bluuebunny/crossref_metadata_2025 huggingface dataset:
Handover Management of Net-Drones for Future Internet Platforms
Authors: Park Kyung-Nam , Kang Jin-Hyeok , Cho Byeong-Moon , Park Kyung-Joon , Kim Hwangnam
Published: March 2016

The advent of the Internet of things (IoT) is changing the way how we interact with the physical world. However, the current Internet suffers from exponential increase in bandwidth demand. In order to resolve the bandwidth issue, we can consider aerial networks by unmanned aerial vehicles (UAV) or the so-called drones for establishing a three-dimensional mobile network in an ad hoc manner. By deploying a network from the sky, we can use the otherwise idle wireless medium and high mobility free from ground obstacles. Aerial networks are especially effective for supporting the temporary surge of population as well as disaster areas because building an additional network infrastructure requires extensive time. In this paper, we propose an efficient handover mechanism for aerial networks in the three-dimensional space, which significantly differs from the conventional two-dimensional schemes. The proposed scheme adjusts the height of a drone and the distance between the drones. To this end, we use the seamless handover success probability and the false handover initiation probability in order to evaluate the optimal coverage decision algorithm. To the best of our knowledge, the proposed scheme is the first attempt for resolving handover of net-drones in the three-dimensional space.
A Comparison of Clinical Outcomes of Dislocated Intraocular Lens Fixation between In Situ Refixation and Conventional Exchange Technique Combined with Vitrectomy
Authors: Eum Sun Jung , Kim Myung Jun , Kim Hong Kyun
Published: March 2016

Purpose. To evaluate surgical efficacy of in situ refixation technique for dislocated posterior chamber intraocular lens (PCIOL).Methods. This was a single-center retrospective case series. 34 patients (34 eyes) who underwent sclera fixation for dislocated IOLs combined with vitrectomy were studied. Of 34 eyes, 17 eyes underwent IOL exchange and the other 17 eyes underwent in situ refixation.Results. Mean follow-up period was 6 months. Mean logMAR best corrected visual acuity (BCVA) was not significantly different between the groups 6 months after surgery (0.10±0.03in the IOL exchange group and0.10±0.05in the refixation group;p=0.065). Surgically induced astigmatism (SIA) was significantly lower in the refixation group (0.79±0.41) than in the IOL exchange group (1.29±0.46) (p=0.004) at 3 months, which persisted to 6 months (1.13±0.18in the IOL exchange group and0.74±0.11in the refixation group;p=0.006). Postoperative complications occurred in 3 eyes in the IOL exchange group (17.6%) and 2 eyes in the refixation group (11.8%). However, all of the patients were well managed without additional surgery.Conclusion. The in situ refixation technique should be preferentially considered if surgery is indicated since it seemed to produce a sustained less SIA compared to IOL exchange.
Systematic Review of Multidisciplinary Chronic Pain Treatment Facilities
Authors: Fashler Samantha R. , Cooper Lynn K. , Oosenbrug Eric D. , Burns Lindsay C. , Razavi Shima , Goldberg Lauren , Katz Joel
Published: March 2016

This study reviewed the published literature evaluating multidisciplinary chronic pain treatment facilities to provide an overview of their availability, caseload, wait times, and facility characteristics. A systematic literature review was conducted using PRISMA guidelines following a search of MEDLINE, PsycINFO, and CINAHL databases. Inclusion criteria stipulated that studies be original research, survey more than one pain treatment facility directly, and describe a range of available treatments. Fourteen articles satisfied inclusion criteria. Results showed little consistency in the research design used to describe pain treatment facilities. Availability of pain treatment facilities was scarce and the reported caseloads and wait times were generally high. A wide range of medical, physical, and psychological pain treatments were available. Most studies reported findings on the percentage of practitioners in different health care professions employed. Future studies should consider using more comprehensive search strategies to survey facilities, improving clarity on what is considered to be a pain treatment facility, and reporting on a consistent set of variables to provide a clear summary of the status of pain treatment facilities. This review highlights important information for policymakers on the scope, demand, and accessibility of pain treatment facilities.
Indefinite Kernel Network withlq-Norm Regularization
Authors: Qu Zhongfeng , Sun Hongwei
Published: March 2016

We study the asymptotical properties of indefinite kernel network withlq-norm regularization. The framework under investigation is different from classical kernel learning. Positive semidefiniteness is not required by the kernel function. By a new step stone technique, without any interior cone condition for input spaceXandLτcondition for the probability measureρX, satisfied error bounds and learning rates are deduced.
Incorporating Family Function into Chronic Pain Disability: The Role of Catastrophizing
Authors: Akbari Fatemeh , Dehghani Mohsen , Khatibi Ali , Vervoort Tine
Published: March 2016

Background. Observers’ responses to pain are recently investigated to more comprehensively explain chronic pain (CP) and disability. However, the role of family context, defined as interference in roles, communication, and problem-solving, and how (i.e., through which mechanisms) these variables contribute to CP related disability have yet to be examined.Objectives. The aim of the present study is to examine family context in relationship to pain catastrophizing, fear of movement, and depression and its role in understanding CP disability. Three different models were examined.Methods. A total sample of 142 patients with musculoskeletal chronic pain was recruited to examine the role of fear of movement, pain intensity, pain catastrophizing, and depression in relationship to family functioning as predictors of disability.Results. Findings indicated that two models showed acceptable fit, but one of them revealed superior fit indices. Results of the model with superior fit indices indicated that family dysfunction may contribute to catastrophic thinking, which, in turn, contributes to patients’ disability through increasing fear of movement and depression.Discussion. The current study provides further support for the notion that the impact of emotional and cognitive variables upon CP-related disability can be better understood when we consider the social context of pain patients and family function in particular.
Chronic Neck Pain and Cervico-Craniofacial Pain Patients Express Similar Levels of Neck Pain-Related Disability, Pain Catastrophizing, and Cervical Range of Motion
Authors: Muñoz-García Daniel , Gil-Martínez Alfonso , López-López Almudena , Lopez-de-Uralde-Villanueva Ibai , La Touche Roy , Fernández-Carnero Josué
Published: March 2016

Background. Neck pain (NP) is strongly associated with cervico-craniofacial pain (CCFP). The primary aim of the present study was to compare the neck pain-related disability, pain catastrophizing, and cervical and mandibular ROM between patients with chronic mechanical NP and patients with CCFP, as well as asymptomatic subjects. Methods. A total of 64 participants formed three groups. All participants underwent a clinical examination evaluating the cervical range of motion and maximum mouth opening, neck disability index (NDI), and psychological factor of Pain Catastrophizing Scale (PCS). Results. There were no statistically significant differences between patients with NP and CCFP for NDI and PCS (P>0.05). One- way ANOVA revealed significant differences for all ROM measurements. The post hoc analysis showed no statistically significant differences in cervical extension and rotation between the two patient groups (P>0.05). The Pearson correlation analysis shows a moderate positive association between NDI and the PCS for the group of patients with NP and CCFP. Conclusion. The CCFP and NP patient groups have similar neck disability levels and limitation in cervical ROM in extension and rotation. Both groups had positively correlated the NDI with the PCS.
Effectiveness of Second through Sixth Line SalvageHelicobacter pyloriTreatment: Bismuth Quadruple Therapy is Almost Always a Reasonable Choice
Authors: Shaikh Tahir , Fallone Carlo A.
Published: March 2016

Aim.There is a paucity of data on the efficacy of empiricH. pyloritreatment after multiple treatment failures. The aim of this study is to examine the efficacy of empiric salvage therapy as a second through sixth line treatment.Methods.In this single gastroenterology center prospective study in Montreal, Canada, patients with failedH. pyloritreatment were offered empiric salvage therapy based on the patients’ previous antibiotic exposure. Enrollment occurred after 1–5 previous failed attempts and eradication determined at least 4 weeks after completion of treatment.Results.205 treatments were attempted in 175 patients using 7 different regimens. Eradication was achieved in 154 attempts (PP = 81% (154/191), ITT = 75% (154/205)). Bismuth quadruple therapy (BQT) had higher eradication success (PP = 91% (102/112), ITT = 84% (102/121)) when compared to all PPI triple therapies combined (PP = 66% (49/74), absolute risk reduction (ARR): 25% (95% CI: 13–37), ITT = 62% (49/79), ARR: 22% (95% CI: 10–35), andp<0.001) and when compared to levofloxacin triple therapy (PP = 66% (40/61), ARR: 26% (95% CI: 13–39), ITT = 61% (40/66), and ARR: 24% (95% CI: 10–37)). Eradication was achieved in a high proportion with BQT on attempt two (PP = 94% (67/71), ITT = 91% (67/74)), three (PP = 85% (17/20), ITT = 71% (17/24)), four (PP = 100% (11/11), ITT = 92% (11/12)), and five (PP = 86% (6/7), ITT = 75% (6/8)). Patients with previous combined bismuth and tetracycline exposure had a lower proportion of eradication compared to patients without such an exposure (PP: 60% (6/10) versus 95% (94/99), ARR: 35% (95% CI: 11–64), andp<0.001; ITT: 55% (6/11) versus 90% (94/105), ARR: 35% (95% CI: 10–62), andp<0.01).Conclusions.Salvage therapy with a bismuth quadruple regimen is superior to triple therapies and is effective for second through fifth line empirical treatment (≥85% PP, ≥70% ITT). Successful eradication is significantly lower with BQT if a similar bismuth based regimen was used in the past.
A Nested Case-Control Study of Association between Metabolome and Hypertension Risk
Authors: Hao Yongchen , Wang Ying , Xi Lu , Li Guoqi , Zhao Fan , Qi Yue , Liu Jing , Zhao Dong
Published: March 2016

We aimed to explore novel small metabolites that associated with hypertension risk in a population-based nested case-control study. Among 460 individuals with optimal blood pressure (<120/80 mmHg) at baseline, 55 progressed to hypertension during 5 years of follow-up. Twenty-nine cases of incident hypertension and 29 controls, matched for age, sex, and baseline systolic blood pressure, were included in this study. Serum metabolites were measured by gas chromatography-tandem mass spectrometry. t-test and logistic regression analysis were applied to investigate the association between metabolites and incident hypertension. Among the 241 metabolites identified in this study, baseline levels of 26 metabolites were significantly different between hypertension and control groups. After adjusting for body mass index, smoking, and drinking, 16 out of the 26 metabolites were still associated with hypertension risk including four amino acids. Amino acids were negatively associated with risk of future hypertension, with odds ratio (OR) ranging from 0.33 to 0.53. Two of these amino acids were essential amino acids including threonine and phenylalanine. Higher level of lyxose, a fermentation product of gut microbes, was associated with higher risk of hypertension. Our study identified multiple metabolites that associated with hypertension risk. These findings implied that low amino acid levels and gut microbiome might play an important role in the pathogenesis of hypertension.
Promoter Methylation and mRNA Expression of Response Gene to Complement 32 in Breast Carcinoma
Authors: Eskandari-Nasab Ebrahim , Hashemi Mohammad , Rafighdoost Firoozeh
Published: March 2016

Background. Response gene to complement 32 (RGC32), induced by activation of complements, has been characterized as a cell cycle regulator; however, its role in carcinogenesis is still controversial. In the present study we comparedRGC32promoter methylation patterns and mRNA expression in breast cancerous tissues and adjacent normal tissues.Materials and Methods. Sixty-three breast cancer tissues and 63 adjacent nonneoplastic tissues were included in our study.Design. Nested methylation-specific polymerase chain reaction (Nested-MSP) and quantitative PCR (qPCR) were used to determineRGC32promoter methylation status and its mRNA expression levels, respectively.Results. RGC32 methylation pattern was not different between breast cancerous tissue and adjacent nonneoplastic tissue (OR = 2.30, 95% CI = 0.95–5.54). However, qPCR analysis displayed higher levels ofRGC32mRNA in breast cancerous tissues than in noncancerous tissues (1.073 versus 0.959;P=0.001), irrespective of the promoter methylation status. The expression levels and promoter methylation ofRGC32were not correlated with any of patients’ clinical characteristics (P>0.05).Conclusion. Our findings confirmed upregulation of RGC32 in breast cancerous tumors, but it was not associated with promoter methylation patterns.
Characterization ofClostridium difficileStrains in British Columbia, Canada: A Shift from NAP1 Majority (2008) to Novel Strain Types (2013) in One Region
Authors: Jassem Agatha N. , Prystajecky Natalie , Marra Fawziah , Kibsey Pamela , Tan Kennard , Umlandt Patricia , Janz Loretta , Champagne Sylvie , Gamage Bruce , Golding George R. , Mulvey Michael R. , Henry Bonnie , Hoang Linda M. N.
Published: March 2016

Background.Clostridium difficileis a major cause of gastrointestinal illness. Epidemic NAP1 strains contain toxins A and B, a deletion in repressortcdC, and a binary toxin.Objectives. To determine the molecular epidemiology ofC. difficilein British Columbia and compare between two time points in one region.Methods.C. difficileisolates from hospital and community laboratories (2008) and one Island Health hospital laboratory (2013) were characterized by pulsed-field gel electrophoresis, PCR-ribotyping, toxin possession,tcdCgenotype, and antimicrobial susceptibility.Results. In 2008, 42.7% of isolates had NAP1 designation. Hospital-collected isolates were associated with older patients and more NAP1 types. Unlike other isolates, most NAP1 isolates possessed binary toxin and a 19 bp loss intcdC. All isolates were susceptible to metronidazole and vancomycin. A 2013 follow-up revealed a 28.9% decrease in NAP1 isolates and 20.0% increase in isolates without NAP designation in one region. Then, community-associated cases were seen in younger patients, while NAP types were evenly distributed. Isolates without NAP designation did not cluster with a PFGE pattern or ribotype.Conclusions. Evaluation ofC. difficileinfections within British Columbia revealed demographic associations, epidemiological shifts, and characteristics of strain types. Continuous surveillance ofC. difficilewill enable detection of emerging strains.
The Implications of Tobacco Smoking on Acute Postoperative Pain: A Prospective Observational Study
Authors: Chiang Han-Liang , Chia Yuan-Yi , Lin Huey-Shyan , Chen Chen-Hsiu
Published: March 2016

Background. The clinical importance of cigarette smoking on acute postoperative pain perception is not fully understood.Methods. To determine whether smokers who underwent major surgery need more postoperative opiate than do nonsmokers. We prospectively enrolled 407 male and 441 female participants who underwent in-hospital surgery. Current-smokers were compared with nonsmokers and past-smokers about opiate use during the first 72 h after surgery.Results. A greater proportion of males had more smoking history than females. The average age of male current-smokers is smaller than both nonsmokers and past-smokers. The surgical type (upper abdomen, lower abdomen, extremities, spine, and others) and duration of surgery have no differences between current-smokers, past-smokers, and nonsmokers. Statistically, the male current-smokers required more opiate analgesics during the first 72 h following surgery compared with the male nonsmokers and past-smokers; furthermore, the male current-smokers reported higher pain intensity when moving and at rest on day 1 after surgery.Conclusions. In this study, the male current-smokers required more morphine in the first 72 h after surgery than did the nonsmokers and past-smokers. Furthermore, smoking was more prevalent among the males than the females. Health care providers must be aware of the potential for increased narcotic requirements in male current-smokers.
Therapeutic Outcome of Second Primary Malignancies in Patients with Well-Differentiated Thyroid Cancer
Authors: Liou Miaw-Jene , Tsang Ngan-Ming , Hsueh Chuen , Chao Tzu-Chieh , Lin Jen-Der
Published: March 2016

Background.The aims of this study were to analyze the clinical characteristics of SPM in patients with well-differentiated thyroid cancer and to determine the long-term prognosis in patients with double malignancies.Materials and Methods.We retrospectively analyzed 2,864 patients with well-differentiated thyroid cancer and a mean age of44.0±14.4years. Of these, 200 (7.0%) were diagnosed with SPM, 115 of which were diagnosed with metachronous SPM.Results.Of 2,864 patients, 163 (5.7%) patients died of thyroid cancer and 301 (10.5%) died of any cause by the end of the follow-up period. Multivariate analysis identified age, SPM, external radiotherapy, TNM stage, and postoperative serum Tg level to be factors independently associated with decreased survival. Of 200 patients with SPM, 74 (37.0%) died. In comparison to the anachronous and synchronous groups, the metachronous SPM group had a higher mean age; more advanced tumor, node, and metastasis stage; lower remission rate; higher postoperative radioactive iodide (131I) accumulated dose; a higher proportion of patients who underwent external radiotherapy; and higher thyroid cancer and total mortality rates.Conclusions.Patients with well-differentiated thyroid carcinoma and metachronous SPM had worse prognoses compared to patients without SPM.
A Case of Nonunion Avulsion Fracture of the Anterior Tibial Eminence
Authors: Atsumi Satoru , Arai Yuji , Nakagawa Shuji , Inoue Hiroaki , Ikoma Kazuya , Fujiwara Hiroyoshi , Kubo Toshikazu
Published: March 2016

Avulsion fracture of the anterior tibial eminence is an uncommon injury. If bone union does not occur, knee extension will be limited by impingement of the avulsed fragment and knee instability will be induced by dysfunction of the anterior cruciate ligament (ACL). This report describes a 55-year-old woman who experienced an avulsion fracture of the right anterior tibial eminence during recreational skiing. Sixteen months later, she presented at our hospital with limitation of right knee extension. Plain radiography showed nonunion of the avulsion fracture region, and arthroscopy showed that the avulsed fragment impinged the femoral intercondylar notch during knee extension. The anterior region of the bony fragment was debrided arthroscopically until the knee could be extended completely. There was no subsequent instability, and the patient was able to climb a mountain 6 months after surgery. These findings indicate that arthroscopic debridement of an avulsed fragment for nonunion of an avulsion fracture of the anterior tibial eminence is a minimally invasive and effective treatment for middle-aged and elderly patients with a low level of sports activity.
λ-Augmented Tree for Robust Data Collection in Advanced Metering Infrastructure
Authors: Kamto Joseph , Qian Lijun , Li Wei , Han Zhu
Published: March 2016

Tree multicast configuration of smart meters (SMs) can maintain the connectivity and meet the latency requirements for the Advanced Metering Infrastructure (AMI). However, such topology is extremely weak as any single failure suffices to break its connectivity. On the other hand, the impact of a SM node failure can be more or less significant: a noncut SM node will have a limited local impact compared to a cut SM node that will break the network connectivity. In this work, we design a highly connected tree with a set of backup links to minimize the weakness of tree topology of SMs. A topology repair scheme is proposed to address the impact of a SM node failure on the connectivity of the augmented tree network. It relies on a loop detection scheme to define the criticality of a SM node and specifically targets cut SM node by selecting backup parent SM to cover its children. Detailed algorithms to create such AMI tree and related theoretical and complexity analysis are provided with insightful simulation results: sufficient redundancy is provided to alleviate data loss at the cost of signaling overhead. It is however observed that biconnected tree provides the best compromise between the two entities.
Micro/Nanostructure and Tribological Characteristics of Pressureless Sintered Carbon Nanotubes Reinforced Aluminium Matrix Composites
Authors: Manikandan P. , Sieh R. , Elayaperumal A. , Le H. R. , Basu S.
Published: March 2016

This study reports the manufacture, microstructure, and tribological behaviour of carbon nanotube reinforced aluminium composites against pure aluminium. The specimens were fabricated using powder metallurgy method. The nanotubes in weight percentages of 0.5, 1.0, 1.5, and 2.0 were homogeneously dispersed and mechanically alloyed using a high energy ball milling. The milled powders were cold compacted and then isothermally sintered in air. The density of all samples was measured using Archimedes method and all had a relative density between 92.22% and 97.74%. Vickers hardness increased with increasing CNT fraction up to 1.5 wt% and then reduced. The microstructures and surfaces were investigated using high resolution scanning electron microscope (SEM). The tribological tests showed that the CNT reinforced composites displayed lower wear rate and friction coefficient compared to the pure aluminium under mild wear conditions. However, for severe wear conditions, the CNT reinforced composites exhibited higher friction coefficient and wear rate compared to the pure aluminium. It was also found that the friction and wear behaviour of CNT reinforced composites is significantly dependent on the applied load and there is a critical load beyond which CNTs could have adverse impact on the wear resistance of aluminium.
Early Adaptation and Acquired Resistance to CDK4/6 Inhibition in Estrogen Receptor–Positive Breast Cancer
Authors: Herrera-Abreu Maria Teresa , Palafox Marta , Asghar Uzma , Rivas Martín A. , Cutts Rosalind J. , Garcia-Murillas Isaac , Pearson Alex , Guzman Marta , Rodriguez Olga , Grueso Judit , Bellet Meritxell , Cortés Javier , Elliott Richard , Pancholi Sunil , Lord Christopher J. , Baselga José , Dowsett Mitch , Martin Lesley-Ann , Turner Nicholas C. , Serra Violeta
Published: March 2016

Small-molecule inhibitors of the CDK4/6 cell-cycle kinases have shown clinical efficacy in estrogen receptor (ER)-positive metastatic breast cancer, although their cytostatic effects are limited by primary and acquired resistance. Here we report that ER-positive breast cancer cells can adapt quickly to CDK4/6 inhibition and evade cytostasis, in part, via noncanonical cyclin D1-CDK2–mediated S-phase entry. This adaptation was prevented by cotreatment with hormone therapies or PI3K inhibitors, which reduced the levels of cyclin D1 (CCND1) and other G1–S cyclins, abolished pRb phosphorylation, and inhibited activation of S-phase transcriptional programs. Combined targeting of both CDK4/6 and PI3K triggered cancer cell apoptosis in vitro and in patient-derived tumor xenograft (PDX) models, resulting in tumor regression and improved disease control. Furthermore, a triple combination of endocrine therapy, CDK4/6, and PI3K inhibition was more effective than paired combinations, provoking rapid tumor regressions in a PDX model. Mechanistic investigations showed that acquired resistance to CDK4/6 inhibition resulted from bypass of cyclin D1–CDK4/6 dependency through selection of CCNE1 amplification or RB1 loss. Notably, although PI3K inhibitors could prevent resistance to CDK4/6 inhibitors, they failed to resensitize cells once resistance had been acquired. However, we found that cells acquiring resistance to CDK4/6 inhibitors due to CCNE1 amplification could be resensitized by targeting CDK2. Overall, our results illustrate convergent mechanisms of early adaptation and acquired resistance to CDK4/6 inhibitors that enable alternate means of S-phase entry, highlighting strategies to prevent the acquisition of therapeutic resistance to these agents. Cancer Res; 76(8); 2301–13. ©2016 AACR.
No Association between the Mitochondrial Genome and Prostate Cancer Risk: The Multiethnic Cohort
Authors: Giorgi Elena E. , Li Yuqing , Caberto Christian P. , Beckman Kenneth B. , Lum-Jones Annette , Haiman Christopher A. , Le Marchand Loïc , Stram Daniel O. , Saxena Richa , Cheng Iona
Published: March 2016

Background: Mitochondria are involved in many processes that are central to the life and death of a cell. Oxidative phosphorylation (OXPHOS), in particular, is known to be altered in carcinogenesis, leading to an increase in the production of reactive oxidative species and glycolysis, one of the hallmarks of cancer cells. Because of this, genetic variation in the mitochondrial genome, which encodes for part of the OXPHOS pathway, has been suggested to play a role in many cancers, including prostate cancer.

Methods: We comprehensively examined the role of the mitochondrial genome and prostate cancer risk in 4,086 prostate cancer cases and 3,698 controls from the Multiethnic Cohort (MEC), testing 350 mitochondrial SNPs (mtSNPs) in five racial/ethnic populations—Africans, Asian Americans, Europeans, Latinos, and Native Hawaiians. Logistic regression was conducted to examine single mitochondrial SNP and haplogroup associations. The sequence kernel association test was conducted for gene and pathway analysis.

Results: Eleven mtSNPs and haplogroup N were nominally associated with overall prostate cancer risk at P < 0.05. The mitochondrial DNA-encoded OXPHOS pathway, complexes, and genes were not associated with prostate cancer risk. No significant associations were identified after multiple testing corrections (all FDR q > 0.20).

Conclusions: The mitochondrial genome was not associated with prostate cancer risk in our study of 7,784 subjects from the MEC.

Impact: Our comprehensive study does not support the role of the mitochondrial genome in the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev; 25(6); 1001–3. ©2016 AACR.
Therapeutic Targeting of miR-29b/HDAC4 Epigenetic Loop in Multiple Myeloma
Authors: Amodio Nicola , Stamato Maria Angelica , Gullà Anna Maria , Morelli Eugenio , Romeo Enrica , Raimondi Lavinia , Pitari Maria Rita , Ferrandino Ida , Misso Gabriella , Caraglia Michele , Perrotta Ida , Neri Antonino , Fulciniti Mariateresa , Rolfo Christian , Anderson Kenneth C. , Munshi Nikhil C. , Tagliaferri Pierosandro , Tassone Pierfrancesco
Published: March 2016

Epigenetic abnormalities are common in hematologic malignancies, including multiple myeloma, and their effects can be efficiently counteracted by a class of tumor suppressor miRNAs, named epi-miRNAs. Given the oncogenic role of histone deacetylases (HDAC) in multiple myeloma, we investigated whether their activity could be antagonized by miR-29b, a well-established epi-miRNA. We demonstrated here that miR-29b specifically targets HDAC4 and highlighted that both molecules are involved in a functional loop. In fact, silencing of HDAC4 by shRNAs inhibited multiple myeloma cell survival and migration and triggered apoptosis and autophagy, along with the induction of miR-29b expression by promoter hyperacetylation, leading to the downregulation of prosurvival miR-29b targets (SP1, MCL-1). Moreover, treatment with the pan-HDAC inhibitor SAHA upregulated miR-29b, overcoming the negative control exerted by HDAC4. Importantly, overexpression or inhibition of miR-29b, respectively, potentiated or antagonized SAHA activity on multiple myeloma cells, as also shown in vivo by a strong synergism between miR-29b synthetic mimics and SAHA in a murine xenograft model of human multiple myeloma. Altogether, our results shed light on a novel epigenetic circuitry regulating multiple myeloma cell growth and survival and open new avenues for miR-29b–based epi-therapeutic approaches in the treatment of this malignancy. Mol Cancer Ther; 15(6); 1364–75. ©2016 AACR.
Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats
Authors: El-Shemi Adel Galal , Refaat Bassem , Kensara Osama Adnan , Mohamed Amr Mohamed , Idris Shakir , Ahmad Jawwad
Published: March 2016

Colorectal cancer is a common cancer with high mortality rate. Despite being the standard anti–colorectal cancer drug, 5-fluorouracil (5-FU) exhibits only limited therapeutic benefits. Herein, we investigated whether paricalcitol, a synthetic vitamin D analogue with potential antitumor properties, would enhance the chemopreventive efficacy of 5-FU on an intermediate-term (15 weeks) model of colorectal tumors induced by azoxymethane (AOM) in rats. After AOM injection, 5-FU was administered during the 9th and 10th weeks (12 mg/kg/day for 4 days, then 6 mg/kg every other day for another 4 doses), whereas paricalcitol (2.5 μg/kg/day; 3 days/week) was given from the 7th to the 15th week. At week 15, the animals were euthanized and their resected colons were examined macroscopically and microscopically. Quantitative RT-PCR was used to measure the transcription activities of Wnt, β-catenin, DKK-1, CDNK-1A, NF-κB, and COX-2 genes, and ELISA was used to quantify the protein levels of β-catenin, COX-2, HSP90, and VEGF. IHC was additionally used to measure β-catenin, HSP90, and inducible nitric oxide synthase (iNOS). Compared with their individual therapy, combination of 5-FU and paricalcitol showed more significant reducing effect on numbers of grown tumors and large aberrant crypts foci. Mechanistically, paricalcitol and 5-FU had cooperated together to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and HSP-90 more, and to upregulate the expression of antitumorigenesis DKK-1 and CDNK-1A, compared with their monotherapies. Our findings suggest that combined use of paricalcitol with 5-FU exhibits an augmenting chemopreventive effect against colorectal tumors, and might potentially be useful for chemoprevention in colorectal cancer patients. Cancer Prev Res; 9(6); 491–501. ©2016 AACR.
Lack of Serum Creatinine Decrease After Coronary Angiography Despite Prophylactic Hydration After Routine Coronary Angiography/Angioplasty in Stable Angina Patients - Pilot Study
Authors: Burchardt Pawel , Rzezniczak Janusz , Synowiec Tomasz , Angerer Dariusz , Palasz Anna , Zurawski Jakub
Published: March 2016

Background/Aims: To prevent contrast induced renal dysfunction a periprocedural prophylactic hydration is applied. Due to dilution it should cause a drop in serum creatinine concentration (SCR). Surprisingly, no reduction in SCR after contrast admission is found in up to 25% of patients as early as 12-18 hours after coronary angiography/angioplasty. This study aims to find a clinical explanation as well as predict circumstances for this phenomenon. Methods: Retrospective clinical and laboratory data was used from 341 patients who underwent elective coronary angiography/angioplasty, received a prophylactic hydration, and had serum creatinine concentration measured prior to, and 12-18 hours after invasive procedure with iodine contrast administration. To exclude an improper hydration due to no creatinine decrease, the number of red blood cells was analysed as well as hemoglobin and hematocrit in blood donations collected during the study time points. Results: The resulting lack of serum creatinine reduction could be explained by dehydration (measured by increase in number of RBC, HGB and HCT) only in 13.5% , 10.8 %, and 20% of cases, respectively. Any form of abnormal glucose metabolism combined with either baseline serum creatinine concentration <0.87 mg/dL or creatinine clearance >86.77 mL/min, or GFR by CKD EPI >80.08 mL/min/1.73 m2, or GFR by MDRD >74.48 mL/min/1.73 m2 were the predictors for no creatinine decrease at outcome. Additionally, it was demonstrated that the lack of creatinine decrease was more often observed among those patients whose initial renal function was better than in the subjects with reduction of SCR. Conclusions: This observation requires further prospective investigation on extended group of patients.
Anaemia in Patients with Inflammatory Bowel Disease - A Nationwide Cross-Sectional Study
Authors: Portela Francisco , Lago Paula , Cotter José , Gonçalves Raquel , Vasconcelos Helena , Ministro Paula , Lopes Susana , Eusébio Marta , Morna Henrique , Cravo Marilia , Peixe Paula , Cremmers Isabel , Sousa Helena , Deus João , Duarte Maria , Magro Fernando ,   on behalf of CAPOR Investigators and GEDII
Published: March 2016

Background: Anaemia is the most common complication in patients with inflammatory bowel disease (IBD). This study aims to assess the prevalence of anaemia in IBD patients and to know its characteristics with regard to the main IBD clinical features. Methods: An observational cross-sectional multicentre study was conducted. We included all patients who had an appointment at the 15 participating centres during the period of 1 month, and who met the following selection criteria: age ≥18, diagnosis of IBD. Disease activity was evaluated by Harvey-Bradshaw Index (HBI) for Crohn's disease (CD), and by Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). Results: One thousand three hundred and thirteen patients, were included: 54.8% female, mean age 42.8 (interquartile range (25th-75th): 31-53 years), 59% had a diagnosis of CD, 39% of UC and 2% IBD unclassified. The median follow-up since diagnosis was 7 years. The ongoing treatment was aminosalicylates (63.1%), corticosteroids (11.6%), immunomodulators (36.4%) and anti-tumour necrosis factor (27.3%). Anaemia was identified in 244 patients, representing a prevalence of 18.6% (95% CI 16.6-20.9). A majority of cases (90%) have mild/moderate anaemia (mean haemoglobin 11.3 ± 0.8 g/dl). Anaemia was significantly higher in females (p = 0.006), but there were no differences between CDs (19.1%) and UCs (17.7%; p = 0.688). Anaemia was more frequent in patients with active disease (HBI >4; SCCAI >2) than in those in clinical remission (33.6 vs. 15.6%, p < 0.001) and in patients on steroids (36.8%) vs. other treatments (p < 0.001). Only 47% of patients with anaemia were under any specific treatment (oral iron 67%; intravenous iron 41%). Conclusion: Anaemia was more frequent in patients with active disease and in those on corticosteroids. The treatment of anaemia still seems undervalued, whereas more than half of anaemic patients were not receiving any specific treatment and the use of oral iron prevails contrarily to current recommendations.
Factors Effecting Mastalgia
Authors: Eren Tunc , Aslan Adem , Ozemir Ibrahim A. , Baysal Hakan , Sagiroglu Julide , Ekinci Ozgur , Alimoglu Orhan
Published: March 2016

Background: Breast pain is one of the leading complaints that ends up with referral to breast surgery clinics. The purpose of the present study was to investigate the factors that cause mastalgia, and its relation with benign or malignant breast disease. Methods: The study was performed in 700 patients. Data obtained from surveys, and imaging findings were prospectively recorded, and analyzed. Results: The mean age was 45.20 ± 10.78 years. The mastalgia group included 500 cases; the asymptomatic group comprised 200 individuals. Stressful lifestyle, caffeine consumption, and smoking were associated with mastalgia (p < 0.05). Rates of women who had breast fed 3 times or more were higher in the mastalgia group (p < 0.05). Increased breast density, and breast imaging-reporting and data system (BI-RADS) 2 mammography findings were related with mastalgia (p < 0.05). Cysts and fibroadenomas were more common in the mastalgia group (p < 0.05). The incidence of a past history of malignant breast disease was significantly higher in the mastalgia group (p < 0.05). Conclusions: Stress, caffeine, smoking, lactation frequency, and benign disorders were factors detected to be related with mastalgia. Although a significant relation between mastalgia and malignant breast disease was detected in our study, more controlled studies are still required to investigate this issue further.
Calcium Acetate/Magnesium Carbonate and Cardiovascular Risk Factors in Chronic Hemodialysis Patients
Authors: Matias Patrícia João , Jorge Cristina , Azevedo Ana , Laranjinha Ivo , Navarro David , Mendes Marco , Amaral Tiago , Ferreira Carina , Aires Inês , Gil Célia , Stuard Stefano , Ferreira Aníbal
Published: March 2016

Background/Aim: Calcium acetate/magnesium carbonate (CaMg) is a recent phosphate binder that has been shown to have protective cardiovascular (CV) effects in animal models. The aim of this study was to evaluate the relationship between CaMg therapy and CV risk markers like pulse pressure (PP), left ventricular mass index (LVMI) and valvular calcifications compared to sevelamer or no phosphate binder (NPB) therapy in chronic hemodialysis (HD) patients. Methods: We performed a 48-month prospective study in 138 HD patients under hemodiafiltration with a dialysate Mg concentration of 0.5 mmol/l. Patients underwent treatment with CaMg or sevelamer for at least 36 months or NPB therapy. Demographic, clinical, biochemical and echocardiographic parameters were evaluated at baseline and after a 48-month period. Results: At the end of the study, patients who had taken CaMg showed a significant reduction in PP (p < 0.001), LVMI (p = 0.003), aortic (p = 0.004) and mitral valve calcifications (p = 0.03) compared with NPB patients. Patients under CaMg showed a significant reduction of PP (p < 0.001), LVMI (p = 0.01) and aortic valve calcifications (p = 0.02) compared to sevelamer patients. In a multivariable analysis, CaMg therapy was negatively associated with progression of LVMI (p = 0.02) and aortic valve calcifications (p = 0.01). Patients under CaMg showed higher serum Mg levels (0.93 ± 0.14 mmol/l) compared to patients under sevelamer (0.87 ± 0.13) or NPB patients (0.82 ± 0.12; p < 0.001). Conclusions: In prevalent HD patients, the use of CaMg over 48 months was associated with a reduction of PP and LVMI and with a stabilization of aortic valve calcifications. These protective and promising results of this new phosphate binder need to be confirmed in randomized controlled studies.
Ecotoxicological Perspectives of Sex Determination
Authors: Mizoguchi Beatriz A. , Valenzuela Nicole
Published: March 2016

Sex determination or the commitment of the embryo to its sexual fate is a fundamental developmental process with paramount consequences in ecology and evolution. This process, whether triggered by environmental factors or genotypic constitution, can be derailed by environmental contaminants that alter the endocrine system, which is a key component of the regulatory network underlying vertebrate sex determination. Here, we review the molecular basis of sex determination, the endocrine components of its regulation, the maternal and endogenous sources of hormones to the developing embryo, and the routes through which endocrine disrupting chemicals (EDCs) affect gonadal development in reptiles, especially turtles. Among EDCs, we focus on PCBs, BPA, pesticides like atrazine, nitrates, and heavy metals. We also consider whether adaptation might be possible in the face of persistent chemical insult and conclude that, while plausible, contemporary environmental change may outpace adaptive evolution, particularly for many species that are already endangered and suffer from small population sizes.
Comparison of Outcomes with Arteriovenous Fistula and Arteriovenous Graft for Vascular Access in Hemodialysis: A Prospective Cohort Study
Authors: Park Hoon Suk , Kim Woo Jeong , Kim Yong Kyun , Kim Hyung Wook , Choi Bum Soon , Park Cheol Whee , Kim Young Ok , Yang Chul Woo , Kim Yong Lim , Kim Yon Su , Kang Shin-Wook , Kim Nam-Ho , Jin Dong-Chan
Published: March 2016

Background: Poor vessel quality and limited life expectancy in the elderly may make arteriovenous fistula (AVF) less ideal than arteriovenous graft (AVG) or catheter for vascular access (VA) in hemodialysis (HD). Methods: A total of 946 adult incident HD patients from clinical research center registry for end-stage renal disease prospective cohort in South Korea were analyzed for outcomes with AVF and AVG. Results: Overall, AVF was associated with better patient survival only in male (p < 0.001) and diabetic (p = 0.004) patients, although it was superior to AVG in access patency, regardless of diabetes mellitus status and gender. AVG (vs. AVF; hazard ratio (HR) 2.282; 95% CI 1.071-4.861; p = 0.032) was associated with poor patient survival. In elderly patients (≥65 years), AVF was associated with survival benefit only in male (p < 0.001) and diabetic (p = 0.04) patients, and with better access patency only in female (p = 0.05) and diabetic (p = 0.04) patients. AVG (vs. AVF; HR 3.158; 95% CI 1.080-9.238; p = 0.036) was associated with poor patient survival. In septuagenarian patients, AVF was associated only with survival benefit (p = 0.01) and there was no advantage in access patency (p = 0.12). However, AVF was superior to AVG in both access patency (p = 0.001) and patient survival (p = 0.03) even with propensity matching. Conclusion: AVF is the more desirable VA and its survival benefits warrant its consideration in septuagenarian patients although a prolonged life expectancy is essential to realize the potential benefits of AVF.
Aberrant Methylation of the E-Cadherin Gene Promoter Region in Endometrium and Ovarian Endometriotic Cysts of Patients with Ovarian Endometriosis
Authors: Li Yan , An Dong , Guan Ying-xia , Kang Shan
Published: March 2016

The loss of E-cadherin expression plays an important role in the development of endometriosis, but the molecular mechanism is not clear to date. It has been confirmed that the hypermethylation of the CpG island may be an important molecular mechanism in the transcriptional inactivation of E-cadherin gene (CDH1) in many cancers. The present study investigated the methylation status of CDH1 promoter region in ovarian endometriotic cysts and the endometrium of women with ovarian endometriosis. The results showed that the frequency of CDH1 promoter methylation in eutopic (26%), ectopic tissues (32%) of women with ovarian endometriosis was significantly higher than that of endometrium tissue of women without endometriosis (8%). Further, results of the study showed that the expression level of mRNA and protein of E-cadherin in methylation-positive tissues was significantly lower than that in methylation-negative tissues (p = 0.023 and 0.035, respectively). Pearson's correlation coefficients analysis showed the level of CDH1 mRNA expression was closely related to the level of E-cadherin protein expression. The results implied that the aberrant methylation of the CDH1 promoter region in the endometrium of the women may contribute, at least in part, to the development of ovarian endometriosis.
ЕПІДЕМІОЛОГІЧНІ АСПЕКТИ БІОЛОГІЧНОЇ БЕЗПЕКИ ТА ЇХ ЗВ’ЯЗОК З ПОДІЯМИ НА СХОДІ ДЕРЖАВИ
Authors: Krushelnytsky O. D. , Іvanko O. M. , Ohorodnіychuk I. V.
Published: March 2016

Розглянуті питання можливого впливу на епі-
демічну безпеку України подій, які відбуваються на
південному сході держави, та інших актуальних
воєнних загроз. Спрогнозовані напрямки можливих
змін епідемічної ситуації і створені вербально-логічні
моделі, відповідні передбаченим змінам, виділені ілюзії
щодо інфекційної захворюваності в Україні, порушене
питання необхідності протиепідемічних і профілак-
тичних заходів.
Ключові слова: біологічна безпека, епідеміологічні
аспекти, зброя масового ураження, тероризм, ілюзія,
модель.
ПАТОГЕНЕТИЧНІ ПІДХОДИ ДО ЛІКУВАННЯ РОТАВІРУСНОЇ ІНФЕКЦІЇ У ДІТЕЙ
Authors: Naumenko O. M.
Published: March 2016

Наведено результати лікування 134 дітей віком від
3 міс. до 5 років з діагнозом ротавірусної інфекції. Дослі-
джено ефективність використання схеми терапії ро-
тавірусної інфекції у дітей з комбінації Saccharomyces
boulardii та суміші NAN безлактозний на основі аналізу
клінічної симптоматики та лабораторних показників.
Встановлено, що використання такого поєднання
сприяє зменшенню тривалості основних клінічних
проявів рота-вірусної інфекції (РВІ) та прискорює елі-
мінацію вірусу з кишечнику.
Ключові слова: ротавірусна інфекція, безлактозне
харчування, діти.
ЛАЙМ-БОРЕЛІО З У ПРАЦІВНИКІВ ЛІСОВИХ ГОСПОДАРСТВ ТЕРНОПІЛЬСЬКОЇ ОБЛАСТІ
Authors: Shkilna M. I.
Published: March 2016

339 працівників лісових господарств Тернопільської
області дали відповіді на питання уніфікованої міжна-
родної анкети-опитувальника. Вивчено поширеність
інфікування бореліями даного контингенту населення.
Проведено аналіз результатів серологічного дослі-
дження залежно від професійної діяльності обстеже-
них. Антитіла хоча б одного класу IgM і/чи IgG до B.
burgdorferi sensu lato (B. burgdorferi sensu stricto, B. afzeliі
та B. garinii) (позитивні або проміжні результати) ви-
явлено у 43,1 % працюючих.
Ключові слова: Хвороба Лайма, Borrelia burgdorferi,
діагностика, анкетування, працівники лісових госпо-
дарств Тернопільської області
ЧИ ВІДПОВІДАЄ КЛІНІЧНА РЕМІСІЯ РЕЦИДИВНОГО ОБСТРУКТИВНОГО БРОНХІТУ ВІДСУТНОСТІ ІМУНОЛОГІЧНИХ ЗМІН У РЕСПІРАТОРНОМУ ТРАКТІ ДІТЕЙ?
Authors: Yukhymenko O. O.
Published: March 2016

Проведено дослідження ролі вмісту інтерлейкінів
(ІЛ)-4, -6, -8, -10 в слині у пацієнтів з рецидивним об-
структивним бронхітом (РОБ) під час ремісії і здорових
дітей. Встановлено, що за відсутності клінічних про-
явів РОБ у цих дітей тривають імунопатологичні про-
цеси. Показано, що за даними анамнезу, особливостями
клінічних проявів і результатами визначення ІЛ-4, -6,
-8, -10 в слині в групі дітей з РОБ можна розмежувати
дві підгрупи: пацієнтів з інфекційно-асоційованим РОБ
і захворюванням, що має алергічний генез. Для дітей з
алергічним генезом хвороби характерним є обтяжений
алергологічний анамнез у сім’ї, атопічний дерматит
на першому році життя, розвиток загострення після
контакту з тваринами або переважно під час цвітіння
рослин, відсутність вираженої температурної реакції
під час розвитку бронхообструктивного синдрому в по-
єднанні з істотно підвищеним вмістом ІЛ-4 в слині. Для
пацієнтів з інфекційно-асоційованим РОБ характерна
відсутність алергічних захворювань у батьків та інших
членів сім’ї, сезонність загострень з листопада по
квітень, розвиток загострень бронхообструктивного
синдрому в поєднанні з фебрильною температурою
тіла і катаральними явищами, а також підвищенням
вмісту в слині рівнів ІЛ-6, -8 і зниженням вмісту ІЛ-10.
Зазначені особливості можуть враховуватися при
оцінці прогнозу перебігу захворювання та визначенні
підходів до диференційованої терапії.
Ключові слова: діти, респіраторні інфекції, реци-
дивний обструктивний бронхіт.
ПЕРИПЕТІЇ ДІАГНОСТИКИ БАРТОНЕЛЬОЗУ
Authors: Kopcha V. S. , Kadubets O. Ya.
Published: March 2016

Описано випадки типового перебігу хвороби котя-
чої подряпини, а також поєднання фелінозу та Лайм-
бореліозу. Диференціювання з іншими органічними при-
чинами та відповідні лабораторні аналізи дали змогу
встановити діагноз й провести успішне лікування.
Ключові слова: бартонельоз, Лайм-бореліоз, лабо-
раторна діагностика.