bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Chronic Periodontitis in HIV-Seropositive Subjects and the General Population in the Ga-Rankuwa Area, South Africa
Authors: Khammissa Razia , Feller Liviu , Altini Mario , Fatti Paul , Lemmer Johan
Published: August 2012

The effect of HIV infection on the prevalence and the rate of progression of chronic periodontitis is not clear. The aim of this study was to compare parameters associated with the severity of chronic periodontitis in terms of periodontal probing depths, gingival recession, plaque indexes, and bleeding indexes of HIV-seropositive subjects and healthy age-matched control subjects, and of HIV-seropositive subjects on highly active antiretroviral therapy and those not receiving such treatment. Two cohorts of subjects with chronic periodontitis were recruited for this study over a period of six months. There were 30 HIV-seropositive subjects, and 30 control subjects. Periodontal probing depths, gingival marginal recession, plaque indexes, and bleeding indexes were compared by HIV serostatus, the use of highly active antiretroviral therapy, and CD4+ T-cell counts. All participants were black persons between the age of 18 and 45 and were of a similar socioeconomic status and age. The results of this study indicate that chronic periodontitis in HIV-seropositive subjects is similar in terms of mean periodontal probing depth, gingival marginal recession, plaque index, and bleeding index to that in healthy age-matched control subjects, and a low CD4+ T-cell count does not appear to be a risk factor for increased severity of chronic periodontitis.
Optimal Control Channel Selection for Wireless Channel Assignment
Authors: Zhong Sheng
Published: August 2012

In wireless channel assignment, control channels are often needed for coordination among wireless devices. In this paper, we propose an algorithm for finding the optimal set of control channels given a number of wireless devices and the ranges of channels these devices can access.
PET Tracers for Clinical Imaging of Breast Cancer
Authors: Peñuelas Iván , Domínguez-Prado Inés , García-Velloso María J. , Martí-Climent Josep M. , Rodríguez-Fraile Macarena , Caicedo Carlos , Sánchez-Martínez María , Richter José A.
Published: August 2012

Molecular imaging of breast cancer has undoubtedly permitted a substantial development of the overall diagnostic accuracy of this malignancy in the last years. Accurate tumour staging, design of individually suited therapies, response evaluation, early detection of recurrence and distant lesions have also evolved in parallel with the development of novel molecular imaging approaches. In this context, positron emission tomography (PET) can be probably seen as the most interesting molecular imaging technology with straightforward clinical application for such purposes. Dozens of radiotracers for PET imaging of breast cancer have been tested in laboratory animals. However, in this review we shall focus mainly in the smaller group of PET radiopharmaceuticals that have lead through into the clinical setting. PET imaging can be used to target general metabolic phenomena related to tumoural transformation, including glucose metabolism and cell proliferation, but can also be directed to specific hormone receptors that are characteristic of the breast cancer cell. Many other receptors and transport molecules present in the tumour cells could also be of interest for imaging. Furthermore, molecules related with the tumour microenvironment, tumour induced angiogenesis or even hypoxia could also be used as molecular biomarkers for breast cancer imaging.
Common Fixed Point Theorems for a Class of Twice Power Type Contraction Maps in G‐Metric Spaces
Authors: Ye Hongqing , Gu Feng
Published: August 2012

We introduce a new twice power type contractive condition for three mappings in G‐metric spaces, and several new common fixed point theorems are established in complete G‐metric space. An example is provided to support our result. The results obtained in this paper differ from other comparable results already known.
Measuring the Performance of River Basins: Application of Total Factor Productivity Approach to Andhra Pradesh, India
Authors: Palanisami K. , Ranganathan C. R.
Published: August 2012

Total Factor Productivity (TFP) measures the growth in output which is not accounted for by inputs. Data Envelopment Analysis which forms the basis for the computation of Malmquist TFP index is used in this paper to study the performance of different river basins in Andhra Pradesh state, India. The results indicated that average technical efficiency of all the basins is only 66%. In all the basins there was a decline in growth of agricultural output during the first two decades, viz., 1979-1980 to 1988-1989 and it had picked in the last decade (1999-2000). All the river basins have TFP change greater than 1 indicating progress in agricultural productivity. Out of the 40 river basins, 14 river basins have technical efficiency change less than 1 indicating decline in TFP growth whereas all the basins have technical changes greater than 1 implying that there is shift in production frontier over years. In general, within the TFP, technical change contributed more than technical efficiency change. Looking at the future options for increasing the agricultural output in the river basins, it is important to focus on improving the TFP growth compared to increasing the quantities of physical inputs.
Mechanisms of Resistance to Epidermal Growth Factor Receptor Inhibitors and Novel Therapeutic Strategies to Overcome Resistance in NSCLC Patients
Authors: Lin Luping , Bivona Trever G.
Published: August 2012

The epidermal growth factor receptor (EGFR) is a well-characterized oncogene that is frequently activated by somatic kinase domain mutations in non-small cell lung cancer (NSCLC). EGFR TKIs are effective therapies for NSCLC patients whose tumors harbor an EGFR activating mutation. However, EGFR TKI treatment is not curative in patients because of both primary and secondary treatment resistance. Studies over the last decade have identified mechanisms that drive primary and secondary resistance to EGFR TKI treatment. The elucidation of mechanisms of resistance to EGFR TKI treatment provides a basis for the development of therapeutic strategies to overcome resistance and enhance outcomes in NSCLC patients. In this paper, we summarize the mechanisms of resistance to EGFR TKIs that have been identified to date and discusses potential therapeutic strategies to overcome EGFR TKI resistance in NSCLC patients.
Redox Status Is Critical for Stemness in Skin Equivalents
Authors: Choi Hye-Ryung , Kang Youn-A , Shin Jung-Won , Na Jung-Im , Huh Chang-Hun , Park Kyoung-Chan
Published: August 2012

The skin is constantly exposed to environmental oxidative stress. Skin equivalent (SE) models are three-dimensional systems in which cell-cell or cell-matrix interactions can be investigated. In this study, the effects of vitamin C or plant extracts with high antioxidant activities were tested. There was no significant difference in the epidermal thickness, but the basal cells became cuboidal when vitamin C or plant extracts were supplemented. Furthermore, immunohistochemical staining showed linear and intense staining ofα6 andβ1 integrin along the basement membrane in vitamin C or plant extract treated models. The p63 and PCNA were also stained. Results showed that the number of p63 and PCNA positive cells was higher in the vitamin C or plant extract treated models than in the control SEs. Although the relationship between oxidative stress and stem cells is not known, our results suggest that redox status affects the stemness and the proliferative potential of epidermal basal cells by modulating microenvironment to epidermal basal stem cells.
Solving Constrained Global Optimization Problems by Using Hybrid Evolutionary Computing and Artificial Life Approaches
Authors: Wu Jui-Yu
Published: August 2012

This work presents a hybrid real‐coded genetic algorithm with a particle swarm optimization (RGA‐PSO) algorithm and a hybrid artificial immune algorithm with a PSO (AIA‐PSO) algorithm for solving 13 constrained global optimization (CGO) problems, including six nonlinear programming and seven generalized polynomial programming optimization problems. External RGA and AIA approaches are used to optimize the constriction coefficient, cognitive parameter, social parameter, penalty parameter, and mutation probability of an internal PSO algorithm. CGO problems are then solved using the internal PSO algorithm. The performances of the proposed RGA‐PSO and AIA‐PSO algorithms are evaluated using 13 CGO problems. Moreover, numerical results obtained using the proposed RGA‐PSO and AIA‐PSO algorithms are compared with those obtained using published individual GA and AIA approaches. Experimental results indicate that the proposed RGA‐PSO and AIA‐PSO algorithms converge to a global optimum solution to a CGO problem. Furthermore, the optimum parameter settings of the internal PSO algorithm can be obtained using the external RGA and AIA approaches. Also, the proposed RGA‐PSO and AIA‐PSO algorithms outperform some published individual GA and AIA approaches. Therefore, the proposed RGA‐PSO and AIA‐PSO algorithms are highly promising stochastic global optimization methods for solving CGO problems.
Social Networks and Memory over 15 Years of Followup in a Cohort of Older Australians: Results from the Australian Longitudinal Study of Ageing
Authors: Giles Lynne C. , Anstey Kaarin J. , Walker Ruth B. , Luszcz Mary A.
Published: August 2012

The purpose was to examine the relationship between different types of social networks and memory over 15 years of followup in a large cohort of older Australians who were cognitively intact at study baseline. Our specific aims were to investigate whether social networks were associated with memory, determine if different types of social networks had different relationships with memory, and examine if changes in memory over time differed according to types of social networks. We used five waves of data from the Australian Longitudinal Study of Ageing, and followed 706 participants with an average age of 78.6 years (SD 5.7) at baseline. The relationships between five types of social networks and changes in memory were assessed. The results suggested a gradient of effect; participants in the upper tertile of friends or overall social networks had better memory scores than those in the mid tertile, who in turn had better memory scores than participants in the lower tertile. There was evidence of a linear, but not quadratic, effect of time on memory, and an interaction between friends’ social networks and time was apparent. Findings are discussed with respect to mechanisms that might explain the observed relationships between social networks and memory.
A Note on Child Policy and Fertility in an Overlapping Generations Small Open Economy: When the Labour Market Institutions Matter
Authors: Fanti Luciano , Gori Luca
Published: August 2012

We examine how fertility reacts to the public provision of child allowances in a small open economy with overlapping generations. When the labour market is competitive, we find that a child allowance policy acts as a fertility-enhancing device. In contrast, when the labour market is unionised the child policy may be ineffective.
Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients with Diabetic Peripheral Neuropathic Pain
Authors: Skljarevski Vladimir , Frakes Elijah P. , Sagman Doron , Lipsius Sarah , Heinloth Alexandra N. , Dueñas Tentori Héctor J.
Published: August 2012

We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE) study that examine duloxetine 40 and 60 mg once daily (QD) in patients with diabetic peripheral neuropathic pain (DPNP). In all placebo-controlled studies, duloxetine showed significantly (P≤.01) greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure) compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P≤.05) greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P≤.01) for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction) ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P≤.01) between treatment groups in 3 out of 4 studies. The open-label study showed maintenance of analgesic effect of duloxetine in DPNP. In the duloxetine groups, 4.3% to 14.9% of patients discontinued because of adverse events (placebo groups: 2.6% to 7.4%). Most commonly reported treatment-emergent adverse events were nausea, somnolence, and headache. Duloxetine 40 and 60 mg QD was efficacious and well tolerated in the management of DPNP.
Efficient Capacity-Based Joint Quantized Precoding and Transmit Antenna Selection Using Cross-Entropy Method for Multiuser MIMO Systems
Authors: Chen Jung-Chieh , Chiu Min-Han , Yang Yi-Syun , Liao Kuan-Yuen , Li Chih-Peng
Published: August 2012

The current paper considers the joint precoding and transmit antenna selection to reduce hardware cost, such as radio-frequency chains, associated with antennas in the downlink of multiuser multiple-input multiple-output systems with limited feedback. The joint precoding and transmit antenna selection algorithm requires an exhaustive search of all possible combinations and permutations to find the optimum solution at the transmitter, thus resulting in extremely high computational complexity. To reduce the computational load while still maximizing channel capacity, the cross-entropy (CE) method is adopted to determine the suboptimum solution. Compared with the conventional genetic algorithm and random search method, the CE method provides better performance under the same computational complexity, as shown by the simulation results.
Adsorptive Separation Studies of β‐Carotene from Methyl Ester Using Mesoporous Carbon Coated Monolith
Authors: Muhammad M. , Ali Khan Moonis , Choong T. S. Y.
Published: August 2012

Adsorption of β‐carotene on mesoporous carbon coated monolith (MCCM) from methyl ester as a solvent was investigated. Kinetics and thermodynamics parameters have been evaluated. Maximum β‐carotene adsorption capacity was 22.37 mg/g at 50 °C. Process followed Langmuir isotherm. The adsorption was endothermic and spontaneous. Contact time studies showed increase in adsorption capacity with increase in β‐carotene initial concentration and temperature. Pseudo‐second‐order model was applicable to the experimental data. The value of activation energy confirmed physical adsorption process.
Dielectric, Thermodynamic, and Computational Studies of Hydrogen Bonded Binary Mixtures of N‐Methylaniline with Propan‐1‐ol and Isopropyl Alcohol
Authors: Krishna T. Vijaya , Sastry S. Sreehari , Ha Sie Tiong , Murthy V. R. K.
Published: August 2012

The molecular interactions between the polar systems N‐methylaniline with alcohols, propan‐1‐ol, and isopropyl alcohol for various mole fractions at different temperatures are studied by determining the dielectric permittivity using LF impedance analyzer, microwave bench, and Abbe′s refractometer in radio, microwave, and optic frequency regions, respectively. Dipole moment, excess dipole moment, excess Helmholtz free energy, excess permittivity, excess inverse relaxation time, and excess thermodynamical values are calculated using experimental data. Hamiltonian quantum mechanical calculations are performed using PC Spartan and ArgusLab modeling softwares for both pure and equimolar binary systems of N‐methyl aniline with alcohols.
A Combined Synthetic and DFT Study on the Catalyst‐Free and Solvent‐Assisted Synthesis of 1,3,4‐Oxadiazole‐2‐thiol Derivatives
Authors: Soleiman-Beigi Mohammad , Aryan Reza , Yousofizadeh Maryam , Khosravi Shima
Published: August 2012

A novel practical and efficient catalyst‐free method for the synthesis of 5‐substituted 1,3,4‐oxadiazole‐2‐thiols has been developed, which is assisted by reaction solvent (DMF). The solvent effects on product selectivity were studied based on Onsager’s reaction field theory of electrostatic solvation. The ab initio theoretical studies on the effect of solvents on the process also supported the suitability of DMF as the reaction medium for the preparation of 1,3,4‐oxadiazole‐2‐thiol derivatives.
New Strategies in Sarcoma Therapy: Linking Biology and Novel Agents
Authors: Janeway Katherine A. , Maki Robert G.
Published: August 2012

The ability to better interrogate the genetic state of a given cancer is giving rise to a new paradigm in cancer therapeutics in which the specific genetic alterations that give rise to the cancer inform the therapeutic decision-making for that specific patient. Sarcomas of soft tissue and bone represent model diseases that underscore this paradigm. However, many barriers prevent linkage of one of the 75 or more different types of sarcoma to novel therapeutic agents. In the present perspective, the authors outline key therapeutic opportunities and hurdles in clinical sarcoma research, focusing on specific examples of sarcomas that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations. Focused clinical trial design, ideally with several biomarker or histology-specific arms, is one means to be simultaneously parsimonious and inclusive. Clin Cancer Res; 18(21); 5837–44. ©2012 AACR.
Drug Resistance to Inhibitors of the Human Double Minute-2 E3 Ligase Is Mediated by Point Mutations of p53, but Can Be Overcome with the p53 Targeting Agent RITA
Authors: Jones Richard J. , Bjorklund Chad C. , Baladandayuthapani Veerabhadran , Kuhn Deborah J. , Orlowski Robert Z.
Published: August 2012

The human double minute (HDM)-2 E3 ubiquitin ligase plays a key role in p53 turnover and has been validated preclinically as a target in multiple myeloma (MM) and mantle cell lymphoma (MCL). HDM-2 inhibitors are entering clinical trials, and we therefore sought to understand potential mechanisms of resistance in lymphoid models. Wild-type p53 H929 MM and Granta-519 MCL cells resistant to MI-63 or Nutlin were generated by exposing them to increasing drug concentrations. MI-63-resistant H929 and Granta-519 cells were resistant to Nutlin, whereas Nutlin-resistant cells displayed cross-resistance to MI-63. These cells also showed cross-resistance to bortezomib, doxorubicin, cisplatin, and melphalan, but remained sensitive to the small molecule inhibitor RITA (reactivation of p53 and induction of tumor cell apoptosis). HDM-2 inhibitor-resistant cells harbored increased p53 levels, but neither genotoxic nor nongenotoxic approaches to activate p53 induced HDM-2 or p21. Resequencing revealed wild-type HDM-2, but mutations were found in the p53 DNA binding and dimerization domains. In resistant cells, RITA induced a G2–M arrest, upregulation of p53 targets HDM-2, PUMA, and NOXA, and PARP cleavage. Combination regimens with RITA and MI-63 resulted in enhanced cell death compared with RITA alone. These findings support the possibility that p53 mutation could be a primary mechanism of acquired resistance to HDM-2 inhibitors in MCL and MM. Furthermore, they suggest that simultaneous restoration of p53 function and HDM-2 inhibition is a rational strategy for clinical translation. Mol Cancer Ther; 11(10); 2243–53. ©2012 AACR.
Evaluating the Therapeutic Potential of a Non-Natural Nucleotide That Inhibits Human Ribonucleotide Reductase
Authors: Ahmad Md. Faiz , Wan Qun , Jha Shalini , Motea Edward , Berdis Anthony , Dealwis Chris
Published: August 2012

Human ribonucleotide reductase (hRR) is the key enzyme involved in de novo dNTP synthesis and thus represents an important therapeutic target against hyperproliferative diseases, most notably cancer. The purpose of this study was to evaluate the ability of non-natural indolyl-2′-deoxynucleoside triphosphates to inhibit the activity of hRR. The structural similarities of these analogues with dATP predicted that they would inhibit hRR activity by binding to its allosteric sites. In silico analysis and in vitro characterization identified one particular analogue designated as 5-nitro-indolyl-2′-deoxyribose triphosphate (5-NITP) that inhibits hRR. 5-NITP binding to hRR was determined by isothermal titration calorimetry. X-ray crystal structure of 5-NITP bound to RR1 was determined. Cell-based studies showed the anti-cancer effects of the corresponding non-natural nucleoside against leukemia cells. 5-NITP binds to hRR with micromolar affinity. Binding does not induce hexamerization of hRR1 like dATP, the native allosteric inhibitor of hRR that binds with high affinity to the A-site. The X-ray crystal structure of Saccharomyces cerevisiae RR1-5-NITP (ScRR1-5-NITP) complex determined to 2.3 Å resolution shows that 5-NITP does not bind to the A-site but rather at the S-site. Regardless, 5-nitro-indolyl-2′-deoxynucleoside (5-NIdR) produces cytostatic and cytotoxic effects against human leukemia cells by altering cell-cycle progression. Our studies provide useful insights toward developing new inhibitors with improved potency and efficacy against hRR. Mol Cancer Ther; 11(10); 2077–86. ©2012 AACR.
Effectiveness of Low-Frequency rTMS and Intensive Speech Therapy in Poststroke Patients with Aphasia: A Pilot Study Based on Evaluation by fMRI in Relation to Type of Aphasia
Authors: Abo Masahiro , Kakuda Wataru , Watanabe Motoi , Morooka Azusa , Kawakami Katsuya , Senoo Atsushi
Published: August 2012

Aim: To assess the safety and clinical efficacy of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) combined with intensive speech therapy (ST) in poststroke patients with aphasia. Subjects and Methods: Twenty-four patients with left-hemispheric stroke and aphasia were subjected. During 11-day hospitalization, each patient received 10 treatment sessions consisting of 40-min 1-Hz LF-rTMS and 60-min intensive ST, excluding Sundays. The scalp area for stimulation was selected based on the findings of fMRI with language tasks and the type of aphasia. LF-rTMS was applied to the inferior frontal gyrus (IGF) for patients with nonfluent aphasia and to the superior temporal gyrus (STG) for patients with fluent aphasia. Results: On pretreatment fMRI, the most activated areas were in the left hemisphere (n = 16) and right hemisphere (n = 8). The types of aphasia were nonfluent (n = 14) and fluent (n = 10). The LF-rTMS was applied to the right STG (n = 5), left STG (n = 5), right IFG (n = 11) and left IFG (n = 3). Nonfluent aphasic patients showed significant improvement of auditory comprehension, reading comprehension and repetition. Fluent aphasic patients showed significant improvement in spontaneous speech only. Conclusion: The fMRI with aphasic type-based therapeutic LF-rTMS/intensive ST for chronic aphasia seems feasible and a potentially useful neurorehabilitative protocol.
PSMC1 Gene in Parkinson’s Disease
Authors: Gómez-Garre Pilar , Jesús Silvia , Carrillo Fátima , Cáceres-Redondo Maria Teresa , Bernal-Bernal Inmaculada , Carballo Manuel , Gao Lin , Mir Pablo
Published: August 2012

Background: Impairment of the ubiquitin-proteasome system has been suggested to play an important role in the pathogenesis of Parkinson’s disease (PD). The 26S proteasome regulatory subunit 1 is encoded by the gene PSMC1 in humans. PSMC1 knockout mice showed a PD-like phenotype. Our aim was to analyze the association between variations in this gene and the susceptibility to develop PD. Methods: We included 283 PD patients (165 males and 118 females) with a mean age of 63.6 ± 11.2 years (mean age at onset 55.4 ± 12.7 years), and 316 unrelated control subjects (193 males and 123 females) with a mean age of 61.5 ± 12.3 years. Four polymorphisms, providing haplotype information of PSMC1, were genotyped using TaqMan assays. Moreover, in order to identify new variations, all exons of the PSMC1 gene and their exon-intron boundaries were analyzed using high-resolution melting analysis. Results: Minor allele frequencies in PD patients and control subjects were similar. The gene coding sequence analysis showed no variation associated with the disease either. Conclusions: Our results suggest that there is no association between variations or haplotypes in the PSMC1 gene and PD, indicating that this gene is probably not involved in the pathogenesis of PD.
Selected Cytokine Profiles during Remission in Bipolar Patients
Authors: Remlinger-Molenda Agnieszka , Wojciak Pawel , Michalak Michal , Karczewski Jacek , Rybakowski Janusz K.
Published: August 2012

Objectives: The aim of the study was to examine the cytokine status in bipolar patients during immediate remission after acute episodes of mania or depression and in patients with sustained (≥6 months) remission, compared with healthy controls. Methods: The study was performed on 121 bipolar patients, of whom 35 were in immediate remission after mania, 41 were in immediate remission after depression, and 45 were in >6-month remission on lithium monotherapy or lithium combined with other drugs. The control group consisted of 78 healthy individuals without any history of psychiatric or immunological illnesses. Serum concentrations of IL-1β, IL-2, IL-6, IL-10, TNF-α and IFN-γ were determined using the Human Th1/Th2 Cytometric Bead Array method. Results: The concentration of IL-10 was higher in patients in remission after mania and the concentration of IFN-γ was higher in those in remission after depression than in healthy controls. On the other hand, cytokine concentrations in patients with sustained remission were not different from those of healthy subjects. Conclusions: The results obtained in this study show that sustained remission in bipolar patients achieved mostly by lithium maintenance brings the cytokine status to a level similar to healthy control subjects.
Can a Screening Questionnaire Accurately Identify Mild Parkinsonian Signs
Authors: Dahodwala Nabila , Kubersky Lee , Siderowf Andrew ,   on behalf of the PARS investigators
Published: August 2012

Background: Mild parkinsonian signs (MPS) are early features that, when present, increase the risk of neurodegenerative disease and mortality. Current methods to identify MPS are limited to neurological examination. Our objective was to assess the ability of a 9-item Parkinson’s Disease Screening Questionnaire (PDSQ), which has high sensitivity in the detection of overt Parkinson’s disease (PD), to detect MPS. Methods: Measures including the PDSQ, Unified Parkinson’s Disease Rating Scale and University of Pennsylvania Smell Identification Test were administered to 267 participants without neurodegenerative disease. Two published definitions of MPS were used to classify cases. Results: PDSQ scores were higher for cases compared to controls (p < 0.001 for the first case definition and 0.07 for the second). However, the questionnaire had low sensitivity (47 and 59%) and specificity (62 and 63%) in the detection of MPS. Adding factors such as age, gender and smell test score to the questionnaire in a predictive model only marginally improved the test characteristics. Conclusion: The results show the screening questionnaire does not accurately identify MPS. More accurate tests are needed to improve the detection of this early syndrome which can lead to motor disability, neurodegenerative disease and mortality.
Long-Term Outcome of Preoperative Disrupted Inner/Outer Segment Junctions Assessed Using Spectral-Domain Optical Coherence Tomography in Patients with Idiopathic Epiretinal Membrane
Authors: Inoue Maiko , Arakawa Akira , Yamane Shin , Kadonosono Kazuaki
Published: August 2012

Purpose: To evaluate the anatomic and functional outcomes as assessed by spectral-domain optical coherence tomography in patients with a preoperative disrupted or irregular photoreceptor inner/outer segment (IS/OS) junction who underwent idiopathic epiretinal membrane (ERM) surgery and were followed for at least 2 years. Methods: We retrospectively studied all of the patients with idiopathic ERM who had a preoperative disrupted IS/OS junction and were scheduled to undergo a transconjunctival 25-gauge vitrectomy between September 2007 and October 2009. All of the patients who had a 2-year or longer follow-up period were included in the study. The best-corrected visual acuity (BCVA) and structural changes in the IS/OS junction were examined before and 3, 6, 12, and 24 months after surgery. Furthermore, patients were divided into two groups based on whether the preoperative disrupted IS/OS junction had been caused by a lamellar macular hole (LMH type) or swelling as a result of ERM traction (S type). Morphologic changes in the IS/OS junctions of each type were also investigated. Results: A total of 17 patients were identified in this study. Overall, a significantly better postoperative BCVA was seen after surgery; in particular, the BCVA at 24 months was significantly better than that at 12 months (p = 0.018). Although the disrupted IS/OS junction appeared normal in 1 out of 17 eyes at 12 months, 7 eyes appeared normal at 24 months. These 7 eyes showed significant postoperative improvement in BCVA compared with the remaining 10 eyes (p = 0.045, p = 0.021, p = 0.019, and p = 0.015 at 3, 6, 12, and 24 months, respectively). The preoperative disrupted IS/OS junction was classified as LMH type in 8 eyes and as S type in 9 eyes. The LMH type, rather than the S type, tended to show a persistently disrupted IS/OS junction at 24 months, although the difference was not significant. Conclusion: Anatomic and functional recovery of preoperative disrupted IS/OS junctions can be acquired even after more than 1 year postoperatively. However, eyes with persistent irregularities of the IS/OS junction at a 2-year follow-up, especially those with LMH type irregularities, might have a limited visual improvement.
A 32-Year-Old Male with Recurrent Hypothermia and Hypotension of Unknown Cause
Authors: Liu Ying , Zhou Lan , Beereddy Ranadhir Reddy , Kim Dong Soo , Blum David , Lahiri Asok K. , Carrey Zev , Alaie Dariush , Petrillo Richard L.
Published: August 2012

Objective: To report a rare case with hypothermia, hypotension and thrombocytopenia. Clinical Presentation and Intervention: A 32-year-old male presented with recurrent hypothermia, hypotension and thrombocytopenia. He had reduced sensitivity to the environmental temperature, but had no structural brain abnormalities on MRI. The patient recovered completely with warming and supportive treatments. Conclusion: This case showed that rare cases of idiopathic hypothermia, hypotension and thrombocytopenia should be managed clinically and warming and supportive treatments were successful.
Influence of the Quality of Endodontic Treatment and Coronal Restorations on the Prevalence of Apical Periodontitis in a Turkish Cypriot Population
Authors: Kalender Atakan , Orhan Kaan , Aksoy Umut , Basmaci Fatma , Er Faruk , Alankus Aslıhan
Published: August 2012

Objectives: The aim of this study was to assess the prevalence of periapical lesions in root canal-treated teeth in a Turkish Cypriote population and to investigate the influence of the quality of root canal fillings and coronal restorations on the prevalence of periapical lesions. Subjects and Methods: The sample for this cross-sectional study consisted of 1,006 adult patients seeking routine dental care. Patients who had received dental care in the last 2 years were excluded. Radiographs of 2,200 root canal-treated teeth were evaluated. The teeth were grouped according to the radiographic quality of the root canal filling and the coronal restoration. Periapical status was assessed using periapical index (PAI) scores. Results: Of the 2,200 root canal-treated teeth, 1,364 (62%) had apical periodontitis as compared with 1,364 (5.5%) of the total sample. Root-filled teeth classified as adequately treated had apical periodontitis in 223 (26.6%) cases compared with 1,192 (87.7%) in teeth classified as inadequately root filled. PAI 1 scores of adequate root canal treatment were significantly higher than in inadequate root canal treatment, regardless of the quality or presence of coronal restorations (p < 0.01). Conclusion: Our findings showed a high prevalence of periapical pathology with or without endodontic treatment and poor technical standard of both root fillings and coronal restorations of root-treated teeth. Hence, we suggest the need for better education for dental health providers so that they can perform better root canal treatments and coronal restorations.
Serum Granulocyte Colony-Stimulating Factor and Alzheimer’s Disease
Authors: Barber Robert C. , Edwards Melissa I. , Xiao Guanghua , Huebinger Ryan M. , Diaz-Arrastia Ramon , Wilhelmsen Kirk C. , Hall James R. , O’Bryant Sid E. ,   for the Texas Alzheimer’s Research and Care Consortium
Published: August 2012

Background: Granulocyte colony-stimulating factor (G-CSF) promotes the survival and function of neutrophils. G-CSF is also a neurotrophic factor, increasing neuroplasticity and suppressing apoptosis. Methods: We analyzed G-CSF levels in 197 patients with probable Alzheimer’s disease (AD) and 203 cognitively normal controls (NCs) from a longitudinal study by the Texas Alzheimer’s Research and Care Consortium (TARCC). Data were analyzed by regression with adjustment for age, education, gender and APOE4 status. Results: Serum G-CSF was significantly lower in AD patients than in NCs (β = –0.073; p = 0.008). However, among AD patients, higher serum G-CSF was significantly associated with increased disease severity, as indicated by lower Mini-Mental State Examination scores (β = –0.178; p = 0.014) and higher scores on the global Clinical Dementia Rating (CDR) scale (β = 0.170; p = 0.018) and CDR Sum of Boxes (β = 0.157; p = 0.035). Conclusions: G-CSF appears to have a complex relationship with AD pathogenesis and may reflect different pathophysiologic processes at different illness stages.
Impact of Physical Fitness and Daily Energy Expenditure on Sleep Efficiency in Young and Older Humans
Authors: Oudegeest-Sander Madelijn H. , Eijsvogels Thijs H.M. , Verheggen Rebecca J.H.M. , Poelkens Fleur , Hopman Maria T.E. , Jones Helen , Thijssen Dick H.J.
Published: August 2012

Background: Physical activity is known to influence sleep efficiency. Relatively little is known about the relationship between physical activity and sleep efficiency in young and older humans and the impact of exercise training on sleep efficiency in healthy older individuals. Objectives: To determine the relationship between physical fitness and daily energy expenditure with sleep efficiency in young and older subjects, and assess the effect of 12-month exercise training on sleep efficiency in healthy older participants. Methods: The relationship between physical fitness (maximal cycling test) and daily energy expenditure (accelerometry) with sleep efficiency (accelerometry) was examined cross-sectionally in 12 healthy young adults (27 ± 5 years) and 21 healthy older participants (69 ± 3 years). Subsequently, the effect of 12-month exercise training (n = 11) or control period (n = 10) on sleep efficiency in older participants was examined using a randomized controlled trial. Results: Daily energy expenditure and sleep efficiency did not differ between young and older subjects. A significant correlation was found between energy expenditure and sleep efficiency (r = 0.627, p = 0.029) in young adults, but not in older participants (r = –0.158, p = 0.49). Physical fitness did not correlate with sleep efficiency in either group. Exercise training significantly improved physical fitness (15.0%, p < 0.001), but failed to alter sleep characteristics such as sleep efficiency, sleep onset latency and awakenings. Conclusions: We found that young adults with higher daily energy expenditure have greater sleep efficiency, whilst this relationship is diminished with advanced age. In contrast, we found no correlation between physical fitness and sleep characteristics in healthy young or older participants, which may explain the lack of improvement in sleep characteristics in older participants with 12-month exercise training. Exercise training may be more successful in subjects with existing sleep disturbances to improve sleep characteristics rather than in healthy older subjects.
Loss of Function of hNa
v
1.5 by a ZASP1 Mutation Associated With Intraventricular Conduction Disturbances in Left Ventricular Noncompaction
Authors: Xi Yutao , Ai Tomohiko , De Lange Enno , Li Zhaohui , Wu Geru , Brunelli Luca , Kyle W. Buck , Turker Isik , Cheng Jie , Ackerman Michael J. , Kimura Akinori , Weiss James N. , Qu Zhilin , Kim Jeffrey J. , Faulkner Georgine , Vatta Matteo
Published: August 2012

Background—

Defects of cytoarchitectural proteins can cause left ventricular noncompaction, which is often associated with conduction system diseases. We have previously identified a p.D117N mutation in the LIM domain-binding protein 3–encoding Z-band alternatively spliced PDZ motif gene (ZASP) in a patient with left ventricular noncompaction and conduction disturbances. We sought to investigate the role of p.D117N mutation in the
LBD3
NM_001080114.1 isoform (ZASP1-D117N) for the regulation of cardiac sodium channel (Na
v
1.5) that plays an important role in the cardiac conduction system.

Methods and Results—

Effects of ZASP1-wild-type and ZASP1-D117N on Na
v
1.5 were studied in human embryonic kidney-293 cells and neonatal rat cardiomyocytes. Patch-clamp study demonstrated that ZASP1-D117N significantly attenuated
I
Na
by 27% in human embryonic kidney-293 cells and by 32% in neonatal rat cardiomyocytes. In addition, ZASP1-D117N rightward shifted the voltage-dependent activation and inactivation in both systems. In silico simulation using Luo-Rudy phase 1 model demonstrated that altered Na
v
1.5 function can reduce cardiac conduction velocity by 28% compared with control. Pull-down assays showed that both wild-type and ZASP1-D117N can complex with Na
v
1.5 and telethonin/T-Cap, which required intact PDZ domains. Immunohistochemical staining in neonatal rat cardiomyocytes demonstrates that ZASP1-D117N did not significantly disturb the Z-line structure. Disruption of cytoskeletal networks with 5-iodonaphthalene-1-sulfonyl homopiperazine and cytochalasin D abolished the effects of ZASP1-D117N on Na
v
1.5.

Conclusions—

ZASP1 can form protein complex with telethonin/T-Cap and Na
v
1.5. The left ventricular noncompaction-specific ZASP1 mutation can cause loss of function of Na
v
1.5, without significant alteration of the cytoskeletal protein complex. Our study suggests that electric remodeling can occur in left ventricular noncompaction subject because of a direct effect of mutant ZASP on Na
v
1.5.
Stroke Assessment With Diffusional Kurtosis Imaging
Authors: Hui Edward S. , Fieremans Els , Jensen Jens H. , Tabesh Ali , Feng Wuwei , Bonilha Leonardo , Spampinato Maria V. , Adams Robert , Helpern Joseph A.
Published: August 2012

Background and Purpose—

Despite being the gold standard technique for stroke assessment, conventional diffusion MRI provides only partial information about tissue microstructure. Diffusional kurtosis imaging is an advanced diffusion MRI method that yields, in addition to conventional diffusion information, the diffusional kurtosis, which may help improve characterization of tissue microstructure. In particular, this additional information permits the description of white matter (WM) in terms of WM-specific diffusion metrics. The goal of this study is to elucidate possible biophysical mechanisms underlying ischemia using these new WM metrics.

Methods—

We performed a retrospective review of clinical and diffusional kurtosis imaging data of 44 patients with acute/subacute ischemic stroke. Patients with a history of brain neoplasm or intracranial hemorrhages were excluded from this study. Region of interest analysis was performed to measure percent change of diffusion metrics in ischemic WM lesions compared with the contralateral hemisphere.

Results—

Kurtosis maps exhibit distinct ischemic lesion heterogeneity that is not apparent on apparent diffusion coefficient maps. Kurtosis metrics also have significantly higher absolute percent change than complementary conventional diffusion metrics. Our WM metrics reveal an increase in axonal density and a larger decrease in the intra-axonal (D
a
) compared with extra-axonal diffusion microenvironment of the ischemic WM lesion.

Conclusions—

The well-known decrease in the apparent diffusion coefficient of WM after ischemia is found to be mainly driven by a significant drop in the intra-axonal diffusion microenvironment. Our results suggest that ischemia preferentially alters intra-axonal environment, consistent with a proposed mechanism of focal enlargement of axons known as axonal swelling or beading.
Hyperintense Vessels on Acute Stroke Fluid-Attenuated Inversion Recovery Imaging
Authors: Cheng Bastian , Ebinger Martin , Kufner Anna , Köhrmann Martin , Wu Ona , Kang Dong-Wha , Liebeskind David , Tourdias Thomas , Singer Oliver C. , Christensen Soren , Warach Steve , Luby Marie , Fiebach Jochen B. , Fiehler Jens , Gerloff Christian , Thomalla Götz ,   on behalf of the Stroke Imaging Repository (STIR) Investigators
Published: August 2012

Background and Purpose—

Hyperintense vessels (HVs) have been observed in fluid-attenuated inversion recovery imaging of patients with acute ischemic stroke and been linked to slow flow in collateral arterial circulation. Given the potential importance of HV, we used a large, multicenter data set of patients with stroke to clarify which clinical and imaging factors play a role in HV.

Methods—

We analyzed data of 516 patients from the previously published PRE-FLAIR study (
PRE
dictive value of
FLAIR
and DWI for the identification of acute ischemic stroke patients ≤3 and ≤4.5 hours of symptom onset—a multicenter study) study. Patients were studied by MRI within 12 hours of symptom onset. HV were defined as hyperintensities in fluid-attenuated inversion recovery corresponding to the typical course of a blood vessel that was not considered the proximal, occluded main artery ipsilateral to the diffusion restriction. Presence of HV was rated by 2 observers and related to clinical and imaging findings.

Results—

Presence of HV was identified in 240 of all 516 patients (47%). Patients with HV showed larger initial ischemic lesion volumes (median, 12.3 versus 4.9mL;
P
<0.001) and a more severe clinical impairment (median National Institutes of Health Stroke Scale 10.5 versus 6;
P
<0.001). In 198 patients with MR angiography, HVs were found in 80% of patients with vessel occlusion and in 17% without vessel occlusion. In a multivariable logistic regression model, vessel occlusion was associated with HV (OR, 21.7%; 95% CI, 9.6–49.9;
P
<0.001). HV detected vessel occlusion with a specificity of 0.86 (95% CI, 0.80–0.90) and sensitivity of 0.76 (95% CI, 0.69–0.83).

Conclusions—

HVs are a common finding associated with proximal arterial occlusions and more severe strokes. HVs predict arterial occlusion with high diagnostic accuracy.
Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage
Authors: Falcone Guido J. , Biffi Alessandro , Devan William J. , Jagiella Jeremiasz M. , Schmidt Helena , Kissela Brett , Hansen Björn M. , Jimenez-Conde Jordi , Giralt-Steinhauer Eva , Elosua Roberto , Cuadrado-Godia Elisa , Soriano Carolina , Ayres Alison M. , Schwab Kristin , Pera Joanna , Urbanik Andrzej , Rost Natalia S. , Goldstein Joshua N. , Viswanathan Anand , Pichler Alexander , Enzinger Christian , Norrving Bo , Tirschwell David L. , Selim Magdy , Brown Devin L. , Silliman Scott L. , Worrall Bradford B. , Meschia James F. , Kidwell Chelsea S. , Montaner Joan , Fernandez-Cadenas Israel , Delgado Pilar , Broderick Joseph P. , Greenberg Steven M. , Roquer Jaume , Lindgren Arne , Slowik Agnieszka , Schmidt Reinhold , Flaherty Matthew L. , Kleindorfer Dawn O. , Langefeld Carl D. , Woo Daniel , Rosand Jonathan
Published: August 2012

Background and Purpose—

Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN.

Methods—

We conducted a prospective multicenter case–control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables.

Results—

No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02–1.21;
P
=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07–1.30;
P
=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04–1.31;
P
=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01–1.31;
P
=0.04). Similar results were obtained when using a weighted score.

Conclusion—

Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.
Long-Term Mortality in Patients With Stroke of Undetermined Etiology
Authors: Nam Hyo Suk , Kim Hyeon Chang , Kim Young Dae , Lee Hye Sun , Kim Jinkwon , Lee Dong Hyun , Heo Ji Hoe
Published: August 2012

Background and Purpose—

The determination of stroke etiology is essential for planning treatment for stroke prevention. However, the etiology of stroke is undetermined in many patients.

Methods—

During a 10-year period, consecutive patients with acute ischemic stroke were enrolled. The stroke etiology was determined based on the Trial of ORG 10172 in Acute Stroke Treatment classification. Long-term mortality and causes of death were identified using death certificates. The standardized mortality ratio was calculated to compare the mortality in patients with stroke and that in the general Korean population.

Results—

In total, 3278 patients were enrolled and followed-up for a median of 3.4 years (interquartile range, 1.5–5.7). The stroke subtype was undetermined in 37% because of negative evaluation (21.2%), multiple causes (10.6%), and incomplete evaluation (4.8%). Poor functional outcome at 3 months (modified Rankin scale score >2) was more frequent in patients with an incomplete evaluation than in those with the other stroke subtypes (49.6% vs 24.5%;
P
<0.001). During follow-up, 781 patients (23.8%) died. The overall cumulative death rate was highest in patients with an incomplete evaluation (12.7% within 30 days, 25.5% within 1 year, and 35.7% within 3 years), followed by those with cardioembolism. Multivariate analysis after adjusting for covariates including initial stroke severity, the mortality of patients with an incomplete evaluation was second lowest after cardioembolism, whereas that in patients with a negative evaluation was low.

Conclusions—

Long-term mortality in patients with an incomplete evaluation was quite high. Etiologic work-up helps to better define the stroke subtype and determine the prognosis.