bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards an optical biopsy for the diagnosis of breast cancer in vivo by endogenous fluorescence spectroscopy
Authors: Alchab Lama , Dupuis Guillaume , Balleyguier Corinne , Mathieu Marie‐Christine , Fontaine‐Aupart Marie‐Pierre , Farcy René
Published: December 2009

The techniques of medical imaging allow the detection of suspect lesions in the breast, but they do not always evidence the malignant nature of these lesions. Breast biopsies and histological analyses are therefore implemented to establish a diagnosis. In order to reduce the number of these invasive procedures, a portable clinical system was designed based upon the excitation of Endogenous Fluorescence in vivo at 405 nm via a fiber‐optics probe included in a disposable needle of small diameter (<1 mm). From the fluorescence signal, the authors are able to discriminate between diseased and healthy areas of human breast biopsies. Stronger fluorescence intensity and systematic spectral red shift of the tumor areas were observed. These results are confirmed by confocal microscopy. This new instrument is promising for the minimally invasive diagnosis of breast tumors in vivo with an appreciable limitation of patient trauma and of operational and financial cost. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Photodynamic therapy induces microRNA‐210 and ‐296 expression in HeLa cells
Authors: Kushibiki Toshihiro
Published: December 2009

Apoptosis‐related microRNAs (miRNAs), the expression levels of which were observed to increase after photodynamic therapy (PDT), were identified as markers of PDT efficacy. miRNAs form a class of small endogenous RNAs that play important regulatory roles by targeting mRNA for cleavage or translational repression. miRNAs contribute to diverse biological processes, including development, cell growth, apoptosis, and hematopoiesis, which suggests a role in cancer development. However, no previous reports have described a relationship between apoptosis and miRNA expression after PDT. In this study, apoptosis‐related miRNA levels were characterized by real‐time PCR after PDT in HeLa cells. miR‐210 and miR‐296 expression levels increased 1 hour after PDT, although the other apoptosis‐related miRNA (miR‐7, miR‐148a, miR‐204, and miR‐216) expression levels were unchanged. Since miR‐210 is the most prominent miRNA consistently stimulated under hypoxic conditions and VEGF is capable of increasing miR‐296 expression levels, these data suggest that hypoxia induced by PDT induces miR‐210 expression, followed by an increase of VEGF expression and miR‐296 expression. These results constitute the first report of an analysis of miRNA expression after PDT using talaporfin sodium as a photosensitizer, demonstrating that miR‐210 and miR‐296 expression levels are markers of PDT efficacy in HeLa cells. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effects of intravitreal bevacizumab (Avastin®) therapy on retrobulbar blood flow parameters in patients with neovascular age‐related macular degeneration
Authors: Mete Ahmet , Saygılı Oguzhan , Mete Alper , Bayram Metin , Bekır Necdet
Published: December 2009

Background.

To investigate the effects of intravitreal bevacizumab on retrobulbar circulation in patients with neovascular age‐related macular degeneration (AMD).

Method.

Thirty patients with neovascular age‐related macular degeneration were assessed prospectively by both color Doppler imaging and fundus fluorescein angiography. Spectral Doppler analysis allowed the measurement of the maximum velocity (Vmax) and minimum velocity (Vmin) of the central retinal vein (CRV), and peak systolic (PSV), end‐diastolic (EDV) velocities of blood flows, and pulsatility index (PI) and resistance index (RI) values in the central retinal artery (CRA), nasal and temporal posterior ciliary arteries (NPCA, TPCA), and ophthalmic artery (OA). The t test for paired samples was used to compare retrobulbar blood flow values before and after intravitreal bevacizumab injection.

Result.

PSV and EDV of the NPCA and PSV of the TPCA were significantly decreased after intravitreal bevacizumab injection (p < 0.05). There was no statistically significant difference in the other parameters.

Conclusion.

Our results suggest that intravitreal bevacizumab therapy has a measurable effect on retrobulbar blood flow. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2010
Rosai‐Dorfman disease of the subglottis diagnosed by ultrasound‐guided fine‐needle aspiration biopsy: A case report
Authors: Tseng Yi‐Lun , Lin Yu‐Chin , Lo Cheng‐Yu , Liao Li‐Jen
Published: December 2009

We report a case of subglottic narrowing caused by an extranodal deposit of sinus histiocytosis in a 55‐year‐old man. To the best of our knowledge, no previous reports have described diagnosis using sonographic‐guided fine‐needle aspiration cytology for Rosai‐Dorfman disease of the subglottis. This patient was diagnosed by sonographic‐guided fine‐needle aspiration biopsy, which revealed lymphocytes, plasma cells, and many foamy, multinuclear histiocytes with preserved lymphocytes in their cytoplasm (emperipolesis). The patient underwent an incisional biopsy of the tumor and received postoperative steroids and low‐dose chemotherapy. The subglottic tumor was markedly regressed 6 months later. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2010
Detection of lead in Zea mays by dual‐energy X‐ray microtomography at the SYRMEP beamline of the ELETTRA synchrotron and by atomic absorption spectroscopy
Authors: Reale Lucia , Kaiser Jozef , Pace Loretta , Lai Antonia , Flora Francesco , Angelosante Bruno Antonella , Tucci Adele , Zuppella Paola , Mancini Lucia , Tromba Giuliana , Ruggieri Fabrizio , Fanelli Maria , Malina Radomir , Liška Miroslav , Poma Anna
Published: December 2009

This study is related to the application of the X‐ray dual‐energy microradiography technique together with the atomic absorption spectroscopy (AAS) for the detection of lead on Zea mays stem, ear, root, and leaf samples. To highlight the places with lead intake, the planar radiographs taken with monochromatic X‐ray radiation in absorption regime with photon energy below and above the absorption edge of a given chemical element, respectively, are analyzed and processed. To recognize the biological structures involved in the intake, the dual‐energy images with the lead signal have been compared with the optical images of the same Z. mays stem. The ear, stem, root, and leaf samples have also been analyzed with the AAS technique to measure the exact amount of the hyperaccumulated lead. The AAS measurement revealed that the highest intake occurred in the roots while the lowest in the maize ears and in the leaf. It seems there is a particular mechanism that protects the seeds and the leaves in the intake process. Microsc. Res. Tech., 2010. © 2009 Wiley‐Liss, Inc.

This article was published online on 1 December 2009. An error was subsequently identified. This notice is included in the online and print version to indicate that both have been corrected 19 February 2010.
Use of direct fluorescence labeling and confocal microscopy to determine the biodistribution of two protein therapeutics, Cerezyme® and Ceredase®
Authors: Piepenhagen Peter A. , Vanpatten Scott , Hughes Heather , Waire James , Murray James , Andrews Laura , Edmunds Tim , O'Callaghan Michael , Thurberg Beth L.
Published: December 2009

Efficient targeting of therapeutic reagents to tissues and cell types of interest is critical to achieving therapeutic efficacy and avoiding unwanted side effects due to offtarget uptake. To increase assay efficiency and reduce the number of animals used per experiment during preclinical development, we used a combination of direct fluorescence labeling and confocal microscopy to simultaneously examine the biodistribution of two therapeutic proteins, Cerezyme® and Ceredase®, in the same animals. We show that the fluorescent tags do not interfere with protein uptake and localization. We are able to detect Cerezyme and Ceredase in intact cells and organs and demonstrate colocalization within target cells using confocal microscopy. In addition, the relative amount of protein internalized by different cell types can be quantified using cell type‐specific markers and morphometric analysis. This approach provides an easy and straightforward means of assessing the tissue and cell type‐specific biodistribution of multiple protein therapeutics in target organs using a minimal number of animals. Microsc. Res. Tech. 2010. © 2009 Wiley‐Liss, Inc.
Decomposition of N‐hydroxylated compounds during atmospheric pressure chemical ionization
Authors: Eichenberger Silvan , Méret Michaël , Bienz Stefan , Bigler Laurent
Published: November 2009

N‐Hydroxylated polyamine derivatives were found to decompose during the ionization process of liquid chromatography‐atmospheric pressure chemical ionization‐mass spectrometry (LC‐APCI‐MS) experiments. The phenomenon was studied with a model compound, a synthetic N‐hydroxylated tetraamine derivative. It was found that reduction, oxidation and water elimination occurred during APCI to generate the corresponding amine, N‐oxide, and imine. The investigation further revealed that decomposition of hydroxylamines during APCI depends upon the concentration of the analyte and on the acidity of the solution introduced into the ionization source. The pH‐dependence of decomposition was utilized for the development of an MS method that allows for the unambiguous identification of NOH functionalities. This method was applied for the study of natural products including polyamine toxins from the venom of the spider Agelenopsis aperta and mayfoline, a cyclic polyamine derivative of the shrub Maytenus buxifolia. Copyright © 2009 John Wiley & Sons, Ltd.
Human nucleus pulposus cells significantly enhanced biological properties in a coculture system with direct cell‐to‐cell contact with autologous mesenchymal stem cells
Authors: Watanabe Takuya , Sakai Daisuke , Yamamoto Yukihiro , Iwashina Toru , Serigano Kenji , Tamura Futoshi , Mochida Joji
Published: December 2009

Activated nucleus pulposus (NP) cells can be reinserted into the disc to inhibit intervertebral disc degeneration. Experimental studies in animals showed that using a coculture system with direct cell‐to‐cell contact with mesenchymal stem cells (MSCs) significantly upregulated the biological activity of NP cells. The purpose of this study is to determine whether this activation of NP cells by autologous MSCs is applicable to human cells in vitro. Human NP tissue was obtained from surgical specimens and MSCs from bone marrow of 10 subjects. Six‐well culture plates and inserts were used for culture; 1.0 × 104 NP cells were seeded onto each insert and incubated alone, in standard coculture with 1.0 × 104 MSCs, or cocultured with direct cell‐to‐cell contact. NP cell proliferation, DNA synthesis, and proteoglycan (PG) synthesis were evaluated. Chromosome abnormalities in the activated NP cells and tumorigenesis of the cells were evaluated in an additional 10 patients by microscopic examination for segmented cells and histological assessment of activated cells transplanted into nude mice. Cell proliferation, DNA synthesis, and PG synthesis were significantly upregulated. The positive effects of the coculture system with direct cell‐to‐cell contact seen in animal studies were also confirmed in human cells. Chromosome abnormalities and tumorigenesis were not observed in the activated NP cells. In conclusion, a coculture system with direct cell‐to‐cell contact demonstrated a significant positive effect, enhancing the biological properties of human NP cells, as it did in animal models. These results should prove useful for conducting trials leading to the clinical use of activated NP cell transplantation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:623–630, 2010
Estrogen modulates iodoacetate‐induced gene expression in bovine cartilage explants
Authors: Sniekers Yvonne H. , van Osch Gerjo J.V.M. , Jahr Holger , Weinans Harrie , van Leeuwen Johannes P.T.M.
Published: December 2009

Estrogen loss may be involved in onset or progression of osteoarthritis. Estrogen receptors are present in chondrocytes, thus estrogen may exert effects directly on cartilage. However, studies on direct estrogen effects on cartilage are limited. We investigated, in an in vitro cartilage explant model, whether estrogen prevents damage or stimulates repair after damage induced by addition of iodoacetate (IA), as an experimental model for osteoarthritis. We used healthy bovine cartilage explants. Prevention experiment: Explants precultured with/without estradiol (E) for 3 days were cultured with IA for 4 h on day 0, and subsequently cultured as in preculture: with/without E. Explants were harvested at day 2 for gene expression analysis. Repair experiment: At day 0, explants were cultured with IA for 4 h on day 0, and subsequently cultured without E or with E. Explants were harvested at days 2, 10, and 14 for gene expression analysis. IA transiently downregulated most genes tested, whereas vascular endothelial growth factor (VEGF) was upregulated on day 2. On day 14, transforming growth factor β (TGFB)1 and TGFB3 were upregulated, and matrix metalloproteinase (MMP)13 and VEGF downregulated. Estradiol affected gene expression of aggrecan (AGC)1, MMP2, MMP14, tissue inhibitor of metalloproteinase (TIMP)2, TGFB2, and TGFB3. Prevention experiment: Estradiol did not significantly affect IA‐induced changes in gene expression (no significant interaction). Repair experiment: Estradiol affected IA‐induced changes in expression of collagen (COL)2, MMP2, MMP3, MMP13, MMP14, TIMP2, TGFB2, TGFB3, and VEGF. Estradiol affects expression of anabolic and catabolic genes in bovine cartilage explants and modulates the effects of IA. These effects of estradiol may be beneficial for cartilage maintenance and repair. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:607–615, 2010
Supraspinatus tendon repair into a bony trough in the rabbit: Mechanical restoration and correlative imaging
Authors: Trudel Guy , Ramachandran Nanthan , Ryan Stephen E. , Rakhra Kawan , Uhthoff Hans K.
Published: December 2009

Recurrence of tears is a common complication after rotator cuff surgery. Retearing seems to occur early after surgery and may be attributed to too early or too vigorous exercises. We found no experimental data correlating the strength of the rotator cuff early after surgery and imaging. Our objectives were to measure the peak load to failure of rabbit supraspinatus tendon–bone constructs at early times postoperatively, to determine their mode of failure, and to determine whether computed tomography (CT) can predict their strength. We divided one supraspinatus tendon of 40 adult female white New Zealand rabbits and, after resection of the enthesis, sutured the tendon into a bony trough. Ten rabbits were killed immediately and 10 each at 1, 2, and 6 weeks postoperatively. The explanted tendons of both shoulders were imaged on CT and tested to failure. Compared to normal tendons (mean 210 ± 42 N), the mean strength was very low at 0 weeks (57 ± 21 N) and 1 week (86 ± 33 N) (both p < 0.05); it had recovered by 6 weeks (324 ± 66 N). Early on, suture pullout was the most common mode of failure, whereas at 6 weeks, mid‐substance tears predominated (p < 0.05). Hypoattenuation on CT was associated with increased strength of the tendon–bone construct (p < 0.05). The strength of the surgical construct is very low in the early postoperative period. Therefore, the shoulder should be submitted only to loads not interfering with healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:710–715, 2010
The Degradation and Adsorption Behaviors of Enzyme on Poly(butylene succinate) Single Crystals
Authors: Jiang Xi , Yang Ju‐Ping , Wang Xiao‐Hong , Zhou Jian‐Jun , Li Lin
Published: December 2009

The enzymatic degradation behavior of poly(butylene succinate) (PBS) single crystals with a lipase from Pseudomonas cepacia (lipase PS) is monitored using atomic force microscopy (AFM) in phosphate buffer at pH 6.8 and 40 °C. In‐situ AFM results show that enzymatic degradation of the single crystal starts from the crystal edges rather than the chain‐folded surfaces and the lamellar thickness remains constant during the whole degradation process. Total internal reflection fluorescence microscopy (TIRFM) is used for the first time to study the adsorption behavior of lipase onto the PBS crystal surface. The results clearly show that the enzyme molecules preferentially adsorb on the lateral surfaces of the single crystal but not on the chain‐folded surfaces. AFM force–distance curve measurements and force–volume imaging obtained using a lipase‐immobilized AFM tip show that small and large adhesive forces exist in the flat‐on and edge‐on areas of a PBS banded spherulite, respectively, which correspond to the chain‐folded surface and lateral edges of a single crystal.

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Functional Amyloids Used by Organisms: A Lesson in Controlling Assembly
Authors: Smith Andrew M. , Scheibel Thomas
Published: December 2009

Amyloid has been studied primarily in relation to the disease states that it causes in humans, but in recent years, a range of proteins have been identified that self‐assemble to a β‐sheet rich fold as part of their native function and as such have been termed as functional amyloids.1 These functional amyloids fulfil a range of tasks within cells and extracellularly. In this paper, we will discuss the concept of functional amyloids, specifically in the sense of a structural component for the producing organism. Additionally, we will discuss how these organisms have controlled amyloid formation so that it only occurs at specific locations and at a desired time.

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Alternating Encapsulation of Water‐Soluble Components in a One‐Dimensional Structure
Authors: Park Chul Ho , Lee Jonghwi
Published: November 2009

A novel multi‐compound electrospinning method is described, using high‐conductivity aqueous solutions for the inner fluid and low‐conductivity polymeric solutions for the outer fluids. The driving fluid among inner fluids at the equivalent conductivity is switched at a certain frequency. The switching of the Taylor cone results in the alternative embedding of inner components. Also, the number of inner capillaries is proportional to the encapsulation components. Therefore, our method might be useful to alternatively encapsulate a variety of water‐soluble materials in fibers.

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Studying and Suppressing Olefin Isomerization Side Reactions During ADMET Polymerizations
Authors: Fokou Patrice A. , Meier Michael A. R.
Published: December 2009

Olefin isomerization side reactions that occur during ADMET polymerizations were studied by preparing polyesters via ADMET and subsequently degrading these polyesters via transesterification with methanol. The resulting diesters, representing the repeating units of the previously prepared polyesters, were then analyzed by GC‐MS. This strategy allowed quantification of the amount of olefin isomerization that took place during ADMET polymerization with second generation ruthenium metathesis catalysts. In a second step, it was shown that the addition of benzoquinone to the polymerization mixture prevented the olefin isomerization. Therefore, second generation ruthenium metathesis catalysts may now be used for the preparation of well‐defined polymers via ADMET with very little isomerization, which was not possible before.

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On the assessment of the value of the seasonal forecast information
Authors: Kumar Arun
Published: December 2009

Seasonal climate forecasts are now routinely produced at many operational and research centres. With the availability of the emerging technology of seasonal climate predictions for managing risks, however, it has proven difficult to quantify the value of seasonal climate forecasts in various applications. The definition of the value in the context of the use of the Seasonal Forecast Information (SFI) is the net benefit a user (or society) incurs as a result of change in management practices in response to the availability of the SFI.

A review of the difficulties associated with the value assessment of the SFI is presented. The paper includes a broad overview of pathways how the SFI is used by the various users and applications. The discussion then summarizes difficulties associated with isolating the benefits of the use of the SFI leading to the current paradigm where the value assessments from the use of the SFI are hard to quantify. Copyright © 2009 Royal Meteorological Society
Helium‐3 MR q‐space imaging with radial acquisition and iterative highly constrained back‐projection
Authors: O'Halloran Rafael L. , Holmes James H. , Wu Yu‐Chien , Alexander Andrew , Fain Sean B.
Published: December 2009

An undersampled diffusion‐weighted stack‐of‐stars acquisition is combined with iterative highly constrained back‐projection to perform hyperpolarized helium‐3 MR q‐space imaging with combined regional correction of radiofrequency‐ and T1‐related signal loss in a single breath‐held scan. The technique is tested in computer simulations and phantom experiments and demonstrated in a healthy human volunteer with whole‐lung coverage in a 13‐sec breath‐hold. Measures of lung microstructure at three different lung volumes are evaluated using inhaled gas volumes of 500 mL, 1000 mL, and 1500 mL to demonstrate feasibility. Phantom results demonstrate that the proposed technique is in agreement with theoretical values, as well as with a fully sampled two‐dimensional Cartesian acquisition. Results from the volunteer study demonstrate that the root mean squared diffusion distance increased significantly from the 500‐mL volume to the 1000‐mL volume. This technique represents the first demonstration of a spatially resolved hyperpolarized helium‐3 q‐space imaging technique and shows promise for microstructural evaluation of lung disease in three dimensions. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.
Enhancement of gas‐filled microbubble R2* by iron oxide nanoparticles for MRI
Authors: Chow April M. , Chan Kannie W. Y. , Cheung Jerry S. , Wu Ed X.
Published: December 2009

Gas‐filled microbubbles have the potential to become a unique intravascular MR contrast agent due to their magnetic susceptibility effect, biocompatibility, and localized manipulation via ultrasound cavitation. However, microbubble susceptibility effect is relatively weak when compared with other intravascular MR susceptibility contrast agents. In this study, enhancement of microbubble susceptibility effect by entrapping monocrystalline iron oxide nanoparticles (MIONs) into polymeric microbubbles was investigated at 7 T in vitro. Apparent T2 enhancement (ΔR2*) induced by microbubbles was measured to be 79.2 ± 17.5 sec−1 and 301.2 ± 16.8 sec−1 for MION‐free and MION‐entrapped polymeric microbubbles at 5% volume fraction, respectively. ΔR2* and apparent transverse relaxivities (r2*) for MION‐entrapped polymeric microbubbles and MION‐entrapped solid microspheres (without gas core) were also compared, showing the synergistic effect of the gas core with MIONs. This is the first experimental demonstration of microbubble susceptibility enhancement for MRI application. This study indicates that gas‐filled polymeric microbubble susceptibility effect can be substantially increased by incorporating iron oxide nanoparticles into microbubble shells. With such an approach, microbubbles can potentially be visualized with higher sensitivity and lower concentrations by MRI. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.
Reliability and precision of pseudo‐continuous arterial spin labeling perfusion MRI on 3.0 T and comparison with 15O‐water PET in elderly subjects at risk for Alzheimer's disease
Authors: Xu Guofan , Rowley Howard A. , Wu Gaohong , Alsop David C. , Shankaranarayanan Ajit , Dowling Maritza , Christian Bradley T. , Oakes Terrence R. , Johnson Sterling C.
Published: December 2009

Arterial spin labeling (ASL) offers MRI measurement of cerebral blood flow (CBF) in vivo, and may offer clinical diagnostic utility in populations such as those with early Alzheimer's disease (AD). In the current study, we investigated the reliability and precision of a pseudo‐continuous ASL (pcASL) sequence that was performed two or three times within one hour on eight young normal control subjects, and 14 elderly subjects including 11 with normal cognition, one with AD and two with Mild Cognitive Impairment (MCI). Six of these elderly subjects including one AD, two MCIs and three controls also received 15O‐water positron emission tomography (PET) scans 2 h before their pcASL MR scan. The instrumental reliability of pcASL was evaluated with the intraclass correlation coefficient (ICC). The ICCs were greater than 0.90 in pcASL global perfusion measurements for both the young and the elderly groups. The cross‐modality perfusion imaging comparison yielded very good global and regional agreement in global gray matter and the posterior cingulate cortex. Significant negative correlation was found between age and the gray/white matter perfusion ratio (r = –0.62, p < 0.002). The AD and MCI patients showed the lowest gray/white matter perfusion ratio among all the subjects. The data suggest that pcASL provides a reliable whole brain CBF measurement in young and elderly adults whose results converge with those obtained with the traditional 15O‐water PET perfusion imaging method. pcASL perfusion MRI offers an alternative method for non‐invasive in vivo examination of early pathophysiological changes in AD. Copyright © 2009 John Wiley & Sons, Ltd.
Proper generalized decomposition of multiscale models
Authors: Chinesta F. , Ammar A. , Cueto E.
Published: December 2009

In this paper the coupling of a parabolic model with a system of local kinetic equations is analyzed. A space–time separated representation is proposed for the global model (this is simply the radial approximation proposed by Pierre Ladeveze in the LATIN framework (Non‐linear Computational Structural Mechanics. Springer: New York, 1999)). The originality of the present work concerns the treatment of the local problem, that is first globalized (in space and time) and then fully globalized by introducing a new coordinate related to the different species involved in the kinetic model. Thanks to the non‐incremental nature of both discrete descriptions (the local and the global one) the coupling is quite simple and no special difficulties are encountered by using heterogeneous time integrations. Copyright © 2009 John Wiley & Sons, Ltd.
Hemophagocytic lymphohistiocytosis in Texas: Observations on ethnicity and race
Authors: Niece J. Allyson , Rogers Zora R. , Ahmad Naveed , Langevin Anne‐Marie , McClain Kenneth L.
Published: December 2009

Background

Early recognition and aggressive treatment of hemophagocytic lymphohistiocytosis (HLH) has changed a uniformly fatal disease to one 55% survive. We examined the diagnosis and treatment of pediatric patients with HLH from the three largest academic medical centers in Texas for information on modern non‐study treatment and survival. In contrast with previously reported series, the racial and ethnic composition of Texas provided a unique opportunity to evaluate the impact of race and ethnicity on survival with HLH.

Procedure

A retrospective chart review of local oncology and pathology databases identified 70 patients with HLH from 1992 to 2007. Median age was 1.8 years (range 0.1–16.5 years) and 43% were Latino.

Results

We identified 70 patients with an overall survival of 67% after a median follow‐up of 3 months (range 1–139 months). Twenty patients (29%) underwent stem cell transplant (SCT). Seven patients (18%) had mutations in the Perforin, Munc 13‐4, or Syntaxin‐11 genes, consistent with primary disease. Calculated cross‐sectional prevalence of HLH in Texas from our study is 1 in 100,000 children. The effect of Latino ethnicity on survival was not statistically significant.

Conclusion

HLH is a rare but potentially treatable illness with modern aggressive therapy. Though treatment is more standardized for HLH, the role of race and ethnicity as risk factors for development of disease and impact on outcome may warrant further investigation. Pediatr Blood Cancer 2010;54:424–428. © 2009 Wiley‐Liss, Inc.
Working memory in survivors of childhood acute lymphocytic Leukemia: Functional neuroimaging analyses
Authors: Robinson Kristen E. , Livesay Katherine L. , Campbell Laura K. , Scaduto Mary , Cannistraci Christopher J. , Anderson Adam W. , Whitlock James A. , Compas Bruce E.
Published: December 2009

Background

Research on the physical and psychological late effects of treatment of childhood cancer has led to the identification of significant long‐term neurocognitive deficits experienced by some survivors, particularly in the areas of memory and executive functioning. Despite indications of deficits based on cognitive assessment, the identification of specific mechanisms of neurocognitive deficits using neuroimaging techniques has yet to be adequately considered.

Procedure

This study used functional neuroimaging techniques to examine working memory and executive functioning deficits of survivors of childhood acute lymphocytic leukemia (ALL), as compared to age‐ and gender‐matched healthy controls.

Results

There was a trend for ALL survivors to perform more poorly on a working memory task in terms of overall accuracy. Additionally, survivors displayed significantly greater activation in areas underlying working memory (dorsolateral and ventrolateral prefrontal cortex) and error monitoring (dorsal and ventral anterior cingulate cortex).

Conclusions

These results support the theory of compensatory activation in necessary brain regions in order to complete tasks in pediatric ALL survivors, similar to that observed in multiple sclerosis patients. Concurrent examination of testing and brain imaging enables the connection of behavioral observations with underlying neurological characteristics of deficits in survivors and may help provide insight into mechanisms through which deficits appear. Pediatr Blood Cancer 2010;54:585–590. © 2009 Wiley‐Liss, Inc.
Media attention and the influence on the reporting odds ratio in disproportionality analysis: an example of patient reporting of statins
Authors: van Hunsel Florence , van Puijenbroek Eugène , de Jong‐ van den Berg Lolkje , van Grootheest Kees
Published: December 2009

Aim

To study the influence of media attention about statins and ADRs on the level of disproportionality, expressed as the reporting odds ratio (ROR) for statins in the Lareb database, based on patients' reports.

Methods

Patient reports about statins, before and after the broadcast of a consumer programme about statins, were compared. In order to calculate the correlation between the ROR for patient‐statin reports between the period before and after the broadcast a Pearson correlation‐coefficient (r) was calculated. The type of reported ADRs associated with statins before and after the broadcast was compared both on the level of system organ class (SOC) and preferred terms (PT).

Results

Pearson's Correlation‐coefficient for the comparison of RORs before and after the broadcast was 0.83. In respect to specific ADRs, no differences were found in reporting on SOC level before and after the broadcast, except for the SOCMusculoskeletal and connective tissue disorders. For ADRs that were specifically mentioned during the broadcast, no differences were found except for an increased number of myalgia and arthralgia reports.

Conclusion

Our study demonstrates that media attention does not necessarily influence the relative reporting by patients expressed as RORs in the national ADR database. On SOC level only inMusculoskeletal and connective tissue disordersthe relative reporting increased. For myalgia and arthralgia, there was a proportional increase of reporting within the statin class but not for the other ADRs that were explicitly mentioned in the TV programme about statins. Copyright © 2009 John Wiley & Sons, Ltd.
Comparative analysis of the secretory proteome of human adipose stromal vascular fraction cells during adipogenesis
Authors: Kim Jaeyoon , Choi Yoon Sup , Lim Seyoung , Yea Kyungmoo , Yoon Jong Hyuk , Jun Dong‐Jae , Ha Sang Hoon , Kim Jung‐Wook , Kim Jae Ho , Suh Pann‐Ghill , Ryu Sung Ho , Lee Taehoon G.
Published: December 2009

Adipogenesis is a complex process that is accompanied by a number of molecular events. In this study, a proteomic approach was adopted to identify secretory factors associated with adipogenesis. A label‐free shotgun proteomic strategy was implemented to analyze proteins secreted by human adipose stromal vascular fraction cells and differentiated adipocytes. A total of 474 proteins were finally identified and classified according to quantitative changes and statistical significances. Briefly, 177 proteins were significantly upregulated during adipogenesis (Class I), whereas 60 proteins were significantly downregulated (Class II). Changes in the expressions of several proteins were confirmed by quantitative RT‐PCR and immunoblotting. One obvious finding based on proteomic data was that the amounts of several extracellular modulators of Wnt and transforming growth factor‐β (TGF‐β) signaling changed during adipogenesis. The expressions of secreted frizzled‐related proteins, dickkopf‐related proteins, and latent TGF‐β‐binding proteins were found to be altered during adipogenesis, which suggests that they participate in the fine regulation of Wnt and TGF‐β signaling. This study provides useful tools and important clues regarding the roles of secretory factors during adipogenic differentiation, and provides information related to obesity and obesity‐related metabolic diseases.
Environmental proteomics: Analysis of structure and function of microbial communities
Authors: Schneider Thomas , Riedel Kathrin
Published: December 2009

Prokaryotic and eukaryotic microorganisms make a vital contribution to biogeochemical cycles by decomposing virtually all natural compounds and thereby exert a lasting effect on biosphere and climate. The rapidly growing number of metagenomic sequences together with revolutionary advances in bioinformatics and protein analyses have opened completely new horizons to investigate the molecular basis of such complex processes. Proteomics has contributed substantially to our understanding of individual organisms at the cellular level as it offers excellent possibilities to probe many protein functions and responses simultaneously. However, it has not yet been widely applied in microbial ecology, although most proteins have an intrinsic metabolic function which can be used to relate microbial activities to the identity of defined organisms in multispecies communities. Albeit still in its infancy, environmental proteomics enables simple protein cataloging, comparative and semi‐quantitative proteomics, analyses of protein localization, discovery of post‐translational modifications, and even determination of amino‐acid sequences and genotypes by strain‐resolved proteogenomics. This review traces the historical development of environmental proteomics and summarizes milestone publications in the field. In conclusion, we briefly discuss current limitations of microbial community proteomics but also the potential of emerging technologies to shape the future of metaproteome analyses.
De novo sequencing of peptides by MS/MS
Authors: Seidler Joerg , Zinn Nico , Boehm Martin E. , Lehmann Wolf D.
Published: December 2009

The current status of de novo sequencing of peptides by MS/MS is reviewed with focus on collision cell MS/MS spectra. The relation between peptide structure and observed fragment ion series is discussed and the exhaustive extraction of sequence information from CID spectra of protonated peptide ions is described. The partial redundancy of the extracted sequence information and a high mass accuracy are recognized as key parameters for dependable de novo sequencing by MS. In addition, the benefits of special techniques enhancing the generation of long uninterrupted fragment ion series for de novo peptide sequencing are highlighted. Among these are terminal 18O labeling, MSn of sodiated peptide ions, N‐terminal derivatization, the use of special proteases, and time‐delayed fragmentation. The emerging electron transfer dissociation technique and the recent progress of MALDI techniques for intact protein sequencing are covered. Finally, the integration of bioinformatic tools into peptide de novo sequencing is demonstrated.
Contribution of proteomics toward solving the fascinating mysteries of the biogenesis of the envelope of Escherichia coli
Authors: Leverrier Pauline , Vertommen Didier , Collet Jean‐François
Published: December 2009

The cell envelope of Gram‐negative bacteria is a complex macromolecular structure that is essential for their viability. Little is known on how the proteins which are secreted to the envelope fold into their unique three‐dimensional structure. Several folding factors, including chaperones and protein folding catalysts involved in disulfide bond formation, have been identified in the periplasm. The characterization of these proteins has advanced our understanding of envelope biogenesis, although many fundamental questions remain unanswered. In particular, we still do not know how β‐barrel proteins are transported through the periplasm and inserted into the outer membrane. Here, we discuss the recent discoveries that have shed new light on the mechanisms that ensure the correct folding of envelope proteins. We have paid particular attention to the significant contribution of proteomic studies.
Cell‐free synthesis‐based protein microarrays and their applications
Authors: Chandra Harini , Srivastava Sanjeeva
Published: December 2009

The entire complement of proteins expressed by the genome of an organism under a set of defined conditions represents the proteome. The need for rapid, efficient, and high‐throughput technologies to understand the proteome of organisms have resulted in the development of protein microarrays. Traditional, cell‐based technologies for the generation of protein arrays involve laborious and protracted procedures, which also pose several other technical problems. These limitations have been suitably overcome by cell‐free expression systems that carry out rapid, in situ synthesis of proteins from their corresponding DNA templates. This article provides an overview of commonly used cell‐free systems that have been used for the generation of protein microarrays, with special emphasis on the diverse applications of cell‐free synthesis‐based protein microarrays.
Peptide and protein quantification: A map of the minefield
Authors: Vaudel Marc , Sickmann Albert , Martens Lennart
Published: December 2009

The increasing popularity of gel‐free proteomics technologies has created a strong demand for compatible quantitative analysis methods. As a result, a plethora of different techniques has been proposed to perform gel‐free quantitative analysis of proteomics samples. Each of these methods comes with certain strengths and shortcomings, and they often are dedicated to a specific purpose. This review will present a brief overview of the main methods, organized by their underlying concepts, and will discuss the issues they raise with a focus on data processing. Finally, we will list the available software that can help with the data processing from quantitative experiments. We hope that this review will thus enable researchers to find the most appropriate method available for their research objectives, and can also serve as a basis for creating a reliable data processing strategy.
Nanobiocatalysis for protein digestion in proteomic analysis
Authors: Kim Jungbae , Kim Byoung Chan , Lopez‐Ferrer Daniel , Petritis Konstantinos , Smith Richard D.
Published: December 2009

The process of protein digestion is a critical step for successful protein identification in bottom‐up proteomic analyses. To substitute the present practice of in‐solution protein digestion, which is long, tedious, and difficult to automate, many efforts have been dedicated for the development of a rapid, recyclable and automated digestion system. Recent advances of nanobiocatalytic approaches have improved the performance of protein digestion by using various nanomaterials such as nanoporous materials, magnetic nanoparticles, and polymer nanofibers. Especially, the unprecedented success of trypsin stabilization in the form of trypsin‐coated nanofibers, showing no activity decrease under repeated uses for 1 year and retaining good resistance to proteolysis, has demonstrated its great potential to be employed in the development of automated, high‐throughput, and on‐line digestion systems. This review discusses recent developments of nanobiocatalytic approaches for the improved performance of protein digestion in speed, detection sensitivity, recyclability, and trypsin stability. In addition, we also introduce approaches for protein digestion under unconventional energy input for protein denaturation and the development of microfluidic enzyme reactors that can benefit from recent successes of these nanobiocatalytic approaches.
Analysis of proteomic changes associated with sperm capacitation through the combined use of IPG‐strip pre‐fractionation followed by RP chromatography LC‐MS/MS analysis
Authors: Baker Mark A. , Reeves Gabi , Hetherington Louise , Aitken R. John
Published: November 2009

Following ejaculation, mammalian spermatozoa undergo an obligatory process known as capacitation, which enables these cells to bind to and fertilize an oocyte. Since spermatozoa are transcriptionally and translationally silent, the functional metamorphosis of these cells during capacitation is accomplished entirely by PTMs. Despite the importance of this process, very few studies have attempted to define the precise nature of the proteomic changes that allow spermatozoa to attain a capacitated state. Here we report the use of an IPG‐strip pre‐fractionation approach to isolate and purify tryptic peptides derived from mouse spermatozoa exhibiting varying degrees of capacitation. Following focusing, the strips were cut into 1 cm segments, the peptides extracted and run into a mass spectrometer. Label‐free, quantitative analysis of proteomic changes associated with capacitation was then performed. In total, we found 210 significant peptide changes. Of these, we could conclusively interpret the tandem mass spectra of 71 peptides, corresponding to 52 protein changes during capacitation. Many proteins including VDAC2, Fascin‐3 and sorbitol dehydrogenase (SORD) have not previously been implicated in this process. To validate our data, we were able to show significant upregulation of SORD activity during capacitation, suggesting that the polyol pathway is activated during this process.
Characterization of Low‐Temperature Microwave Plasma Treatment With and Without UV Light for Disinfection
Authors: Shimizu Tetsuji , Nosenko Tetyana , Morfill Gregor Eugen , Sato Takehiko , Schmidt Hans‐Ulrich , Urayama Takuya
Published: December 2009

Chemical characteristics and bactericidal properties of two low‐temperature atmospheric‐pressure Ar plasma devices are investigated: one of them with UV and the other with almost no UV on treated samples. The control of the UV radiation is achieved by two nozzles. One has a straight shape, and the other has a 90°‐bent. The bent nozzle blocks the light produced inside the torch, whilst allowing the plasma gas to reach the samples. The use of the straight nozzle allows the treatment by both the plasma gas and UV. We demonstrate that even an almost UV‐free plasma treatment has bactericidal properties. Our measurements suggest that reactive species represent the main bactericidal factor of our low‐temperature plasma.

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Effects of airway pressure release ventilation on blood pressure and urine output in children
Authors: Kamath Sameer S. , Super Dennis M. , Mhanna Maroun J.
Published: December 2009

Objective

Increased intrathoracic pressures during airway pressure release ventilation (APRV) may compromise systemic venous return resulting in decreased cardiac output and renal perfusion. We sought to study the short‐term effect of APRV on blood pressure (BP) and urine output (UO) in children with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).

Design

Retrospective cohort study.

Patients

All patients with ALI/ARDS who were admitted to our Pediatric Intensive Care Unit (PICU) between 1/00 and 06/04, and who were ventilated with APRV (for at least 12 hr) for worsening oxygenation while on conventional ventilation (CV).

Measurements and Results

Medical records were reviewed for patients' demographics, Pediatric Risk of Mortality (PRISM III) score, admitting diagnosis, ventilator settings, gas exchange data, heart rate (HR), central venous pressure (CVP), blood pressure (BP), UO, and use of other therapies [sedatives, pressors, inotropes, and intravenous fluid (IVF)]. Eleven patients met our inclusion and exclusion criteria with a mean age of 6.2 ± 4.8 years (range: 1–15 years), a weight of 35.5 ± 29.5 kg (range: 12–90 kg), and a PRISM score of 18.4 ± 9.6 (range: 2–36). Within 10 hrs of APRV, patients' mean airway pressure (Paw) increased from 16.1 ± 6.6 to 21.1 ± 5.5 cm of H2O (P = 0.04). Despite a higher Paw there were no differences in HR, CVP, BP, UO, IVF and use of other therapies while on CV or APRV (P > 0.10).

Conclusion

In children with ALI/ARDS, despite a higher Paw, APRV does not affect BP or UO. Pediatr Pulmonol. 2010; 45:48–54. © 2009 Wiley‐Liss, Inc.
Costs of Treating Children With Complicated Pneumonia: A Comparison of Primary Video‐Assisted Thoracoscopic Surgery and Chest Tube Placement
Authors: Shah Samir S. , Ten Have Thomas R. , Metlay Joshua P.
Published: December 2009

Objectives

To describe charges associated with primary video‐assisted thoracoscopic surgery (VATS) and primary chest tube placement in a multicenter cohort of children with empyema and to determine whether pleural fluid drainage by primary VATS was associated with cost‐savings compared with primary chest tube placement.

Study Design

Retrospective cohort study.

Setting and Participants

Administrative database containing inpatient resource utilization data from 27 tertiary care children's hospitals. Patients between 12 months and 18 years of age diagnosed with complicated pneumonia were eligible if they were discharged between 2001 and 2005 and underwent early (within 2 days of index hospitalization) pleural fluid drainage.

Main Exposure

Method of pleural fluid drainage, categorized as VATS or chest tube placement.

Results

Pleural drainage in the 764 patients was performed by VATS (n = 50) or chest tube placement (n = 714). There were 521 (54%) males. Median hospital charges were $36,320 [interquartile range (IQR), $24,814–$62,269]. The median pharmacy and radiologic imaging charges were $5,884 (IQR, $3,142–$11,357) and $2,875 (IQR, $1,703–$4,950), respectively. Adjusting for propensity score matching, patients undergoing primary VATS did not have higher charges than patients undergoing primary chest tube placement.

Conclusions

In this multicenter study, we found that the charges incurred in caring for children with empyema were substantial. However, primary VATS was not associated with higher total or pharmacy charges than primary chest tube placement, suggesting that the additional costs of performing VATS are offset by reductions in length of stay (LOS) and requirement for additional procedures. Pediatr Pulmonol. 2010; 45:71–77. © 2009 Wiley‐Liss, Inc.
Cost‐effectiveness modelling in osteoporosis: alternatives to NICE
Authors: Brown Pam
Published: December 2009

The cost‐effectiveness modelling used by NICE in its 2008 guidance on the prevention of osteoporotic fracture in postmenopausal women has recently been challenged. Here, the author presents alternative cost‐effectiveness analyses and discusses the disparities with that published by NICE. Copyright © 2009 Wiley Interface Ltd