bluuebunny/crossref_metadata_2025 huggingface dataset:
Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's disease
Authors: Winblad Bengt , Kawata Ariane K. , Beusterien Kathleen M. , Thomas Simu K. , Wimo Anders , Lane Roger , Fillit Howard , Blesa Rafael
Published: April 2007

Background

Family caregivers comprise a critical component in the care of Alzheimer's disease (AD) patients. Among their many tasks, caregivers are responsible for administering and managing medications. Effective interventions incorporate the needs of both the AD patient and the caregiver, and understanding treatment preferences may maximize intervention effectiveness. Transdermal patches may offer advantages over conventional oral formulations.

Methods

A 24‐week randomized controlled trial compared the rivastigmine patch to the rivastigmine capsule and placebo in patients with probable AD. At baseline and Weeks 8 and 24, the AD Caregiver Preference Questionnaire (ADCPQ) was used to evaluate caregiver expectations, preferences and satisfaction with treatment. Double‐dummy treatment blinding ensured that caregiver preference for the patch or capsule was not confounded by perceptions of efficacy or tolerability. Reasons for preference were also elicited. The analytic sample included caregivers who completed the ADCPQ at Weeks 8 and/or 24.

Results

One thousand and fifty‐nine caregivers completed the ADCPQ. More than 70% of caregivers preferred the rivastigmine patch to the capsule. The patch was significantly preferred to the capsule with respect to ease of following the schedule and ease of use. Caregivers indicated greater satisfaction overall, greater satisfaction with administration, and less interference with daily life with the patch versus the capsule (all p ≤ 0.01).

Conclusion

Caregivers of AD patients preferred the patch to the capsule for drug delivery. Preference for the rivastigmine patch could potentially lead to improved compliance and improved clinical benefits. Copyright © 2007 John Wiley & Sons, Ltd.
The construction of standard gamble utilities
Authors: van Osch Sylvie M. C. , Stiggelbout Anne M.
Published: April 2007

Health effects for cost‐effectiveness analysis are best measured in life years, with quality of life in each life year expressed in terms of utilities. The standard gamble (SG) has been the gold standard for utility measurement. However, the biases of probability weighting, loss aversion, and scale compatibility have an inconclusive effect on SG utilities. We determined their effect on SG utilities using qualitative data to assess the reference point and the focus of attention. While thinking aloud, 45 healthy respondents provided SG utilities for six rheumatoid arthritis health states. Reference points, goals, and focuses of attention were coded. To assess the effect of scale compatibility, correlations were assessed between focus of attention and mean utility. The certain outcome served most frequently as reference point, the SG was perceived as a mixed gamble. Goals were mostly mentioned with respect to this outcome. Scale compatibility led to a significant upward bias in utilities; attention lay relatively more on the low outcome and this was positively correlated with mean utility. SG utilities should be corrected for loss aversion and probability weighting with the mixed correction formula proposed by prospect theory. Scale compatibility will likely still bias SG utilities, calling for research on a correction. Copyright © 2007 John Wiley & Sons, Ltd.
The role of private providers in treating child diarrhoea in Latin America
Authors: Waters Hugh R. , Hatt Laurel E. , Black Robert E.
Published: April 2007

Diarrhoeal disease, a leading cause of child mortality, disproportionately affects children in low‐income countries – where private and non‐governmental providers are often an important source of health care. We use 10 Living Standards Measurement Surveys from Latin America to model the choice of care for child diarrhoea in the private sector compared to the public sector. A total of 36.8% of children in the combined data set saw a private provider rather than a public one when taken for treatment. Each additional quintile of household economic status is associated with an increase of 6.5 percentage points in the probability that a child with diarrhoea is taken to a private provider (p<0.001).

However, treatments provided in the private sector are manifestly of worse quality than in the public sector. A total of 33.0% of children visiting a public provider received Oral Rehydration Solution, compared to 13.7% of those visiting a private provider. Conversely, children treated by a private provider are more likely to receive drugs, most commonly unnecessary antibiotics. Ironically, when it comes to treatment for child diarrhoea, wealthier and better educated households in Latin America are paying for treatment in the private sector that is ineffective in comparison with treatments that are commonly and inexpensively available. Copyright © 2007 John Wiley & Sons, Ltd.
IgVH gene mutation status and genomic imbalances in chronic lymphocytic leukaemia with increased prolymphocytes (CLL/PL)
Authors: Balogh Zsófia , Reiniger Lilla , Deák Linda , Bödör Csaba , Csomor Judit , Szepesi Ágota , Gagyi Éva , Kopper László , Matolcsy András
Published: April 2007

Chronic lymphocytic leukaemia (CLL) with increased prolymphocytes (CLL/PL) has been defined by the World Health Organization (WHO) classification and considered as a progressive and clinically aggressive variant of CLL. To further characterize the biological features of this disease, we performed IgVH gene mutational status, FISH and high‐resolution comparative genomic hybridization (HR‐CGH) analysis in 17 cases of CLL/PL. All CLL/PL utilized members of VH1, VH3 and VH4 families, with the highest prevalence of the VH1‐69 gene. In all but one cases analyzed, the VH genes were unmutated. The FISH and HR‐CGH analyses showed frequent occurrence of trisomy 12, del(11)(q23), del(17)(p13) and genetic imbalances, but recurrent genetic lesion characteristic for CLL/PL was not found. The follow‐up HR‐CGH analysis of two cases showed that increase of prolymphocytes in the course of CLL or CLL/PL are associated with clonal evolution and selection of the tumour clone. In conclusion, this study suggests that CLL/PL is a relatively homogeneous disease regarding VH gene mutation, but heterogeneous regarding genetic lesions. The heterogeneity and high number of genomic imbalances found in CLL/PL suggest that a genome‐wide instability of the neoplastic cells may play a role in the development of the disease. Copyright © 2007 John Wiley & Sons, Ltd.
SELDI‐TOF MS versus prostate specific antigen analysis of prospective plasma samples in a nested case–control study of prostate cancer
Authors: Skytt Åsa , Thysell Elin , Stattin Pär , Stenman Ulf‐Håkan , Antti Henrik , Wikström Pernilla
Published: April 2007

There is an urgent need for better biomarkers for detection of clinically significant prostate cancer (PCa). Recent studies suggest that surface enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF MS) analysis of serum may provide diagnostic information. The aim of this study was to investigate if PCa cases could be identified by applying predefined SELDI‐TOF analysis conditions on prospectively, uniformly collected plasma samples from PCa cases and matched controls. Prospective samples from 387 incident PCa cases and an equal number of controls, matched for age and time for recruitment, were analyzed by SELDI‐TOF MS (IMAC30/Cu chip) and multivariate classification analysis. Prospective prostate specific antigen levels were subjected to ROC curve analysis giving an AUC of 0.87 for the total cohort with a median lag time between blood sampling and diagnosis of 6.1 years. No markers were found by SELDI‐TOF MS that significantly discriminated between cases and controls in the total cohort or in subanalysis of cases with less than 2 years between blood donation and diagnosis (n = 42). Cases with aggressive disease at the time of diagnosis who gave blood less than 4 years prior to diagnosis (n = 23) could however be separated from their controls (sensitivity 70%, specificity 83%) by a model based on SELDI‐TOF MS and OPLS‐DA data analysis. We were thus not able to confirm previous results with SELDI‐TOF MS identifying men with PCa from healthy individuals, but we report an optimal experimental set‐up for verification of markers for early detection of cancer in prospectively collected samples. © 2007 Wiley‐Liss, Inc.
Over‐expression of parathyroid hormone Type 1 receptor confers an aggressive phenotype in osteosarcoma
Authors: Yang Rui , Hoang Bang H. , Kubo Tadahiko , Kawano Hirotaka , Chou Alexander , Sowers Rebecca , Huvos Andrew G. , Meyers Paul A. , Healey John H. , Gorlick Richard
Published: April 2007

Osteosarcoma is the most common primary bone malignancy in children and is associated with rapid bone growth. Parathyroid hormone‐related peptide (PTHrP) signaling via parathyroid hormone Type 1 receptor (PTHR1) is important for skeletal development and is involved in bone metastases in other tumors. The aim of this study was to investigate the status of PTHrP/PTHR1 and its possible role in osteosarcoma. In a preliminary screening, a higher level of PTHR1 mRNA, but not PTHrP, was found in 4 osteosarcoma xenografts as compared with 4 standard cell lines, or 5 patient derived cell lines (p < 0.05) using quantitative RT‐PCR. It was therefore extended to 55 patient specimens, in which a significantly higher level of PTHR1 mRNA was detected in metastatic or relapsed samples than those from primary sites (p < 0.01). Cell behavior caused by PTHR1 overexpression was further studied in vitro using PTHR1 transfected HOS cell line as a model. Over‐expression of PHTR1 resulted in increased proliferation, motility and Matrigel invasion without addition of exogenous PTHrP suggesting an autocrine effect. Importantly, the aggressiveness in PTHR1‐expressing cells was completely reversed by RNAi mediated gene knockdown. In addition, PTHR1 over‐expression led to delayed osteoblastic differentiation and upregulation of genes involved in extracellular matrix production, such as TGF‐β1 and connective tissue growth factor. When cocultured with bone marrow derived monocytes, PTHR1 transfected HOS cells induced a greater number of osteoclasts. This study suggests that PTHR1 over‐expression may promote osteosarcoma progression by conferring a more aggressive phenotype, and forming a more favorable microenvironment. © 2007 Wiley‐Liss, Inc.
Comparative assessment of hardening of demineralized dentin under lining materials using an ultramicroindentation system
Authors: Schmidlin Patrick R. , Zehnder Matthias , Imfeld Thomas , Swain Michael V.
Published: April 2007

The aim of the current in vitro study was to evaluate the influence of three lining materials with a reported mineralizing capacity on hardness and elasticity of demineralized dentin. Four standardized microcavities were prepared in exposed dentin surfaces of 16 extracted human molars each. Dentin was demineralized in 0.5M EDTA for 2 h. One microcavity was left empty. The others were filled with a resin‐modified glass ionomer cement (RMGIC), a bioactive glass S53P4 suspension, and a prototype Ca‐PO4 cement. Teeth were then immersed in deionized water or simulated oral fluid. After 3 weeks, hardness and composite elastic modulus of the dentin subjacent to the microcavities were assessed under wet conditions using the ultramicroindentation system (UMIS). After immersion in deionized water, there was no significant improvement of the mechanical properties of dentin irrespective of the material applied beforehand, indicating a lack of direct material effects. Exposure to simulated oral fluid resulted in significantly (p < 0.05) higher hardness and composite elastic modulus values of the dentin subjacent to empty microcavities and counterparts lined with bioactive glass compared to corresponding dentin under the RMGIC. UMIS profiles showed little variance. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2007
Development and in vivo testing of a Nitinol tracheal stent
Authors: Vearick Samanta B. , Michelon Marcelo D. O. , Schaeffer Lirio , Xavier Rogério G. , Kuhl Gabriel , Sanches Paulo R. S. , Duarte Marcos E. S.
Published: April 2007

This article describes the development of a Nitinol tracheal stent (HCPA NiTi‐stent) and its application in a feline animal model. Straight‐annealed, bright‐polished Nitinol wire (55.8%Ni‐44.2%Ti) was weaved around a 40‐mm‐long metal fixture with 8‐mm diameter. The prototypes were submitted to different times of shape‐setting heat treatment (530°C), which resulted in stents of different colors and caused some variation in length and diameter. The prototypes were then submitted to compression testing, and the most resistant pieces, requiring the greatest force to achieve a 25% reduction in diameter and presenting the least variation in length and diameter (dark blue, 9 min of heat treatment), were submitted to fatigue testing. After that, only dark blue stents were manufactured and implanted in felines. No migration, tracheal stenosis, or any other type of damage were observed after 40 weeks. The integrity of the tracheal wall in contact with the stent was confirmed by macro and microscopic analyses. The development and in vivo testing of the HCPA NiTi‐stent were successful. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2007
Development of the wing‐attached rod for acceleration of “Biotube” vascular grafts fabrication in vivo
Authors: Sakai Osamu , Kanda Keiichi , Ishibashi‐Ueda Hatsue , Takamizawa Keiichi , Ametani Akihiro , Yaku Hitoshi , Nakayama Yasuhide
Published: April 2007

To accelerate the fabrication of in vivo tissue‐engineered autologous vascular prosthetic tissues, the “Biotube,” a novel wing‐attached rod mold was designed for a tissue rolling technique based on a two‐step in body tissue incubation (IBTI) process. The new mold consisted of a silicone rod (3‐mm diameter, 23‐mm length) partly connected to a poly(ethylene terephthalate) film (a wing, 23 × 19 × 0.1 mm). While the molds were embedded into the dorsal subcutaneous pouches of rabbits for 2 weeks (primary IBTI), they were encapsulated fully with thin connective tissues. After removal of the wing materials, the remaining saccular membranous tissues were rolled up on the core tubular tissues that had formed around the silicone rods. Following another 2‐week embedding of the assembled tissues (secondary IBTI), the layered tissues fused to each other to form compliant and stiff tubular tissues, “Rolled Biotubes.” The wall thickness of the Rolled Biotubes was about 800 μm and the burst strength was about 4000 mmHg, both of which were significantly higher than those of Biotubes prepared by one‐step, 4‐week IBTI or two‐step, 2‐week IBTI (p < 0.05). A Rolled Biotube could be applied as middle or large caliber arterial prostheses. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2007
Adhesive performance of dentin bonding agents applied in vivo and in vitro. Effect of intrapulpal pressure and dentin depth
Authors: Hebling Josimeri , Castro Fabrício L. A. , Costa Carlos A. S.
Published: April 2007

The purpose of this study was to evaluate the influence of intrapulpal pressure and dentin depth on bond strengths of an etch‐and‐rinse and a self‐etching bonding agent to dentin in vitro and in vivo. Twenty‐four pairs of premolars were randomly divided into four groups (n = 6) according to the dentin bonding agent, Single Bond and Clearfil SE Bond, and intrapulpal pressure, null or positive. Each tooth of the pair was further designated to be treated in vivo or in vitro. The intrapulpal pressure was controlled in vivo by the delivery of local anesthetics containing or not a vasoconstrictor, while in vitro, it was achieved by keeping the teeth under hydrostatic pressure. Class I cavities were prepared and the dentin bonding agents were applied followed by incremental resin restoration. For the teeth treated in vitro, the same restorative procedures were performed after a 6 month‐storage period. Beams with 1 mm2 cross‐sectional area were prepared and microtensile tested. Clearfil SE Bond was not influenced by any of the variables of the study, while bond strengths produced in vitro were significantly higher for Single Bond. Overall, lower bond strengths were produced in deep dentin, which reached statistical significance when Single Bond was applied under physiological or simulated intrapulpal pressure. In conclusion, in vitro bonding may overestimate the immediate adhesive performance of more technique‐sensitive dentin bonding systems. The impact of intrapulpal pressure on bond strength seems to be more adhesive dependent than dentin morphological characteristics related to depth. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2007
Chitosan/poly(vinyl alcohol) blending hydrogel coating improves the surface characteristics of segmented polyurethane urethral catheters
Authors: Yang Shu‐Hua , Lee Yu‐Sheng J. , Lin Feng‐Huei , Yang Jen‐Ming , Chen Ko‐shau
Published: April 2007

Segmented polyurethane (SPU) is commonly used to manufacture urethral catheters. Surface modifications for SPU catheters are needed to reduce friction and protein adsorption, in order to minimize catheter‐related complications, including urethral trauma, encrustation, catheter obstruction, bacterial colonization, and infection. In this study, a four‐step surface modification method was developed to create a thin lubricious layer of chitosan/poly(vinyl alcohol) (PVA) hydrogel on the SPU catheter. Modification steps included oxidation of the SPU surface, functionalities modification, carbodiimide reaction and coupling, and hydrogel crosslinking. The success of each modification step was confirmed by Fourier transform infrared spectroscopy. Measurement of the water contact angle revealed that hydrogel coating created a highly hydrophilic surface and atomic force microscope analyses demonstrated that the surface was slippery. Protein absorption of the SPU catheter was significantly reduced by coating hydrogel. Chitosan in the hydrogel could provide antimicrobial activity, and the hydrogel coating SPU samples showed significant antibacterial effects in this study. In summary, the four‐step modification method developed in this study provided a simple and effective way to coat the surface of SPU catheters with a chitosan/PVA blending hydrogel that could help to minimize the risk of complications related to the use of urethral catheters. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2007
Effects of a ferric chloride primer on collagen‐depleted dentin bonding between tri‐n‐butylborane initiated self‐curing resin and dentin
Authors: Soeno Kohyoh , Taira Yohsuke , Ito Shuichi , Atsuta Mitsuru , Pashley David. H.
Published: April 2007

This study was designed to evaluate the micro‐tensile bond strength between a carboxylic resin and dentin, when the dentin surface was modified with an experimental dentin primer. The three primers tested were ED primer II (ED), 0.3% ferric chloride aqueous solution (FE), and ED containing 0.3% ferric chloride (ED/FE). Three commercial dentin conditioners [40% phosphoric acid, 10% NaOCl, and 10% citric acid with 3% ferric chloride (10‐3)] were also used. The coronal surfaces of extracted human molars were ground flat to dentin. The dentin surfaces were treated with phosphoric acid, NaOCl, or with one of the primers. The 10‐3 was used without phosphoric acid or NaOCl as a control. A composite material rod was bonded to the dentin surface with 4‐META/MMA‐TBB resin. After 24‐h immersion in 37°C distilled water, 0.9 mm × 0.9 mm composite‐dentin beams cut from the bonded specimens were stressed to failure in tension at 0.6 mm/min. The bond strengths were also evaluated after 5000 thermocycles. The bond strength of the group ED/FE was significantly higher than those of the 10‐3, ED, and FE. After 5000 thermocycling, 10‐3, ED and FE showed significant decrease in bond strength, although no significant decrease was seen for ED/FE. It was concluded that dentin surface treatment with phosphoric acid, NaOCl, and the ED/FE primer improved the bonding (p < 0.05) between 4‐META/MMA‐TBB resin and dentin, with or without thermocycling, while the bond strengths in the control group fell 34% following 5000 thermocycles. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2007
Ofloxacin‐delivery system of a polyanhydride and polylactide blend used in the treatment of bone infection
Authors: Chen Liaobin , Wang Hui , Wang Jun , Chen Man , Shang Liang
Published: April 2007

We developed a local drug‐release system consisting of two biodegradable polymers, poly(sebacic anhydride) (PSA) and poly‐D,L‐lactide (PLA), for the treatment of chronic osteomyelitis. PSA and PLA were dissolved and blended at different ratios in tetrahydrofuran. Ofloxacin was loaded with an 8:1 weight ratio of the blend to the drug. The ofloxacin‐containing beads of the PSA/PLA blend were made by preheating and compressing them in a mold. The in vitro drug release showed that changing the ratio between the two polymers caused the effective ofloxacin‐release duration to vary from 6 to 68 days. The ofloxacin‐containing beads with 10% PSA and 90% PLA produced an inhibition zone for the bacteria Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa within 89 days of the experiment. The in vivo drug release of the beads in rabbits demonstrated that the average ofloxacin concentration in the local bone was 20.1 ± 10.3 μg/g, while that in the plasma was 35.6 ± 18.8 ng/mL, within 8 weeks. Roentgenography, bacterial cultures, and histological examinations showed that the local release of ofloxacin by the beads could cure osteomyelitis in rabbits. Our findings suggested that using PSA/PLA blends with different ratios as carriers for antibiotics might be useful in the treatment of chronic osteomyelitis and in the prophylaxis of bone infection. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2007
First‐trimester sonography: Is the fetus exposed to high levels of acoustic energy?
Authors: Sheiner Eyal , Shoham‐Vardi Ilana , Hussey Michael J. , Pombar Xavier , Strassner Howard T. , Freeman Jody , Abramowicz Jacques S.
Published: April 2007

Purpose.

As a form of energy, diagnostic ultrasound has bioeffects on living tissues. The thermal index (TI), TIS (TI for soft tissue), TIB (TI for bone), TIC (TI for cranial bone) expresses the potential for rise in temperature at the ultrasound beam's focal point. The mechanical index (MI) indicates the potential for the ultrasound beam to induce inertial cavitation in tissues. The goal of this study was to characterize the acoustic output of clinical ultrasound instruments, as expressed by TI and MI, during routine first‐trimester sonographic examinations.

Methods.

A prospective observational study was conducted. First‐trimester patients were randomly selected from those scheduled for viability scans. An obstetrician collected data. Sonographers were blinded to the data being sought, which included gestational age, duration of the examination, and every variation in the MI and TI during each sonographic examination.

Results.

A total of 52 first‐trimester examinations were evaluated. The mean gestational age was 8.9 ± 1.9 weeks. The mean duration of the sonographic examinations was 8.1± 1.4 minutes. During the examinations, there were 178 MI variations (mean ± SD, 0.9 ± 0.3) and 167 TI variations (mean ± SD, 0.2 ± 0.1).

Conclusion.

First‐trimester sonographic examinations are associated with a negligible rise in TI. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007
Short humerus: An additional antenatal sonographic feature of OFDS type II
Authors: Pradhan Mandakini , Manisha  , Sankar Hariharan
Published: April 2007

The prevalence of skeletal dysplasia in the neonatal period is 2.4/10,000 births; it accounts for 1–2% of perinatal deaths, mainly stillbirths. A long bone measurement of less than −4 standard deviations is a definitive indication of skeletal dysplasia, whereas measurement between −2 and −4 standard deviations warrants detailed sonographic examination for other associated anomalies to arrive at a diagnosis. We report a case of oral‐facial‐digital syndrome type II that presented antenatally with polyhydramnios, short humerus, polydactyly, and duplicated thumb. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007
Sonographic diagnosis of uncomplicated first‐trimester pregnancy in the rudimentary horn of a unicornuate uterus
Authors: Taori Kishor , Saha Bimal Kumar , Shah Deepal , Khadaria Narottam , Jadhav Vijay , Jawale Rajesh
Published: April 2007

Although pregnancy in a rudimentary uterine horn is rare, the correct diagnosis of this condition on routine sonographic examination is critical, because its natural history usually involves the rupture of the pregnant horn during the second or third trimester, resulting in life‐threatening bleeding. We report a case in which the diagnosis of right unicornuate uterus with a left noncommunicating rudimentary horn was made in the first trimester on routine sonographic examination. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
Prolonged expression of a lysosomal enzyme in mouse liver after Sleeping Beauty transposon‐mediated gene delivery: implications for non‐viral gene therapy of mucopolysaccharidoses
Authors: Aronovich Elena L. , Bell Jason B. , Belur Lalitha R. , Gunther Roland , Koniar Brenda , Erickson David C. C. , Schachern Patricia A. , Matise Ilze , McIvor R. Scott , Whitley Chester B. , Hackett Perry B.
Published: April 2007

Background

The Sleeping Beauty (SB) transposon system is a non‐viral vector system that can integrate precise sequences into chromosomes. We evaluated the SB transposon system as a tool for gene therapy of mucopolysaccharidosis (MPS) types I and VII.

Methods

We constructed SB transposon plasmids for high‐level expression of human β‐glucuronidase (hGUSB) or α‐L‐iduronidase (hIDUA). Plasmids were delivered with and without SB transposase to mouse liver by rapid, high‐volume tail‐vein injection. We studied the duration of expressed therapeutic enzyme activity, transgene presence by PCR, lysosomal pathology by toluidine blue staining and cell‐mediated immune response histologically and by immunohistochemical staining.

Results

Transgene frequency, distribution of transgene and enzyme expression in liver and the level of transgenic enzyme required for amelioration of lysosomal pathology were estimated in MPS I and VII mice. Without immunomodulation, initial GUSB and IDUA activities in plasma reached > 100‐fold of wild‐type (WT) levels but fell to background within 4 weeks post‐injection. In immunomodulated transposon‐treated MPS I mice plasma IDUA persisted for over 3 months at up to 100‐fold WT activity in one‐third of MPS I mice, which was sufficient to reverse lysosomal pathology in the liver and, partially, in distant organs. Histological and immunohistochemical examination of liver sections in IDUA transposon‐treated WT mice revealed inflammation 10 days post‐injection consisting predominantly of mononuclear cells, some of which were CD4‐ or CD8‐positive.

Conclusions

Our results demonstrate the feasibility of achieving prolonged expression of lysosomal enzymes in the liver and reversing MPS disease in adult mice with a single dose of therapeutic SB transposons. Copyright © 2007 John Wiley & Sons, Ltd.
The impact of polyadenylation signals on plasmid nuclease‐resistance and transgene expression
Authors: Azzoni Adriano R. , Ribeiro Sofia C. , Monteiro Gabriel A. , Prazeres Duarte M.F.
Published: April 2007

Background

Efficient delivery and expression of plasmids (pDNA) is a major concern in gene therapy and DNA vaccination using non‐viral vectors. Besides the use of adjuvants, the pDNA vector itself can be designed to maximize survival in nuclease‐rich environments. Homopurine‐rich tracts in polyadenylation sequences have been previously shown to be especially important in pDNA resistance.

Methodology

The effect of modifications in the poly A sequence of a model pDNA vector (pVAX1GFP) on nuclease resistance and transgene expression was investigated. Four poly A sequences were studied: bovine growth hormone (BGH), mutant BGH, SV40 and a synthetic poly A. Plasmid resistance (half‐life) was assessed through in vitro incubations with mammalian nucleases. The impact in transgene expression was studied by quantifying pDNA, mRNA, and GFP expression in CHO, hybridoma and HeLa cells.

Results and conclusions

In vitro and cell culture studies indicate that plasmids containing the SV40 and the synthetic poly A sequences present significant improvements in nuclease resistance (up to two‐fold increase in half‐life). However, RT‐PCR analysis demonstrated that significant reduction in mRNA steady‐state levels were responsible for a decrease in transgene expression and detected transfection level of CHO and hybridoma cells when using the more resistant plasmids. Interestingly, transfection of HeLa cells demonstrated that both poly A efficiency and plasmid resistance interfere significantly in transgene expression. The results strongly suggest that the choice of the poly A is important, not only for mRNA maturation/stability, but also for pDNA resistance, and should thus be taken into consideration in the design and evaluation of pDNA vectors. Copyright © 2007 John Wiley & Sons, Ltd.
Docking and molecular dynamics simulation of the Azurin–Cytochrome c551 electron transfer complex
Authors: Bizzarri Anna Rita , Brunori Elena , Bonanni Beatrice , Cannistraro Salvatore
Published: April 2007

We coupled protein–protein docking procedure with molecular dynamics (MD) simulation to investigate the electron transfer (ET) complex Azurin–Cytochrome c551 whose transient character makes difficult a direct experimental investigation. The ensemble of complexes generated by the docking algorithm are filtered according to both the distance between the metal ions in the redox centres of the two proteins and to the involvement of suitable residues at the interface. The resulting best complex (BC) is characterized by a distance of 1.59 nm and involves Val23 and Ile59 of Cytochrome c551. The ET properties have been evaluated in the framework of the Pathways model and compared with experimental data. A 60 ns long MD simulation, carried on at full hydration, evidenced that the two protein molecules retain their mutual spatial positions upon forming the complex. An analysis of the ET properties of the complex, monitored at regular time intervals, has revealed that several different ET paths are possible, with the occasional intervening of water molecules. Furthermore, the temporal evolution of the geometric distance between the two redox centres is characterized by very fast fluctuations around an average value of 1.6 nm, with periodic jumps at 2 nm with a frequency of about 70 MHz. Such a behaviour is discussed in connection with a nonlinear dynamics of protein systems and its possible implications in the ET process are explored. Copyright © 2007 John Wiley & Sons, Ltd.
Biomolecular recognition of glycosylated β3‐peptides by GalNAc specific lectins
Authors: Norgren Anna S. , Geitmann Matthis , Danielson U. Helena , Arvidsson Per I.
Published: April 2007

The molecular recognition of a novel kind of hybrid conjugates, composed of artificial biomimetic β‐peptide oligomers with an O‐linked natural N‐acetyl‐galactosamine (the Tn‐antigen) residue, by four different GalNAc specific lectins was investigated using surface plasmon biosensor technology. The influence of the peptide and the glycosyl moiety on the recognition was studied using two glycosylated β3‐heptapeptides, a glycosylated α‐heptapeptide, two β‐amino acid containing dipeptides, and monomeric αGalNAc‐O‐Thr.

Although all four lectins displayed a decreased affinity for the carbohydrate residue when attached to a peptide, as compared to the monomeric Tn‐antigen, the peptide part was found to have distinct effects on the binding kinetics—indicating that varying degrees of protein–peptide interactions occurred in the recognition process. Likewise, the lectins did not discriminate between β3‐peptides and the α‐peptide, but the β‐linkage of the galactose had a detrimental effect for at least two of the lectins. Copyright © 2007 John Wiley & Sons, Ltd.
Functional lung imaging using hyperpolarized gas MRI
Authors: Fain Sean B. , Korosec Frank R. , Holmes James H. , O'Halloran Rafael , Sorkness Ronald L. , Grist Thomas M.
Published: April 2007

The noninvasive assessment of lung function using imaging is increasingly of interest for the study of lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma. Hyperpolarized gas MRI (HP MRI) has demonstrated the ability to detect changes in ventilation, perfusion, and lung microstructure that appear to be associated with both normal lung development and disease progression. The physical characteristics of HP gases and their application to MRI are presented with an emphasis on current applications. Clinical investigations using HP MRI to study asthma, COPD, cystic fibrosis, pediatric chronic lung disease, and lung transplant are reviewed. Recent advances in polarization, pulse sequence development for imaging with Xe‐129, and prototype low magnetic field systems dedicated to lung imaging are highlighted as areas of future development for this rapidly evolving technology. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Time‐resolved contrast‐enhanced carotid imaging using undersampled projection reconstruction acquisition
Authors: Du Jiang , Fain Sean B. , Korosec Frank R. , Grist Thomas M. , Mistretta Charles A.
Published: April 2007

Purpose

To investigate the utility of nonuniform angular spacing of projections in a three‐dimensional (3D) hybrid undersampled projection reconstruction (PR) acquisition for contrast‐enhanced (CE) time‐resolved carotid imaging.

Materials and Methods

Carotid CE magnetic resonance angiography (CE‐MRA) was performed on seven healthy volunteers using a time‐resolved hybrid sequence that combined undersampled PR acquisition in‐plane and Cartesian slice encoding through‐plane. The undersampling streak artifact comes mainly from the superior–inferior (S/I) direction in carotid imaging and is suppressed by nonuniform distribution of the projections. Phantom and volunteer studies were performed to demonstrate its efficacy.

Results

The undersampling streak artifact was significantly suppressed through a nonuniform distribution of the projection angles with more projections aligned along the S/I direction. The hybrid PR sequence combined with nonuniform distribution of the projection angles provided time‐resolved images of the carotid arteries with high temporal resolution (two seconds per frame) and high spatial resolution (1.0 × 1.0 × 1.5 mm3) simultaneously.

Conclusion

High‐resolution dynamic imaging of the carotid arteries is feasible with the use of a hybrid undersampled PR acquisition. Undersampling streak artifact can be suppressed significantly through nonuniform distribution of the projections. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Transient signal changes in diffusion‐weighted stimulated echoes during neuronal stimulation at 3T
Authors: Goerke Ute , Möller Harald E.
Published: April 2007

Purpose

To develop a sensitive method for detecting minute transient signal changes that can arise due to variations in the extravascular apparent self‐diffusion coefficient, D, during neuronal activation.

Materials and Methods

A three‐pulse sequence that reads out a moderately diffusion‐weighted (DW) primary echo (PRE) and a heavily DW stimulated echo (STE) was employed to investigate whether small transient signal changes in extravascular D occur in response to a visual stimulus. Contributions to signal changes caused by subtle differences in the transient variations of the apparent transverse relaxation constant, T2, between the PRE and STE were also quantified.

Results

On z‐maps obtained from the STE, more voxels showed significant stimulus‐related signal changes compared to maps of the PRE. The average maximum signal change of the STE was larger than that of the PRE. The observed increase in the relative signal change was independent of the strength of the diffusion weighting.

Conclusion

The STE is more sensitive to neuronal activity than the PRE. The discrepancy between the two echoes does not arise from transient changes in D, but from subtle differences in stimulus‐related variations of T2 between the two echoes. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
MRCP imaging at 3.0 T vs. 1.5 T: Preliminary experience in healthy volunteers
Authors: Isoda Hiroyoshi , Kataoka Masako , Maetani Yoji , Kido Aki , Umeoka Shigeaki , Tamai Ken , Koyama Takashi , Nakamoto Yuji , Miki Yukio , Saga Tsuneo , Togashi Kaori
Published: April 2007

Purpose

To evaluate the impact of magnetic resonance cholangiopancreatography (MRCP) imaging at 1.5T and 3.0T on image quality.

Materials and Methods

Fourteen volunteers were examined at both 1.5T and 3.0T using MRCP imaging performed with a breath‐held two‐dimensional (2D) half‐Fourier acquired single‐shot turbo spin‐echo (HASTE) thick‐slab sequence, a free‐breathing navigator‐triggered three‐dimensional (3D) turbo spin‐echo (TSE) sequence with prospective acquisition correction, and a heavily T2‐weighted (T2W) sequence with breath‐held multislice HASTE. All images were scored for visualization of the biliary and pancreatic ducts, severity of artifacts, image noise, and overall image quality.

Results

MRCP imaging at 3.0T yielded a significant improvement in overall image quality compared to 1.5T. We found a trend for superior visualization of the biliary and pancreatic ducts at 3.0T. Heavily T2W imaging with thin sections (1.4 mm) at 3.0T provided diagnostic images and better visualization of the biliary and pancreatic ducts than heavily T2W imaging with standard sections (2.8 mm) at 3.0T.

Conclusion

Our experience suggests that MRCP imaging at 3.0T has the potential to provide excellent images. High‐resolution heavily T2W imaging with a small voxel size (1.3 × 1.3 × 1.4 mm) at 3.0T can provide diagnostic images and allow evaluation of small pathologies of the bile and pancreatic ducts, which 1.5T MRI cannot sufficiently visualize. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
T1 measurement of flowing blood and arterial input function determination for quantitative 3D T1‐weighted DCE‐MRI
Authors: Cheng Hai‐Ling Margaret
Published: April 2007

Purpose

To propose a simple, accurate method for measuring T1 in flowing blood and the arterial input function (AIF), and to evaluate the impact on dynamic contrast‐enhanced MRI (DCE‐MRI) quantification of pharmacokinetic parameters.

Materials and Methods

A total of 10 rabbits were scanned at 1.5 Tesla and administered a bolus of Gadomer. Preinjection T1 and AIF measurements were acquired in the iliac arteries using a rapid three‐dimensional (3D) spoiled gradient recalled echo (SPGR) approach. Correction was made for imperfect B1 fields, in‐flow, and partial volume effects. DCE‐MRI parameters blood volume (vb) and endothelial transfer constant (Ktrans) in resting skeletal muscle were estimated from pharmacokinetic analysis using individually measured AIFs. Literature comparisons were made to assess accuracy.

Results

Blood T1 was more accurate and precise after correction for B1 and partial volume errors (1267 ± 72 msec). Measured AIFs followed reported biexponential decay characteristics for Gadomer clearance in rabbits. Parameters vb (2.47 ± 0.65%) and Ktrans (3.6 ± 1.0 × 10–3 minute–1) derived from AIFs based on corrected blood T1s were more reproducible and in better agreement with literature values.

Conclusion

The proposed method enables accurate in vivo blood T1 and AIF measurements and can be easily implemented in a range of DCE‐MRI applications to improve both the accuracy and reproducibility of pharmacokinetic parameters. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Calf muscle perfusion at peak exercise in peripheral arterial disease: Measurement by first‐pass contrast‐enhanced magnetic resonance imaging
Authors: Isbell David C. , Epstein Frederick H. , Zhong Xiaodong , DiMaria Joseph M. , Berr Stuart S. , Meyer Craig H. , Rogers Walter J. , Harthun Nancy L. , Hagspiel Klaus D. , Weltman Arthur , Kramer Christopher M.
Published: April 2007

Purpose

To develop a contrast‐enhanced magnetic resonance (MR) technique to measure skeletal muscle perfusion in peripheral arterial disease (PAD).

Materials and Methods

A total of 11 patients (age = 61 ± 11 years) with mild to moderate symptomatic PAD (ankle‐brachial index [ABI] = 0.75 ± 0.08) and 22 normals were studied using an MR‐compatible ergometer. PAD and normalmax (Nlmax; N = 11) exercised to exhaustion. Nllow (N = 11) exercised to the same workload achieved by PAD. At peak exercise, 0.1 mm/kg of gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) was infused at 3–4 cm3/second followed by a saline flush at the same rate. A dual‐contrast gradient echo (GRE) sequence enabled simultaneous acquisition of muscle perfusion and arterial input function (AIF). The perfusion index (PI) was defined as the slope of the time‐intensity curve (TIC) in muscle divided by the arterial TIC slope.

Results

Median workload was 120 Joules in PAD, 210 Joules in Nllow, and 698 Joules in Nlmax (P < 0.001 vs. Nllow and PAD). Median PI was 0.29 in PAD (25th and 75th percentiles [%] = 0.20, 0.40), 0.48 in Nllow (25th, 75th % = 0.36, 0.62; P < 0.02 vs. PAD), and 0.69 in Nlmax (25th, 75th % = 0.5, 0.77; P < 0.001 vs. PAD). Area under the ROCcurve for PI differentiating patients from Nlmax was 0.95 (95% confidence interval [CI] = 0.77–0.99).

Conclusion

Peak‐exercise measurement of lower limb perfusion with dual‐contrast, first‐pass MR distinguishes PAD from normals. This method may be useful in the study of novel therapies for PAD. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Finite‐difference time‐domain simulation of dispersive features smaller than the grid spacing
Authors: Pernice W. H. P. , Payne F. P. , Gallagher D. F. G.
Published: April 2007

A novel approach for the interpolation of dispersive materials for use in the finite‐difference time‐domain (FDTD) method is presented. The method allows for the simulation of geometrical structures that cannot be aligned to the discretized grid. Materials overlapping multiple cells are described by averaging flux densities in the cells concerned. This method provides an efficient way to simulate structures that are smaller than the minimum grid size. A formulation for an absorbing boundary condition using the uniform perfectly matched layer approach is given for the complex dispersive material model. The approach is validated by analysing reflection from metal sheets extending into multiple grid cells and two‐dimensional photonic crystals. Excellent agreement between analytical calculations and FDTD simulations is obtained for the simulation of real metal structures. Copyright © 2007 John Wiley & Sons, Ltd.
Incoherent backward photon echo in ruby upon excitation through an optical fiber
Authors: Samartsev V V , Shegeda A M , Shkalikov A V , Karimullin K R , Mitrofanova T G , Zuikov V A
Published: April 2007

The results of an experimental investigation of the incoherent photon echo in ruby (with Cr3+ concentration equal to 0.16 wt%) at T=1.7 K are presented. Optical fiber with length 3 m and diameter 100 μm was used for delivery of the first exciting pulse to a sample. The dependence of the IPE intensity on the excitation wavelength within the width of R1 absorption line was studied. The IPE decay curve was obtained and the phase relaxation time was found to be equal to 98 ns.
Laser induced fluorescence based optical fiber probe for analyzing bacteria
Authors: Sandeep P M , Rajeev S W B , Sheeba M , Bhat S G , Nampoori V P N
Published: April 2007

Optical fiber based laser induced fluorescence (LIF) measurements were carried out using Rhodamine B to analyze two different species of bacteria, a Gram-positive bacteria namely Bacillus smithii, and Vibrio alginolyticus, a Gram-negative bacteria. The fiber sensor was clearly able to distinguish between the two species of bacteria. Quenching effect of the dye Rhodamine B by Bacillus smithii was observed. The effect of dye on the samples was also studied in detail.
Bose-Einstein condensation and gauge symmetry breaking
Authors: Yukalov V I
Published: April 2007

The fundamental problem is analyzed, the relation between Bose-Einstein condensation and spontaneous gauge symmetry breaking. This relation is largerly misunderstood in physics community. Numerous articles and books contain the statement that, though gauge symmetry breaking helps for describing Bose-Einstein condensation, but the latter, in principle, does not require any symmetry breaking. This, however, is not correct. The analysis is based on the known mathematical theorems. But in order not to overcomplicate the presentation and to make it accessible to all readers, technical details are often omitted here. The emphasis is made on the following basic general facts: Spontaneous breaking of gauge symmetry is the necessary and sufficient condition for Bose-Einstein condensation. Condensate fluctuations, in thermodynamic limit, are negligible. Their catastrophic behavior can arise only as a result of incorrect calculations, when a Bose-condensed system is described without gauge symmetry breaking. It is crucially important to employ the representative statistical ensembles equipped with all conditions that are necessary for a unique and mathematically correct description of the given statistical system. Only then one is able to develop a self-consistent theory, free of paradoxes.
Repetition rate continuously controllable passively Q-switched Nd:YAG bonded microchip laser
Authors: Lei H , Gong M , Ping Y , Qiang L
Published: April 2007

A stable repetition rate continuously controllable passively Q-switched Nd:YAG bonded microchip laser is presented. A 0.8 mm-thickness 7 mm-diameter Nd:YAG crystal at 1.6 at.% is adapted as active medium and the saturable absorber for passively Q-switched pulse generating, a 0.2 mm-thickness 6.8-mm diameter Cr4+:YAG piece was thermal bonded into the Nd:YAG after primary optical contact. By using pulse pump and controlling the duty cycle of electric pulse and temperature of laser diode, a 1 W C-mount packaged fast-collimated laser diode, we can continuously achieve repetition rate from 1 kHz to 10 kHz as active Q-switched laser. The delay time at 10 kHz is 90 μs, while the single pulse energy is 2.8 μJ with pulse width of 2 ns.
CoCal‐2 – A simple toolbox to prove authenticity of milk chocolate
Authors: Buchgraber Manuela , Androni Simona
Published: April 2007

CoCal‐2 offers an important measure to assess compliance with labelling provisions of milk chocolate as laid down in Directive 2000/36/EC. By performing a single triacylglycerol analysis using gas liquid chromatography several useful pieces of information can be determined, i. e., (i) the milk fat content of the chocolate sample, (ii) the contribution of triacylglycerols originating from milk fat, (iii) the presence/absence of cocoa butter equivalents, and (iv) the amount of vegetable fat present in milk chocolate.