bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Incident Diabetes Mellitus in Basrah, Iraq
Authors: Mansour Abbas Ali , Al-Jazairi Meelad Imad
Published: July 2007

Background: New-onset diabetes was associated with a 90% increase in risk of all-cause mortality and a 120% increase in risk of cardiovascular mortality compared with study participants without diabetes. The aim of this study was to study prospectively the predictors of incident diabetes mellitus in Basrah, Iraq, with special emphasis on predictive performance of the four anthropometric variables of obesity, namely body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHpR) or waist-to-height ratio (WHtR). Material and Methods: A total of 13,730 subjects (7,101 males and 6,629 females) diabetes-free at baseline were followed for a mean of 5 years (January 2001 to end of December 2006). Results: There were 935 (6.80%) cases of incident diabetes (513 males and 422 females). All anthropometric indices (BMI, WC, WHpR, WHtR) were higher among those with incident diabetes (p < 0.001). In both sexes, WHpR has the strongest associations with incident diabetes that was gender-insensitive (AUC = 0.74 in males and 0.72 in females) followed by WC and then BMI which has the weakest association with incident diabetes. On multivariable logistic regression, only hypertension (OR 1.66; 95% CI 1.41–1.96; p < 0.001) was associated with incident diabetes. All anthropometric indices were significantly associated with incident diabetes except WHtR. There was no association between incident diabetes and gender, age, stroke, and ischemic heart disease. Conclusion: In both sexes, WHpR has the strongest associations with incident diabetes, followed by WC then BMI which has the weakest association with incident diabetes, while WHtR has no association. Hypertension is the only non-anthropometric variable associated with incident diabetes.
Physical Performance and School Physical Education in Overweight Spanish Children
Authors: Casajús José A. , Leiva María T. , Villarroya Adoración , Legaz Alejandro , Moreno Luis A.
Published: July 2007

Aims: To evaluate the effect of physical performance and extracurricular organized physical activities (EOPA) in normal- and overweight children. Methods: A random sample of 1,068 schoolchildren (7–12 years old) representative of the region of Aragon (Spain) was selected and divided into normal-, overweight and obese groups based on previously published body mass index reference standards. Physical performance was assessed by the European physical test battery. EOPA were estimated when children performed at least 3 h per week during the previous year in addition to school physical education. Results: Overweight and obese subjects had lower performances on all tests requiring propulsion or lifting of the body mass (standing-broad jump, sit-ups, bent-arm hangs, speed shuttle run and endurance shuttle run) when compared with normal-weight counterparts (p < 0.001). The overweight and obese children showed greater hand grip strength measures than the normal-weight ones (p < 0.001). Plate tapping and sit reach test scores were similar in both groups. The participation in EOPA was similar in normal- and overweight or obese groups; however, a significant increase with age was observed (p < 0.01). Conclusion: In this age group, overweight was not related to EOPA participation. Overweight children had poorer results on weight-bearing tasks. The good results in static strength, coordination and speed of limb movements in overweight children should be considered in the promotion of physical activity programs for overweight children.
Follow-Up of Cholesteatoma Surgery: Open versus Closed Tympanoplasty
Authors: Stankovic Milan
Published: July 2007

Background: There are no universally accepted opinions about the choice of surgical technique and outcome of surgery for cholesteatoma in different age groups and localizations. Methods: A prospective study of 758 patients with cholesteatomas was performed. They were divided into three age groups: children younger than 9 years, adolescents aged 10–16 years, and adults. Cholesteatoma was classified as: attic, sinus and tensa cholesteatoma. Classical canal wall-up or wall-down tympanoplasty was performed in all the cases, and reoperation was done later if needed. Anatomical and functional results were followed up regularly, and evaluated 3 years after the operations. Results: During the postoperative course, after 3 years, retraction of the neomembrane was found in 23.8% of younger children, 27.6% of adolescents, and in 9.9% of adults. Recurrent cholesteatomas were more than twice as frequent in children (19.0%) as in adults (9.4%). Reoperation was performed in 38.1% of children and in 9.4% adults. In one fourth of pediatric cholesteatoma reoperations, conversion to open tympanoplasty was done. Retraction and recurrent disease were present in about 10% of attic and sinus cholesteatomas, and in 15.5% of tensa cholesteatomas. Conclusion: Postoperative audiological results of cholesteatoma surgery in children are comparable to adults. Retraction pockets, recurrent cholesteatomas and reoperations are twice as frequent in the pediatric group as in adults. The worst anatomical and functional results are achieved in tensa cholesteatomas. The age of the patient and localization of cholesteatoma are very important factors that determine the type of surgical procedure and the results of surgery for middle ear cholesteatoma. A closed technique is better for attic and sinus cholesteatomas, while in tensa cholesteatomas, an open technique seems more appropriate.
A Randomized, Double-Blind Study to Assess the Efficacy and Safety of Valtropin, a Biosimilar Growth Hormone, in Children with Growth Hormone Deficiency
Authors: Peterkova Valentina , Arslanoglu Ilknur , Bolshova-Zubkovskaya Elena , Romer Tomasz , Zdravkovic Dragan , Kratzsch Jürgen , Ji Hyi-Jeong , Savoy Conrad , Saenger Paul
Published: July 2007

Valtropin is a recombinant human GH (rhGH) manufactured using a novel yeast expression system, classed as a ‘biosimilar’. Valtropin was compared with Humatrope in children with GH deficiency (GHD). Treatment-naive, prepubertal children with GHD were randomized to Valtropin (n = 98) or Humatrope (n = 49) for 1 year. Standing height was measured 3-monthly and height velocity (HV) calculated. Serum IGF-I, IGFBP-3 and GH antibodies were determined centrally. HV at 1 year was 11.3 ± 3.0 cm/year with Valtropin and 10.5 ± 2.8 cm/year with Humatrope. Treatment difference was 0.09 cm/year with 95% confidence limits of –0.71, 0.90, within the preset non-inferiority limit of –2.0 cm/year. Height standard deviation (SD) scores were increased in both treatment arms with no acceleration of bone maturation. IGF-I and IGFBP-3 were increased comparably for both treatments. Adverse events showed no clinically relevant differences between treatment groups. Anti-GH antibodies were detected in 3 (3.1%) Valtropin and 1 (2.0%) Humatrope patients and the growth pattern was indistinguishable from the rest of the cohort. The 1-year efficacy and safety profile of Valtropin, a new biosimilar rhGH, are equivalent to the comparator rhGH, Humatrope. Valtropin can be used for the treatment of children with GHD and longer term data will fully establish its efficacy and safety profile.
Exercise Endurance before and after Long-Term Noninvasive Ventilation in Patients with Chronic Respiratory Failure
Authors: Schönhofer Bernd , Dellweg Dominic , Suchi Stefan , Köhler Dieter
Published: July 2007

Background: Noninvasive mechanical ventilation (NIV) is known to reduce hypoventilation and improves respiratory and peripheral muscle endurance in patients with chronic respiratory failure (CRF) due to thoracic restriction. Objectives: To compare the effect of short-term NIV on endurance in patients with CRF due to thoracorestriction and chronic obstructive pulmonary disease (COPD) and to evaluate differences in spiroergometric data during exercise testing. Methods: Thirty-five patients with CRF due to COPD and 24 patients with CRF due to thoracorestriction entered the trial. Constant work rate exercise testing at 75% of the maximal workload, pulmonary function and arterial blood gas testing were performed before and after 3 months of NIV. Measurements were compared between and within groups. Results: The non-COPD group increased their exercise time significantly from 4.7 ± 1.81 to 6.59 ± 3.15 min (p = 0.0032). There was no change in the COPD group (4.57 ± 2.19 min before and 5.39 ± 3.09 min after NIV, p = 0.09). CO2 levels at rest fell in both groups (COPD 52.30 ± 7.77 to 46.06 ± 4.61 mm Hg and non-COPD 47.82 ± 5.19 to 43.79 ± 4.15 mm Hg). While COPD patients increased their minute ventilation (13.47 ± 2.73 to 14.88 ± 2.67 l/min), non-COPD patients decreased their oxygen uptake from 6.27 ± 1.61 to 5.54 ± 1.35 ml/kg. Conclusions: NIV improved endurance only in the non-COPD group. This and the reduction in CO2 are achieved by lowering energetic requirements. COPD patients though decreased their resting CO2 by increased minute ventilation.
How Peer Proximity Moderates Indirect Media Influence on Adolescent Smoking
Authors: Paek Hye-Jin , Gunther Albert C.
Published: July 2007

This study examines direct and indirect impacts of antismoking media messages on adolescents' smoking attitudes and intentions to smoke. Elaborating on the influence of presumed influence model, this study incorporates the moderating role of peer proximity (i.e., proximal versus distal peers). Analyzing direct effects in a survey of 1,687 middle school students, we find that antismoking media messages have unexpected effects among both ever-smokers (experimenters and established smokers) and never-smokers. But analysis of indirect paths reveal significant effects in the intended direction. In addition, these effects are moderated by peer proximity. Respondents' perception that proximal peers, but not distal peers, are more influenced by such messages lead to a significant decrease in their favorable thoughts toward smoking and intention to smoke. The data suggest that antismoking messages may only achieve their desired effect via the indirect influence path.
Grounding the Management of Liabilities in the Risk Analysis Framework
Authors: Phillips Peter W. B. , Smyth Stuart
Published: July 2007

Discussions of socioeconomic liability and compensation must necessarily start from an understanding of the socioeconomic, legal, and scientific basis for identifying, assessing, managing, and apportioning blame for hazards related to innovations. Public discussions about the nature of the liability challenge related to genetically modified (GM) crops and other modified organisms have focused less on direct, traditional health, public safety, technical, or environmental failures (e.g., innovations that generate hazards directly for users or indirectly to bystanders) and more on socioeconomic concerns, such as comingled product that offends product quality standards. This article examines the theoretical and legal underpinnings of the current risk analysis framework used in most Organization for Economic Cooperation and Development countries and uses it to assess two areas of significant controversy—the release of herbicide-tolerant canola and flax varieties in Western Canada. The article offers lessons for the management of liabilities arising from the introduction of GM crops.
Intellectual Property Law as an Internal Limit on Intellectual Property Rights and Autonomous Source of Liability for Intellectual Property Owners
Authors: Judge Elizabeth F.
Published: July 2007

This article considers the interplay between intellectual property rights and classic property rights raised by Hoffman v. Monsanto (2005) and advances the idea that intellectual property law can serve as an autonomous source of liability for intellectual property owners. The article develops the conceptual advantages of demarcating physical and intellectual properties and allocating rights and responsibilities based on the respective property sphere. It introduces a theoretical Hohfeldian framework, in which the grant of a positive limited-term monopoly right entails a corresponding duty, to establish intellectual property law as a source of internal limits on intellectual property rights. The article is a prolegomena to a detailed matrix of those rights and duties within intellectual property law. This matrix could support patentee duties that go beyond public disclosure of the invention and could establish patent law as an alternative legal framework to tort law to address harms caused by inventions.
Adventitious Presence of Patented Genetically Modified Organisms on Private Premises: Is Intent Necessary for Actions in Infringement Against the Property Owner?
Authors: Mgbeoji Ikechi
Published: July 2007

The law of patents has long struggled with the status of intent in determining liability for infringement. This struggle has recently been given a sharper edge by the emergence of biotechnological products with the inherent ability of auto-dispersal and regeneration. The question thus is whether a person on whose backyard a patented genetic organism has grown without the active intervention of that person is liable in infringement to the patentee of that organism. This article examines the ramifications of the legal conundrum and argues that on a proper construction of the theories of liability in patent law intent to infringe is necessarily crucial if the nature of the subject matter of the patent makes it unjust and absurd to argue otherwise.
Research on the Structure and Performance of Bacterial Magnetic Nanoparticles
Authors: Lei Han  , Li Shuang-Yan , Yong Yang  , Zhao Feng-Mei , Jie Huang  , Jin Chang
Published: July 2007

Magnetite nanocrystals have been widely used in many fields. Recently, a new magnetite nanocrystals, called magnetosome, has been found in magnetotactic bacteria. In this article, we researched on the properties of magnetosomes in detail, such as crystalline, morphology, crystal-size distributions, vitro cytotoxicity, and magnetic properties and quantified primary amino groups on the magnetosomes membrane surface by fluorescamine assay for the first time. From the results, it was clear that magnetosomes have more potential in the biomedical applications than synthetic magnetite.
Properties of Zinc Releasing Surfaces for Clinical Applications
Authors: Lusvardi G. , Malavasi G. , Menabue L. , Menziani M.C. , Pedone A. , Segre U. , Aina V. , Perardi A. , Morterra C. , Boccafoschi F. , Gatti S. , Bosetti M. , Cannas M.
Published: July 2007

Two series of glasses of general formula (2-p) SiO2·1.1Na 2O·CaO·pP2O5·xZnO (p=0.10, 0.20; x=0.0, 0.16, 0.35, and 0.78) have been analyzed for physico-chemical surface features before and after contact with simulated body fluid, morphological characteristics, and osteoblast-like cells behavior when cultured on them. The resulted good cell adhesion and growth, along with nonsignificant changes of the focal contacts, allow the authors to indicate HZ5 and HP5Z5 glasses as the ones having optimal ratio of Zn/P to maintain acceptable cell behavior, comparable to the bioactive glass (Bioglass®) used as a control; results are also rationalized by means of three-dimensional models derived by molecular dynamic simulations, with decomposition and conversion rates optimized with respect to the parent Hench's Bioglass®.
Design and Analysis of a Superelastic SMA Damper
Authors: Zuo Xiao-Bao , Li Ai-Qun , Chen Qing-Fu
Published: July 2007

Based on the superelasticity of shape memory alloy (SMA), a superelastic SMA damper is designed, and its analytical model has been established and verified by experimental results. Numerical simulation is carried out to investigate the effects of the damper's parameters on its behaviors, such as groove depth, SMA wire amount, and friction coefficient, temperature and displacement amplitude. Results show that initial stiffness, external force, and dissipated energy of the SMA damper increase linearly with groove depth, SMA amount, and friction coefficient. Under different displacement amplitudes, the shapes of the external force—displacement curve of the damper are polygons, such as triangle, quadrangle, and pentagon, respectively, hence the SMA damper is a variable-stiffness type damper. In addition, experimental results indicate that the model can be used to simulate the mechanical behavior of the damper.
Performance Improvement of a Rotary MR Fluid Actuator Based on Electromagnetic Design
Authors: Nam Yun-Joo , Moon Young-Jin , Park Myeong-Kwan
Published: July 2007

This study presents an electromagnetic design methodology for a rotary magnetorheological (MR) fluid actuator. In order to improve the performance of the MR fluid actuator, the magnetic field should be effectively applied to the MR fluid. Therefore, it is important that the magnetic circuit composed of the MR fluid, the ferromagnetic material for magnetic flux path, and the electromagnetic coil is well designed. For this purpose, two effective approaches are proposed: one is to shorten the magnetic flux path by removing the unnecessary bulk of the yoke in order to improve the static characteristic of the MR fluid actuator, and the other is to increase the magnetic reluctance of the magnetic circuit by minimizing the cross-sectional area of the yoke through which the magnetic flux passes in order to improve the dynamic and hysteretic characteristics. The effectiveness of the proposed design methodology is verified through magnetic analysis and a series of basic experiments.
Damage Detection for Framed RCC Buildings using ANN Modeling
Authors: Kanwar Varinder , Kwatra Naveen , Aggarwal Pankaj
Published: July 2007

A structure is evaluated, after an earthquake, to find out whether it is usable or requires repair and retrofitting. The natural time period, damping, and mode shape are the primary dynamic characteristics of any structure that is related to seismic forces during an earthquake event. Periodic monitoring using vibration measurements is one of the most effective nondestructive methods to identify the damage level. A significant deviation in natural frequencies or damping ratios from the undamaged states indicates the possible occurrence of damage. In the present study, the dynamic characteristics of a 2D rigid frame of a reinforced concrete building are obtained analytically under different levels of damage. Further, using an artificial neural network (ANN) model the authors have developed a correlation between the damage in the frame of the reinforced concrete building with its known dynamic characteristics. Use of such correlations for evaluating the health status of the buildings has been discussed.
Increasing incidence of multiple sclerosis among women in Lorraine, Eastern France
Authors: Debouverie M. , Pittion-Vouyovitch S. , Louis S. , Roederer T. , Guillemin F.
Published: July 2007

This study aims to describe the prevalence and incidence rates of multiple sclerosis (MS) in Lorraine, France, and its secular trend from 1990 to 2002. Cases were sourced from the regional network of MS healthcare workers in the Lorraine region and include all cases with definite or probable MS according to Poser's criteria. We identified 2718 patients with MS on 31 December 2004. The prevalence rate was 120/100 000 (95% confidence interval [CI]: 119—121). Between 1990 and 2002, the average age- and sex-adjusted annual incidence rate was 5.5/100 000 (95% CI: 4.4—6.6). During this same period, there was a significant increase in overall incidence in women but not in men. The mean age at MS onset, disability score five years after onset, number of relapses during the first five years, and proportion of first attack with sequelae or polysymptomatic symptoms were not significantly different between each annual cohort during the study period. The prevalence and incidence rates of MS we found in our study were higher than in previous studies in France. The increase in incidence of MS between 1990 and 2002, mostly in women, was not related to better ascertainment of patients with mild disability. Multiple Sclerosis 2007; 13: 962—967. http://msj.sagepub.com
Validity of performance scales for disability assessment in multiple sclerosis
Authors: Marrie R.A. , Goldman M.
Published: July 2007

Researchers increasingly use self-reported health status assessments, but these require validation. Performance Scales (PS) is a self-report measure for multiple sclerosis (MS)-associated disability, assessing mobility, bowel/bladder, fatigue, sensory, vision, cognition, spasticity and hand function. The criterion validity of the total PS score was established using the Expanded Disability Status Scale (EDSS), but the construct and criterion validity of the individual subscales have not been established. We assessed the criterion and construct validity of the PS subscales. Forty-four patients with MS completed PS, and these criterion measurements: neurological examination (EDSS), the Multiple Sclerosis Functional Composite (MSFC), contrast acuity testing, and the Multiple Sclerosis Quality of Life Inventory. We assessed criterion and construct validity with Spearman rank correlations between PS subscales and the other measurements. PS correlated with the MSFC ( r = -0.58, P < 0.0001). The mobility, hand, vision, fatigue and bladder subscales correlated with their criterion measures ( r = 0.59—0.77, P < 0.0001). The sensory subscale correlated weakly with the sensory functional system score ( r = 0.39, P = 0.01 ), and the cognitive subscale did not correlate with the PASAT ( r = -0.17, P = 0.26). This study supports the criterion and construct validity of PS overall, and its mobility, hand, vision, fatigue, and bladder subscales. Further assessment of the cognitive, sensory and spasticity subscales is needed. Multiple Sclerosis 2007; 13: 1176—1182. http://msj.sagepub.com
Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study
Authors: Pöhlau D. , Przuntek H. , Sailer M. , Bethke F. , Koehler J. , König N. , Heesen C. , Späth P. , Andresen I.
Published: July 2007

In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS ( n = 34) and SPMS ( n = 197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group ( P = 0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions.

In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks ( P = 0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score.

In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group ( P = 0.028). The difference was significant in PPMS ( P = 0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance ( P = 0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS. Multiple Sclerosis 2007; 13: 1107—1117. http://msj.sagepub.com
Cultural Influences in Negotiations
Authors: Metcalf Lynn E. , Bird Allan , Peterson Mark F. , Shankarmahesh Mahesh , Lituchy Terri R.
Published: July 2007

Empirical work systematically comparing variations across a range of countries is scarce. A comprehensive framework having the potential to yield comparable information across countries on 12 negotiating tendencies was proposed more than 20 years ago by Weiss and Stripp; however, the framework was never operationalized or empirically tested. A review of the negotiation and cross cultural research that have accumulated over the last two decades led to refinements in the definition of the dimensions in the framework. We operationalized four dimensions in the Negotiation Orientations Framework and developed the Negotiation Orientations Inventory (NOI) to assess individual orientations on those four dimensions. Data were collected from a sample of 1000 business people and university students with business experience from Finland, Mexico, Turkey, and the United States. Results are presented and further scale development is discussed. Findings establish the utility of the dimensions in the framework in making comparisons between the four countries.
Transformational Leadership in India
Authors: Singh Niti , Krishnan Venkat R.
Published: July 2007

This article reports on three studies that used a combination of methods to develop a measure of transformational leadership in India. The grounded theory approach was followed for generating the initial item-pool ( n = 250). In the second study ( n = 379), an exploratory factor analysis was conducted, followed by a confirmatory factor analysis, which resulted in a six-factor model. The factors show support for both universal as well as unique cultural dimensions. In the third study ( n = 202; 101 manager—subordinate dyads) survey data were collected and support was found for sound psychometric properties of the new scale, including incremental, discriminant, convergent, and predictive validity. The new scale explained significant variance over and above the variance explained by the currently existing scale for measuring transformational leadership.
Artificial neural network models for prediction of intestinal permeability of oligopeptides
Authors: Jung Eunkyoung , Kim Junhyoung , Kim Minkyoung , Jung Dong Hyun , Rhee Hokyoung , Shin Jae-Min , Choi Kihang , Kang Sang-Kee , Kim Min-Kook , Yun Cheol-Heui , Choi Yun-Jaie , Choi Seung-Hoon
Published: July 2007

Background

Oral delivery is a highly desirable property for candidate drugs under development. Computational modeling could provide a quick and inexpensive way to assess the intestinal permeability of a molecule. Although there have been several studies aimed at predicting the intestinal absorption of chemical compounds, there have been no attempts to predict intestinal permeability on the basis of peptide sequence information. To develop models for predicting the intestinal permeability of peptides, we adopted an artificial neural network as a machine-learning algorithm. The positive control data consisted of intestinal barrier-permeable peptides obtained by the peroral phage display technique, and the negative control data were prepared from random sequences.

Results

The capacity of our models to make appropriate predictions was validated by statistical indicators including sensitivity, specificity, enrichment curve, and the area under the receiver operating characteristic (ROC) curve (the ROC score). The training and test set statistics indicated that our models were of strikingly good quality and could discriminate between permeable and random sequences with a high level of confidence.

Conclusion

We developed artificial neural network models to predict the intestinal permeabilities of oligopeptides on the basis of peptide sequence information. Both binary and VHSE (principal components score V ectors of H ydrophobic, S teric and E lectronic properties) descriptors produced statistically significant training models; the models with simple neural network architectures showed slightly greater predictive power than those with complex ones. We anticipate that our models will be applicable to the selection of intestinal barrier-permeable peptides for generating peptide drugs or peptidomimetics.
Peripheral nervous system manifestations in a Sandhoff disease mouse model: nerve conduction, myelin structure, lipid analysis
Authors: McNally Melanie A , Baek Rena C , Avila Robin L , Seyfried Thomas N , Strichartz Gary R , Kirschner Daniel A
Published: July 2007

Background

Sandhoff disease is an inherited lysosomal storage disease caused by a mutation in the gene for the β-subunit (Hexb gene) of β-hexosaminidase A (αβ) and B (ββ). The β-subunit together with the GM2 activator protein catabolize ganglioside GM2. This enzyme deficiency results in GM2 accumulation primarily in the central nervous system. To investigate how abnormal GM2 catabolism affects the peripheral nervous system in a mouse model of Sandhoff disease (Hexb-/-), we examined the electrophysiology of dissected sciatic nerves, structure of central and peripheral myelin, and lipid composition of the peripheral nervous system.

Results

We detected no significant difference in signal impulse conduction velocity or any consistent change in the frequency-dependent conduction slowing and failure between freshly dissected sciatic nerves from the Hexb+/- and Hexb-/- mice. The low-angle x-ray diffraction patterns from freshly dissected sciatic and optic nerves of Hexb+/- and Hexb-/- mice showed normal myelin periods; however, Hexb-/- mice displayed a ~10% decrease in the relative amount of compact optic nerve myelin, which is consistent with the previously established reduction in myelin-enriched lipids (cerebrosides and sulfatides) in brains of Hexb-/- mice. Finally, analysis of lipid composition revealed that GM2 content was present in the sciatic nerve of the Hexb-/- mice (undetectable in Hexb+/-).

Conclusion

Our findings demonstrate the absence of significant functional, structural, or compositional abnormalities in the peripheral nervous system of the murine model for Sandhoff disease, but do show the potential value of integrating multiple techniques to evaluate myelin structure and function in nervous system disorders.
Interleukin-6 Genetic Variability and Adiposity: Associations in Two Prospective Cohorts and Systematic Review in 26,944 Individuals
Authors: Qi Lu , Zhang Cuilin , van Dam Rob M. , Hu Frank B.
Published: July 2007

Context: IL-6 (IL6) is an immune-modulating cytokine associated with obesity in humans.

Objective: Our objective was to assess the associations between the genetic variability of IL6 gene and adiposity and long-term changes.

Design and Subjects: We determined the linkage disequilibrium-tagging single-nucleotide polymorphisms of IL6 gene in 2255 healthy women and 980 healthy men from two prospective cohorts. We also conducted a metaanalysis on the associations between polymorphism −174G>C (rs1800795) and adiposity.

Results: IL6 haplotype 222211 (possessing rs2069827, rs1800797, rs1800795, rs1554606, rs2069861, and rs1818879; 1 codes the common and 2 codes the minor alleles) was consistently and significantly associated with greater waist circumference (P = 0.009 in men; P = 0.0003 in women) and baseline body mass index (BMI) (P = 0.01 in men; P = 0.046 in women) compared with the most common haplotype 111112. Haplotype 222211 was also associated with significantly higher early-adulthood BMI in women (P = 0.007). The haplotype-associated difference in BMI persisted significantly during the follow-up. A 5′ promoter polymorphism, rs2069827, was consistently associated with significantly higher early-adulthood BMI, baseline BMI, and waist circumference in men (carriers vs. noncarriers, P = 0.01, 0.007, and 0.008) and women (P = 0.01, 0.10, and 0.0016). The data from this study and a metaanalysis of 26,944 individuals did not support substantial relations between the best-studied polymorphism, −174G>C, and adiposity.

Conclusions: Our data from two independent cohorts indicate that the variability of the IL6 gene is significantly associated with adiposity. Such associations are less likely to be caused by polymorphism −174G>C.
Gone with the Wnts: β-Catenin, T-Cell Factor, Forkhead Box O, and Oxidative Stress in Age-Dependent Diseases of Bone, Lipid, and Glucose Metabolism
Authors: Manolagas Stavros C. , Almeida Maria
Published: July 2007

The Wnt/β-catenin signaling pathway affects several biological processes ranging from embryonic development, patterning, and postembryonic stem cell fate, to bone formation and insulin secretion in adulthood. β-Catenin mediates canonical Wnt signaling by binding to and activating members of the T-cell factor (TCF) transcription factor family. Similar to the Wnt/β-catenin pathway, oxidative stress influences fundamental cellular processes including stem cell fate and has been linked to aging and the development of age-related diseases. However, the molecular details of the pathogenetic effects of oxidative stress on the homeostasis of many different tissues remain unclear. β-Catenin has been recently implicated as a pivotal molecule in defense against oxidative stress by serving as a cofactor of the forkhead box O (FOXO) transcription factors. In addition, it has been shown that oxidative stress is a pivotal pathogenetic factor of age-related bone loss and strength in mice, leading to, among other changes, a decrease in osteoblast number and bone formation. These particular cellular changes evidently result from diversion of the limited pool of β-catenin from TCF- to FOXO-mediated transcription in osteoblastic cells. Fascinatingly, attenuation of Wnt-mediated transcription, resulting from an autosomal-dominant missense mutation in LRP6, a coreceptor for the Wnt-signaling pathway, has been linked recently genetically not only to premature osteoporosis, but also to coronary artery disease as well as several features of the metabolic syndrome including hyperlipidemia, hypertension, and diabetes, but not obesity. In this minireview, we highlight evidence linking the age-associated oxidative stress with FOXOs, Wnt/β-catenin signaling, osteoblastogenesis, adipogenesis, osteoporosis, and several features of the metabolic syndrome. We hypothesize that antagonism of Wnt signaling by oxidative stress with increasing age may be a common molecular mechanism contributing to the development not only of involutional osteoporosis, but several pathologies such as atherosclerosis, insulin resistance, and hyperlipidemia, all of which become more prevalent with advancing age.
PIASxβ is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts
Authors: Ali Md. Moksed , Yoshizawa Tatsuya , Ishibashi Osamu , Matsuda Akio , Ikegame Mika , Shimomura Junko , Mera Hisashi , Nakashima Kazuhisa , Kawashima Hiroyuki
Published: July 2007

We recently reported that tensile stress induces osteoblast differentiation and osteogenesis in the mouse calvarial suture in vitro. Using this experimental system, we identified PIASxβ, a splice isoform of Pias2, as one of the genes most highly upregulated by tensile stress. Further study using cell culture revealed that this upregulation was transient and was accompanied by upregulation of other differentiation markers, including osterix, whereas expression of Runx2 was unaffected. Runx2 and osterix are the two master proteins controlling osteoblast differentiation, with Runx2 being upstream of osterix. Targeted knockdown of PIASxβ by small interfering RNA (siRNA) markedly suppressed osteoblastic differentiation and matrix mineralization, whereas transient overexpression of PIASxβ caused the exact opposite effects. Regardless of PIASxβ expression level, Runx2 expression remained constant. Reporter assays demonstrated that osterix enhanced its own promoter activity, which was further stimulated by PIASxβ but not by its sumoylation-defective mutant. NFATc1 and NFATc3 additionally increased osterix transcriptional activity when co-transfected with PIASxβ. Because osterix has no consensus motif for sumoylation, other proteins are probably involved in the PIASxβ-mediated activation and NFAT proteins may be among such targets. This study provides the first line of evidence that PIASxβ is indispensable for osteoblast differentiation and matrix mineralization, and that this signaling molecule is located between Runx2 and osterix.
Let’s Play with Valence Isomers: The Influence of Different Main Group Elements on Their Relative Stability
Authors: Soleilhavoup Michele , Bertrand Guy
Published: July 2007

Valence isomers are compounds featuring the same fragments connected in different ways. In this personal account, we describe how we first met by serendipity this kind of isomerism, and how later on we used the specific properties of phosphorus and boron to prepare two types of valence isomers that are not accessible with elements exclusively from the first long row. In the carbon series, benzene is calculated to be 608 kJ mol−1 lower in energy than its singlet diradical valence isomer, the anti-tricyclohexylene, but a tetraphosphorus analogue of the latter has been isolated. According to calculations, the parent amidinium salt is 541 kJ mol−1 more stable than its three-membered heterocyclic valence isomer, but in the phosphorus series, the difference in energy between the open and closed forms is only a few kJ mol−1; provided the right substituents are used, the cyclic form can be isolated. Lastly, among butadiene valence isomers, singlet cyclobutane-1,3-diyls were predicted only as transition states for the inversion of bicyclo[1.1.0]butane. In marked contrast, 1,3-dibora-2,4-diphosphacyclobutane-1,3-diyls can be prepared by valence isomerization of the corresponding butadiene derivatives and isolated under conventional experimental conditions.
Development of New Methods to Introduce Unnatural Functional Molecules into Native Proteins for Protein Engineering
Authors: Nakata Eiji , Tsukiji Shinya , Hamachi Itaru
Published: July 2007

Proteins are one of the most sophisticated biomolecules that play important roles in many biological processes and recently have attracted much attention as a key molecular player in new fields of nanobio-science and -technology. To use protein molecules, suitable molecular interfaces for maintaining, regulating, and/or expanding the structure and activity of natural proteins are highly desirable. In addition, development of flexible strategies and new concepts to manipulate protein structures at precise atomic levels is an important challenge from the viewpoint of organic chemistry. In this account, we highlight two unique chemistry-based strategies, developed by our group, for incorporating unnatural molecules into natural proteins, which include (i) reconstitution of chemically modified cofactors with apo-proteins or -enzymes, and (ii) post-(photo)affinity labeling modification of natural proteins. Using these methods, various unnatural molecules were incorporated into natural proteins without any genetic manipulation to produce semi-artificial proteins, of which the function can be regulated, modulated, and/or read-out with help of the incorporated unnatural functionalities.
Dual Fluorescence in a Schiff Base Derived from an Acridinedione Dye. Excited State Intramolecular Proton Transfer
Authors: Thiagarajan Viruthachalam , Ramamurthy Perumal
Published: July 2007

Newly synthesized nonconjugated, but covalently linked, bichromophoric systems (ADDSA) contain a salicylideneaniline (SA) moiety linked to an acridinedione (ADD) fluorophore via a covalent bond. The absorption and fluorescence characteristics of the ADDSA systems in various solvents reveal that the dual fluorescence originates from two different chromophores in the same molecule. The solvent polarity independent, long wavelength anomalous emission originates from the keto form of SA moiety via excited state intramolecular proton transfer (ESIPT). The ESIPT pathway was further confirmed by the benzylideneaniline (BA) and ADD moieties coupled non-proton transfer model system (ADDBA). Absence of the longer wavelength anomalous emission in the steady state as well as the shorter lifetime component in the time-resolved study for ADDBA system supports ESIPT mechanism for long wavelength anomalous emission in ADDSA system.
Dichroic Measurements on Dicationic and Tetracationic Porphyrins on Clay Surfaces with Visible-Light-Attenuated Total Reflectance
Authors: Eguchi Miharu , Tachibana Hiroshi , Takagi Shinsuke , Tryk Donald A , Inoue Haruo
Published: July 2007

Complexes formed with synthetic clay minerals and dicationic and tetracationic porphyrins were prepared. The Soret bands of the multicationic porphyrins shifted to longer wavelength upon the formation of a complex with clay. The clay sheets themselves and the porphyrin molecules on the clay surface were examined by use of atomic force microscopy (AFM) and polarized visible-light-attenuated total reflectance (ATR) spectroscopy (PV-ATR) with a waveguide system. The flat adsorption of the clay sheets on the glass substrates was confirmed by AFM. A theoretical treatment of the analysis by ATR spectroscopy was derived. The orientations of the multicationic porphyrin molecules on the clay sheets in water turned out to be nearly parallel (<5°) to the clay surface, based on the PV-ATR analysis.
Synthesis and Crystal Structures of Fluorinated Chromophores for Second-Order Nonlinear Optics
Authors: Umezawa Hirohito , Okada Shuji , Oikawa Hidetoshi , Matsuda Hiro , Nakanishi Hachiro
Published: July 2007

Partially fluorinated skeleton of 4-[2-(4-dimethylamino-2,3,5,6-tetrafluorophenyl)ethynyl]-2,3,5,6-tetrafluoro-N,N,N-trimethylanilinium (2) was synthesized as a second-order nonlinear optical (NLO) material to decrease the absorption around 1.3 and 1.5 μm, which deteriorates the device efficiency. Several salts of 2 were prepared, and we found that the trifluoromethanesulfonate salt of 2 (2b) had a shorter absorption-maximum wavelength compared to that of 4-nitroaniline (pNA). From hyper-Rayleigh scattering (HRS) measurement, the β value of 2b was found to be about 8 times greater than that of pNA. We also performed X-ray crystallographic analysis of 2b and estimated NLO coefficient (d) by the oriented gas model. We found that diagonal component of 2b (d11=610 pm V−1) was about 14 times greater than that of 2-methyl-4-nitroaniline and off-diagonal component of 2b (d12=155 pm V−1) was about 6.5 times greater than that of N-(4-nitrophenyl)-l-prolinol. Compound 2b should be an excellent candidate for NLO applications.
Preparation of Acid-Functionalized Poly(phenylene oxide)s and Poly(phenylene sulfone) and Their Proton Conductivity
Authors: Tago Takahiro , Kuwashiro Norikazu , Nishide Hiroyuki
Published: July 2007

A series of highly acid-functionalized poly(phenylene oxide)s and poly(phenylene sulfone) were prepared and proton conductivity in their membranes is discussed. Phosphorylated poly(phenylene oxide)s were prepared via the oxidative polymerization of phosphonoxyphenols in alkaline water, along with a facile monomer preparation. A poly(phenylene oxide) bearing a sulfamide acid group was prepared by reacting amidosulfate with the corresponding carboxylated poly(phenylene oxide). A sulfonated poly(phenylene sulfone) was prepared by hydrogen peroxide oxidation of the sulfonated poly(phenylene sulfide). All these acid-functionalized polymers showed appropriate thermal stability based on the aromatic backbone. The polymers had a high ion-exchange capacity, were water-soluble, but gave transparent and flexible membranes after compositing with the poly(ethylene oxide). Some of the membranes displayed a high proton conductivity of 10−4 S cm−1 at 120 °C under dry conditions.
Trends in abnormal cancer screening results in the United States of America
Authors: Yabroff K Robin , Freedman Andrew , Brown Martin L , Ballard-Barbash Rachel , McNeel Timothy , Taplin Stephen
Published: July 2007

Background: Although recent trends in the use of recommended breast and cervical cancer screening have been well documented in the USA, little is known about trends in the prevalence of abnormal screening results.

Methods: Trends in abnormal screening results for mammography and Papanicolaou (Pap) smear were assessed descriptively using data from the 1987 and 2000 National Health Interview Surveys. Estimates were stratified by sociodemographic characteristics of the populations who reported ever receiving screening. All comparisons were evaluated with two-sided tests of statistical significance.

Results: The age-standardized prevalence of abnormal Pap smears increased from 12.9% (95% confidence interval [CI] 12.1–13.8%) of women ever screened in 1987 to 20.3% (95% CI 19.5–21.0%) in 2000, and the age-standardized prevalence of abnormal mammogram results increased from 18.8% (95% CI 17.0–20.7%) to 21.6% (95% CI 20.5–22.7%) of women ever screened over the same period. Among women aged 40 years and older who reported ever receiving both a Pap smear and a mammogram, 29.6% (95% CI: 27.3–32.2%) in 1987 and 35% (95% CI: 33.8–36.2%) in 2000 reported either an abnormal Pap smear or an abnormal mammogram. In 2000, abnormal screening results were positively associated with reported frequency of recent screening ( P<0.001).

Conclusions: A substantial portion of women in the USA reporting cancer screening also report having had abnormal results, although the magnitude of trends between 1987 and 2000 vary by screening test. Additional research is needed to assess the relative contributions of changes in classification of test results, test characteristics and changes in underlying screening histories to increases in abnormal screening results.
Prevalence of neural tube defect pregnancies in England and Wales from 1964 to 2004
Authors: Morris J K , Wald N J
Published: July 2007

Objectives: To determine the prevalence of pregnancies with a neural tube defect (NTD) in England and Wales between 1964 and 2004 and to estimate the relative impact of antenatal screening and a change in the incidence of these defects on the prevalence of births with NTDs.

Settings: Use of data published by the Office for National Statistics (ONS) on terminations of pregnancies with an NTD and births with an NTD from 1964 to 2004.

Methods: Estimates were made of the total number of terminations of pregnancies and births with an NTD by taking account of the under-reporting of these terminations and births using a previously described method. In 1995 ONS started to report the number of terminations with an NTD rather than the total numbers of terminations with a central nervous system (CNS) malformation that had previously been used to estimate the number of NTD terminations. Adjustment was made for this and new estimates of the total number of NTD pregnancies were produced to 2004.

Results: There were an estimated 969 pregnancies with NTDs (168 (17%) births and 801(83%) terminations) in England and Wales in 2004. An estimated 44% of NTD terminations and 32% of births were not reported as such. The birth prevalence per 1000 decreased fallen 93% from 3.6 in 1964 to 0.3 in 2004, 59% due to an underlying decrease in the prevalence of NTDs and 34% due to screening diagnosis and subsequent termination of affected pregnancies.

Conclusion: The prevalence of NTD pregnancies decreased by around two per 1000 from 1964 to 1990 and thereafter remained fairly constant. The prevalence of NTD pregnancies is substantially underestimated if it is based only on reported NTD births (by 88%) and also if it is based on reported NTD births and terminations (by 52%), because most NTD pregnancies in England and Wales are terminated following antenatal screening and most of these terminations are not reported.