bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of antineutrophil cytoplasmic autoantibody vasculitides: The role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis
Authors: Lionaki Sophia , Blyth Elizabeth R. , Hogan Susan L. , Hu Yichun , Senior Brent A. , Jennette Caroline E. , Nachman Patrick H. , Jennette J. Charles , Falk Ronald J.
Published: September 2012

Objective

To compare the usefulness of 3 currently used classification systems in predicting the outcomes of treatment resistance, disease relapse, end‐stage renal disease (ESRD), and death in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

Methods

Three classification systems were applied to 502 patients with biopsy‐proven AAV: 1) the Chapel Hill Consensus Conference (CHCC) definition with categories for granulomatosis with polyangiitis (GPA) (Wegener's), microscopic polyangiitis (MPA), and kidney‐limited disease; 2) the European Medicines Agency (EMA) system with categories for GPA and MPA; and 3) classification based on ANCA with specificity for myeloperoxidase (MPO ANCA) versus ANCA with specificity for proteinase 3 (PR3 ANCA). Outcomes included treatment resistance, relapse, ESRD, and death. Proportional hazards models were compared between systems using an information‐theoretic approach to rank models by predictive fit. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) and P values are reported.

Results

ANCA specificity was predictive of relapse, with PR3 ANCA–positive patients almost twice as likely to relapse as those with MPO ANCA (HR 1.89 [95% CI 1.33–2.69], P = 0.0004), and ANCA specificity had the best predictive model fit (model rank 1) compared to the CHCC and EMA systems. The CHCC and EMA systems did not predict relapse. By ANCA specificity, categories of GPA, MPA, and kidney‐limited disease did not distinguish differences in probability of relapse‐free survival. None of the systems predicted treatment resistance, ESRD, or death.

Conclusion

ANCA specificity independently predicts relapse among patients with AAV with renal disease. Classification and diagnostic systems that incorporate ANCA specificity, such as PR3 ANCA–positive MPA and MPO ANCA–positive MPA, provide a more useful tool than the clinical pathologic category alone for predicting relapse.
Smad3 controls β‐1,3‐glucuronosyltransferase 1 expression in rat nucleus pulposus cells: Implications of dysregulated expression in disc disease
Authors: Wu Qianghua , Wang Jianru , Skubutyte Renata , Kepler Christopher K. , Huang Zonggui , Anderson D. Greg , Shapiro Irving M. , Risbud Makarand V.
Published: September 2012

Objective

To study the regulation of expression of β‐1,3‐glucuronosyltransferase 1 (GlcAT‐1), an important regulator of glycosaminoglycan (GAG) synthesis, by Smad3 in nucleus pulposus (NP) cells.

Methods

GlcAT‐1 expression was examined in rat NP and anulus fibrosus (AF) cells treated with transforming growth factor β (TGFβ). The effects of Smad signaling and Smad suppression on GlcAT‐1 were examined in rat NP cells. GlcAT‐1 expression was analyzed in the discs of Smad3‐null mice and in degenerated human NP tissue.

Results

TGFβ increased the expression of GlcAT‐1 in rat NP but not rat AF cells. Suppression of GlcAT‐1 promoter activity was evident with dominant‐negative ALK‐5 (DN‐ALK‐5). Cotransfection with Smad3 strongly induced promoter activity independent of TGFβ. Bioinformatics analysis indicated the presence of several Smad binding sites in the promoter; deletion analysis showed that the region between −274 and −123 bp was required for Smad3 response. DN‐Smad3, Smad 3 small interfering RNA, and Smad7 strongly suppressed basal as well as TGFβ‐induced promoter activity. Induction of promoter activity by Smad3 was significantly blocked by DN‐Smad3; Smad7 had a very small effect. Lentiviral transduction of NP cells with short hairpin RNA Smad3 resulted in a decrease in GlcAT‐1 expression and accumulation of GAG. Compared to wild‐type mice, significantly lower expression of GlcAT‐1 was seen in the discs of Smad3‐null mice. Analysis of degenerated human NP tissue specimens showed no positive correlation between GlcAT‐1 and TGFβ expression. Moreover, isolated cells from degenerated human tissue showed a lack of induction of GlcAT‐1 expression following TGFβ treatment, suggesting an altered response.

Conclusion

Our findings demonstrate that in healthy NP cells, the TGFβ–Smad3 axis serves as a regulator of GlcAT‐1 expression. However, an altered responsiveness to TGFβ during disc degeneration may compromise GAG synthesis.
1‐Aryl‐4‐Silylmethyl[60]fullerenes: Synthesis, Properties, and Photovoltaic Performance
Authors: Matsuo Yutaka , Oyama Hiromi , Soga Iwao , Okamoto Toshihiro , Tanaka Hideyuki , Saeki Akinori , Seki Shu , Nakamura Eiichi
Published: September 2012

The efficient nucleophilic addition of aryl Grignard reagents (aryl=4‐MeOC6H4, 4‐Me2NC6H4, Ph, 4‐CF3C6H4, and thienyl) to C60 in the presence of DMSO produced 1,2‐arylhydro[60]fullerenes after acid treatment. The reactions of the anions of these arylhydro[60]fullerenes with either dimethylphenylsilylmethyl iodide or dimethyl(2‐isopropoxyphenyl)silylmethyl iodide yielded the target compounds, 1‐aryl‐4‐silylmethyl[60]fullerenes. The properties and structures of these 1‐aryl‐4‐silylmethyl[60]fullerenes (aryl=4‐MeOC6H4, thienyl) were examined by electrochemical studies, X‐ray crystallography, flash‐photolysis time‐resolved microwave‐conductivity (FP‐TRMC) measurements, and electron‐mobility measurements by using a space‐charge‐limited current (SCLC) model. Organic photovoltaic devices with a polymer‐based bulk heterojunction structure and small‐molecule‐based p–n and p–i–n heterojunction configurations were fabricated by using 1‐aryl‐4‐silylmethyl[60]fullerenes as an electron acceptor. The most efficient device exhibited a power‐conversion efficiency of 3.4 % (short‐circuit current density: 8.1 mA/ cm2, open‐circuit voltage: 0.69 V, fill factor: 0.59).
Aortic rupture and sac expansion after endovascular repair of abdominal aortic aneurysm
Authors: Holt P J E , Karthikesalingam A , Patterson B O , Ghatwary T , Hinchliffe R J , Loftus I M , Thompson M M
Published: September 2012

Background

Long-term concerns about the durability of endovascular aortic aneurysm repair (EVAR) remain after the publication of controlled trials. Increased expertise in endograft technology, case selection and postoperative reintervention has created a need for reappraisal of the longer-term efficacy of EVAR using contemporary data.

Methods

Patients undergoing infrarenal EVAR between 2004 and 2010 were studied prospectively. Morphological compliance with manufacturers' instructions for use (IFU) was established using three-dimensional computed tomography. The primary outcome measures were all-cause and aneurysm-related mortality, postoperative rupture, reintervention and sac expansion. These adverse events were reported using Kaplan–Meier survival analysis, with comparison within, or outside IFU by the log rank test.

Results

Some 478 patients of median age 76 years had a median aneurysm diameter of 62·9 mm. Median follow-up was 44 (range 11–94) months; 198 (41·4 per cent) were compliant with IFU. The 30-day mortality rate was 2·1 per cent (10 of 478 patients): nine (2·0 per cent) of 455 patients who had elective and one (4 per cent) of 23 patients who had non-elective surgery. Aneurysm-related mortality was 0·897 deaths per 100 person-years, and all-cause mortality was 8·558 deaths per 100 person-years, with significantly lower survival outside IFU (P = 0·012). Two patients had a late rupture (0·138 per 100 person-years), of whom one died. There were 6·120 reinterventions per 100 person-years, with no difference for aneurysms treated outside IFU (P = 0·136). Primary sac expansion occurred in 6·721 per 100 person-years and secondary sac expansion in 4·142 per 100 person-years.

Conclusion

In this series EVAR had a lower aneurysm-related mortality rate than demonstrated in early controlled trials, and with lower sac expansion rates than reported from image repositories. Data from earlier studies should be applied to current practice with caution.
Determination of limonin in dog plasma by liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study
Authors: Liu Shi‐jia , Zhou Ling , Zhang Jun , Yu Bo‐yang , Li Chang‐yin , Liu Zi‐xiu , Ju Wen‐zheng
Published: September 2012

A highly sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the determination of limonin in beagle dog plasma using nimodipine as internal standard. The analyte and internal standard (IS) were extracted with ether followed by a rapid isocratic elution with 10 mm ammonium acetate buffer–methanol (26:74, v/v) on a C18 column (150 × 2.1 mm i.d.) and subsequent analysis by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 469.4 → 229.3 and m/z 417.2 → 122.0 were used to measure the analyte and the IS. The assay was linear over the concentration range of 0.625–100 ng/mL for limonin in dog plasma. The lower limit of quantification was 0.312 ng/mL and the extraction recovery was >90.4% for limonin. The inter‐ and intra‐day precision of the method at three concentrations was less than 9.9%. The method was successfully applied to pharmacokinetic study of limonin in dogs. Copyright © 2012 John Wiley & Sons, Ltd.
The stable o‐phthalaldehyde‐ferrocene/6‐ferrocenyl‐1‐hexanethiol pre‐column derivatization high‐performance liquid chromatography of dimethylarginine by novel dual fluorescence and electrochemical detector
Authors: Suzuki Katsuhiro , Katayama Masatoki , Takamatsu Kiyoshi , Kaneko Satoru , Ishikawa Hiromichi , Tsukimura Takahiro , Togawa Tadayasu
Published: September 2012

Monomethylarginine, asymmetric dimethylarginine and symmetric dimethylarginine were separated on a Wakopak Combi ODS with an acetonitrile–100 mm potassium phosphate buffer (pH 7.0; 1:1, v/v). Dimethylarginines were derived from o‐phthalaldehyde for the fluorescence detector and from 6‐ferrocenyl‐1‐hexanethiol for the electrochemical detector. The detection limits of the dimethylarginines in spiked plasma were 0.3–0.5 pmol by electrochemical detection and 1–2 pmol by fluorescence detection. The detection limits were improved over 30 times by electrochemical detection and 10 times by fluorescence detection compared with previous reports. In previous derivatization liquid chromatography, the reaction solutions, o‐phthalaldehyde, 2‐mercaptethanol and dimethylarginines were unstable and required quick derivatization at 4°C. By our proposed pre‐column methods, the dimethylarginines were derivatized at room temperature and the fluorescent products were stable for 6 h. The manipulation performance was greatly advanced compared with previous LC reports. This is the first report on stable and sensitive dimethylarginines by dual detection. The selectivity was also improved by dual detection. The proposed method was applied to preliminary monitoring of dimethylargines in plasma and urine. Copyright © 2012 John Wiley & Sons, Ltd.
2′‐Deoxyribonucleoside Phosphoramidate Triphosphate Analogues as Alternative Substrates for E. coli Polymerase III
Authors: Giraut Anne , Abu El‐asrar Rania , Marlière Philippe , Delarue Marc , Herdewijn Piet
Published: September 2012

Thermostable bacterial polymerases like Taq, Therminator and Vent exo− are able to perform DNA synthesis by using modified DNA precursors, a property that is exploited in several therapeutic and biotechnological applications. Viral polymerases are also known to accept modified substrates, and this has proven crucial in the development of antiviral therapies. However, non‐thermostable polymerases of bacterial origin, or engineered variants, that have similar substrate tolerance and could be used for synthetic biology purposes remain to be identified.

 We have identified the α subunit of Escherichia coli polymerase III (Pol III α) as a bacterial polymerase that is able to recognise and process as substrates several pyrophosphate‐modified dATP analogues in place of its natural substrate dATP for template‐directed DNA synthesis. A number of dATP analogues featuring a modified pyrophosphate group were able to serve as substrates during enzymatic DNA synthesis by Pol III α. Features such as the presence of potentially chelating chemical groups and the size and spatial flexibility of the chemical structure seem to be of major importance for the modified leaving group to play its role during the enzymatic reaction. In addition, we could establish that if the pyrophosphate group is altered, deoxynucleotide incorporation proceeds with an efficiency varying with the nature of the nucleobase. Our results represent a great step towards the achievement of a system of artificial DNA synthesis hosted by E. coli and involving the use of altered nucleotide precursors for nucleic acid synthesis.
Progress and Prospects of Pyrrole‐Imidazole Polyamide–Fluorophore Conjugates as Sequence‐Selective DNA Probes
Authors: Vaijayanthi Thangavel , Bando Toshikazu , Pandian Ganesh N. , Sugiyama Hiroshi
Published: September 2012

Recently, the versatility of N‐methylpyrrole (Py)‐N‐methylimidazole (Im) polyamide conjugates, which have been developed from the DNA‐binding antibiotics distamycin A and netropsin, has been shown. These synthetic small molecules can permeate cells to bind with duplex DNA in a sequence‐specific manner, and hence can influence gene expression in vivo. Accordingly, several reports demonstrating the sequence specificity and biological activity of Py‐Im polyamides have accumulated. However, the benefits of Py‐Im polyamides, in particular those conjugated with fluorophores, has been overlooked. Moreover, clear directions for the employment of these attractive artificial small molecules have not yet been shown. Here, we present a detailed overview of the current and prospective applications of Py‐Im polyamide–fluorophore conjugates, including sequence‐specific recognition with fluorescence emission properties, and their potential roles in biological imaging.
Synthesis and Characterization of Terminal [Re(XCO)(CO)2(triphos)] (X=N, P): Isocyanate versus Phosphaethynolate Complexes
Authors: Alidori Simone , Heift Dominikus , Santiso‐Quinones Gustavo , Benkő Zoltán , Grützmacher Hansjörg , Caporali Maria , Gonsalvi Luca , Rossin Andrea , Peruzzini Maurizio
Published: September 2012

The terminal rhenium(I) phosphaethynolate complex [Re(PCO)(CO)2(triphos)] has been prepared in a salt metathesis reaction from Na(OCP) and [Re(OTf)(CO)2(triphos)]. The analogous isocyanato complex [Re(NCO)(CO)2(triphos)] has been likewise prepared for comparison. The structure of both complexes was elucidated by X‐ray diffraction studies. While the isocyanato complex is linear, the phosphaethynolate complex is strongly bent around the pnictogen center. Computations including natural bond orbital (NBO) theory, natural resonance theory (NRT), and natural population analysis (NPA) indicate that the isocyanato complex can be viewed as a classic Werner‐type complex, that is, with an electrostatic interaction between the ReI and the NCO group. The phosphaethynolate complex [Re(PCO)(CO)2(triphos)] is best described as a metallaphosphaketene with a ReI–phosphorus bond of highly covalent character.
Angiotensin Receptor Blockers Worsen Renal Function and Dyspnea on Ticagrelor: A Potential Ticagrelor‐Angiotensin Receptor Blocker Interaction?
Authors: DiNicolantonio James J. , Serebruany Victor L.
Published: September 2012

Ticagrelor is a new antiplatelet agent that was pitted against clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Because ticagrelor is the first oral, reversible, twice‐daily agent, sufficient information on drug interactions is not available. Our objective was to ascertain the safety of ticagrelor with other common medications. The US Food and Drug Administration Complete Response Review indicates that renal adverse events (AEs) and renal function AEs were higher in ticagrelor‐treated patients who were concomitantly treated with angiotensin receptor blockers (ARBs) >50% of study days compared to ticagrelor‐treated patients who did not receive ARBs >50% of study days. Clopidogrel‐treated patients showed a trend for an increase in adverse renal events with ARB use. However, this was not as pronounced as that observed with ticagrelor. Dyspnea was also significantly increased in patients on concomitant ticagrelor‐ARB compared to ticagrelor without concomitant ARB and clopidogrel (21.4% vs 14.6% vs 9.9%, respectively) as well as angioedema (0.15% vs 0.09%). Furthermore, in patients with a baseline estimated glomerular filtration rate (eGFR) <30 mL/min, the risk of major bleeding, death, and renal failure was increased in patients on ticagrelor compared to patients on clopidogrel. In patients on ticagrelor, ARBs significantly increased the frequency of renal related AEs, renal function AEs, and dyspnea. Moreover, in patients with a baseline eGFR <30 mL/min, the risk of major bleeding, death, and renal failure was increased in patients on ticagrelor compared to patients on clopidogrel.

Dr. Serebruany is listed as an inventor for the US patent application: TREATING CARDIAC ARRHYTHMIAS, HEART FAILURE, PERIPHERAL ARTERY DISEASE AND STROKE WITH CYCLOPENTYL‐TRIAZOLO‐PYRIMIDINE OR DERIVATIVE THEREOF (USN 61/253,829) assigned to HeartDrug™ Research, and received funding for research studies with clopidogrel, and consultant fees from both clopidogrel and ticagrelor manufacturers.
Synthesis–Structure–Morphology Interplay of Bimetallic “Core–Shell” Carbon Nitride Nano‐electrocatalysts
Authors: Di Noto Vito , Negro Enrico , Polizzi Stefano , Agresti Filippo , Giffin Guinevere A.
Published: September 2012

An extensive morphological and structural study of two bimetallic “core–shell” carbon nitride nano‐electrocatalysts with active sites based on Pt and Ni or on Pt and Fe is reported. The core–shell electrocatalysts are obtained by the pyrolysis of a precursor obtained by decorating a support composed of conducting particles with a hybrid inorganic–organic material. The electrocatalysts were investigated by high‐resolution TEM, powder X‐ray diffraction, and μ‐Raman spectroscopy. The morphological and structural information presented here provides 1) insight into the microscopic features, affecting the electrochemical performance of the electrocatalyst materials determined in both ex situ measurements and single‐cell configurations; and 2) an opportunity to study the effect of the different precursor chemistries on the structure and morphology of the bimetallic core–shell carbon nitride nano‐electrocatalysts.
Determining how defects in connexin43 cause skeletal disease
Authors: Ton Quynh V. , Iovine M. Kathryn
Published: September 2012

Gap junction channels mediate direct cell–cell communication via the exchange of second messengers, ions, and metabolites from one cell to another. Mutations in several human connexin (cx) genes, the subunits of gap junction channels, disturb the development and function of multiple tissues/organs. In particular, appropriate function of Cx43 is required for skeletal development in all vertebrate model organisms. Importantly, it remains largely unclear how disruption of gap junctional intercellular communication causes developmental defects. Two groups have taken distinct approaches toward defining the tangible molecular changes occurring downstream of Cx43‐based gap junctional communication. Here, these strategies for determining how Cx43 modulates downstream events relevant to skeletal morphogenesis were reviewed. genesis 51:75–82, 2013. © 2012 Wiley Periodicals, Inc.
Historical demographic dynamics underlying local adaptation in the presence of gene flow
Authors: Ribeiro Ângela M. , Lopes Ricardo J. , Bowie Rauri C. K.
Published: September 2012

The range of a species is the result of the relative contribution of spatial tracking of environmental requirements and adaptation to ecological conditions outside the ancestral niche. The appearance of novel habitats caused by climatic oscillation can promote range expansion and accompanying demographic growth. The demographic dynamics of populations leave a signal in \ patterns. We modeled three competing scenarios pertaining to the circumstance of a range expansion by the Karoo Scrub‐Robin into newly available habitat resulting from the increasing aridification of southern Africa. Genetic variation was contrasted with the theoretical expectations of a spatial range expansion, and compared with data of a putative adaptive trait. We infer that this bird likely colonized the arid zone, as a consequence of adaptive evolution in a small peripheral population, followed by an expansion with recurrent exchange of migrants with the ancestral populations.
Lewis Acid Promoted Double Bond Isomerization of Tetrahydroxanthones
Authors: Linsenmeier Anna M. , Bräse Stefan
Published: September 2012

Herein, a method for the isomerization of the double bonds in tetrahydroxanthones is reported. Tetrahydroxanthones are readily available from salicylaldehydes and cycloalkenones and undergo isomerization upon treatment with AlCl3. The mechanism of the isomerization and follow‐up chemistry of the products were investigated. Follow‐up chemistry such as asymmetric Corey–Bakshi–Shibata (CBS) reduction provides highly functionalized tetrahydroxanthones.
Genetic variation within the Hypodontus macropi (Nematoda: Strongyloidea) complex from macropodid marsupial hosts in Australia
Authors: Chilton Neil B. , Jabbar Abdul , Huby‐Chilton Florence , Jex Aaron , Gasser Robin B. , Beveridge Ian
Published: September 2012

Genetic variation was investigated in the strongylid nematode Hypodontus macropi from macropodid marsupials using the second internal transcribed spacer of ribosomal DNA. A total of 547 specimens from ten species of hosts, representing all of the known hosts of the parasite, from across the Australian continent was examined. Phylogenetic analyses revealed distinct genetic clades in each of Macropus agilis, M. dorsalis, M. rufogriseus, M. bicolor, Petrogale persephone, Thylogale billardierii and T. stigmatica. A further clade contained all specimens from M. robustus and M. rufus, together with two examples of host switching by nematodes into M. fuliginosus. The latter clade was subdivided into three subclades, one comprising specimens occurring in M. robustus erubescens, M. rufus and M. fuliginosus, the second in M. r. woodwardi and the third in M. r. robustus suggesting a relationship between the subclades and the subspecies of M. robustus. The extent of the genetic differences and the fact that several of them occur in broad sympatry suggests that H. macropi as currently defined morphologically may represent as many as ten cryptic species. Limited evidence was found for co‐speciation between hosts and parasites; rather most relationships were better explained by host switching.
Quality control of next‐generation sequencing library through an integrative digital microfluidic platform
Authors: Thaitrong Numrin , Kim Hanyoup , Renzi Ronald F. , Bartsch Michael S. , Meagher Robert J. , Patel Kamlesh D.
Published: September 2012

We have developed an automated quality control (QC) platform for next‐generation sequencing (NGS) library characterization by integrating a droplet‐based digital microfluidic (DMF) system with a capillary‐based reagent delivery unit and a quantitative CE module. Using an in‐plane capillary–DMF interface, a prepared sample droplet was actuated into position between the ground electrode and the inlet of the separation capillary to complete the circuit for an electrokinetic injection. Using a DNA ladder as an internal standard, the CE module with a compact LIF detector was capable of detecting dsDNA in the range of 5–100 pg/μL, suitable for the amount of DNA required by the Illumina Genome Analyzer sequencing platform. This DMF‐CE platform consumes tenfold less sample volume than the current Agilent BioAnalyzer QC technique, preserving precious sample while providing necessary sensitivity and accuracy for optimal sequencing performance. The ability of this microfluidic system to validate NGS library preparation was demonstrated by examining the effects of limited‐cycle PCR amplification on the size distribution and the yield of Illumina‐compatible libraries, demonstrating that as few as ten cycles of PCR bias the size distribution of the library toward undesirable larger fragments.
Factors predisposing to chyle leakage following thyroid cancer surgery without lateral neck dissection
Authors: Lee Yong Sang , Kim Bup‐Woo , Chang Hang‐Seok , Park Cheong Soo
Published: September 2012

Background

The aims of this study were to assess the clinicopathologic features of patients with chyle leakage following thyroid cancer surgery without lateral neck dissection and to evaluate the factors associated with chyle leakage.

Methods

Of 3137 patients who underwent thyroid surgery between January 2006 and December 2007, 2314 patients (73.8%) satisfied our inclusion criteria. Patients were divided into those with (group I, n = 14) and without (group II, n = 2300) chyle leakage.

Results

There were no significant differences between the 2 groups in clinicopathologic features including age, body mass index, extent of thyroidectomy, pathologic type, tumor size, multiplicity, capsular invasion, and coexisting thyroiditis. In univariate and multivariate analyses, male sex, age >45 years, and number of harvested central nodes were significantly associated with chyle leakage.

Conclusions

If extensive central compartment node dissection is needed, meticulous dissection is required, especially in male patients, and aged >45 years, even without lateral neck dissection. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Extended voice‐sparing surgery in selected pyriform sinus carcinoma: Techniques and outcomes
Authors: Hamoir Marc , Fievez Juliette , Schmitz Sandra , Velasco Dorris , Lengele Benoît
Published: September 2012

Background

Organ‐preservation approaches are frequently favored in the treatment of advanced pyriform sinus carcinoma. In selected cases, use of free flaps allows voice‐sparing surgery.

Methods

Thirteen patients underwent conservative extended laryngopharyngectomy. In 11 patients, the resection included the supraglottic larynx, whereas the whole hemilarynx was resected in 2. Reconstruction was achieved with a radial forearm free flap with the palmaris longus tendon. In hemilarynx resection, a costal graft was also used. Functional results were assessed by nasofibroscopy and swallowing videofluoroscopic tests.

Results

At 12 months, no patient was gastrostomy dependent, whereas 1 patient remained tracheostomy dependent. At 1, 3, and 5 years, the locoregional control was 100%, 100%, and 83%; overall survival was 69.4%, 46.3%, and 30.8%; and disease‐specific survival was 81.2%, 54.5%, and 36.4%, respectively.

Conclusions

In selected patients, extended conservative laryngopharyngectomy challenges the oncologic results of organ‐preservation protocols and allows a good quality of life. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1482–1489, 2013
Factors controlling the temporal variability in dissolved oxygen regime of salmon spawning gravels
Authors: Sear D. A. , Pattison I. , Collins A. L. , Newson M. D. , Jones J. I. , Naden P. S. , Carling P. A.
Published: September 2012

Dissolved oxygen (DO) plays a critical role in the development of the juvenile stages of benthic spawning fish and salmonids in particular. Factors influencing the DO regime within spawning gravels include the accumulation of fine sediment, penetration of groundwater or surface water into the gravels, thermal regime, and the consumption of oxygen by sediment and its associated organic fractions. In this field study, we quantify the DO regime within an artificial salmon redd at high temporal resolution. The environment within the redd is shown to be complex, with large variations in DO. Application of a numerical model (SIDO‐UK) enables for the first time, the quantification of the relative contributions to DO consumption from thermal regime, sediment accumulation and sediment oxygen demand. Sediment accumulation is shown to have a minor impact on DO in the redd whereas upwelling groundwater is identified as the most likely cause of the major changes in DO. Bed mobility has a minor impact on DO regime of the redd. The effects of fine sediment and oxygen supply on salmon embryo survival are estimated. Implications for river catchment management and prospects for future research are discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Phasor‐flim analysis of NADH distribution and localization in the nucleus of live progenitor myoblast cells
Authors: Wright Belinda K. , Andrews Laura M. , Jones Mark R. , Stringari Chiara , Digman Michelle A. , Gratton Enrico
Published: September 2012

Analysis of the cellular distributions of coenzymes including NADH may aid in understanding a cells metabolic status. We altered serum concentration (0, 2, and 10%) to induce living myoblast cells to undergo the early stages of differentiation. Through microscopy and phasor‐FLIM, we spatially mapped and identified variations in the distribution of free and bound NADH. Undifferentiated cells displayed abundant free NADH within the nucleus along with specific regions of more bound NADH. Complete serum starvation dramatically increased the fraction of bound NADH in the nucleus, indicating heightened requirement for transcriptional processes. In comparison, cells exposed to 2% serum exhibited intermediate free nuclear NADH fraction. Overall our results suggest an order of events in which a cell metabolic status alters significantly during the early stages of serum induced differentiation. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Risk factors for unplanned transfer to intensive care within 24 hours of admission from the emergency department in an integrated healthcare system
Authors: Delgado M. Kit , Liu Vincent , Pines Jesse M. , Kipnis Patricia , Gardner Marla N. , Escobar Gabriel J.
Published: September 2012

BACKGROUND:

Emergency department (ED) ward admissions subsequently transferred to the intensive care unit (ICU) within 24 hours have higher mortality than direct ICU admissions.

DESIGN, SETTING, PATIENTS:

Describe risk factors for unplanned ICU transfer within 24 hours of ward arrival from the ED.

METHODS:

Evaluation of 178,315 ED non‐ICU admissions to 13 US community hospitals. We tabulated the outcome of unplanned ICU transfer by patient characteristics and hospital volume. We present factors associated with unplanned ICU transfer after adjusting for patient and hospital differences in a hierarchical logistic regression.

RESULTS:

There were 4,252 (2.4%) non‐ICU admissions transferred to the ICU within 24 hours. Admitting diagnoses most associated with unplanned transfer, listed by descending prevalence were: pneumonia (odds ratio [OR] 1.5; 95% confidence interval [CI] 1.2–1.9), myocardial infarction (MI) (OR 1.5; 95% CI 1.2–2.0), chronic obstructive pulmonary disease (COPD) (OR 1.4; 95% CI 1.1–1.9), sepsis (OR 2.5; 95% CI 1.9–3.3), and catastrophic conditions (OR 2.3; 95% CI 1.7–3.0). Other significant predictors included: male sex, Comorbidity Points Score >145, Laboratory Acute Physiology Score ≥7, arriving on the ward between 11 PM and 7 AM. Decreased risk was found with admission to monitored transitional care units (OR 0.83; 95% CI 0.77–0.90) and to higher volume hospitals (OR 0.94 per 1,000 additional annual ED inpatient admissions; 95% CI 0.91–0.98).

CONCLUSIONS:

ED patients admitted with respiratory conditions, MI, or sepsis are at modestly increased risk for unplanned ICU transfer and may benefit from better triage from the ED, earlier intervention, or closer monitoring to prevent acute decompensation. More research is needed to determine how intermediate care units, hospital volume, time of day, and sex affect unplanned ICU transfer. Journal of Hospital Medicine 2013. © 2012 Society of Hospital Medicine
MRI assessment of percutaneous ablation of liver tumors: Value of subtraction images
Authors: Tatli Servet , Acar Murat , Tuncali Kemal , Sadow Cheryl A. , Morrison Paul R. , Silverman Stuart G.
Published: September 2012

Purpose:

To evaluate the value of subtraction images when using MRI to assess liver tumors treated with percutaneous ablation.

Materials and Methods:

Following percutaneous ablation of 35 liver tumors, two abdominal radiologists, blinded to outcomes, independently reviewed follow‐up MRI examinations for tumoral enhancement suggestive of residual/recurrent tumor and rated their confidence level. After one year, the readers reviewed the same examinations with added subtraction images. Accuracy of the detection of residual/recurrent tumor and contrast‐to‐noise ratios (CNR; for tumoral enhancement‐to‐liver, tumoral enhancement‐to‐ablation zone, and ablation zone‐to‐liver) were calculated with and without subtraction images and compared using Wilcoxon signed rank test. Interobserver variability was computed using Kappa (κ) statistics.

Results:

Residual/recurrent tumor was present in 8 (23.5%) of 34 tumors. Accuracy of detecting residual/recurrent tumor with subtraction images and interobserver agreement (κ = 0.72, good) were better than accuracy of detecting residual/recurrent tumor and interobserver agreement (κ = 0.57, moderate) of enhanced MR images without subtraction. Mean CNR of subtraction images was significantly higher than that of enhanced MR images for tumoral enhancement‐to‐liver (0.2 ± 5 versus 11.6 ± 14.4, P = 0.03), tumoral enhancement‐to‐ablation zone (10.1 ± 12.5 versus 34.4 ± 29.4, P = 0.02), and ablation zone‐to‐liver (11.8 ± 13.3 versus 102.5 ± 238.4, P = 0.03).

Conclusion:

When using MRI, subtraction images help both detect and exclude residual/recurrent tumor following percutaneous liver ablations. J. Magn. Reson. Imaging 2013;37:407–413. © 2012 Wiley Periodicals, Inc.
Subcutaneous tumor volume measurement in the awake, manually restrained mouse using MRI
Authors: Kersemans Veerle , Cornelissen Bart , Allen Philip D. , Beech John S. , Smart Sean C.
Published: September 2012

Purpose:

To describe a combination of techniques using the excellent volumetric capacities of magnetic resonance imaging (MRI) while avoiding anesthesia and maintaining high‐throughput capability for tumor volume measurement in the awake mouse. This approach presents an alternative to calipers which, although cheap, fast, and easy to use, introduce many biases for tumor volume estimation.

Materials and Methods:

The murine CaNT subcutaneous xenograft model was used. A quiet and modestly T2‐weighted spin‐echo scan was acquired at 4.7T (TE = 15 msec, TR = 1100 msec, 0.5 mm isotropic resolution) while the awake mouse was held by hand in the magnet. This method was compared to standard MR in the anesthetized mouse and caliper measurements.

Results:

The combination of techniques used allows rapid, accurate, and reproducible measurement of subcutaneous tumor volumes in awake mice. It is less sensitive to both intra‐ and interoperator‐derived biases and avoids confounds from the compliance of the fat and skin around the tumor, as well as from the tumor itself. Moreover, the data remain available for retrieval and scrutiny and reanalysis.

Conclusion:

Rapid, accurate, and precise tumor volumetry can be performed in the awake mouse by handheld positioned MR. J. Magn. Reson. Imaging 2013;37:1499–1504. © 2012 Wiley Periodicals, Inc.
Determination of polyamines in human plasma by high‐performance liquid chromatography coupled with Q‐TOF mass spectrometry
Authors: Liu Ran , Bi Kaishun , Jia Ying , Wang Qian , Yin Ran , Li Qing
Published: September 2012

A high‐performance liquid chromatography coupled with Q‐time of flight mass spectrometry (HPLC/Q‐TOF MS) method was developed and validated for the determination of 1, 3‐diaminopropane, putrescine, cadaverine, spermidine and spermine in human plasma. The plasma samples were first pretreated by 10% HClO4 and then derived by benzoyl chloride with 1, 6‐diaminohexane as internal standard. The derived polyamines were separated on a C18 column using a gradient program. The detection was performed on a Q‐TOF MS by positive ionization mode. Calibration curve for each polyamine was obtained in the concentration range of 0.4 ~ 200.0 ng • ml−1, with limit of detection of 0.02 ~ 0.1 ng • ml−1. The intra‐ and inter‐day RSD for all polyamines were 2.5–14.0% and 2.9 ~ 13.4%, respectively. The method was applied to determine the polyamines in human plasma from cancer patients and healthy volunteers. Results showed that the mean levels of polyamines in the plasma of cancer patients were higher than that of healthy volunteers, which suggested that the plasma polyamines could be employed as cancer diagnostic indicators in clinical testing. Copyright © 2012 John Wiley & Sons, Ltd.
Silver (Ι)‐assisted enantiomeric analysis of ginsenosides using electrospray ionization tandem mass spectrometry
Authors: Yu Qing , Yu Binbin , Yang Hongmei , Li Xue , Liu Shuying
Published: September 2012

For identification of ginsenoside enantiomers, electrospray ionization mass spectrometry (ESI‐MS) was used to generate silver complexes of the type [ginsenoside + Ag]+. Collision induced dissociation of the silver‐ginsenoside complexes produced fragment ions by dehydration, allowing differentiation of ginsenoside enantiomers by the intensity of [M + Ag − H2O]+ ion. In the meanwhile, an approach based on the distinct profiles of enantiomer‐selective fragment ion intensity varied with collision energy was introduced to refine the identification and quantitation of ginsenoside enantiomers. Five pairs of enantiomeric ginsenosides were distinguished and quantified on the basis of the distribution of fragment ion [M + Ag − H2O]+. This method was also extended to the identification of other type of ginsenoside isomers such as ginsenoside Rb2 and Rb3. For demonstrating the practicability of this novel approach, it was utilized to analyze the molar ratio of 20‐(S) and 20‐(R) type enantiomeric ginsenosides in enantiomer mixture in red ginseng extract. The generation of characteristic fragment ion [M + Ag − H2O]+ likely results from the reduction of potential energy barrier of dehydration because of the catalysis of silver ion. The mechanism of enantiomer identification of ginsenosides was discussed from the aspects of computational modeling and internal energy. Copyright © 2012 John Wiley & Sons, Ltd.
Infrared laser ablation sample transfer for on‐line liquid chromatography electrospray ionization mass spectrometry
Authors: Park Sung‐Gun , Murray Kermit K.
Published: September 2012

We have demonstrated an on‐line laser ablation sampling system and coupling of the system to liquid chromatography (LC) using an infrared (IR) laser to ablate and transfer materials into a flowing solvent stream. With this approach, samples are deposited on a microscope slide mounted on a translation stage and ablated in transmission geometry using a pulsed mid‐IR laser. The ablated material is captured in an exposed flowing solvent stream that carries the ablated material to the electrospray source. Post‐ablation separation is accomplished using a capillary column downstream of the capture zone. The performance of the system was assessed using peptide and protein mixtures ablated from the target and analyzed with and without LC separation. Copyright © 2012 John Wiley & Sons, Ltd.
Full genomic analysis of a human rotavirus G1P[8] strain isolated in South Korea
Authors: Cho Min‐Kyu , Jheong Weon‐Hwa , Lee Sung‐Geun , Park Chul Jong , Jung Kum Hee , Paik Soon‐Young
Published: September 2012

A rotavirus G1P[8] strain C1‐81 was isolated from a 5‐month‐old female infant admitted to hospital with fever and severe diarrhea in Incheon, South Korea. To investigate its full genomic relatedness and its group, the full genome of strain C1‐81 was determined. Based on a full genome classification system, C1‐81 was shown to possess the typical Wa‐like genotype constellation: G1‐P[8]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1. On the basis of sequence similarities, the strain was shown to be the closest related strain to contemporary human rotavirus strains with recent strains isolated in Asia. This C1‐81 strain showed the highest degree of nucleic acid similarity (98.8% and 97%) to G1 B4633‐03 and P[8] (Thai‐1604 and Dhaka8‐02), respectively. This is the first report that group A rotavirus was analyzed with G1P[8] in South Korea. The study of the complete genome of the virus will help understanding of the evolution of rotavirus. J. Med. Virol. 85:157–170, 2012. © 2012 Wiley Periodicals, Inc.
Characterization of hepatitis B virus mutations in untreated patients co‐infected with HIV and HBV based on complete genome sequencing
Authors: Tangkijvanich Pisit , Sa‐Nguanmoo Pattaratida , Avihingsanon Anchalee , Ruxrungtham Kiat , Poovorawan Kittiyod , Poovorawan Yong
Published: September 2012

Co‐infection of HBV with HIV results in an accelerated course of HBV‐associated chronic liver disease. Several studies have shown that viral mutations are related to disease progression in mono‐infection with HBV. However, it is unclear whether HBV mutation patterns might differ between co‐infected and mono‐infected patients. To compare the frequencies and mutation patterns in the HBV genome between co‐infection and mono‐infection. Twenty‐four treatment‐naïve co‐infected and 31 treatment‐naïve mono‐infected Thai patients were included. HBV mutations were characterized by whole genome sequencing of virus serum samples. The clinical features and frequency of known clinically significant mutations were compared between the two groups. No significant difference between the groups was found with respect to sex, age and HBeAg. However, HBV DNA levels were significantly higher in co‐infected patients. The distribution of HBV genotypes was comparable between the two groups and restricted mostly to sub‐genotypes C1 and B2. An isolate with recombinants of genotypes G/C1 was also identified in a patient with co‐infection. There was no difference in the prevalence of mutations in the enhancer II/basal core promoter/precore region, pre‐S/S and polymerase genes between the two groups. In conclusion, dual infections tend to engender increased HBV DNA levels. There was no major difference in the frequencies of common HBV mutations between co‐infected and mono‐infected patients. Thus, HBV mutations may not contribute to disease pathogenesis in Thai patients with co‐infection. J. Med. Virol. 85:16–25, 2012. © 2012 Wiley Periodicals, Inc.
Determination of musk fragrances in sewage sludge by pressurized liquid extraction coupled to automated ionic liquid‐based headspace single‐drop microextraction followed by GC‐MS/MS
Authors: Vallecillos Laura , Borrull Francesc , Pocurull Eva
Published: September 2012

A method for the quantitative determination of ten musk fragrances extensively used in personal care products from sewage sludge was developed by using a pressurized liquid extraction (PLE) followed by an automated ionic liquid‐based headspace single‐drop microextraction and gas chromatography‐tandem mass spectrometry. The influence of main factors on the efficiency of PLE was studied. For all musks, the highest recovery values were achieved using 1 g of pretreated sewage sludge, H2O/methanol (1:1) as an extraction solvent, a temperature of 80°C, a pressure of 1500 psi, an extraction time of 5 min, 2 cycles, a 100% flush volume, a purge time of 120 s, and 1 g Florisil as in‐cell clean‐up extraction sorbent. The use and optimization of an in‐cell clean‐up sorbent was necessary to remove fatty interferents of the PLE extract that make the subsequent ionic liquid‐based headspace single‐drop microextraction difficult. Validation parameters, namely LODs and LOQs, ranged from 0.5–1.5 to 2.5–5 ng/g, respectively. Good levels of intra‐ and interday repeatabilities were obtained analyzing sewage sludge samples spiked at 10 ng/g (n = 3, RSDs < 10%). The method applicability was tested with sewage sludge from different wastewater treatment plants. The analysis revealed the presence of all the polycyclic musks studied at concentrations higher than the LOQs, ranging from 6 to 530 ng/g. However, the nitro musk concentrations were below the LOQs or, in the case of musk xylene, was not detected.
Segmenting Cruise Passengers Visiting Uruguay: a Factor–Cluster Analysis
Authors: Brida Juan Gabriel , Scuderi Raffaele , Seijas María Nela
Published: September 2012

The study aims to provide a better understanding of cruise travel from passengers' characteristics and experience in two ports of call in Uruguay. A multivariate market segmentation analysis was used, on the basis of 5151 survey data collected during the 2008–2009 and 2009–2010 seasons. A correspondence analysis revealed the underlying latent factors in the set of variables. A hierarchical clustering from correspondence analysis segmented the sample into homogeneous groups. Finally, a decision tree highlighted the most predictive variables for each cluster. The study identifies distinct segments by country of residence, occupation, locations visited in Uruguay, satisfaction and previous visits to the country. Copyright © 2012 John Wiley & Sons, Ltd.
Neck dissection through a facelift incision
Authors: Melvin Thuy‐Anh N. , Eliades Steven J. , Ha Patrick K. , Fakhry Carole , Saunders John M. , Califano Joseph A. , Blanco Ray G. F.
Published: September 2012

Objectives/Hypothesis:

To determine the feasibility and safety of neck dissection through a facelift incision.

Study Design:

Prospective case series.

Methods:

Cadavers and live subjects underwent neck dissection using a facelift incision with and without endoscopic assistance. In the live facelift neck dissection (FLND), the preoperative surgical indications, staging, adjuvant therapy, intraoperative technical procedure, pathology reports on lymph nodes, and short‐term outcomes were reviewed.

Results:

FLND was successfully performed in four cadavers and four live subjects, including selective (less than five neck levels removed) and comprehensive (levels I–V removed) neck dissections. All levels were accessible through this approach, with additional retraction required for levels I and IV. Endoscopic assistance was required in one neck dissection for adequate visualization. Short‐term complications and number of excised lymph nodes were comparable to those from traditional neck dissection approaches.

Conclusions:

Open neck dissection through a facelift incision is feasible and offers an alternate approach to traditional incisions. This can be performed without requiring robotic assistance and with endoscopic assistance only in certain cases. Endoscopic assistance can offer enhanced visualization of the surgical field and complement open direct approaches in neck dissection. Although FLND offers improved cosmetic outcomes when compared to those of traditional neck incisions, further study is required to determine its efficacy and indications.
Fibroblast autophagy in fibrotic disorders
Authors: Principe Domenico Del , Lista Pasquale , Malorni Walter , Giammarioli Anna Maria
Published: September 2012

Fibrotic disorders are multistage progressive processes that often arise from different causes and are commonly associated with chronic inflammation. Excessive deposition of extracellular matrix is the hallmark of many fibrotic diseases. This may be due to an excess of fibroblast recruitment and activation, as well as to their differentiation in myofibroblasts. These events may be triggered by cytokines, chemokines and growth factors released by lymphocytes or macrophages. The excessive production of extracellular matrix is apparently due to alterations of metabolic pathways in activated fibroblasts. It has been suggested that a defective autophagy, an important subcellular pathway with multiple homeostatic roles, also recognized as a key component of both innate and acquired immunity, could play a role. In this review we illustrate recent insights in the field, suggesting the possible implication of the immune system in orchestrating the fibrotic response via the modulation of autophagic pathways.