bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary Game Theory‐Based Collaborative Sensing Model in Emergency CRAHNs
Authors: GVK Sasirekha , Bapat Jyotsna
Published: November 2012

Game theory has been a tool of choice for modeling dynamic interactions between autonomous systems. Cognitive radio ad hoc networks (CRAHNs) constituted of autonomous wireless nodes are a natural fit for game theory‐based modeling. The game theory‐based model is particularly suitable for “collaborative spectrum sensing” where each cognitive radio senses the spectrum and shares the results with other nodes such that the targeted sensing accuracy is achieved. Spectrum sensing in CRAHNs, especially when used in emergency scenarios such as disaster management and military applications, needs to be not only accurate and resource efficient, but also adaptive to the changing number of users as well as signal‐to‐noise ratios. In addition, spectrum sensing mechanism must also be proactive, fair, and tolerant to security attacks. Existing work in collaborative spectrum sensing has mostly been confined to resource efficiency in static systems using request‐based reactive sensing resulting in high latencies. In this paper, evolutionary game theory (EGT) is used to model the behavior of the emergency CRAHNS, providing an efficient model for collaborative spectrum sensing. The resulting implementation model is adaptive to the changes in its environment such as signal‐to‐noise ratio and number of users in the network. The analytical and simulation models presented validate the system design and the desired performance.
Agent‐Based Modeling and Genetic Algorithm Simulation for the Climate Game Problem
Authors: Wang Zheng , Zhang Jingling
Published: November 2012

The cooperative game of global temperature lacks automaticity and emotional jamming. To solve this issue, an agent‐based modelling method is developed based on Milinski’s noncooperative game experiments. In addition, genetic algorithm is used to improve the investment strategy of each agent. Simulations are carried out by designing different coding schemes, mutation schemes, and fitness functions. It is demonstrated that the method can achieve maximum benefits under the premise of the agent non‐cooperative game through encouraging optimal individuals. The results provide a sound basis for developing tools and methods to support the simulation of climate game strategy that involves multiple stakeholders.
Limit Cycle Bifurcations from a Nilpotent Focus or Center of Planar Systems
Authors: Han Maoan , Romanovski Valery G.
Published: November 2012

We study analytic properties of the Poincaré return map and generalized focal values of analytic planar systems with a nilpotent focus or center. We use the focal values and the map to study the number of limit cycles of this kind of systems and obtain some new results on the lower and upper bounds of the maximal number of limit cycles bifurcating from the nilpotent focus or center. The main results generalize the classical Hopf bifurcation theory and establish the new bifurcation theory for the nilpotent case.
Improvement of Depression after Treatment of Dural Arteriovenous Fistula: A Case Report and a Review
Authors: Nakagawa Minoru , Sugiu Kenji , Tokunaga Koji , Sakamoto Chihoko , Fujiwara Kenjiro
Published: November 2012

Patients with dural arteriovenous fistulas (DAVFs) in the transverse-sigmoid sinus suffer from several symptoms: bruit, headache, visual impairment, and so on. But depression is rare in patients with DAVF. The authors reported a rare case presenting the improvement of depression after the treatment of a dural arteriovenous fistula in the left transverse-sigmoid sinus. A 46-year-old male had suffered from depression and was treated with antidepressants at a local hospital for four years. The patient was temporarily laid off due to his depression. Afterwards, he had Gerstmann's syndrome and came to our hospital. A DAVF in the left transverse-sigmoid sinus was demonstrated on the angiogram. The DAVF was successfully treated with endovascular surgery, coil embolization of the isolated diseased sinus through the mastoid emissary vein which was a draining vein from the fistula. After this treatment, his depression as well as Gerstmann's syndrome was improved and the quantity of the antidepressants decreased. The patient returned to work without any antidepressant two years after the treatment. DAVFs might be one of the causes of depression. It may be necessary to evaluate cerebral vessels in patients suffering from depression by using MRA or 3D-CTA even if there are not any abnormal findings on plain CT scans.
Factors Affecting Medical Students’ Uptake of the 2009 Pandemic Influenza A (H1N1) Vaccine
Authors: Lee Siang I. , Aung Ei M. , Chin Ik S. , Hing Jeremy W. , Mummadi Sanghamitra , Palaniandy Ghunavadee D. , Jordan Rachel
Published: November 2012

Background. Pandemic influenza vaccination rate amongst healthcare workers in England 2009/2010 was suboptimal (40.3%). Targeting medical students before they enter the healthcare workforce is an attractive future option. This study assessed the H1N1 vaccine uptake rate amongst medical students and factors that influenced this. Methods. Anonymised, self-administered questionnaire at a medical school. Results. The uptake rate amongst 126 medical students offered the vaccine was 49.2% and intended uptake amongst 77 students was 63.6%. Amongst those offered the vaccine, the strongest barriers to acceptance were fear of side effects (67.9%), lack of vaccine information (50.9%), lack of perceived risk (45.3%), and inconvenience (35.8%). Having a chronic illness (OR 3.4 (95% CI 1.2–10.2)), 4th/5th year of study (OR 3.0 (95% CI 1.3–7.1)), and correct H1N1 knowledge (OR 2.6 (95% CI 1.1–6.0)) were positively associated with uptake. Non-white ethnicity was an independent negative predictor of uptake (OR 0.4 (95% CI 0.2–0.8)). Students who accepted the H1N1 vaccine were three times more likely (OR 3.1 (95% CI 1.2–7.7)) to accept future seasonal influenza vaccination. Conclusion. Efforts to increase uptake should focus on routine introduction of influenza vaccine and creating a culture of uptake during medical school years, evidence-based education on vaccination, and improving vaccine delivery.
Developmental Programming of Hypertension and Kidney Disease
Authors: Chong Euming , Yosypiv Ihor V.
Published: November 2012

A growing body of evidence supports the concept that changes in the intrauterine milieu during “sensitive” periods of embryonic development or in infant diet after birth affect the developing individual, resulting in general health alterations later in life. This phenomenon is referred to as “developmental programming” or “developmental origins of health and disease.” The risk of developing late-onset diseases such as hypertension, chronic kidney disease (CKD), obesity or type 2 diabetes is increased in infants born prematurely at <37 weeks of gestation or in low birth weight (LBW) infants weighing <2,500 g at birth. Both genetic and environmental events contribute to the programming of subsequent risks of CKD and hypertension in premature or LBW individuals. A number of observations suggest that susceptibility to subsequent CKD and hypertension in premature or LBW infants is mediated, at least in part, by reduced nephron endowment. The major factors influencingin uteroenvironment that are associated with a low final nephron number include uteroplacental insufficiency, maternal low-protein diet, hyperglycemia, vitamin A deficiency, exposure to or interruption of endogenous glucocorticoids, and ethanol exposure. This paper discusses the effect of premature birth, LBW, intrauterine milieu, and infant feeding on the development of hypertension and renal disease in later life as well as examines the role of the kidney in developmental programming of hypertension and CKD.
Fractional Order Difference Equations
Authors: Mohan J. Jagan , Deekshitulu G. V. S. R.
Published: November 2012

A difference equation is a relation between the differences of a function at one or more general values of the independent variable. These equations usually describe the evolution of certain phenomena over the course of time. The present paper deals with the existence and uniqueness of solutions of fractional difference equations.
Existence of Multiple Solutions for a Singular Elliptic Problem with Critical Sobolev Exponent
Authors: Xiu Zonghu
Published: November 2012

We consider the existence of multiple solutions of the singular elliptic problem , u(x) → 0 as |x| → +∞, where x ∈ ℝN, 1 < p < N, a < (N − p)/p, a ≤ b ≤ a + 1, r, s > 1, p* = Np/(N − pd), d = a + 1 − b. By the variational method and the theory of genus, we prove that the above‐mentioned problem has infinitely many solutions when some conditions are satisfied.
Atypical Vascular Involvement in a Case of Behçet's Disease
Authors: Rodríguez Morata Alejandro , Hidalgo Conde Ana , de la Cruz Cosme Carlos , Gómez Ramírez Susana , Gómez Medialdea Rafael
Published: November 2012

Introduction. Behçet's disease (BD) is a form of vasculitis of unknown etiology which is rare in our environment. It is characterized by a variety of clinical manifestations and usually affects young adults. Recurrent oral and genital ulcers are a characteristic and extremely frequent symptom, but mortality is linked with more significant symptoms such as aortic pseudoaneurysm, pulmonary pseudoaneurysm, and cerebral venous thrombosis.Patient and Method. We present a case of a young male with atypical BD and severe polyvascular involvement (previous cerebral venous thrombosis and current peripheral venous thrombosis, acute ischemia, and peripheral arterial pseudoaneurysm) who required urgent surgical intervention due to a symptomatic external iliac pseudoaneurysm.Result. The pseudoaneurysm was successfully treated, we performed an iliofemoral bypass, and we treated it with steroids and immunosuppressive therapy.Conclusions. These rare clinical manifestations highlight the importance of considering BD in young patients, even in usual cases of vascular intervention, whether arterial or venous in nature.
Research on Analysis Method of Traffic Congestion Mechanism Based on Improved Cell Transmission Model
Authors: Dong Hongzhao , Ma Shuai , Guo Mingfei , Liu Dongxu
Published: November 2012

To analyze the spreading regularity of the initial traffic congestion, the improved cell transmission model (CTM) is proposed to describe the evolution mechanism of traffic congestion in regional road grid. Ordinary cells and oriented cells are applied to render the crowd roads and their adjacent roads. Therefore the traffic flow could be simulated by these cells. Resorting to the proposed model, the duration of the initial traffic congestion could be predicted and the subsequent secondary congestion could be located. Accordingly, the spatial diffusion of traffic congestion could be estimated. At last, taking a road network region of Hangzhou city as an example, the simulation experiment is implemented to verify the proposed method by PARAMICS software. The result shows that the method could predict the duration of the initial congestion and estimate its spatial diffusion accurately.
A Rare Cause of Secondary Amyloidosis: Common Variable Immunodeficiency Disease
Authors: Kadiroğlu Ali Kemal , Yıldırım Yaşar , Yılmaz Zülfükar , Kayabaşı Hasan , Avcı Yahya , Yıldırım M. Serdar , Yılmaz M. Emin
Published: November 2012

The common variable immunodeficiency disease (CVID) is the most common symptomatic primary antibody deficiency. It is the most frequently observed cause of panhypogammaglobulinemia in adults. Here, we present a case of systemic amyloidosis that developed secondary to the common variable immunodeficiency disease causing recurrent infections in a young female patient. A 24-year-old female patient, who was under treatment at the gynecology and obstetrics clinic for pelvic inflammatory disease, was referred to our clinic when she was observed to have swellings in her legs, hands, and face. She had proteinuria at a rate of 3.5 gr/day, and her serum albumin was 1.5 gr/dl. The levels of immunoglobulins are IgG: 138 mg/dl, IgA: 22,6 mg/dl, and IgM: 16,8 mg/dl. The renal USG revealed that the kidneys were observed to be enlarged. Since the patient had recurrent infections, hypogammaglobulinemia, nephrotic range proteinuria, and enlarged kidneys in the renal USG, she was thought to have type AA amyloidosis and therefore underwent a renal biopsy. The kidney biopsy revealed amyloid (+). So the patient was diagnosed with AA type of amyloidosis secondary to common variable immunodeficiency disease. A treatment regimen (an ACE inhibitor and a statin) with monthly administration of intravenous immunoglobulin was started.
A Review of Complementary and Alternative Treatments for Autism Spectrum Disorders
Authors: Lofthouse Nicholas , Hendren Robert , Hurt Elizabeth , Arnold L. Eugene , Butter Eric
Published: November 2012

Given the severe and chronic problems associated with Autism Spectrum Disorders (ASD) and the limitations of available treatments, there exists a large public health need for additional interventions. As more parents are inquiring about complementary and alternative treatments (CATs), both parents and practitioners require up-to-date information about them and whether and how to integrate them into treatment. After presenting data on CAT usage patterns for ASD, we review 13 ingestible (i.e., orally administered) and 6 noningestible (i.e., externally administered) CATs for ASD. For each CAT we briefly describe its definition; rationale for use; current research support, limitations, and future directions; safety issues; and whether we currently recommend, not recommend, or find it acceptable for the treatment of ASD. We conclude this paper with recommendations for future research and ten clinical recommendations for practitioners.
Social Determinants of Stroke as Related to Stress at Work among Working Women: A Literature Review
Authors: Toivanen Susanna
Published: November 2012

In adult life, many of the social determinants of health are connected to working life. Yet, our knowledge of the role of work-related factors for the risk of stroke is fairly limited. In contemporary occupational health research, the Demand-Control Model (DCM) is frequently used to measure work stress. Previous literature reviews of the association of work stress and cardiovascular disease (CVD) do not include stroke as a specific outcome. Results regarding work stress and the risk of CVD are less evident in working women. With the focus on working women, the purpose of the present paper was to review the current research into the DCM in relation to stroke and to scrutinize potential gender differences. A literature search was performed and eight studies from three countries were identified. Based on the reviewed studies, there is some evidence that high psychological demands, low job control, and job strain are associated with increased stroke risk in women as well as in men. Any major reduction in deaths and disability from stroke is likely to come from decreasing social inequalities in health, and reducing work stress has a potential to contribute to a reduced risk of stroke in working populations.
Prescription of Chinese Herbal Medicine and Selection of Acupoints in Pattern-Based Traditional Chinese Medicine Treatment for Insomnia: A Systematic Review
Authors: Yeung Wing-Fai , Chung Ka-Fai , Poon Maggie Man-Ki , Ho Fiona Yan-Yee , Zhang Shi-Ping , Zhang Zhang-Jin , Ziea Eric Tat-Chi , Wong Taam Vivian
Published: November 2012

Traditional Chinese medicine (TCM) treatments are often prescribed based on individuals' pattern diagnoses. A systematic review of Chinese and English literatures on TCM pattern differentiation, treatment principle, and pattern-based treatment for insomnia has therefore been conducted. A total of 227 studies, 17916 subjects, and 87 TCM patterns were analyzed. There was a limited consistency in pattern-based TCM treatment of insomnia across practitioners. Except for Gui Pi Tang, An Shen Ding Zhi Wan, and Wen Dan Tang which were used more commonly fordeficiency of both the heart and spleen,internal disturbance of phlegm-heat, andqi deficiency of the heart and gallbladder, respectively, the selection of herbal formula for other patterns and pattern-based prescription of individual herbs and acupoints were not consistent. Suanzaoren (Semen Z. spinosae), Fuling (Poria), Yejiaoteng (Caulis P. multiflori), Gancao (Radix Glycyrrhizae), Baishao (Radix P. alba), Shenmen (HT7), Yintang (EX-HN3), Sanyinjiao (SP6), Baihui (GV20), Anmian (EX-HN22), and Sishencong (EX-HN1) were commonly used, but nonspecifically for many patterns. Treatment principles underlying herb and acupoint selection were seldom reported. Although many studies were reviewed, the study quality and diagnostic process were inadequate. More high quality studies are needed to examine the additional benefits of pattern differentiation and pattern-based TCM treatment.
Mobile Base Station and Clustering to Maximize Network Lifetime in Wireless Sensor Networks
Authors: Jerew Oday , Blackmore Kim , Liang Weifa
Published: November 2012

Using a mobile base station (BS) in a wireless sensor network can alleviate nonuniform energy consumption among sensor nodes and accommodate partitioned networks. In the work of Jerew and Liang (2009) we have proposed a novel clustering‐based heuristic algorithm for finding a trajectory of the mobile BS that strikes a nontrivial tradeoff between the traffic load among sensor nodes and the tour time constraint of the mobile BS. In this paper, we first show how to choose the number of clusters to ensure there is no packet loss as the BS moves between clusters. We then provide an analytical solution to the problem in terms of the speed of the mobile BS. We also provide analytical estimates of the unavoidable packet loss as the network size increases. We finally conduct experiments by simulation to evaluate the performance of the proposed algorithm. The results show that the use of clustering in conjunction with a mobile BS for data gathering can significantly prolong network lifetime and balance energy consumption of sensor nodes.
Resveratrol Produces Neurotrophic Effects on Cultured Dopaminergic Neurons through Prompting Astroglial BDNF and GDNF Release
Authors: Zhang Feng , Wang Yan-Ying , Liu Hang , Lu Yuan-Fu , Wu Qin , Liu Jie , Shi Jing-Shan
Published: November 2012

Increasing evidence indicated astroglia-derived neurotrophic factors generation might hold a promising therapy for Parkinson’s disease (PD). Resveratrol, naturally present in red wine and grapes with potential benefit for health, is well known to possess a number of pharmacological activities. Besides the antineuroinflammatory properties, we hypothesized the neuroprotective potency of resveratrol is partially due to its additional neurotrophic effects. Here, primary rat midbrain neuron-glia cultures were applied to investigate the neurotrophic effects mediated by resveratrol on dopamine (DA) neurons and further explore the role of neurotrophic factors in its actions. Results showed resveratrol produced neurotrophic effects on cultured DA neurons. Additionally, astroglia-derived neurotrophic factors release was responsible for resveratrol-mediated neurotrophic properties as evidenced by the following observations: (1) resveratrol failed to exert neurotrophic effects on DA neurons in the cultures without astroglia; (2) the astroglia-conditioned medium prepared from astroglia-enriched cultures treated with resveratrol produced neurotrophic effects in neuron-enriched cultures; (3) resveratrol increased neurotrophic factors release in the concentration- and time-dependent manners; (4) resveratrol-mediated neurotrophic effects were suppressed by blocking the action of the neurotrophic factors. Together, resveratrol could produce neurotrophic effects on DA neurons through prompting neurotrophic factors release, and these effects might open new alternative avenues for neurotrophic factor-based therapy targeting PD.
Compound Optical Film Using Gray Scale Mask Embedded with Microvoids
Authors: Pan C. T. , Chen Y. C. , Chen Y. J. , Wang W. C. , Yang H. C. , Wu H. C.
Published: November 2012

This study presents a compound optical film to improve luminance and uniformity to apply in side-LED (light-emitting diode) backlight module. LIGA (lithographie galvanoformung abformung) technology, soft lithography, and homemade gray scale mask were combined to fabricate microlens array. Optical film with variable size microlens array embedded with microvoids was designed and manufactured. FRED software was used to simulate optical performance. Microvoids were quantitatively embedded in the PDMS (polydimethylsiloxane) optical film. Under the quantitative control of air pressure, those microvoids inside the optical film can cause light diffusion. The compound optical film with embedded microvoids, multiaspect ratio, and variable size microlens array can be fabricated quickly without substrate. Luminance colorimeter BM-7A from TOPCON was used to carry out the optical measurement. According to the measured data, the compound optical film with embedded microvoids can enhance the luminance up to 5% and the uniformity up to 6.5%  ~  8.4%. The optical efficiency can be improved via the compound optical film.
Structures and Spectroscopy Studies of Two M(II)-Phosphonate Coordination Polymers Based on Alkaline Earth Metals (M = Ba, Mg)
Authors: Ma Kui-Rong , Wei Chun-Li , Zhang Yu , Kan Yu-He , Cong Ming-Hui , Yang Xiao-Jing
Published: November 2012

The two examples of alkaline-earth M(II)-phosphonate coordination polymers, [Ba2(L)(H2O)9]·3H2O (1) and [Mg1.5(H2O)9]·(L-H2)1.5·6H2O (2) (H4L = H2O3PCH2N(C4H8)NCH2PO3H2),N,N′-piperazinebis(methylenephosphonic acid), (L-H2= O3PH2CHN(C4H8)NHCH2PO3) have been hydrothermally synthesized and characterized by elemental analysis, FT-IR, PXRD, TG-DSC, and single-crystal X-ray diffraction. Compound1possesses a 2D inorganic-organic alternate arrangement layer structure built from 1D inorganic chains through the piperazine bridge, in which the ligand L−4shows two types of coordination modes reported rarely at the same time. In1, both crystallographic distinct Ba(1) and Ba(2) ions adopt 8-coordination two caps and 9-coordination three caps triangular prism geometry structures, respectively. Compound2possesses a zero-dimensional mononuclear structure with two crystallographic distinct Mg(II) ions. Free metal cations  [MgO6]n2+and uncoordinated anions(L-H2)n2-are joined together by static electric force. Results of photoluminescent measurement indicate three main emission bands centered at 300 nm, 378.5 nm, and 433 nm for1and 302 nm, 378 nm, and 434.5 nm for2(λex=235 nm), respectively. The high energy emissions could be derived from the intraligandπ∗-ntransition stations ofH4L(310 nm and 382 nm,λex=235 nm), while the low energy emission (>400 nm) of1-2may be due to the coordination effect with metal(II) ions.
The MFN2 V705I Variant Is Not a Disease-Causing Mutation: A Segregation Analysis in a CMT2 Family
Authors: Albulym Obaid M. , Zhu Danqing , Reddel Stephen , Kennerson Marina , Nicholson Garth
Published: November 2012

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of disorders affecting both motor and sensory neurons in the peripheral nervous system. Mutations in the MFN2 gene cause an axonal form of CMT, CMT2A. The V705I variant in MFN2 has been previously reported as a disease-causing mutation in families with CMT2. We identified an affected index patient from an Australian multigenerational family with the V705I variant. Segregation analysis showed that the V705I variant did not segregate with the disease phenotype and was present in control individuals with an allele frequency of 4.4%. We, therefore, propose that the V705I variant is a polymorphism and not a disease-causing mutation as previously reported.
Male Adolescent Substance Use Disorder and Attention-Deficit Hyperactivity Disorder: A Review of the Literature
Authors: Eme Robert
Published: November 2012

Approximately, one-third of male adolescents in treatment for a substance use disorder (SUD) also have an Attention-Deficit Hyperactivity Disorder (ADHD). This strongly suggests that ADHD is a major risk factor for the development of SUD which practitioners must address if they are to provide adequate treatment for adolescents with SUD/ADHD. This paper supports a causal role for ADHD in the development of SUD and examines the developmental mechanisms whereby ADHD increases risk for SUD. These mechanisms include increased risk for conduct disorder, academic failure, deviant peer affiliation, engaging in risk behaviors, and self-medication. Assessment and treatment recommendations for those comorbid for SUD/ADHD are provided.
Spectroscopic Characterization of Poly(ortho-Aminophenol) Film Electrodes: A Review Article
Authors: Tucceri Ricardo , Arnal Pablo Maximiliano , Scian Alberto Néstor
Published: November 2012

This paper refers to spectroscopic studies carried out to identify the products ofo-aminophenol electro-oxidation and elucidate the structure of electrochemically synthesized poly(o-aminophenol) (POAP) films. Spectroscopic studies of the redox conversion of POAP are also reviewed.
Pharmacological Inhibition of the Wnt Acyltransferase PORCN Prevents Growth of WNT-Driven Mammary Cancer
Authors: Proffitt Kyle David , Madan Babita , Ke Zhiyuan , Pendharkar Vishal , Ding Lijun , Lee May Ann , Hannoush Rami N. , Virshup David M.
Published: November 2012

Porcupine (PORCN) is a membrane bound O-acyltransferase that is required for Wnt palmitoylation, secretion, and biologic activity. All evaluable human Wnts require PORCN for their activity, suggesting that inhibition of PORCN could be an effective treatment for cancers dependent on excess Wnt activity. In this study, we evaluated the PORCN inhibitor Wnt-C59 (C59), to determine its activity and toxicity in cultured cells and mice. C59 inhibits PORCN activity in vitro at nanomolar concentrations, as assessed by inhibition of Wnt palmitoylation, Wnt interaction with the carrier protein Wntless/WLS, Wnt secretion, and Wnt activation of β-catenin reporter activity. In mice, C59 displayed good bioavailability, as once daily oral administration was sufficient to maintain blood concentrations well above the IC50. C59 blocked progression of mammary tumors in MMTV-WNT1 transgenic mice while downregulating Wnt/β-catenin target genes. Surprisingly, mice exhibit no apparent toxicity, such that at a therapeutically effective dose there were no pathologic changes in the gut or other tissues. These results offer preclinical proof-of-concept that inhibiting mammalian Wnts can be achieved by targeting PORCN with small-molecule inhibitors such as C59, and that this is a safe and feasible strategy in vivo. Cancer Res; 73(2); 502–7. ©2012 AACR.
CD103 or LFA-1 Engagement at the Immune Synapse between Cytotoxic T Cells and Tumor Cells Promotes Maturation and Regulates T-cell Effector Functions
Authors: Franciszkiewicz Katarzyna , Le Floc'h Audrey , Boutet Marie , Vergnon Isabelle , Schmitt Alain , Mami-Chouaib Fathia
Published: November 2012

T-cell adhesion/costimulatory molecules and their cognate receptors on target cells play a major role in T-cell receptor (TCR)–mediated activities. Here, we compared the involvement of CD103 and LFA-1, and their respective ligands, in the maturation of the cytotoxic immune synapse (cIS) and in the activation of CTL effector functions. Our results indicate that cytotoxicity toward cancer cells and, to a lesser extent, cytokine production by specific CTL require, together with TCR engagement, the interaction of either CD103 with E-cadherin or LFA-1 with ICAM-1. Flow-based adhesion assay showed that engagement of CD103 or LFA-1, together with TCR, enhances the strength of the T-cell/target cell interaction. Moreover, electron microscopic analyses showed that integrin-dependent mature cIS (mcIS) displays a cohesive ultrastructure, with tight membrane contacts separated by extensive clefts. In contrast, immature cIS (icIS), which is unable to trigger target cell lysis, is loose, with multiple protrusions in the effector cell membrane. Experiments using confocal microscopy revealed polarized cytokine release and degranulation at the mcIS associated with target cell killing, whereas icIS is characterized by failure of IFN-γ and granzyme B relocalization. Thus, interactive forces between CTL and epithelial tumor cells, mainly regulated by integrin engagement, correlate with maturity and the ultrastructure of the cIS and influence CTL effector functions. These results provide new insights into molecular mechanisms regulating antitumor CTL responses and may lead to the development of more efficient cancer immunotherapy strategies. Cancer Res; 73(2); 617–28. ©2012 AACR.
Molecular Markers in Key Steroidogenic Pathways, Circulating Steroid Levels, and Prostate Cancer Progression
Authors: Lévesque Éric , Huang Shu-Pin , Audet-Walsh Étienne , Lacombe Louis , Bao Bo-Ying , Fradet Yves , Laverdière Isabelle , Rouleau Mélanie , Huang Chao-Yuan , Yu Chia-Cheng , Caron Patrick , Guillemette Chantal
Published: November 2012

Purpose: Prostate cancer is a heterogeneous genetic disease, and molecular methods for predicting prognosis in patients with aggressive form of the disease are urgently needed to better personalize treatment approaches. The objective was to identify host genetic variations in candidate steroidogenic genes affecting hormone levels and prostate cancer progression.

Experimental Design: The study examined two independent cohorts composed of 526 Caucasian men with organ-confined prostate cancer and 601 Taiwanese men on androgen–deprivation therapy. Caucasians were genotyped for 109 haplotype-tagging single-nucleotide polymorphisms (SNP) in CYP17A1, ESR1, CYP19A1, and HSD3B1, and their prognostic significance on disease progression was assessed using Kaplan–Meier survival curves and Cox regression models. Positive findings, including previously identified SRD5A1, SRD5A2, HSD17B2, HSD17B3, and HSD17B12 polymorphisms, were then explored in Taiwanese men (n = 32 SNPs). The influence of positive markers on the circulating hormonal levels was then appraised in Caucasians using specific and sensitive mass spectrometry–based methods.

Results: After adjusting for known risk factors, variants of CYP17A1 (rs6162), HSD17B2 (rs4243229 and rs7201637), and ESR1 (rs1062577) were associated with progressive disease in both cohorts. Indeed, the presence of these variations was significantly associated with progression in Caucasians (HR, 2.29–4.10; P = 0.0014–2 × 10−7) and survival in Taiwanese patients [HR = 3.74; 95% confidence interval (CI): 1.71–8.19, P = 0.009]. Remarkably, the CYP17A1 rs6162 polymorphism was linked to plasma dehydroepiandrosterone-sulfate (DHEA-S) levels (P = 0.03), HSD17B2 rs7201637 with levels of dihydrotestosterone (P = 0.03), and ESR1 rs1062577 with levels of estrone-S and androsterone-glucuronide (P ≤ 0.05).

Conclusion: This study identifies, in different ethnic groups and at different disease stages, CYP17A1, HSD17B2, and ESR1 as attractive prognostic molecular markers of prostate cancer progression. Clin Cancer Res; 19(3); 699–709. ©2012 AACR.
Acute Megakaryoblastic Leukemia in a Patient with Xeroderma Pigmentosum: Discussion of Pathophysiological, Prognostic, and Toxicological Aspects
Authors: Janjetovic Snjezana , Bacher Ulrike , Haalck Thomas , Janning Melanie , Bokemeyer Carsten , Fiedler Walter
Published: November 2012

Background: Xeroderma pigmentosum (XP) is an autosomal recessive inherited disease characterized by extreme sensitivity to sunlight. Normal individuals harboring XPD polymorphisms are at increased risk for developing acute lymphoblastic leukemia and acute myeloid leukemia (AML). Case Report: A 33-year-old male XP patient was diagnosed with acute megakaryoblastic leukemia with a complex karyotype. He received standard induction chemotherapy with cytarabine and daunorubicin. After the first cycle of chemotherapy, persistence of blasts was seen and a re-induction cycle with cytarabine, fludarabine, and idarubicin was administered resulting in complete remission. Due to the high-risk profile of his AML, allogeneic stem cell transplantation (SCT) was performed. Following a conditioning regimen with busulfan and cyclophosphamide, the patient received a matched related SCT from his HLA-identical sister. Despite the existence of his DNA repair gene mutation, chemotherapy was normally tolerated by the patient. Unfortunately, he died due to severe sepsis and relapse of AML 45 days after SCT. Conclusion: The XPD mutation in our patient may have contributed to the emergence of his high-risk AML. Despite the existence of a DNA repair gene mutation, our XP patient could be treated with full doses of AML-type chemotherapy including allogeneic SCT without encountering unusual toxicity.
Complete Clearance of Ph+ Metaphases after 3 Months Is a Very Early Indicator of Good Response to Imatinib as Front-Line Treatment in Chronic Myelogenous Leukemia
Authors: Latagliata Roberto , Isidori Alessandro , Breccia Massimo , Carmosino Ida , Vozella Federico , Volpicelli Paola , Finsinger Paola , Barulli Sara , Loglisci Giuseppina , Santopietro Michelina , Federico Vincenzo , Diverio Daniela , Nanni Mauro , Mancini Marco , Visani Giuseppe , Alimena Giuliana
Published: November 2012

Aim: To address the incidence and the prognostic role of a very early standard complete cytogenetic response (CCyR) or all Ph– metaphases (MET–, when <20 cells were evaluable). Methods: We revised 182 chronic phase chronic myelogenous leukemia patients treated with frontline imatinib (IM) at two institutions from June 2002 to June 2011. Results: After 3 months of treatment, 138 patients (75.8%) achieved CCyR/MET– while 44 patients (24.2%) still presented Ph+ metaphases (MET+) (<33%, 24 patients; ≥33%, 20 patients). On univariate analysis, palpable spleen enlargement (p < 0.001), WBC count >100.0 × 109/l at onset (p < 0.001), and male gender (p = 0.019) had a negative impact on achievement of CCyR/MET– at 3 months. Among patients with CCyR/MET– after 3 months, there were 15 failures (10.8%) compared to 21 (47.7%) among patients with MET+ (p < 0.001). The 5-year overall survival was 97.0% in patients CCyR/MET– at 3 months and 91.8% in patients MET+ at 3 months (p = 0.277); the 5-year progression-free survival was 88.2% in patients CCyR/MET– at 3 months and 48.4% in patients MET+ at 3 months (p < 0.001). Conclusions: The achievement of CCyR/MET– at 3 months seems to have prognostic relevance and could be a very early and useful indicator of an excellent response to IM beyond European LeukemiaNet guidelines.
Prognostic Significance of Bcl-2, Tumor-Associated Macrophages, and Total Neoplastic and Inflammatory Lymph Node Involvement in Advanced Stage Classical Hodgkin’s Lymphoma
Authors: Jakovic Ljubomir R. , Mihaljevic Biljana S. , Jovanovic Maja D. Perunicic , Bogdanovic Andrija D. , Andjelic Bosko M. , Bumbasirevic Vladimir Z.
Published: November 2012

Background: Although Hodgkin’s lymphoma (HL) is a curable cancer, current treatment strategies based on risk stratification and response modulation are not precise enough. The predictive power of biological and morphological parameters is controversial, with prognostic models not reaching wide acceptance. Patients and Methods: We analyzed the prognostic relevance of 8 parameters in 85 advancedstage classical HL patients, in order to determine whether tissue-based variables could add prognostic value to standard clinical parameters, thus contributing to better risk stratification at presentation. Results: Univariate analysis confirmed 5 indicators of shorter overall survival (OS): Bcl-2 overexpression; increased CD68+ tumor-associated macrophages (TAM); international prognostic score (IPS) > 2; bulky disease; and total lymph node involvement (TLNI) with regard to neoplastic and inflammatory cells. Apart from TLNI, these parameters influenced lower event-free survival (EFS). Multivariate analysis identified 5 independent factors for OS: Bcl-2 overexpression; increased CD68+ TAM; TLNI; IPS > 2; and bulky disease. Increased CD68+ TAM, IPS > 2, and bulky disease affected the EFS. Utilizing the cumulative score of unfavorable prognostic factors for OS, we designed a prognostic model stratifying patients into 4 risk groups (with 0–1, 2, 3, or 4–5 factors), each with progressively reduced OS (p < 0.001). Conclusion: Our findings support the combination of tissue-based variables with clinical parameters at diagnosis, identifying patients who are at higher risk of poor outcome.
Partial Removal of Carious Dentine: A Multicenter Randomized Controlled Trial and 18-Month Follow-Up Results
Authors: Maltz M. , Jardim J.J. , Mestrinho H.D. , Yamaguti P.M. , Podestá K. , Moura M.S. , de Paula L.M.
Published: November 2012

Aim: The aim of this study was to evaluate the effectiveness of partial removal of carious dentine and restoration in a single session (PDR) and stepwise excavation (SW), both of which are treatments for deep carious lesions, in Public Health Services in Brazil. Methods: Inclusion criteria: patients ≥6 years old, permanent molars with deep caries lesions (having a radiolucency halfway or more into dentine) and pulp vitality but absence of spontaneous pain, positive percussion test, and periapical alterations. The subjects received either PDR (test group) or SW (control group). The radiological and clinical exams were performed after a mean time of 18 months. Outcomes: success was defined as pulp sensitivity to cold test and absence of periapical alterations. Results: Of the 299 treatments performed, 146 were SW and 153 were PDR; 122 were amalgam restorations and 168 resin-composite restorations. There were no differences between the groups regarding the baseline characteristics (i.e. age, gender and family income). After 18 months, 212 evaluations were performed, which indicated 99 and 86% success rates in the PDR and SW groups, respectively (p = 0.016). Reasons for failure were: PDR – 1 pulpitis; SW – 8 pulpitis; 1 osteitis; 4 necrosis; 1 endodontic treatment. None of the baseline variables were significantly associated with the outcomes. Conclusion: The retention of carious dentine does not interfere in pulp vitality. Data from this 18-month study suggest that the procedure of reopening the cavity to remove the residual infected dentine is not necessary.
Divalent Cations Enhance Fluoride Binding to Streptococcus mutans and Streptococcus sanguinis Cells and Subsequently Inhibit Bacterial Acid Production
Authors: Domon-Tawaraya H. , Nakajo K. , Washio J. , Ashizawa T. , Ichino T. , Sugawara H. , Fukumoto S. , Takahashi N.
Published: November 2012

One preventive effect of topical fluoride application is derived from the fact that fluoride can inhibit bacterial acid production. Furthermore, divalent cations such as Ca2+ and Mg2+ increase the binding of fluoride to bacterial cells. These findings suggest that exposure of oral bacteria to fluoride in the presence of divalent cations increases fluoride binding to bacterial cells and subsequently enhances fluoride-induced inhibition of bacterial acid production. This study investigated the effects of fluoride exposure (0–20,000 ppm F) in the presence of Ca2+ or Mg2+ prior to glucose challenge on pH fall ability by bacterial sugar fermentation, as well as fluoride binding to bacterial cells by exposure to fluoride, and fluoride release from bacterial cells during bacterial sugar fermentation, using caries-related bacteria, Streptococcus mutans and Streptococcus sanguinis. The pH fall by both streptococci was inhibited by exposure to over 250 ppm F in the presence of Ca2+ (p < 0.01), whereas in the presence of Mg2+, the pH fall by S. mutans and S. sanguinis was inhibited after exposure to over 250 and 950 ppm F, respectively (p < 0.05). The amounts of fluoride binding to and released from streptococcal cells increased with the concentration of fluoride the cells were exposed to in the presence of Mg2+, but were high enough even after 250 ppm F exposure in the presence of Ca2+. The enhanced inhibition of acid production in the presence of divalent cations is probably due to the improved efficiency of fluoride binding to bacterial cells being improved via these divalent cations.
Reduction of Erosion by Protein-Containing Toothpastes
Authors: Jager D.H.J. , Vissink A. , Timmer C.J. , Bronkhorst E. , Vieira A.M. , Huysmans M.C.D.N.J.M.
Published: November 2012

Aim: To assess the effect of protein-containing toothpastes on the progression of dental erosion in situ (with pellicle) and in vitro (without pellicle). Methods: A combined split-mouth (extraoral water or toothpaste brushing) and crossover (type of toothpaste) setup was used. Two protein-containing (high/low concentrations of colostrum) and one nonprotein (placebo) toothpaste were investigated. Sixteen volunteers wore intraoral appliances containing 2 human enamel samples on 3 afternoons for pellicle growth during 90 min. One enamel sample was brushed for 5 s with one of the three toothpastes and subsequently exposed to a slurry of the corresponding toothpaste for 2 min. The other sample was exposed to water. Both samples were subsequently exposed to citric acid (extraorally). Loss of calcium and inorganic phosphate were determined. The same sequence of exposures was applied to 16 enamel samples in an in vitro setup without pellicle. Results: With the in situ-formed pellicle, all toothpastes significantly reduced calcium loss compared to water brushing, although no significant differences were found among toothpastes (p = 0.073). For the loss of phosphate, a significant reduction could be found with the use of the high-protein toothpaste compared to the nonprotein toothpaste. Overall there were only slight differences between the toothpastes. Toothpaste effects were less clear in the in vitro experiment. Conclusion: The addition of proteins to toothpaste shows some promise for the prevention of erosion. Further research is needed to investigate the performance of the protein-containing toothpastes in longer in situ studies with regard to erosive wear.
Chronic Kidney Disease in the Arab World: A Call for Action
Authors: Farag Youssef M.K. , Kari Jameela A. , Singh Ajay K.
Published: November 2012

Chronic kidney disease (CKD) is an emerging non-communicable disease worldwide. The Arab countries have a high prevalence of CKD risk factors, e.g. diabetes, obesity and hypertension. Unfortunately, the magnitude of CKD in the Arab world has not been studied well. This review presents the current data on CKD in the Arab world and proposes a call for action to address this rising epidemic.
Development of Obesity and Polycystic Ovary Syndrome in Adolescents
Authors: Vilmann Lea S. , Thisted Ebbe , Baker Jennifer L. , Holm Jens-Christian
Published: November 2012

Obesity in adolescents is prevalent worldwide. Polycystic ovary syndrome (PCOS) is often associated with obesity in women, and it has serious metabolic and reproductive health implications. Although PCOS does not become clinically visible until early adolescence, its origins are likely much earlier. Therefore, we reviewed the recent literature regarding the mechanisms linking the development of PCOS and obesity in adolescent girls. We found that excess abdominal adipose tissue (AT) initiates metabolic and endocrine aberrations that are central in the progression of PCOS. As an example, abdominal AT impairs insulin action, which interacts with the progression of hyperandrogenism. In addition, excessive androgen levels lead to impaired glucose uptake, which also contributes to insulin resistance, which again increases the deposition of visceral fat. The body composition is influenced by testosterone, which decreases subcutaneous fat lipolysis and influences adipocyte distribution. These mechanisms may explain why PCOS girls have an increased visceral adipose mass independent of body mass index. Therefore, first-line treatment in adolescent PCOS is often lifestyle intervention to prevent the damaging effects of obesity. Pharmacological treatment of adolescent PCOS is not standardized because the long-term effects in adolescents have not yet been evaluated; therefore, drugs should be prescribed cautiously. Although the complex metabolic interrelationships between obesity and PCOS have yet to be fully understood, the co-occurrence of these conditions in adolescent girls tends to increase the severity of the negative health consequences of each condition.
Impaired GH Secretion in Patients with SHOX Deficiency and Efficacy of Recombinant Human GH Therapy
Authors: Vannelli Silvia , Street Maria Elisabeth , Pirazzoli Piero , Bertelloni Silvano , Radetti Giorgio , Capone Lucia , Stasiowska Barbara , Mazzanti Laura , Gastaldi Roberto , Maggio Maria Cristina , Predieri Barbara ,   on behalf of The Italian Society of Pediatric Endocrinology and Diabetology Study Group on Growth Factors and Puberty
Published: November 2012

Background/Aims: Mutations of the short stature homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes cause short stature. GH treatment has been recently proposed to improve height in short patients with SHOX deficiency. The aim of this study was to evaluate GH secretion and analyze growth and safety of recombinant human GH (rhGH) therapy in short children and adolescents with SHOX deficiency. Patients and Design: We studied 16 patients (10 females; 9.7 ± 2.9 years old; height –2.46 ± 0.82 standard deviation score, SDS) with SHOX deficiency. All subjects underwent auxological evaluations, biochemical investigations, and were treated with rhGH (0.273 ± 0.053 mg/kg/week). Results: Impaired GH secretion was present in 37.5% of the studied subjects. Comparing baseline data with those at the last visit, we found that rhGH treatment improved growth velocity SDS (from –1.03 ± 1.44 to 2.77 ± 1.95; p = 0.001), height SDS (from –2.41 ± 0.71 to –1.81 ± 0.87; p < 0.001), and IGF-1 values (from –0.57 ± 1.23 to 0.63 ± 1.63 SDS, p = 0.010) without affecting body mass index SDS. Height SDS measured at the last visit was significantly correlated with chronological age (r = –0.618, p = 0.032), bone age (r = –0.582, p = 0.047) and height SDS (r = 0.938, p < 0.001) at the beginning of treatment. No adverse events were reported on rhGH therapy which was never discontinued. Conclusion: These data showed that impaired GH secretion is not uncommon in SHOX deficiency subjects, and that rhGH therapy may be effective in increasing height in most of these patients independent of their GH secretory status, without causing any adverse events of concern.