu et al. All rights reserved. MicroRNA-381 Negatively Regulates TLR4 Signaling in A549 Cells in Response to LPS Stimulation Tue, 24 Nov 2015 12:12:21 +0000 It is widely reported that miR-381 is dysregulated in various tumors. However, the specific role of miR-381 in respiratory infections has not been reported. To probe this role, A549 cells were pretreated with 1 μg/mL LPS for 24 h. The level of miR-381 was detected using RT-qPCR. The expression of proinflammatory cytokines was determined using an ELISA kit and western blotting. Bioinformatics analysis was used to predict the target genes of miR-381, and a luciferase reporter assay was used to validate the expression of the target genes. miR-381 expression was increased in A549 cells treated with LPS, which is a ligand of TLRs. Further study revealed that the overexpression of miR-381 increased the activity of NF-κB signaling, thereby increasing the expression of IL-6, TNFα, and COX-2. Further study revealed that IκBα was a target gene of miR-381. The upregulation of miR-381 under LPS stimulation contributes to respiratory infections mainly by targeting IκBα. Zhihao Xu, Dapeng Dong, Xiaofei Chen, Huaqiong Huang, and Shenglan Wen Copyright © 2015 Zhihao Xu et al. All rights reserved. Interventional Tools to Improve Prescription and Adherence to Medical Plans Tue, 24 Nov 2015 11:56:50 +0000 Elísio Costa, Anna Giardini, Alexandra Prados-Torres, Caitriona Cahir, and Alessandra Marengoni Copyright © 2015 Elísio Costa et al. All rights reserved. Deep Assessment: A Novel Framework for Improving the Care of People with Very Advanced Alzheimer’s Disease Tue, 24 Nov 2015 11:51:28 +0000 Best practice in understanding and caring for people with advanced Alzheimer’s disease presents extraordinary challenges. Their severe and deteriorating cognitive impairments are such that carers find progressive difficulty in authentically ascertaining and responding to interests, preferences, and needs. Deep assessment, a novel multifaceted framework drawn from research into the experiences of others with severe cognitive impairments, has potential to empower carers and other support professionals to develop an enhanced understanding of people with advanced Alzheimer’s disease and so deliver better calibrated care in attempts to maximize quality of life. Deep assessment uses a combination of techniques, namely, Behaviour State Observation, Triangulated Proxy Reporting, and Startle Reflex Modulation Measurement, to deliver a comprehensive and deep assessment of the inner states (awareness, preferences, likes, and dislikes) of people who cannot reliably self-report. This paper explains deep assessment and its current applications. It then suggests how it can be applied to people with advanced Alzheimer’s disease to develop others’ understanding of their inner states and to help improve their quality of life. An illustrative hypothetical vignette is used to amplify this framework. We discuss the potential utility and efficacy of this technique for this population and we also propose other human conditions that may benefit from research using a deep assessment approach. Gordon Lyons, Michael Arthur-Kelly, Ami Eidels, and Aimee Mavratzakis Copyright © 2015 Gordon Lyons et al. All rights reserved. Lumbar Endoscopic Microdiscectomy: Where Are We Now? An Updated Literature Review Focused on Clinical Outcome, Complications, and Rate of Recurrence Tue, 24 Nov 2015 11:33:18 +0000 Endoscopic disc surgery (EDS) for lumbar spine disc herniation is a well-known but developing field, which is increasingly spreading in the last few years. Rate of recurrence/residual, complications, and outcomes, in comparison with standard microdiscectomy (MD), is still debated and need further data. We performed an extensive review based on the last 6 years of surgical series, systematic reviews, and meta-analyses reported in international, English-written literature. Articles regarding patients treated through endoscopic transforaminal or interlaminar approaches for microdiscectomy (MD) were included in the present review. Papers focused on endoscopic surgery for other spinal diseases were not included. From July 2009 to July 2015, we identified 51 surgical series, 5 systematic reviews, and one meta-analysis reported. In lumbar EDS, rate of complications, length of hospital staying, return to daily activities, and overall patients’ satisfaction seem comparable to standard MD. Rate of recurrence/residual seems higher in EDS, although data are nonhomogeneous among different series. Surgical indication and experience of the performing surgeon are crucial factors affecting the outcome. There is growing but still weak evidence that lumbar EDS is a valid and safe alternative to standard open microdiscectomy. Statistically reliable data obtained from randomized controlled trials (better if multicentric) are desirable to further confirm these results. Giulio Anichini, Alessandro Landi, Federico Caporlingua, André Beer-Furlan, Christian Brogna, Roberto Delfini, and Emiliano Passacantilli Copyright © 2015 Giulio Anichini et al. All rights reserved. Polycyclic Aromatic Hydrocarbons Concentrations in Drinking Water in Villages along the Huai River in China and Their Association with High Cancer Incidence in Local Population Tue, 24 Nov 2015 09:46:24 +0000 This study aims to evaluate the carcinogenic risk of PAHs in the drinking water of counties along the Huai River in China and study their associations with high cancer incidence in local population. We investigated 20 villages with high cancer incidence rates as the risk group and 20 villages with low rates as the control group. Water samples from each village were collected in the winter and summer seasons to analyze the concentrations of 16 PAHs. The carcinogenic risks of the PAHs were calculated for each village using a health risk assessment approach. Results showed that PAHs concentrations in 27.2% of the water samples were higher than the allowable values in China. However, no significant difference in water PAHs concentrations was observed between the risk and control groups (), and no correlation was found between water PAHs concentrations and cancer incidence in these villages. The average upper bound carcinogenic risks were less than in both groups. In conclusion, PAHs were present in the drinking water of the studied villages, but their carcinogenic risks remained within acceptable limits. PAHs in local drinking water might not be the major environmental cause of the high cancer incidences. En chun Pan, Hong Sun, Qiu jin Xu, Qin Zhang, Lin fei Liu, Xiao dong Chen, and Yan Xu Copyright © 2015 En chun Pan et al. All rights reserved.