bluuebunny/crossref_metadata_2025 huggingface dataset:
Solid solution of two diastereomers of [3a(R,S),7a(R,S)]-3-[(1′R)-1-phenylethyl]perhydro-1,3-benzothiazol-2-iminium chloride
Authors: Plutecka Agnieszka , Rychlewska Urszula , Prusinowska Natalia , Gawroński Jacek
Published: November 2010

A mixture of two diastereomers with the configurations (3aS,7aS,1′R) and (3aR,7aR,1′R) forms co-crystals in which there is one unique molecule in the asymmetric unit, but the molecule displays disorder which is a result of the presence of the two diastereomers at the same crystallographic site. Theoretical calculations carried out by the DFT method with the 6-311++G(2df,p) basis set allowed for the estimation of the energy difference between the two diastereomers both in the isolated and the solid state, while the natural bond orbital (NBO), Mulliken, natural population (NPA) and CHelpG analyses helped to establish the electronic structure of the thazolidin-2-imine fragment.
Physiological correlates of seasonal growth patterns in lake trout Salvelinus namaycush
Authors: Morbey Y. E. , Couture P. , Busby P. , Shuter B. J.
Published: November 2010

Physiological correlates of seasonal growth patterns were measured in lake trout Salvelinus namaycush from two populations with contrasting diets (zooplankton‐dominated diet in Louisa Lake; fish‐dominated diet in Opeongo Lake). Fish in Opeongo Lake grew faster and were in better condition than fish in Louisa Lake. The most prominent biochemical difference between populations was higher citrate synthase (CS) and cytochrome c oxidase activity in the white muscle of fish from Opeongo Lake, indicating greater sustained swimming activity in this lake. In contrast, lactate dehydrogenase (LDH) activity in white muscle, an indicator of capacity for burst swimming, was similar between lakes. Nucleoside diphosphate kinase (NDPK) activity in white muscle, an indicator of protein synthesis, was higher in Opeongo Lake than in Louisa Lake but only in the autumn. In both lakes, protein concentration and therefore nutritional status increased as the growing season progressed from spring to summer to autumn. Biochemical indicators of growth and activity showed similar seasonal patterns in the two lakes with the spring characterized by high NDPK, high CS and high LDH activities (i.e. high levels of protein synthesis in association with high aerobic and anaerobic activities). These results suggest high foraging effort and allocation to growth early in the growing season in both lakes.
Linkage disequilibrium and historical effective population size in the Thoroughbred horse
Authors: Corbin L. J. , Blott S. C. , Swinburne J. E. , Vaudin M. , Bishop S. C. , Woolliams J. A.
Published: November 2010

Many genomic methodologies rely on the presence and extent of linkage disequilibrium (LD) between markers and genetic variants underlying traits of interest, but the extent of LD in the horse has yet to be comprehensively characterized. In this study, we evaluate the extent and decay of LD in a sample of 817 Thoroughbreds. Horses were genotyped for over 50 000 single nucleotide polymorphism (SNP) markers across the genome, with 34 848 autosomal SNPs used in the final analysis. Linkage disequilibrium, as measured by the squared correlation coefficient (r2), was found to be relatively high between closely linked markers (>0.6 at 5 kb) and to extend over long distances, with averager2maintained above non‐syntenic levels for single nucleotide polymorphisms (SNPs) up to 20 Mb apart. Using formulae which relate expected LD to effective population size (Ne), and assuming a constant actual population size, Newas estimated to be 100 in our population. Values of historical Ne, calculated assuming linear population growth, suggested a decrease in Nesince the distant past, reaching a minimum twenty generations ago, followed by a subsequent increase until the present time. The qualitative trends observed in Necan be rationalized by current knowledge of the history of the Thoroughbred breed, and inbreeding statistics obtained from published pedigree analyses are in agreement with observed values of Ne. Given the high LD observed and the small estimated Ne, genomic methodologies such as genomic selection could feasibly be applied to this population using the existing SNP marker set.
RT‐qPCR Comparison of mast cell populations in whole blood from healthy horses and those with laminitis
Authors: Brooks S. A. , Bailey E.
Published: November 2010

Inflammatory damage to the digital laminae, a structure responsible for suspension of the distal skeleton within the hoof capsule, results in a painful and often life‐threatening disease in horses called laminitis. There can be many diverse causes of laminitis; however, previous work in the horse has suggested that in each case, the inflammation and resulting tissue damage is consistent with the action of mediators released from mast cells (MC), as well as the downstream consequences of their activation. The recent development of molecular genetics tools to characterize cells based on their transcriptional activity makes a new approach for measuring MCs possible. Healthy thoroughbred horses from a variety of age groups were used to assess the amount of variation in KIT (encoding mast cell growth factor receptor) and TPSB2 (encoding mast cell tryptase beta 2) gene expression present in the population and to establish “normal” values. Horses (n = 9) with a wider range of body condition scores (3–8), because of a more lax management setting that could predispose them to laminitis, had significantly higher KIT expression in circulating peripheral blood cells than horses under individualized management conditions (n = 10) that produced ideal body condition scores (4–6) (mean 2.573‐fold, P < 0.0005). Likewise, horses affected with acute laminitis (n = 11) had elevated expression of TPSB2 (2.760‐fold, P = 0.0011) relative to control horses (n = 15). These data suggest that investigation of MC‐related genes KIT and TPSB2 may be effective to assay MC population and activity. More work is needed to refine the diagnostic criteria to better describe at what point MC activation occurs and illustrate the use of gene expression assays in clinical cases of laminitis. Additionally, MC activation is associated with inflammatory disease in several mammalian species and may prove a valuable therapeutic target in the horse.
Transcription of LINE‐derived sequences in exercise‐induced stress in horses
Authors: Capomaccio S. , Verini‐Supplizi A. , Galla G. , Vitulo N. , Barcaccia G. , Felicetti M. , Silvestrelli M. , Cappelli K.
Published: November 2010

A large proportion of mammalian genomes is represented by transposable elements (TE), most of them being long interspersed nuclear elements 1 (LINE‐1 or L1). An increased expression of LINE‐1 elements may play an important role in cellular stress–related conditions exerting drastic effects on the mammalian transcriptome. To understand the impact of TE on the known horse transcriptome, we masked the horse EST database, pointing out that the amount is consistent with other major vertebrates. A previously developed transcript‐derived fragments (TDFs) dataset, deriving from exercise‐stimulated horse peripheral blood mononuclear cells (PBMCs), was found to be enriched with L1 (26.8% in terms of bp). We investigated the involvement of TDFs in exercise‐induced stress through bioinformatics and gene expression analysis. Results indicate that LINE‐derived sequences are not only highly but also differentially expressed during physical effort, hinting at interesting scenarios in the regulation of gene expression in relation to exercise.
A genome‐wide association study for racing performances in Thoroughbreds clarifies a candidate region near the MSTN gene
Authors: Tozaki T. , Miyake T. , Kakoi H. , Gawahara H. , Sugita S. , Hasegawa T. , Ishida N. , Hirota K. , Nakano Y.
Published: November 2010

Using 1400 microsatellites, a genome‐wide association study (GWAS) was performed to identify genomic regions associated with lifetime earnings and performance ranks, as determined by the Japan Racing Association (JRA). The minimum heritability (h2) was estimated at 7–8% based on the quantitative trait model, suggesting that the racing performance is heritable. Following GWAS with microsatellites, fine mapping led to identification of three SNPs on ECA18, namely, g.65809482T>C (P = 1.05E‐18), g.65868604G>T (P = 6.47E‐17), and g.66539967A>G (P = 3.35E‐14) associated with these performance measures. The haplotype of these SNPs, together with a recently published nearby SNP, g.66493737C>T (P = 9.06E‐16) in strong linkage disequilibrium, also showed a very clear association with the performance (P < 1E‐05). The candidate genomic region contained eight genes annotated by ENSEMBL, including the myostatin gene (MSTN). These findings suggest the presence of a gene affecting the racing performance in Thoroughbred racehorses in this region on ECA18.
Refinement of quantitative trait loci on equine chromosome 10 for radiological signs of navicular disease in Hanoverian warmblood horses
Authors: Lopes M. S. , Diesterbeck U. , Da Câmara Machado A. , Distl O.
Published: November 2010

Navicular disease is characterized by a progressive degenerative alteration of the equine podotrochlea. In this study, we refined a previously identified quantitative trait locus (QTL) on horse chromosome 10 for the abnormal development of canales sesamoidales (DCS) of the navicular bone in Hanoverian warmblood horses. Genotyping was done in 192 Hanoverian warmblood horses from 17 paternal half‐sib groups. The whole marker set comprised 45 markers including seven newly developed microsatellites and 13 single nucleotide polymorphisms (SNPs) within positional candidate genes. Chromosome‐wide significant QTL were confirmed and refined for DCS on horse chromosome (ECA) 10 at 0.16–2.70 Mb and at 14.45–36.37 Mb. Nine microsatellites and three SNP markers reached the highest multipoint Zmeans and LOD scores at 19.34–20.38 Mb and at 23.17–30.73 Mb with genome‐wide error probabilities of P < 0.05. In addition, a significant association of a SNP within VSTM1 and a significant haplotype‐trait association within IRF3 could be shown. These results support a possible role of the candidate genes VSTM1 and IRF3 within the QTL on ECA10 for DCS. This study is a further step towards the identification of the genes responsible for navicular disease in Hanoverian warmblood horses.
Interspersed repeats in the horse (Equus caballus); spatial correlations highlight conserved chromosomal domains
Authors: Adelson D. L. , Raison J. M. , Garber M. , Edgar R. C.
Published: November 2010

The interspersed repeat content of mammalian genomes has been best characterized in human, mouse and cow. In this study, we carried out de novo identification of repeated elements in the equine genome and identified previously unknown elements present at low copy number. The equine genome contains typical eutherian mammal repeats, but also has a significant number of hybrid repeats in addition to clade‐specific Long Interspersed Nuclear Elements (LINE). Equus caballus clade specific LINE 1 (L1) repeats can be classified into approximately five subfamilies, three of which have undergone significant expansion. There are 1115 full‐length copies of these equine L1, but of the 103 presumptive active copies, 93 fall within a single subfamily, indicating a rapid recent expansion of this subfamily. We also analysed both interspersed and simple sequence repeats (SSR) genome‐wide, finding that some repeat classes are spatially correlated with each other as well as with G+C content and gene density. Based on these spatial correlations, we have confirmed that recently‐described ancestral vs. clade‐specific genome territories can be defined by their repeat content. The clade‐specific Short Interspersed Nuclear Element correlations were scattered over the genome and appear to have been extensively remodelled. In contrast, territories enriched for ancestral repeats tended to be contiguous domains. To determine if the latter territories were evolutionarily conserved, we compared these results with a similar analysis of the human genome, and observed similar ancestral repeat enriched domains. These results indicate that ancestral, evolutionarily conserved mammalian genome territories can be identified on the basis of repeat content alone. Interspersed repeats of different ages appear to be analogous to geologic strata, allowing identification of ancient vs. newly remodelled regions of mammalian genomes.
Pleiotropic effects of pigmentation genes in horses
Authors: Bellone R. R.
Published: November 2010

Horses are valued for the beauty and variety of colouration and coat patterning. To date, eleven different genes have been characterized that contribute to the variation observed in the horse. Unfortunately, mutations involving pigmentation often lead to deleterious effects in other systems, some of which have been described in the horse. This review focuses on six such pleiotropic effects or associations with pigmentation genes. These include neurological defects (lethal white foal syndrome and lavender foal syndrome), hearing defects, eye disorders (congenital stationary night blindness and multiple congenital ocular anomalies), as well as horse‐specific melanoma. The pigmentation phenotype, disorder phenotype, mode of inheritance, genetic or genomic methods utilized to identify the genes involved and, if known, the causative mutations, molecular interactions and other susceptibility loci are discussed. As our understanding of pigmentation in the horse increases, through the use of novel genomic tools, we are likely to unravel yet unknown pleiotropic effects and determine additional interactions between previously discovered loci.
Genome‐wide association analysis of osteochondrosis of the tibiotarsal joint in Norwegian Standardbred trotters
Authors: Lykkjen S. , Dolvik N. I. , McCue M. E. , Rendahl A. K. , Mickelson J. R. , Roed K. H.
Published: November 2010

Osteochondrosis (OC), a disturbance in the process of endochondral ossification, is by far the most important equine developmental orthopaedic disease and is also common in other domestic animals and humans. The purpose of this study was to identify quantitative trait loci (QTL) associated with osteochondrosis dissecans (OCD) at the intermediate ridge of the distal tibia in Norwegian Standardbred (SB) using the Illumina Equine SNP50 BeadChip whole‐genome single‐nucleotide polymorphism (SNP) assay. Radiographic data and blood samples were obtained from 464 SB yearlings. Based on the radiographic examination, 162 horses were selected for genotyping; 80 of these were cases with an OCD at the intermediate ridge of the distal tibia, and 82 were controls without any developmental lesions in the joints examined. Genotyped horses descended from 22 sires, and the number of horses in each half‐sib group ranged from 3 to 14. The population structure necessitated statistical correction for stratification. When conducting a case–control genome‐wide association study (GWAS), mixed‐model analyses displayed regions on chromosomes (Equus callabuschromosome – ECA) 5, 10, 27 and 28 that showed moderate evidence of association (P ≤ 5 × 10−5; thisP‐value is uncorrected i.e. not adjusted for multiple comparisons) with OCD in the tibiotarsal joint. Two SNPs on ECA10 represent the most significant hits (uncorrectedP = 1.19 × 10−5in the mixed‐model). In the basic association (chi‐square) test, these SNPs achieved statistical significance with the Bonferroni correction (P = 0.038) and were close in the permuted logistic regression test (P = 0.054). Putative QTL on ECA 5, 10, 27 and 28 represent interesting areas for future research, validation studies and fine mapping of candidate regions. Results presented here represent the first GWAS of OC in horses using the recently released Illumina Equine SNP50 BeadChip.
Mitochondrial DNA insertions in the nuclear horse genome
Authors: Nergadze S. G. , Lupotto M. , Pellanda P. , Santagostino M. , Vitelli V. , Giulotto E.
Published: November 2010

The insertion of mitochondrial DNA in the nuclear genome generates numts, nuclear sequences of mitochondrial origin. In the horse reference genome, we identified 82 numts and showed that the entire horse mitochondrial DNA is represented as numts without gross bias. Numts were inserted in the horse nuclear genome at random sites and were probably generated during the repair of DNA double‐strand breaks. We then analysed 12 numt loci in 20 unrelated horses and found that null alleles, lacking the mitochondrial DNA insertion, were present at six of these loci. At some loci, the null allele is prevalent in the sample analysed, suggesting that, in the horse population, the number of numt loci may be higher than 82 present in the reference genome. Contrary to humans, the insertion polymorphism of numts is extremely frequent in the horse population, supporting the hypothesis that the genome of this species is in a rapidly evolving state.
The effect of rectal ozone on the portal vein oxygenation and pharmacokinetics of propranolol in liver cirrhosis (a preliminary human study)
Authors: Zaky Saad , Fouad Ehab Ahmad , Kotb Hassan Ibrahim Mohamad
Published: November 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Experimental work has shown that ozone protected both the liver and kidney from reperfusion injury through release of mediators of nitric oxide. Rectal ozone increased oxygenation in the intestinal wall (250%), portal vein (134%) and liver parenchyma (127%) in experimental animals. The kinetics of propranolol and other oxidation‐dependent drugs have been reported to be affected due to liver cirrhosis. Several experimental studies have reported improved propranolol clearance through increased hepatic blood flow.

WHAT THIS STUDY ADDS

• This current study looked for evidence in man of improved hepato‐splanchnic oxygenation after rectal ozone. Changes in metabolic pathway via measurement of portal vein oxygenation and the kinetic profile changes of propranolol as an index drug for metabolic oxidation in the liver were measured.

• This small preliminary clinical study showed that improved propranolol clearance was obtained by rectal ozone in humans for the first time. In addition there was also evidence of improved portal vein oxygen tension and saturation after rectal ozone. This study has a potential clinical significance.

AIMThe aim of this study was to investigate the effect of rectal ozone on portal vein oxygenation and the pharmacokinetic changes of propranolol in patients with liver cirrhosis.

METHODSFifteen patients with liver cirrhosis were included They were given a fixed oral dose of propranolol 80 mg on the morning of day 1 after overnight fasting. Blood samples were collected at fixed time intervals for 24 h. Patients were given 12 sessions of rectal ozone of 300 ml of 40% ozone/oxygen mixture. On day 14 another oral dose of 80 mg propranolol was given and blood samples were collected as on day 1. Plasma concentrations of propranolol were measured by HPLC. Portal vein oxygen tension and saturation were measured before and after rectal ozone.

RESULTSPlasma concentrations of propranolol were reduced after ozone therapy with pronounced decreases in the maximum plasma concentration and the area under the plasma concentration–time curve. The changes were consistent with a decrease in propranolol bioavailability. There was a decrease in the elimination half‐life and mean residence time. Portal vein oxygenation significantly increased after rectal ozone.

CONCLUSIONSThe changes in the pharmacokinetics of propranolol probably reflect an increase in the rate and extent of its metabolism resulting from improved portal vein oxygenation attributable to the ozone therapy. The present work highlights that ozone can be an alternative medical measure to improve portal vein oxygenation in liver cirrhosis.
Novel and recurrent connexin 30.3 and connexin 31 mutations associated with erythrokeratoderma variabilis
Authors: Scott C. A. , O’Toole E. A. , Mohungoo M. J. , Messenger A. , Kelsell D. P.
Published: November 2010

Erythrokeratoderma variabilis (EKV) is characterized by fixed hyperkeratotic plaques and transient erythema. Mutations in the genes GJB3 and GJB4, which encode connexin (Cx)31 and Cx30.3, are associated with EKV. We report one novel mutation in Cx31 and one recurrent mutation in Cx30.3 in two different families. One novel rare sequence variant of unknown clinical significance was also identified. This finding extends the spectrum of known EKV-associated mutations.
Efficacy and safety of a new immunoglobulin G product, Gammaplex®, in primary immunodeficiency diseases
Authors: Moy J N , Scharenberg A M , Stein M R , Suez D , Roberts R L , Levy R J , Ballow M , Fasano M B , Dash C H , Leach S J
Published: November 2010

This open-label multi-centre study evaluated a new intravenous immunoglobulin, Gammaplex®, in the treatment of 50 patients with primary immunodeficiency and significant hypogammglobulinaemia. Patients treated previously with other intravenous immunoglobulins received Gammaplex® on their same infusion schedule for 1 year; 22 were on a 21-day and 28 on a 28-day regimen (300–800 mg/kg/infusion). There were no serious, acute bacterial infections, whereas six subjects (12·0%) had at least one such infection in the 6 months before enrolment. Forty subjects (80·0%) had at least one non-serious infection; the median number of infective episodes per subject per year was 3·07. Antibiotics were taken by 38 subjects therapeutically and prophylactically by 16 at some time. Fewer than half (46·0%) missed any time off work or school because of infection or other illness. Trough immunoglobulin (Ig)G levels were above 6·00 g/l in all subjects at all assessments after 15 weeks with two exceptions. Overall, 21·2% of infusions were associated with an adverse event up to 72 h after infusion. The frequency of adverse events increased with infusion rate. Headache was the most common product-related adverse event (7·5% of 703 infusions). In conclusion, Gammaplex® is effective in primary immunodeficiency and is well tolerated.
Effect of soil acidity, soil strength and macropores on root growth and morphology of perennial grass species differing in acid‐soil resistance
Authors: HALING REBECCA E. , SIMPSON RICHARD J. , CULVENOR RICHARD A. , LAMBERS HANS , RICHARDSON ALAN E.
Published: November 2010

It is unclear whether roots of acid‐soil resistant plants have significant advantages, compared with acid‐soil sensitive genotypes, when growing in high‐strength, acid soils or in acid soils where macropores may allow the effects of soil acidity and strength to be avoided. The responses of root growth and morphology to soil acidity, soil strength and macropores by seedlings of five perennial grass genotypes differing in acid‐soil resistance were determined, and the interaction of soil acidity and strength for growth and morphology of roots was investigated. Soil acidity and strength altered root length and architecture, root hair development, and deformed the root tip, especially in acid‐soil sensitive genotypes. Root length was restricted to some extent by soil acidity in all genotypes, but the adverse impact of soil acidity on root growth by acid‐soil resistant genotypes was greater at high levels of soil strength. Roots reacted to soil acidity when growing in macropores, but elongation through high‐strength soil was improved. Soil strength can confound the effect of acidity on root growth, with the sensitivity of acid‐resistant genotypes being greater in high‐strength soils. This highlights the need to select for genotypes that resist both acidity and high soil strength.
Surgical management of biliary complications following living donor liver transplantation
Authors: Khalaf Hatem , Alawi Khalil , Alsuhaibani Hamad , Hegab Bassem , Kamel Yasser , Azzam Ayman , Albahili Hamad , Alsofayan Mohammad , Al Sebayel Mohammed
Published: November 2010

Khalaf H, Alawi K, Alsuhaibani H, Hegab B, Kamel Y, Azzam A, Albahili H, Alsofayan M, Al Sebayel M. Surgical management of biliary complications following living donor liver transplantation. Clin Transplant 2011: 25: 504–510. © 2010 John Wiley & Sons A/S.

Abstract:  Background:  Biliary complications (BC) account for much of the morbidities seen after living donor liver transplantation (LDLT). Surgical reconstruction might be necessary after the failure of endoscopic or percutaneous procedures.

Methods:  Between November 2002 and December 2009, a total of 76 LDLTs were performed. Six patients were excluded from statistical analysis because of early graft or patient loss.

Results:  Of 70, 26 (37.1%) developed BC; 12 (46.2%) were successfully managed by non‐surgical procedures, three (11.5%) died from BC‐related sepsis, one (3.8%) died from BC‐unrelated causes, and 10 (38.5%) underwent surgical reconstruction. Of those 10, four patients had single duct reconstruction, five patients had double ducts reconstruction, and reconstruction was abandoned in one patient because of hepatic artery thrombosis. After a median follow‐up period of 4.5 yr (0.1–6), seven (70%) remained well with no recurrent biliary problems, and three (30%) had recurrent BCs that were managed either conservatively or by retransplantation. Patients who underwent surgical reconstruction had significantly fewer hospital admissions, less need for invasive procedures, and shorter cumulative hospital stay (p < 0.05).

Conclusions:  In our experience, BCs after LDLT were frequently resistant to non‐surgical procedures. Surgical reconstruction is associated with fewer hospital admissions and less need for invasive procedures leading to reduced resources utilization.
Comparing sterile bag rubbing and paint on technique in skin preparation of the hands
Authors: Chou Justin , Choudhary Anwar , Dhillon Raminder S.
Published: November 2010

Background:  The aim of this study was to compare two techniques for surgical site skin preparation in hand surgery.

Methods:  We compared the standard sponge paint technique versus a plastic bag immersion technique using a 10% povidone–iodine with alcohol solution (Betadine, ORION Laboratories Pty Ltd, Balcatta, WA, Australia) to prepare surgical site skin for hand surgery. This sterile bag rubbing technique involves using a sterile plastic bag filled with 60 mL of Betadine solution to immerse the subjects' hand. Samples were taken from 10 subjects for bacteria colony‐forming unit (CFU) counts before and 3 min after surgical site preparation in each group. Outcome measures were preparation time and CFU reduction with a plate impression test using commercially available agar slides.

Results:  The sterile bag rubbing technique significantly reduced (P < 0.0001) the time required for surgical site skin preparation (28 s) compared with the standard technique (86 s). Both techniques were found to have similar efficacy in the reduction of CFU.

Conclusions:  The sterile bag rubbing technique is a quicker alternative method for surgical site preparation in hand surgery and has comparable efficacy to the widely practised standard paint‐on technique.
Altered transcription factor E3 expression in unclassified adult renal cell carcinoma indicates adverse pathological features and poor outcome
Authors: Mir Maria Carmen , Trilla Enrique , de Torres Ines Maria , Panizo Angel , Zlotta Alexander R. , Van Rhijn Bas , Morote Juan
Published: November 2010

What’s known on the subject? and What does the study add?

This is a short series of unclassified RCC with positivity for TFE3 staining an association with poor outcome on those patients’ follow‐up.

The paper supports the idea of TFE3 positivity as a marker for poor outcome in RCC patients. It has already been stated in some manuscripts; however, not in this number of patients.

OBJECTIVES

• To evaluate the clinical and pathologic features and the prognostic relevance of unclassified RCC with – TFE3 over‐expression in our adult series.

• Recent studies suggest that renal cell carcinomas (RCCs) associated with the newly recognized Xp11.2 translocation (transcription factor E3 [TFE3] gene fusions) can be found among adults with RCC showing a very aggressive disease‐course.

MATERIAL AND METHODS

• We evaluated tumour specimens from 25 patients with unclassified RCC morphology out of 298 RCCs in the last 12 years in a tertiary academic centre.

• Immunohistochemistry was performed using monoclonal antibody for TFE3 C‐terminal section, taking nuclear label into consideration. RT‐PCR technique was performed for ASPL‐TFE3 gene fusion on two tumours with available frozen tissue.

RESULTS

• Of the 25 cases analyzed, 8 (32%) showed positivity for TFE3 and 17 were negative for TFE3 staining. Two tumors with ASPL‐TFE3 gene fusion also showed TFE3 over‐expression.

• Fifty percent of the positive patients had lymph node metastatic disease, whereas only one TFE3‐negative patient (5.8%) showed evidence of lymph node spread and cava thrombus at diagnosis. Of the TFE3‐positive patients, three had a vena cava thrombus (37.5%). Seven of the eight positive cases (87.5%) were diagnosed with a high Fuhrman grade (III/IV). In comparison, five of 17 (29.4%) TFE3‐negative patients had a high Fuhrman grade. Five of eight TFE3‐positive patients relapsed rapidly at 3 month follow‐up; conversely none of the negative cases relapsed. At 36‐month mean follow‐up, 5‐year cancer‐specific survival was 15.6% for TFE3‐positive patients and 87.5% for TFE3‐negative patients (P < 0.001).

CONCLUSION

• Patients with unclassified RCC and TFE3 positivity have a grim prognosis due to their advanced stage at presentation and aggressive biologic features compared with the TFE3‐negative unclassified RCC cases.
Radical cystectomy for BCG failure: has the timing improved in recent years?
Authors: Soloway Mark S. , Hepps David , Katkoori Devendar , Ayyathurai Rajinikanth , Manoharan Murugesan
Published: November 2010

Study Type – Therapy (case series)

Level of Evidence 4

What’s known on the subject? and What does the study add?

High‐grade Ta‐T1‐carcinoma in situ bladder cancer is a heterogeneous group; long‐term studies have shown that intravesical BCG therapy can be inadequate in a substantial percentage. Despite concerns about delay in performing RC for patients failing one or more courses of BCG, in our study we have not observed a trend towards a lower pathological stage for patients undergoing RC after BCG.

OBJECTIVE

To analyse if there is a trend in recent years towards performing radical cystectomy (RC) before muscle invasion or extravesical spread after failure of bacille Calmette–Guérin (BCG) for high grade Ta/T1 bladder cancer. Although BCG is indicated for prophylaxis after endoscopic tumour resection there is still a risk of progression.

PATIENTS AND METHODS

A retrospective analysis of our RC database (1992–2008) was performed to identify patients who underwent RC after receiving BCG.

Relevant clinical and pathological data for the patients with clinical stage Ta, T1 and/or Tis at initial transurethral resection of bladder tumour were analysed.

Pathological stage and survival for patients undergoing RC from 2003 to 2007 (group 2) were compared with those for patients operated between 1992 and 2002 (group 1).

RESULTS

A total of 152 patients were included (75 in group 2 and 77 in group 1). Both groups were similar in T‐stage before BCG initiation, number of BCG cycles received and time interval to RC.

There was no change in the proportion of patients undergoing RC with ≥pT2 bladder cancer in recent years (P= 0.5).

Fifty‐two percent of group 2 and 43% of group 1 had ≥pT2 BC. The 5‐year survival was similar.

CONCLUSIONS

Despite concerns about delay in performing RC for patients failing one or more courses of BCG we have not observed a trend towards a lower pathological stage for patients undergoing RC after BCG.

A high proportion of patients have muscle‐invasive bladder cancer; more than 10% have lymph node metastasis.
Proinsulin/C‐peptide ratio, glucagon and remission in new‐onset Type 1 diabetes mellitus in young adults
Authors: Schölin A. , Nyström L. , Arnqvist H. , Bolinder J. , Björk E. , Berne C. , Karlsson F. A. ,   the Diabetes Incidence Study Group in Sweden (DISS)
Published: November 2010

Diabet. Med. 28, 156–161 (2011)

Aims  After initiation of treatment in Type 1 diabetes, a period with lower insulin requirement often follows, reflecting increased insulin sensitivity and improved insulin secretion. We explored if efficiency of proinsulin processing is associated with the remission phenomenon.

Methods  Seventy‐eight patients with new‐onset Type 1 diabetes were followed prospectively for 3 years. Daily insulin dosage, HbA1c, plasma glucose, proinsulin, C‐peptide, glucagon concentrations and islet antibodies were determined at diagnosis and after 3, 6, 9, 12, 18, 24, 30 and 36 months. We studied remission, defined as an insulin dose ≤ 0.3 U kg−1 24 h−1 and HbA1c within the normal range, in relation to the above‐mentioned variables.

Results  A rise and subsequent decline in plasma proinsulin and C‐peptide concentrations was observed. Forty‐five per cent of the patients experienced remission at one or more times, characterized by higher proinsulin and C‐peptide levels, and lower proinsulin/C‐peptide ratios, indicating more efficient proinsulin processing, compared with those not in remission. Non‐remission also tended to be associated with higher glucagon values. Patients entering remission were more often men, had higher BMI at diagnosis, but did not differ at baseline with respect to islet antibody titres compared with patients with no remission.

Conclusions  Remissions after diagnosis of Type 1 diabetes were associated with lower proinsulin/C‐peptide ratios, suggesting more efficient proinsulin processing, and tended to have lower glucagon release than non‐remissions. This indicates that, in remission, the residual islets maintain a secretion of insulin and glucagon of benefit for control of hepatic glucose production.
Differences in minor amputation rate in diabetic foot disease throughout Europe are in part explained by differences in disease severity at presentation
Authors: van Battum P. , Schaper N. , Prompers L. , Apelqvist J. , Jude E. , Piaggesi A. , Bakker K. , Edmonds M. , Holstein P. , Jirkovska A. , Mauricio D. , Ragnarson Tennvall G. , Reike H. , Spraul M. , Uccioli L. , Urbancic V. , van Acker K. , van Baal J. , Ferreira I. , Huijberts M.
Published: November 2010

Diabet. Med. 28, 199–205 (2011)

Objectives  The incidence of minor amputation may vary significantly, and determinants of minor amputation have not been studied systematically. We evaluated minor amputation rate, the determinants of minor amputation and differences in amputation rate between European centres.

Methods  In the Eurodiale study, a prospective cohort study of 1232 patients (1088 followed until end‐point) with a new diabetic foot ulcer were followed on a monthly basis until healing, death, major amputation or up to a maximum of 1 year. Ulcers were treated according to international guidelines. Baseline characteristics independently associated with minor amputation were examined using multiple logistic regression modelling. Based on the results of the multivariable analysis, a disease severity score was calculated for each patient.

Results  One hundred and ninety‐four (18%) patients underwent a minor amputation. Predictors of minor amputation were depth of the ulcer (odds ratio 6.08, confidence interval 4.10–9.03), peripheral arterial disease (odds ratio 1.84, confidence interval 1.30–2.60), infection (odds ratio 1.56, confidence interval 1.05–2.30) and male sex (odds ratio 1.42, confidence interval 0.99–2.04). Minor amputation rate varied between 2.4 and 34% in the centres. Minor amputation rate in centres correlated strongly with disease severity score at the moment of presentation to the foot clinic (r = 0.75).

Conclusions  Minor amputation is performed frequently in diabetic foot centres throughout Europe and is determined by depth of the ulcer, peripheral arterial disease, infection and male sex. There are important differences in amputation rate between the European centres, which can be explained in part by severity of disease at presentation. This may suggest that early referral to foot clinics can prevent minor amputations.
Policy Uncertainty and Economic Reforms in a Monetary Union
Authors: Hefeker Carsten
Published: November 2010

The paper analyzes the relation between monetary uncertainty and government incentives to implement economic reforms in order to reduce structural distortions and make economies more flexible. It is shown that uncertainty about the central bank’s behavior leads to more reforms. I relate this result to the debate about central bank structure in a larger European monetary union.
Patterns and Determinants of Price Changes: Analysing Individual Consumer Prices in Austria
Authors: Rumler Fabio , Stiglbauer Alfred , Baumgartner Josef
Published: November 2010

We provide empirical evidence on the degree and characteristics of price stickiness in Austria by estimating the average frequency of price changes and the duration of price spells from a large dataset of individual price records collected for the computation of the Austrian consumer price index. The mean (median) duration of price spells in Austria amounts to 14 (11) months, but there is considerable heterogeneity across sectors and products. We find that price increases occur only slightly more often than price decreases. For both directions, the average magnitude of price changes is quite large (11% and 14%, respectively). The introduction of the euro cash in January 2002 led to more frequent but, on average, smaller price adjustments than usual. Estimating the probability of a price change in a panel probit model, we find a small but positive effect of the price spell duration on the incidence of price changes. Furthermore, product-specific inflation, the size and the sign of the last price change and the period of the euro introduction significantly affect the probability of a price change.
Functional characterization of a plant‐like sucrose transporter from the beneficial fungus Trichoderma virens. Regulation of the symbiotic association with plants by sucrose metabolism inside the fungal cells
Authors: Vargas Walter A. , Crutcher Frankie K. , Kenerley Charles M.
Published: November 2010

See also the Commentary by Harman
AN AFRICAN THEORY OF BIOETHICS: REPLY TO MACPHERSON AND MACKLIN
Authors: METZ THADDEUS
Published: November 2010

In a prior issue of Developing World Bioethics, Cheryl Macpherson and Ruth Macklin critically engaged with an article of mine, where I articulated a moral theory grounded on indigenous values salient in the sub‐Saharan region, and then applied it to four major issues in bioethics, comparing and contrasting its implications with those of the dominant Western moral theories, utilitarianism and Kantianism. In response to my essay, Macpherson and Macklin have posed questions about: whether philosophical justifications are something with which bioethicists ought to be concerned; why something counts as ‘African’; how medicine is a moral enterprise; whether an individual right to informed consent is consistent with sub‐Saharan values; and when thought experiments help to establish firm conclusions about moral status. These are important issues for the field, and I use this reply to take discussion of them a step or two farther, defending my initial article from Macpherson's and Macklin's critical questions and objections.
Familial longevity is marked by enhanced insulin sensitivity
Authors: Wijsman Carolien A. , Rozing Maarten P. , Streefland Trea C. M. , le Cessie Saskia , Mooijaart Simon P. , Slagboom P. Eline , Westendorp Rudi G. J. , Pijl Hanno , van Heemst Diana ,   On behalf of the Leiden Longevity Study group
Published: November 2010

Insulin resistance is a risk factor for various age‐related diseases. In the Leiden Longevity study, we recruited long‐lived siblings and their offspring. Previously, we showed that, compared to controls, the offspring of long‐lived siblings had a better glucose tolerance. Here, we compared groups of offspring from long‐lived siblings and controls for the relation between insulin and glucose in nonfasted serum (n = 1848 subjects) and for quantitation of insulin action using a two‐step hyperinsulinemic‐euglycemic clamp (n = 24 subjects). Groups of offspring and controls were similar with regard to sex distribution, age, and body mass index. We observed a positive bi‐phasic linear relationship between ln (insulin) levels and nonfasted glucose with a steeper slope from 10.7 mU L−1 insulin onwards in controls compared to offspring (P = 0.02). During the clamp study, higher glucose infusion rate was required to maintain euglycemia during high‐dose insulin infusion (P = 0.036) in offspring, reflecting higher whole‐body insulin sensitivity. After adjustment for sex, age, and fat mass, the insulin‐mediated glucose disposal rate (GDR) was higher in offspring than controls (42.5 ± 2.7 vs. 33.2 ± 2.7 μmol kg−1 min−1, mean ± SE, P = 0.025). The insulin‐mediated suppression of endogenous glucose production and lipolysis did not differ between groups (all P > 0.05). Furthermore, GDR was significantly correlated with the mean age of death of the parents. In conclusion, offspring from long‐lived siblings are marked by enhanced peripheral glucose disposal. Future research will focus on identifying the underlying biomolecular mechanisms, with the aim to promote health in old age.
The Friars Preachers: The First Hundred Years of the Dominican Order
Authors: Prudlo Donald S.
Published: November 2010

The first 100 years of the Dominican order witnessed the transition from a small group of men dedicated to preaching against the Albigensian heresy in southern France, to a transnational order with thousands of members affecting nearly every area of Latin Christendom. This essay is a short bibliographical overview of the state of Dominican studies for the first 100 years of their existence. It touches briefly upon the foundation, the idea of poverty, University study, preaching, inquisitions, female spirituality, and the Dominican relationship to the papacy. It offers a look both at the necessary sources for a study of the Dominicans, as well as a look at new directions in scholarship about the order.
Congenital Systematized Basaloid Follicular Hamartoma with Microphthalmia and Hemimegalencephaly
Authors: Boccaletti Valeria , Accorsi Patrizia , Pinelli Lorenzo , Ungari Marco , Giordano Lucio , Neri Iria , De Panfilis Giuseppe
Published: November 2010

Abstract:  The lines of Blaschko are a cutaneous pattern of mosaicism present in a variety of skin disorders. Developmental abnormalities affecting other tissues derived from the embryonic ectoderm and mesoderm are sometimes associated. Here, we describe a 5‐year‐old boy with basaloid follicular hamartoma affecting the left side of the body in linear multiple bands, following Blaschko lines. Lesions were predominantly hypopigmented macules and streaks, but among these, we could observe brownish atrophic patches and brown papules. Furthermore, ipsilateral hemimegaloencephaly and microphthalmia were present. These findings suggest a neurocutaneous condition recently described by Happle and Tinschert. Its nosologic classification will be discussed.
Retracted: Prevalence and Burden of Headache Disorders: A Comparative Regional Study in China
Authors: Luo Ning , Fang Yannan , Tan Feng , Zhang Qian , Zou Daliang , Cao Xiutang , Xu Xuehua , Bai Hua , Ou Jiangang , Wu Haike , Chen Zilong , Zhou Yane , Wan Saiying , Hong Yan , Wang Jingliang , Ding Minghui , Zhang Aiwu , Zhu Daoyuan , Dun Jun
Published: November 2010

Background.— Since the early 1990s, no study has been undertaken examining the prevalence and burden of headache disorders in China.

Objective.— We conducted a one‐year survey on the prevalence and burden of primary headache in the Chinese provinces of Guangdong and Guangxi. Our study also evaluated the factors behind similarities and differences affecting prevalence in the 2 regions of study.

Methods.— Random samples of 372 local residents in Guangdong and 182 local residents in Guangxi aged 18‐65 years were invited to a face‐to‐face interview.

Results.— The one‐year prevalence of primary headache was 22.6% (84/372) in Guangdong and 41.2% (75/182) in Guangxi. The prevalence of migraine (14.3%, n = 26) in Guangxi was higher than prevalence of migraine (8.3%, n = 31) in Guangdong (P = .03). The ratio of headache cost and household income was 2.1% in Guangdong and 3.7% in Guangxi, the ratio in Guangdong was less than that in Guangxi (P = .001). The diagnostic confirmation rate of migraine was low. No migraineur used triptans drugs to treat migraine in either region.

Conclusion.— Migraine prevalence was higher in the lower‐income region that also contains a higher proportion of ethnic minorities. Although there was no difference of headache cost between the 2 regions, the headache populations in the lower‐income region would relatively suffer a greater financial burden if taking the economic differences between the 2 regions into account. The improvement of diagnostic and therapeutic levels for the treatment of headache, especially migraine, in the 2 regions may be a matter of urgency.
Prevalence of visual field loss following exposure to vigabatrin therapy: A systematic review
Authors: Maguire Melissa J. , Hemming Karla , Wild John M. , Hutton Jane L. , Marson Anthony G.
Published: November 2010

Purpose:  Vigabatrin is an efficacious antiepileptic drug licensed as add‐on therapy in refractory epilepsy and used in infantile spasms. Eight years after licensing, there emerged a strong and possibly causative association with bilateral visual field loss. We report a systematic review ascertaining the magnitude of risk of vigabatrin associated visual field loss (VAVFL) and any clinical predictors of risk.

Methods:  Electronic searches, including MEDLINE (1966–2009), EMBASE (1974–2009), and CINAHL (1982–2009), were conducted. Reports, published in full, of observational studies investigating the prevalence of visual field loss in patients with partial epilepsy treated with vigabatrin were included. Outcomes were the proportion with visual field loss, and the relative risk of VAVFL compared to similar nonexposed patients with epilepsy.

Key Findings:  Thirty‐two studies were identified, which included 1,678 patients exposed to vigabatrin and 406 controls. Of the 1,678 exposed patients, 738 (44%) had visual field loss compared to just 30 (7%) among the 406 controls. The random‐effects estimate for the proportion of adults with visual field loss was 52% [95% confidence interval (CI) 46–59]. The estimate for children was lower at 34% (95% CI 25–42). The relative risk for field loss in vigabatrin‐exposed patients was 4.0 (95% CI 2.9–5.5). Larger mean cumulative dose of vigabatrin and increasing age were associated with a higher proportion of patients with visual field loss.

Significance:  Vigabatrin should be reserved for patients with epilepsy for whom there is no other alternative or for patients who have determined the benefit of ongoing treatment to outweigh the risk of VAVFL.