bluuebunny/crossref_metadata_2025 huggingface dataset:
EASY HOLOGRAPHY
Authors: ARPONEN HEIKKI
Published: September 2013

It is argued that the role of infinite-dimensional asymptotic symmetry groups in gravity theories are essential for a holographic description of gravity and possibly to a resolution of the black hole information paradox. I present a simple toy model in two-dimensional hyperbolic/anti-de Sitter (AdS) space and describe, by very elementary considerations, how the asymptotic symmetry group is responsible for the entropy area law. Similar results apply also in three-dimensional AdS space. The failure of the approach in higher-dimensional AdS spaces is explained and resolved by considering other asymptotically noncompact homogeneous spaces.
COMPARISONS OF THE ODD–EVEN STAGGERING PATTERNS BETWEEN THE Ba–Dy REGION WITH 88 NEUTRONS AND Ra ISOTOPES WITH 88 PROTONS
Authors: MHEEMEED AHMED K.
Published: September 2013

Useful information about the shape transitions of even–even isotones 144 Ba , 146 Ce , 148 Nd , 150 Sm , 152 Gd , 154 Dy with 88 neutrons and 218-226 Ra isotopes with 88 protons are obtained from the ratios of [Formula: see text] as a function of neutron number N or proton number Z and the relations [Formula: see text] and r((I+2)/I) as a function of the angular momentum I. Interacting Boson Model (IBM-1), Bohr–Mottelson Model (BM) and Interacting Vector Boson Model (IVBM) have been employed to study the energy levels for the ground and octupole bands of the above nuclei. The best input parameters for the above approaches which lead to the best fit to experimental data are determined. The ΔI = 1 staggering (odd–even staggering) in octupole bands of the studied nuclei is found to exhibit a "beat" behavior as a function of angular momentum I. Comparisons of the displacement energies δE(I) and the staggering factor ΔE1, γ(I) are presented between the Ba–Dy region with 88 neutrons and Ra isotopes with 88 protons.
Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte proliferation, differentiation, and glucose uptake
Authors: McNelis Joanne C. , Manolopoulos Konstantinos N. , Gathercole Laura L. , Bujalska Iwona J. , Stewart Paul M. , Tomlinson Jeremy W. , Arlt Wiebke
Published: September 2013

Glucocorticoids increase adipocyte proliferation and differentiation, a process underpinned by the local reactivation of inactive cortisone to active cortisol within adipocytes catalyzed by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The adrenal sex steroid precursor dehydroepiandrosterone (DHEA) has been shown to inhibit 11β-HSD1 in murine adipocytes; however, rodent adrenals do not produce DHEA physiologically. Here, we aimed to determine the effects and underlying mechanisms of the potential antiglucocorticoid action of DHEA and its sulfate ester DHEAS in human preadipocytes. Utilizing a human subcutaneous preadipocyte cell line, Chub-S7, we examined the metabolism and effects of DHEA in human adipocytes, including adipocyte proliferation, differentiation, 11β-HSD1 expression, and activity and glucose uptake. DHEA, but not DHEAS, significantly inhibited preadipocyte proliferation via cell cycle arrest in the G1 phase independent of sex steroid and glucocorticoid receptor activation. 11β-HSD1 oxoreductase activity in differentiated adipocytes was inhibited by DHEA. DHEA coincubated with cortisone significantly inhibited preadipocyte differentiation, which was assessed by the expression of markers of early ( LPL) and terminal ( G3PDH) adipocyte differentiation. Coincubation with cortisol, negating the requirement for 11β-HSD1 oxoreductase activity, diminished the inhibitory effect of DHEA. Further consistent with glucocorticoid-opposing effects of DHEA, insulin-independent glucose uptake was significantly enhanced by DHEA treatment. DHEA increases basal glucose uptake and inhibits human preadipocyte proliferation and differentiation, thereby exerting an antiglucocorticoid action. DHEA inhibition of the amplification of glucocorticoid action mediated by 11β-HSD1 contributes to the inhibitory effect of DHEA on human preadipocyte differentiation.
Leflunomide as a Corticosteroid-Sparing Agent in Giant Cell Arteritis and Polymyalgia Rheumatica: A Case Series
Authors: Diamantopoulos Andreas P. , Hetland Helene , Myklebust Geirmund
Published: September 2013

Objectives. Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) affect individuals older than 50 years of age and corticosteroids are the mainstay of treatment. The aim of our study was to explore the role of leflunomide as a corticosteroid-sparing agent in GCA and PMR patients.Methods. Patients with difficult-to-treat GCA and PMR were retrospectively identified in the period from 2010 to 2013. The doses of corticosteroids and CRP values were noted before, after three months, and at the end of the treatment with leflunomide (for patients continuing treatment, censoring date was January 1, 2013).Results. Twenty-three patients were identified (12 with PMR and 11 with GCA). A reduction of 6 mg/dL (CI 95% –10.9–34.2,P=0.05) in CRP and 3.7 mg (CI 95% 0.5–7.0,P=0.03) in prednisolone dose was observed in the PMR group. In GCA patients, the reduction was 12.4 mg/dL (CI 95% 0.7–25.5,P=0.06) in CRP and 6.6 mg (CI 95% 2.8–10.3,P<0.01) in prednisolone dose.Conclusion. Leflunomide seems to be effective as a corticosteroid-sparing agent in patients with difficult-to-treat GCA and PMR. Randomized controlled trials are warranted in order to confirm the usefulness of leflunomide in the therapy of GCA/PMR.
Windowed Least Square Algorithm Based PMSM Parameters Estimation
Authors: Wang Song
Published: September 2013

Stator resistance and inductances ind-axis andq-axis of permanent magnet synchronous motors (PMSMs) are important parameters. Acquiring these accurate parameters is usually the fundamental part in driving and controlling system design, to guarantee the performance of driver and controller. In this paper, we adopt a novel windowed least algorithm (WLS) to estimate the parameters with fixed value or the parameter with time varying characteristic. The simulation results indicate that the WLS algorithm has a better performance in fixed parameters estimation and parameters with time varying characteristic identification than the recursive least square (RLS) and extended Kalman filter (EKF). It is suitable for engineering realization in embedded system due to its rapidity, less system resource possession, less computation, and flexibility to adjust the window size according to the practical applications.
Bifurcations and Parametric Representations of Peakon, Solitary Wave and Smooth Periodic Wave Solutions for a Two-Component Degasperis-Procesi Equation
Authors: He Bin , Meng Qing , Zhang Jinhua
Published: September 2013

By using the bifurcation method of dynamical systems and the method of phase portraits analysis, we consider a two-component Degasperis-Procesi equation:mt=-3mux-mxu+kρρx,  ρt=-ρxu+2ρux,the existence of the peakon, solitary wave and smooth periodic wave is proved, and exact parametric representations of above travelling wave solutions are obtained in different parameter regions.
Association Rule Hiding Based on Intersection Lattice
Authors: Quoc Le Hai , Arch-int Somjit , Arch-int Ngamnij
Published: September 2013

Association rule hiding has been playing a vital role in sensitive knowledge preservation when sharing data between enterprises. The aim of association rule hiding is to remove sensitive association rules from the released database such that side effects are reduced as low as possible. This research proposes an efficient algorithm for hiding a specified set of sensitive association rules based on intersection lattice of frequent itemsets. In this research, we begin by analyzing the theory of the intersection lattice of frequent itemsets and the applicability of this theory into association rule hiding problem. We then formulate two heuristics in order to (a) specify the victim items based on the characteristics of the intersection lattice of frequent itemsets and (b) identify transactions for data sanitization based on the weight of transactions. Next, we propose a new algorithm for hiding a specific set of sensitive association rules with minimum side effects and low complexity. Finally, experiments were carried out to clarify the efficiency of the proposed approach. Our results showed that the proposed algorithm, AARHIL, achieved minimum side effects and CPU-Time when compared to current similar state of the art approaches in the context of hiding a specified set of sensitive association rules.
A Broader View: Microbial Enzymes and Their Relevance in Industries, Medicine, and Beyond
Authors: Gurung Neelam , Ray Sumanta , Bose Sutapa , Rai Vivek
Published: September 2013

Enzymes are the large biomolecules that are required for the numerous chemical interconversions that sustain life. They accelerate all the metabolic processes in the body and carry out a specific task. Enzymes are highly efficient, which can increase reaction rates by 100 million to 10 billion times faster than any normal chemical reaction. Due to development in recombinant technology and protein engineering, enzymes have evolved as an important molecule that has been widely used in different industrial and therapeutical purposes. Microbial enzymes are currently acquiring much attention with rapid development of enzyme technology. Microbial enzymes are preferred due to their economic feasibility, high yields, consistency, ease of product modification and optimization, regular supply due to absence of seasonal fluctuations, rapid growth of microbes on inexpensive media, stability, and greater catalytic activity. Microbial enzymes play a major role in the diagnosis, treatment, biochemical investigation, and monitoring of various dreaded diseases. Amylase and lipase are two very important enzymes that have been vastly studied and have great importance in different industries and therapeutic industry. In this review, an approach has been made to highlight the importance of different enzymes with special emphasis on amylase and lipase in the different industrial and medical fields.
The Effects of Sa-Am Acupuncture Treatment on Respiratory Physiology Parameters in Amyotrophic Lateral Sclerosis Patients: A Pilot Study
Authors: Lee Sangmi , Kim Sungchul
Published: September 2013

Respiratory dysfunction and complications are the most common causes of death in amyotrophic lateral sclerosis. This is a pilot study to observe the changes in respiratory physiology parameters after Sa-am acupuncture treatment. Eighteen ALS patients received Sa-am acupuncture treatment twice a day for 5 days. The EtCO2, SpO2, RR, and pulse rate were measured for 15 min before and during treatment, using capnography and oximetry. Correlation of K-ALSFRS-R scores against measured parameters showed that patients who had high K-ALSFRS-R scores had greater changes in pulse rate after acupuncture stimulation; they also showed a decrease in EtCO2, RR, and pulse rate and an increase in SpO2. A comparison of the mean values of these different parameters before and after Sa-am acupuncture stimulation revealed statistically significant differences (P<0.05) in SpO2and pulse rate, but none in EtCO2and RR. Sa-am acupuncture treatment on ALS patients seems to be more effective in the early stages of the disease. In light of increased SpO2values, Sa-am acupuncture appears to have a greater effect on inspiration rather than on expiration. As a pilot study of acupuncture on ALS patients, this study could be used as a basis for future research.
Clinical Experience of Bronchoscopy-Guided Radiofrequency Ablation for Peripheral-Type Lung Cancer
Authors: Koizumi Tomonobu , Kobayashi Takashi , Tanabe Tsuyoshi , Tsushima Kenji , Yasuo Masanori
Published: September 2013

We have developed a new internal cooled electrode for radiofrequency ablation (RFA) (Japan Application no. 2006-88228) suitable for forceps channel bronchoscopy. Here, we present our clinical experience with bronchoscopy-guided RFA under computed tomography (CT) monitoring for patients with peripheral-type non-small-cell lung cancer (NSCLC). Bronchoscopy-guided RFA was performed in two patients (80 and 70 years old) with NSCLC, who had no lymph node involvement and distant metastases (T1N0M0), but not indicated for surgery because of other complications, such as advanced age, poor pulmonary function, and refusal of thoracic surgery. The locations of the tumors were right S2 and left S3, respectively. Although the tumors showed ground-glass opacity (GGO) with solid components in both cases, radiographic findings changed to reduced mass-like shadow and remained stable for 4 and 3.5 years after bronchoscopy-guided RFA. As the former case developed progressive disease on chest CT, bronchoscopy-guided RFA was repeated in the same lesion, resulting in no change for the subsequent 1 year. There were no adverse reactions during the procedures. Thus, bronchoscopy-guided RFA is a safe and feasible procedure that represents a potentially useful therapeutic tool in local control in medically inoperable patients with stage I NSCLC.
A Globally Convergent Line Search Filter SQP Method for Inequality Constrained Optimization
Authors: Jin Zhong
Published: September 2013

A line search filter SQP method for inequality constrained optimization is presented. This method makes use of a backtracking line search procedure to generate step size and the efficiency of the filter technique to determine step acceptance. At each iteration, the subproblem is always consistent, and it only needs to solve one QP subproblem. Under some mild conditions, the global convergence property can be guaranteed. In the end, numerical experiments show that the method in this paper is effective.
Association of Seat Height and Arm Position on the Five Times Sit-to-Stand Test Times of Stroke Survivors
Authors: Ng Shamay S. M. , Cheung Susanna Y. , Lai Lauren S. W. , Liu Ann S. L. , Ieong Selena H. I. , Fong Shirley S. M.
Published: September 2013

Objectives. To investigate (1) the association of seat height and (2) the association of arm position on the five times sit-to-stand test (FTSTS) times of individuals with stroke.Design. A cross-sectional study.Setting. University-based rehabilitation centre.Subjects. Patients (n=43) with chronic stroke.Methods. The times in completing the FTSTS with different seat height (85%, 100%, and 115% knee height) and arm positions (arms across chest, hands on thighs).Results. FTSTS times were significantly different between 85% and 100% seat heights, and between the 85% and 115% seat heights in both arm positions. However, there was no significant difference between the FTSTS times with the two arm positions at any seat height tested.Conclusion. Seat heights lower than the knee height result in longer FTSTS times, whereas arms positions did not significantly affect the FTSTS times.
A Review of the Effects of Physical Activity and Exercise on Cognitive and Brain Functions in Older Adults
Authors: Bherer Louis , Erickson Kirk I. , Liu-Ambrose Teresa
Published: September 2013

Studies supporting the notion that physical activity and exercise can help alleviate the negative impact of age on the body and the mind abound. This literature review provides an overview of important findings in this fast growing research domain. Results from cross-sectional, longitudinal, and intervention studies with healthy older adults, frail patients, and persons suffering from mild cognitive impairment and dementia are reviewed and discussed. Together these finding suggest that physical exercise is a promising nonpharmaceutical intervention to prevent age-related cognitive decline and neurodegenerative diseases.
A Perspective on Recurrent Vertigo
Authors: Gacek Richard R.
Published: September 2013

The recurrent nature of the 3 most common vestibulopathies suggests a recurrent cause. Histopathology in temporal bones from patients with these syndromes - vestibular neuronitis (VN, n = 7), Ménière's disease (MD, n = 8) and benign paroxysmal positional vertigo (BPPV, n = 5) - shows focal degeneration of vestibular nerve axons and degenerated nearby facial nerve meatal ganglion cells. Transmission electron microscopic confirmation of intracytoplasmic viral particles in surgically excised vestibular nerves from patients with VN and MD support a viral etiology in these vestibulopathies. Antiviral treatment of these syndromes in a series of 211 patients with a 3- to 8-year follow-up resulted in complete control of vertigo in VN (88%), MD (90%) and BPPV (60%).
Effectiveness of the Combined Hearing and Masking Devices on the Severity and Perception of Tinnitus: A Randomized, Controlled, Double-Blind Study
Authors: Oz Isilay , Arslan Fatih , Hizal Evren , Erbek Seyra H. , Eryaman Esra , Senkal Ozgul A. , Ogurlu Terkan , Kizildag Alp Ertunga , Ozluoglu Levent N.
Published: September 2013

Objective: The aim of this study was to evaluate the effect of combined hearing and tinnitus masking devices that are appropriately programmed for acoustic stimulations using wide-band noise over the specific frequency range of tinnitus. Material and Methods: A total of 21 patients were randomly divided into 2 groups. Group I (12 patients) was managed with betahistine dihydrochloride (2HCl) and fitted either with a combined hearing aid or a sound generator, and group II (9 patients) was treated with betahistine 2HCl for 3 months. Audiological tests, pitch matching to determine the frequency of tinnitus, an assessment of tinnitus severity, and subjective scores (visual analog scale, VAS; Mini-Tinnitus Questionnaire) were used to assess the patients in both groups, and a loudness scale was also analyzed in group I. The results were evaluated in a double-blinded manner. Results: Significant decreases in the severity of tinnitus, Mini-Tinnitus Questionnaire score and VAS were observed in both groups. No significant differences were obtained in pitch-matched frequency of tinnitus in the two groups. Conclusion: The findings obtained using either the combined devices or the masking devices with wide-band masking demonstrate that these devices are an effective tinnitus treatment alternative.
Crosslinguistic Application of English-Centric Rhythm Descriptors in Motor Speech Disorders
Authors: Liss Julie M. , Utianski Rene , Lansford Kaitlin
Published: September 2013

Background: Rhythmic disturbances are a hallmark of motor speech disorders, in which the motor control deficits interfere with the outward flow of speech and by extension speech understanding. As the functions of rhythm are language-specific, breakdowns in rhythm should have language-specific consequences for communication. Objective: The goals of this paper are to (i) provide a review of the cognitive-linguistic role of rhythm in speech perception in a general sense and crosslinguistically; (ii) present new results of lexical segmentation challenges posed by different types of dysarthria in American English, and (iii) offer a framework for crosslinguistic considerations for speech rhythm disturbances in the diagnosis and treatment of communication disorders associated with motor speech disorders. Summary: This review presents theoretical and empirical reasons for considering speech rhythm as a critical component of communication deficits in motor speech disorders, and addresses the need for crosslinguistic research to explore language-universal versus language-specific aspects of motor speech disorders.
The Relationship between Executive Function and Falls and Gait Abnormalities in Older Adults: A Systematic Review
Authors: Kearney Fiona C. , Harwood Rowan H. , Gladman John R.F. , Lincoln Nadina , Masud Tahir
Published: September 2013

Background/Objectives: Older adults with dementia have at least a twofold increased risk of falls. Multi-factorial interventions have failed to demonstrate a reduction in falls in this group. Improved understanding of specific cognitive factors and their relationship to gait, balance and falls is required. Methods: Systematic searches of Medline, Embase, PsycInfo, and CINAHL databases from inception to April 2011 were conducted to identify prospective studies in older adults examining executive function and its relationship with falls, balance and gait abnormalities. Two independent reviewers extracted data on study populations, executive function measures and study outcomes. Results: Of 8,985 abstracts identified, 14 studies met inclusion criteria. Eleven studies examined executive function and falls. The remaining studies examined executive function and gait speed decline. Nine studies examining executive function and falls found a relationship between poor executive function and increased fall risk. All 3 studies examining executive function and gait found an association between poor executive function and declines in gait speed. Impaired executive function was associated with more serious falling patterns. Conclusions: Executive function was associated with falls and gait speed slowing in older adults. Future research should consider executive dysfunction as a training target for fall prevention, or as a factor mediating the failure of conventional fall prevention interventions.
Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease Proven by Transient Elastography
Authors: Mikolasevic Ivana , Racki Sanjin , Bubic Ivan , Jelic Ita , Stimac Davor , Orlic Lidija
Published: September 2013

Background/Aim: Preliminary data suggest an association between chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to further investigate the association between NAFLD and decreased kidney function. Methods: A total of 62 patients with CKD were enrolled in the study. Liver stiffness was used to detect liver fibrosis and CAP (controlled attenuation parameter) was used to detect and quantify liver steatosis (Fibroscan®). NAFLD was defined by CAP values ≥238 dB.m-1. Results: CKD stage III was present in 29 patients (46.8%) and CKD stage IV in 33 patients (53.2%). Out of 62 CKD patients 53 (85.5%) had NAFLD and of these 14/53 patients (26.4%) had also liver stiffness >7 kPa. The severity of liver steatosis was positively correlated with serum creatinine (r=0.399;p<0.01) and CRP (r=0.261; p<0.05) and negatively correlated with eGFR (r=-0.413; p<0.01) and serum iron concentration (r=-0.365; p<0.01). Conclusion: The results suggest a high prevalence of NAFLD in CKD patients. The severity of liver steatosis is negatively correlated with kidney function. The study documents the value of ultrasonographic elastography as an effective non-invasive screening method for the diagnosis of NAFLD.
Nutritional and Metabolic Alterations during Continuous Renal Replacement Therapy
Authors: Honoré Patrick M. , De Waele Elisabeth , Jacobs Rita , Mattens Sabrina , Rose Thomas , Joannes-Boyau Olivier , De Regt Jouke , Verfaillie Lies , Van Gorp Viola , Boer Willem , Collin Vincent , Spapen Herbert D.
Published: September 2013

Adequate feeding of critically ill patients under continuous renal replacement therapy (CRRT) remains a challenging issue. We performed a systematic search of the literature published between 1992 and 2012 using the quorum guidelines regarding nutrition in intensive care unit patients treated with CRRT. Daily recommended energy requirements during CRRT are between 25 and 35 kcal/kg with carbohydrates and lipids accounting for 60-70% and 30-40% of calorie intake, respectively. Daily protein needs range from 1.5 to 1.8 g/kg. Indirect calorimetry corrected for CRRT-induced CO2 diversion should be used to more correctly match calorie intake to the real needs. This type of tool is not yet available but hopefully soon. Electrolyte deficit as well as overload have been described during CRRT but, in general, can be easily controlled. Although not strongly evidenced, consensus exists to supplement important micronutrients such as amino acids (glutamine), water-soluble vitamins and trace elements.
Meta-Analysis of Bismuth Quadruple Therapy versus Clarithromycin Triple Therapy for Empiric Primary Treatment of Helicobacter pylori Infection
Authors: Venerito Marino , Krieger Tina , Ecker Thomas , Leandro Gioacchino , Malfertheiner Peter
Published: September 2013

Background: In areas with high clarithromycin resistance, bismuth quadruple therapy (BQT) is recommended instead of clarithromycin triple therapy (CTT) as the first-line treatment for Helicobacter pylori eradication. Methods: Randomized clinical trials (RCTs) comparing BQT to CTT were identified through electronic and manual searches. A meta-analysis was performed to compare the efficacy and tolerability of these two regimens as first-line treatments for H. pylori infection. The effect of antibiotic resistance on treatment efficacy was also analyzed. Results: Twelve RCTs were included. BQT achieved eradication in 77.6% of patients, whereas CTT achieved an eradication rate of 68.9% [risk difference (RD) = 0.06, 95% CI: -0.01/0.13]. A high heterogeneity among the trials was found (χ2 = 50.16, p < 0.00001; I2 = 78%). In the subgroup analysis for treatment duration, the 10-day BQT was more effective than the 7-day CTT (RD = 0.25, 95% CI: 0.18/0.32), whereas no differences were observed between CTT and BQT given for 7 or 10 days. There were no statistical differences in side effects and compliance between both therapies (RD = 0.92, 95% CI: 0.76/1.12, and RD = -0.03, 95% CI: -0.05/0.00, respectively). The effect of antibiotic resistance on eradication rates was reported in 4 of the 12 RCTs. Clarithromycin resistance significantly affected the efficacy of CTT (RD = 0.75, 95% CI: 0.63/0.87), whereas BQT efficacy was not affected by metronidazole resistance (RD = 0.09, 95% CI: -0.06/0.25). Conclusions: The 10-day BQT was more effective than the 7-day CTT as a first-line therapy for H. pylori infection, whereas BQT and CTT for 7 or 10 days yielded similar eradication rates. Compliance and side effect rates were similar for both therapies. BQT overcomes clarithromycin resistance and its efficacy is not affected by metronidazole resistance.
Maintenance Therapy for Acne Vulgaris: Efficacy of a 12-Month Treatment with Adapalene-Benzoyl Peroxide after Oral Isotretinoin and a Review of the Literature
Authors: Bettoli Vincenzo , Borghi Alessandro , Zauli Stefania , Toni Giulia , Ricci Michela , Giari Silvia , Virgili Annarosa
Published: September 2013

Background: The correct therapeutic management of acne should include a maintenance therapy with topical retinoids to prevent recurrences after discontinuing a successful treatment. Objective: To investigate the efficacy of a 12-month maintenance treatment with adapalene 0.1% and benzoyl peroxide (BPO) 2.5% fixed combination gel to control acne relapse after treatment with oral isotretinoin (OI). Methods: The study consisted of 2 phases, namely an active treatment phase (AP) and a maintenance phase (MP). In the AP, 70 consecutive patients with moderate to severe acne were treated with OI until acne remission. Then, patients entered the MP and were treated with adapalene-BPO fixed combination once daily for 12 months. The primary efficacy parameter was the relapse rate during MP. Results: Sixty-eight patients completed the study. Relapse occurred in 2 patients (2.94%). Conclusions: Comparing our findings with published data, the association of a topical retinoid and BPO seems to provide favorable evidence for this combination as maintenance therapy.
The Molecular Chaperone Apolipoprotein J/Clusterin as a Sensor of Oxidative Stress: Implications in Therapeutic Approaches - A Mini-Review
Authors: Trougakos Ioannis P.
Published: September 2013

Background: Organisms are constantly exposed to physiological and environmental stresses and therefore require an efficient surveillance of genome and proteome quality in order to prevent disruption of homeostasis. Central to the intra- and extracellular proteome surveillance system are the molecular chaperones that contribute to both proteome maintenance and clearance. The conventional protein product of the apolipoprotein J/clusterin (CLU) gene is a heterodimeric secreted glycoprotein (also termed as sCLU) with a ubiquitous expression in human tissues. CLU exerts a small heat shock protein-like stress-induced chaperone activity and has been functionally implicated in numerous physiological processes as well as in ageing and most age-related diseases including tumorigenesis, neurodegeneration, and cardiovascular and metabolic syndromes. Objective: The CLU gene is differentially regulated by a wide variety of stimuli due to the combined presence of many distinct regulatory elements in its promoter that make it an extremely sensitive cellular biosensor of environmental and/or oxidative stress. Downstream to CLU gene induction, the CLU protein seems to actively intervene in pathological states of increased oxidative injury due to its chaperone-related property to inhibit protein aggregation and precipitation (a main feature of oxidant injury), as well as due to its reported distribution in both extra- and, most likely, intracellular compartments. Conclusion: On the basis of these findings, CLU has emerged as a unique regulator of cellular proteostasis. Nevertheless, it seemingly exerts a dual function in pathology. For instance, in normal cells and during early phases of carcinogenesis, CLU may inhibit tumor progression as it contributes to suppression of proteotoxic stress. In advanced neoplasia, however, it may offer a significant survival advantage in the tumor by suppressing many therapeutic stressors and enhancing metastasis. This review will critically present a synopsis of recent novel findings that relate to the function of this amazing molecule and support the notion that CLU is a biosensor of oxidative injury; a common link between ageing and all pathologies where CLU has been implicated. Potential future perspectives, implications and opportunities for translational research and the development of new therapies will be discussed.
High Proportions of CD4+ T Cells among Residual Bone Marrow T Cells in Childhood Acute Lymphoblastic Leukemia Are Associated with Favorable Early Responses
Authors: Lustfeld Imke , Altvater Bianca , Ahlmann Martina , Ligges Sandra , Brinkrolf Peter , Rosemann Annegret , Moericke Anja , Rossig Claudia
Published: September 2013

Residual nonmalignant T cells in the bone marrow of patients with acute leukemias may be involved in active immune responses to leukemic cells. Here, we investigated the phenotypic signature of T cells present at diagnosis in 39 pediatric patients with acute lymphoblastic leukemia (ALL) treated within standardized ALL-BFM study protocols. Previously described age associations of lymphocyte subpopulations in the peripheral blood of healthy children were reproduced in leukemic bone marrow. Analysis of individual lymphocyte parameters and risk-associated variables using univariate linear regression models revealed a correlation of higher CD4/CD8 ratios at diagnosis with a favorable bone marrow response on day 15. Separate analysis of CD4+ cells with the CD4+CD25hiFoxP3+ Treg cell phenotype showed that the association was caused by non-Treg CD4+ cells. The association of higher CD4/CD8 ratios with a favorable bone marrow response on day 15 of treatment persisted in a cohort extended to 69 patients. We conclude that CD4+ non-Treg cells in leukemic bone marrow at diagnosis may have a role in early response to treatment. Prospective analysis of the CD4/CD8 ratio in a large cohort of pediatric patients is now needed. Moreover, future experiments will establish the functional role of the individual T cell subsets in immune control in pediatric ALL.
Parodontitis aus systemischer Sicht: Ein erweitertes Behandlungskonzept mit Padma Circosan
Authors: Müller Wolfgang
Published: September 2013

Hintergrund: Parodontitis ist eine chronische Entzündung des Zahnhalteapparats, mit Bildung von bakteriellen Biofilmen in den Gingivaltaschen. Die Entzündungskaskade ist schwer zu unterbrechen und führt zur Zerstörung des Zahnhalteapparats und somit auch zu Knochenabbau sowie zu einem systemischen Entzündungszustand. Dieser kann Erkrankungen wie Atherosklerose, Diabetes, endotheliale Dysfunktion und kardiovaskuläre Ereignisse begünstigen. Falldarstellung: Ein integrativer Behandlungsansatz beinhaltet neben der Behandlung der Parodontitis (in unserer Praxis in Anlehnung an das Würzburger Konzept) auch eine anti-entzündliche Therapie. Die Auswertung von 10 Fallberichten von Patienten mit chronischer Parodontitis, die zusätzlich mit dem Tibetischen Arzneimittel Padma Circosan behandelt wurden, zeigte nach 6 Monaten eine deutliche Reduktion der Stellen mit Sondierungstiefe ≥ 4 mm (-64%) und der Blutung nach Sondierung (-87%). Schlussfolgerung: Aufgrund seiner entzündungshemmenden, antioxidativen und durchblutungsfördernden Wirkungen eignet sich Padma Circosan gut für die additive Behandlung der Parodontitis im Rahmen eines integrativen Therapiekonzepts.
The Effect of Acitretin Treatment on Insulin Resistance, Retinol-Binding Protein-4, Leptin, and Adiponectin in Psoriasis Vulgaris: A Noncontrolled Study
Authors: Karadag Ayse Serap , Ertugrul Derun Taner , Kalkan Goknur , Bilgili Serap Gunes , Celik Huseyin Tugrul , Takci Zennure , Balahoroglu Ragıp , Calka Omer
Published: September 2013

Background/Aim: To investigate the effects of acitretin treatment on insulin resistance (IR) and adipokines, particularly retinol-binding protein (RBP)-4. Methods: Thirty-four patients with chronic plaque psoriasis and a control group of 34 healthy volunteers were recruited in the study. Screening for the parameters was performed before starting and after 3 months of acitretin treatment in the psoriasis group. The control group was only evaluated at the beginning of the study and did not receive placebo. We could not compare our results with a placebo control group because of ethical reasons. Results: Basal adiponectin (p = 0.01), insulin (p < 0.0001) levels and homeostasis model assessment (HOMA) IR (p < 0.0001) were significantly higher in psoriasis patients. After the treatment, insulin (p = 0.014), C peptide (p = 0.011), RBP-4 (p < 0.0001) levels and HOMA-IR (p = 0.008) decreased significantly. Posttreatment leptin (p = 0.036) levels were significantly lower than those of the controls. Posttreatment adiponectin (p = 0.005) and insulin (p = 0.048) levels were higher than those of the controls. Conclusions: This study showed for the first time that RBP-4 levels and IR are decreased significantly with acitretin treatment. This finding is very important in psoriasis patients because psoriasis may cause insulin resistance and diabetes. Further experimental and clinical studies are needed to clarify the effect of acitretin on adipocyte structure and behavior.
Comparative Demography of Two Commensal Macaques in India: Implications for Population Status and Conservation
Authors: Kumar Rishi , Sinha Anindya , Radhakrishna Sindhu
Published: September 2013

Rhesus and bonnet macaques are among the most common primates found in India and have been categorised as being of Least Concern by the IUCN. Despite the wealth of information on their ecology and behaviour, little attention has been paid to their demography or population status. We studied the demographic status of the two species along their common distribution zone in western, central and south-eastern India. Bonnet macaques were largely found in forest areas whereas rhesus macaques were observed more often in human-dominated habitats. The troop sizes of the two species also tended to be largest in different habitats, bonnet macaques in forested areas and rhesus macaques in urban areas. We suggest that the presence of large numbers of rhesus macaques in anthropogenic areas in south-eastern India is not a natural phenomenon but has been caused by human intervention. The bonnet macaque population has decreased in number in the common distribution zone, and as this species, unlike the rhesus macaque, is endemic to India, we strongly recommend the need to reassess its conservation status.
Dyslipidemia in Patients with Chronic and End-Stage Kidney Disease
Authors: Omran Jad , Al-Dadah Ashraf , Dellsperger Kevin C.
Published: September 2013

In this review, we discuss the physiology, diagnosis and treatment of dyslipidemia in patients with chronic and end-stage renal disease. The recent important clinical trials in patients with chronic kidney disease and dyslipidemia are reviewed. Because of the lack of evidence in treating lipid abnormalities in this specific patient population, we propose that future studies should focus on the pathophysiological mechanisms and treatment of dyslipidemia in this special patient population.
The ASCOD Phenotyping of Ischemic Stroke (Updated ASCO Phenotyping)
Authors: Amarenco P. , Bogousslavsky J. , Caplan L.R. , Donnan G.A. , Wolf M.E. , Hennerici M.G.
Published: September 2013

ASCO phenotyping (A: atherosclerosis; S: small-vessel disease; C: cardiac pathology; O: other causes) assigns a degree of likelihood of causal relationship to every potential disease (1 for potentially causal, 2 for causality is uncertain, 3 for unlikely causal but the disease is present, 0 for absence of disease, and 9 for insufficient workup to rule out the disease) commonly encountered in ischemic stroke describing all underlying diseases in every patient. In this new evolution of ASCO called ASCOD, we have added a ‘D' for dissection, recognizing that dissection is a very frequent disease in young stroke patients. We have also simplified the system by leaving out the ‘levels of diagnostic evidence', which has been integrated into grades 9 and 0. Moreover, we have also changed the cutoff for significant carotid or intracranial stenosis from 70% to more commonly used 50% luminal stenosis, and added a cardiogenic stroke pattern using neuroimaging. ASCOD captures and weights the overlap between all underlying diseases present in ischemic stroke patients.
Validity and Applications of the Montreal Cognitive Assessment for the Assessment of Vascular Cognitive Impairment
Authors: Koski Lisa
Published: September 2013

Cognitive impairment is common among patients with stroke or other cerebrovascular disease and influences long-term outcome, including occupational functioning. Recognition and monitoring of mild cognitive impairment is thus essential to good patient care. The Montreal Cognitive Assessment (MoCA) has been suggested as a brief screening test of vascular cognitive impairment. This paper presents a critical review of the research literature evaluating the validity and utility of this test with the aim of informing future clinical and research practice. A total of 30 papers employing the MoCA in the context of cerebrovascular disease were identified. Reporting of the methods and results of such studies tended to fall short of the established reporting guidelines. Under-specification of the exclusion criteria applied and their impact make it difficult to assess the potential impact of sampling bias and loss to follow-up. Nevertheless, content validity evidence suggests that the MoCA covers most of the domains that represent cognitive impairment in cerebrovascular disease, with mixed evidence for its preferential sensitivity to the type of cognitive impairment encountered in the context of vascular disease. Evidence clearly supports the need to establish norms and cut-offs for the MoCA that are culturally appropriate and that are matched to the range of cognitive impairment that is present in the population being assessed. Recent modifications of the MoCA have been developed for assessing patients with visual impairment or restricted mobility, which may reduce the impact of ‘untestability' on cognitive screening in the clinic or research context. The MoCA correlates well with other measures of cognitive and functional abilities in patients with cerebrovascular disease, and may also predict future response to rehabilitation and long-term occupational outcome. Further research is needed to provide evidence for the validity of the MoCA in longitudinal studies. However, it compares favourably to the Mini Mental State Examination as a screening test that is sensitive to the milder forms of cognitive impairment that often accompany cerebrovascular disease.
Cognitive Patterns in Relation to Biomarkers of Cerebrovascular Disease and Vascular Risk Factors
Authors: Miralbell Júlia , López-Cancio Elena , López-Oloriz Jorge , Arenillas Juan Francisco , Barrios Maite , Soriano-Raya Juan José , Galán Amparo , Cáceres Cynthia , Alzamora Maite , Pera Guillem , Toran Pere , Dávalos Antoni , Mataró Maria
Published: September 2013

Background: Risk factors for vascular cognitive impairment (VCI) are the same as traditional risk factors for cerebrovascular disease (CVD). Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. In addition to traditional vascular risk factors (VRF), circulating biomarkers have emerged as potential tools for early diagnoses, as they could provide in vivo measures of the underlying pathophysiology. While VRF have been consistently linked to a VCI profile (i.e., deficits in executive functions and processing speed), the cognitive correlates of CVD biomarkers remain unclear. In this population-based study, the aim was to study and compare cognitive patterns in relation to VRF and circulating biomarkers of CVD. Methods: The Barcelona-AsIA Neuropsychology Study included 747 subjects older than 50, without a prior history of stroke or coronary disease and with a moderate to high vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were derived from factoral analysis: visuospatial skills/speed, verbal memory and verbal fluency. Multiple linear regression was used to assess relationships between cognitive performance (multiple domains) and a panel of circulating biomarkers, including indicators of inflammation, C-reactive protein (CRP) and resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA), thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for insulin resistance index). Analyses were adjusted for age, gender, years of education and depressive symptoms. Results: Traditional VRF were related to lower performance in verbal fluency, insulin resistance accounted for lower performance in visuospatial skills/speed and the metabolic syndrome predicted lower performance in both cognitive domains. From the biomarkers of CVD, CRP was negatively related to verbal fluency performance and increasing ADMA levels were associated with lower performance in verbal memory. Resistin and PAI-1 did not relate to cognitive function performance. Conclusion: Vascular risk factors, and markers of inflammation and endothelial dysfunction predicted lower performance in several cognitive domains. Specifically, cognitive functions associated with CRP are typically affected in VCI and overlap those related to VRF. ADMA indicated a dissociation in the cognitive profile involving verbal memory. These findings suggest that inflammation and endothelial dysfunction might play a role in the predementia cognitive impairment stages.
Cardiac Surgery-Associated Acute Kidney Injury
Authors: Mao Huijuan , Katz Nevin , Ariyanon Wassawon , Blanca-Martos Lourdes , Adýbelli Zelal , Giuliani Anna , Danesi Tommaso Hinna , Kim Jeong Chul , Nayak Akash , Neri Mauro , Virzi Grazia Maria , Brocca Alessandra , Scalzotto Elisa , Salvador Loris , Ronco Claudio
Published: September 2013

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy.
The Cardiorenal Syndrome: What the Cardiologist Needs to Know
Authors: Waldum Bård , Os Ingrid
Published: September 2013

Interactions between the heart and the kidneys are increasingly acknowledged among both cardiologists and nephrologists. The term cardiorenal syndrome now applies to the bidirectional nature of how disease in one organ system affects the function of the other organ system. Cardiovascular disease is a major threat to patients with chronic kidney disease, while renal dysfunction is prevalent in patients with cardiac disease and is a significant predictor of prognosis in cardiac patients. Still, renal patients with cardiac disease have largely been excluded from the clinical trials that have been the basis of modern cardiologic treatment. In this review, the current understanding of the pathophysiological mechanisms involved in the cardiorenal syndrome and potential therapeutic implications will be summarized from a nephrologist's point of view. Probably, fragile cardiorenal patients will benefit from an enhanced collaboration between cardiologists and nephrologists to secure the best treatment given under safe conditions.
Cerebrospinal Fluid Tau Levels Predict Prognosis in Non-Inherited Frontotemporal Dementia
Authors: Borroni Barbara , Benussi Alberto , Cosseddu Maura , Archetti Silvana , Padovani Alessandro
Published: September 2013

Background: The course of frontotemporal dementia (FTD) is heterogeneous and no predictors of survival are currently available. Cerebrospinal fluid (CSF) tau dosage has been demonstrated to be useful in predicting outcome over time in a number of neurological disorders. Objective: To assess CSF tau levels in FTD and to evaluate their prognostic value. Methods: Seventy-seven FTD patients with no mutations in known causative genes were consecutively enrolled, and CSF tau and phospho-tau levels analysed. Each patient was reassessed over time, and survival (i.e. death/bedridden and otherwise) was evaluated. The survival analysis was carried out by Cox proportional hazards regression models. Results: Patients with high CSF tau levels (≥400 pg/ml) had shorter survival than those with low CSF tau levels [hazard ratio (HR) = 3.406; 95% CI: 1.151-10.077; Wald χ2 = 4.902; d.f. = 1; p = 0.027]. The association between tau levels and survival probability was confirmed after adjusting for age, gender, clinical phenotype and FTD clinical dementia rating at enrolment (HR = 3.769; 95% CI: 1.143-12.433; Wald χ2 = 4.748; d.f. = 1; p = 0.029). Neither demographic or clinical characteristics nor CSF phospho-tau levels or apolipoprotein E genotype were significantly associated with prognosis. Conclusions: This study argues that CSF tau levels may be considered in FTD to predict patients' outcome. Establishing in vivo prognostic biomarkers is mandatory to define homogeneous groups for inclusion in future clinical trials and to monitor the effectiveness of future therapeutic approaches.