bluuebunny/crossref_metadata_2025 huggingface dataset:
Vertebrate ancient opsin photopigment spectra and the avian photoperiodic response
Authors: Davies Wayne I. L. , Turton Michael , Peirson Stuart N. , Follett Brian K. , Halford Stephanie , Garcia-Fernandez Jose M. , Sharp Peter J. , Hankins Mark W. , Foster Russell G.
Published: October 2011

In mammals, photoreception is restricted to cones, rods and a subset of retinal ganglion cells. By contrast, non-mammalian vertebrates possess many extraocular photoreceptors but in many cases the role of these photoreceptors and their underlying photopigments is unknown. In birds, deep brain photoreceptors have been shown to sense photic changes in daylength (photoperiod) and mediate seasonal reproduction. Nonetheless, the specific identity of the opsin photopigment ‘sensor’ involved has remained elusive. Previously, we showed that vertebrate ancient (VA) opsin is expressed in avian hypothalamic neurons and forms a photosensitive molecule. However, a direct functional link between VA opsin and the regulation of seasonal biology was absent. Here, we report the
in vivo
and
in vitro
absorption spectra (
λ
max
= ∼490 nm) for chicken VA photopigments. Furthermore, the spectral sensitivity of these photopigments match the peak absorbance of the avian photoperiodic response (
λ
max
= 492 nm) and permits maximum photon capture within the restricted light environment of the hypothalamus. Such a correspondence argues strongly that VA opsin plays a key role in regulating seasonal reproduction in birds.
A 3,000-Loci Transcription Map of Chromosome 3B Unravels the Structural and Functional Features of Gene Islands in Hexaploid Wheat
Authors: Rustenholz Camille , Choulet Frédéric , Laugier Christel , Šafář Jan , Šimková Hana , Doležel Jaroslav , Magni Federica , Scalabrin Simone , Cattonaro Federica , Vautrin Sonia , Bellec Arnaud , Bergès Hélène , Feuillet Catherine , Paux Etienne
Published: October 2011

To improve our understanding of the organization and regulation of the wheat (Triticum aestivum) gene space, we established a transcription map of a wheat chromosome (3B) by hybridizing a newly developed wheat expression microarray with bacterial artificial chromosome pools from a new version of the 3B physical map as well as with cDNA probes derived from 15 RNA samples. Mapping data for almost 3,000 genes showed that the gene space spans the whole chromosome 3B with a 2-fold increase of gene density toward the telomeres due to an increase in the number of genes in islands. Comparative analyses with rice (Oryza sativa) and Brachypodium  distachyon revealed that these gene islands are composed mainly of genes likely originating from interchromosomal gene duplications. Gene Ontology and expression profile analyses for the 3,000 genes located along the chromosome revealed that the gene islands are enriched significantly in genes sharing the same function or expression profile, thereby suggesting that genes in islands acquired shared regulation during evolution. Only a small fraction of these clusters of cofunctional and coexpressed genes was conserved with rice and B. distachyon, indicating a recent origin. Finally, genes with the same expression profiles in remote islands (coregulation islands) were identified suggesting long-distance regulation of gene expression along the chromosomes in wheat.
The effects of sorafenib on the portal hypertensive syndrome in patients with liver cirrhosis and hepatocellular carcinoma – a pilot study
Authors: Pinter M. , Sieghart W. , Reiberger T. , Rohr‐Udilova N. , Ferlitsch A. , Peck‐Radosavljevic M.
Published: October 2011

Aliment Pharmacol Ther 2012; 35: 83–91

Background  Increased intrahepatic vascular resistance and hyperperfusion in the splanchnic circulation are the principal mechanisms leading to portal hypertension in cirrhosis. Several preclinical studies have demonstrated a beneficial effect of the multikinase inhibitor sorafenib on the portal hypertensive syndrome.

Aim  To investigate the effect of sorafenib on hepatic venous pressure gradient (HVPG), systemic hemodynamics and intrahepatic mRNA expression of proangiogenic, profibrogenic and proinflammatory genes.

Methods  Patients with liver fibrosis/cirrhosis and hepatocellular carcinoma were treated with sorafenib 400 mg b.d. HVPG measurement and transjugular liver biopsy were performed at baseline and at week 2. Changes in HVPG and intrahepatic mRNA expression of vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF), RhoA, tumour necrosis factor‐alpha (TNF‐α) and placental growth factor (PlGF) were evaluated.

Results  Thirteen patients (m/f = 12/1; Child–Pugh class A/B = 10/3) were included. The most common aetiology of liver disease was alcohol consumption (n = 7). Eleven patients had an elevated portal pressure, including eight patients with clinically significant portal hypertension. A significant decrease of HVPG (≥ 20% from baseline) was observed in four subjects. In HVPG responders, we observed mRNA downregulation of VEGF, PDGF, PlGF, RhoA kinase and TNF‐α, while no substantial mRNA decrease was found in nonresponders in any of the five genes. In two of the four HVPG responders we observed a dramatic (43–85%) mRNA decrease of all five investigated genes.

Conclusion  Larger controlled clinical trials are needed to demonstrate any potential beneficial effect of sorafenib on portal hypertension in patients with cirrhosis.
Relation of high cytomegalovirus antibody titres to blood pressure and brachial artery flow-mediated dilation in young men: the Cardiovascular Risk in Young Finns Study
Authors: Haarala A , Kähönen M , Lehtimäki T , Aittoniemi J , Jylhävä J , Hutri-Kähönen N , Taittonen L , Laitinen T , Juonala M , Viikari J , Raitakari O T , Hurme M
Published: October 2011

Human cytomegalovirus (CMV) infection is associated with a higher risk of cardiovascular disease in immunocompromised organ transplant patients. It has been linked with the pathogenesis of elevated arterial blood pressure. However, controversy exists as to whether CMV infection is associated with endothelial function, and little is known about its role as a potential risk factor for early atherosclerosis development at a young age. We aimed to discover if CMV antibody titres are associated with early vascular changes (carotid intima-media thickness, carotid artery distensibility and brachial artery flow-mediated dilation), blood pressure elevation or other traditional cardiovascular risk factors. CMV antibody titres were measured in 1074 women and 857 men (aged 24–39 years) taking part in the Cardiovascular Risk in Young Finns study. CMV antibody titres were significantly higher in women compared to men. In men, high CMV antibody titres were associated directly with age (P < 0·001) and systolic (P = 0·053) and diastolic (P = 0·002) blood pressure elevation, and associated inversely with flow-mediated dilation (P = 0·014). In women, CMV antibody titres did not associate with any of the analysed parameters. In a multivariate regression model, which included traditional atherosclerotic risk factors, CMV antibody titres were independent determinants for systolic (P = 0·029) and diastolic (P = 0·004) blood pressure elevation and flow-mediated dilation (P = 0·014) in men. High CMV antibody titres are associated independently with blood pressure and brachial artery flow-mediated dilation in young men. This association supports the hypothesis that common CMV infection and/or an immune response to CMV may lead to impaired vascular function at a young age.
Flow cytometric measurement of cellular FLICE‐inhibitory protein (c‐FLIP) in ovarian carcinoma effusions
Authors: Dong H. P. , Ree Rosnes A. K. , Bock A. J. , Holth A. , Flørenes V. A. , Trope’ C. G. , Risberg B. , Davidson B.
Published: October 2011

H. P. Dong, A. K. Ree Rosnes, A. J. Bock, A. Holth, V. A. Flørenes, C. G. Trope’, B. Risberg and B. Davidson

Flow cytometric measurement of cellular FLICE‐inhibitory protein (c‐FLIP) in ovarian carcinoma effusions

Objective:  The objective of this study was to establish a flow cytometry assay for measuring c‐FLIP in serous effusions. In addition, we studied the clinical relevance in ovarian carcinoma effusions of this inhibitor protein in the death receptor signalling pathway of apoptosis.

Methods:  Two c‐FLIP antibodies were tested using Western blotting and the best performing one was used for titration of c‐FLIP expression in a panel of five cell lines, consisting of ovarian carcinoma, breast carcinoma and malignant mesothelioma. The concentration that provided the best signal‐to‐noise ratio was used for comparison of the performance of three fixation and permeabilization protocols. The best performing protocol was chosen for analysis of 69 ovarian carcinoma effusions. c‐FLIP expression was analysed for association with clinicopathological parameters and survival.

Results:  Rabbit polyclonal c‐FLIP by Abcam and the IntraStain kit by Dako performed best. c‐FLIP expression was detected in tumour cells in all 69 effusions (expression range 21–100%, median = 80%). No association was found between c‐FLIP expression and clinicopathological parameters, including chemoresponse and survival. However, an inverse correlation was found between c‐FLIP levels and expression of the previously studied apoptosis marker cleaved caspase‐3 (P = 0.029).

Conclusions:  An assay for measuring c‐FLIP in cytology specimens is presented. c‐FLIP is frequently expressed in ovarian carcinoma effusions, but its expression appears to be unrelated to disease aggressiveness.
IL28B and interferon‐gamma inducible protein 10 for prediction of rapid virologic response and sustained virologic response in HIV‐HCV‐coinfected patients
Authors: Payer Berit A. , Reiberger Thomas , Aberle Judith , Ferenci Peter , Holzmann Heidemarie , Rieger Armin , Peck‐Radosavljevic Markus ,   for the Vienna HIV‐HCV study group
Published: October 2011

Eur J Clin Invest 2012; 42 (6): 599–606

Background  A polymorphism near the IL28B gene has been shown to be associated with virologic response to antiviral treatment in HCV‐infected patients. The predictive value of interferon‐gamma inducible protein 10 (IP10) on treatment outcome has been described in HCV patients. Data on combining these predictors in HIV‐HCV‐coinfected patients are not available.

Methods  Virologic parameters, IL28B single nucleotide polymorphisms (SNP) and pretreatment serum IP10 were determined in HIV‐HCV‐coinfected patients having completed antiviral therapy with pegylated interferon/ribavirin.

Results  A total of 72 HIV‐HCV‐coinfected patients were included in the study; 68% had HCV genotype (GT)‐1/4 and 32% had HCV GT‐2/3 infections. Rapid virologic response (63% vs. 28%; P = 0·023) and sustained virologic response (SVR: 81% vs. 51%; P = 0·008) rates were significantly higher in C/C vs. non‐C/C patients. Patients with low pretreatment IP10 levels (< 400 pg/mL) achieved significantly higher SVR rates than patients with high (> 400 pg/mL) IP10 levels (78% vs. 13%; P < 0·0001). C/C SNP and low IP10 levels were associated with higher SVR rates in both patients with GT‐1/4 and GT‐2/3. The C/C patients with low IP10 achieved SVR rates of 97% compared with SVR rates of 9% in non‐C/C patients with high IP10.

Conclusion  The IL28B SNP influences rapid viral response, relapse rates and SVR. The combination of IL28B and IP10 represents a predictive model of SVR in HIV‐HCV coinfection.
The effect of autoclaving on torsional moment of two nickel–titanium endodontic files
Authors: King J. B. , Roberts H. W. , Bergeron B. E. , Mayerchak M. J.
Published: October 2011

King JB, Roberts HW, Bergeron BE, Mayerchak MJ. The effect of autoclaving on torsional moment of two nickel–titanium endodontic files. International Endodontic Journal, 45, 156–161, 2012.

Aim  To evaluate the effects of repeated autoclaving on torsional strength of two nickel–titanium (NiTi) rotary endodontic files: Twisted Files (SybronEndo, Orange, CA, USA) and GT Series X files (Dentsply Tulsa Dental Specialties, Tulsa, OK, USA).

Methodology  Four groups of 20 GT Series X (size 20, .06 taper) and four groups of 20 Twisted Files (size 25, .06 taper) were subjected to 0, 1, 3 or 7 autoclave cycles. The nonautoclaved files served as controls. Failure in torsion was recorded using a torsiometer according to ANSI/ADA 58 and ISO 3630‐1 standards. Mean results were analysed using analysis of variance (anova) at a 95% confidence level. Dunnett’s procedure was used for post hoc analysis.

Results  There was no significant difference in torsional moment between the number of autoclave cycles for Twisted Files. However, the mean torque at failure was significantly lower for GT Series X files after three (P < 0.001) and seven (P < 0.001) autoclave cycles. For Twisted Files, there was a significant increase (P < 0.001) in mean number of degrees of rotation to failure with more autoclave cycles compared to nonautoclaved files. For GT Series X files, there was no significant association (P = 0.527) between the number of autoclave cycles and the degrees of rotation to failure.

Conclusions  Repeat autoclaving of unused GT Series X files between three and seven times resulted in a significant reduction in torsional strength, whilst there was no effect observed for Twisted Files.
Temporomandibular disorders, otologic symptoms and depression levels in tinnitus patients
Authors: HILGENBERG P. B. , SALDANHA A. D. D. , CUNHA C. O. , RUBO J. H. , CONTI P. C. R.
Published: October 2011

Summary  The aim of this study was to determine the prevalence of signs and symptoms of temporomandibular disorders (TMD) and otologic symptoms in patients with and without tinnitus. The influence of the level of depression was also addressed. The tinnitus group was comprised of 100 patients with tinnitus, and control group was comprised of 100 individuals without tinnitus. All subjects were evaluated using the research diagnostic criteria for temporomandibular disorders (RDC/TMD) to determine the presence of TMD and depression level. Chi‐square, Spearman Correlation and Mann‐Whitney tests were used in statistical analysis, with a 5% significance level. TMD signs and symptoms were detected in 85% of patients with tinnitus and in 55% of controls (P ≤ 0·001). The severity of pain and higher depression levels were positively associated with tinnitus (P ≤ 0·001). It was concluded that tinnitus is associated with TMD and with otalgia, dizziness/vertigo, stuffy sensations, hypoacusis sensation and hyperacusis, as well as with higher depression levels.
Comparative analysis of mycobacterial NADH pyrophosphatase isoforms reveals a novel mechanism for isoniazid and ethionamide inactivation
Authors: Wang Xu‐De , Gu Jing , Wang Ting , Bi Li‐Jun , Zhang Zhi‐Ping , Cui Zong‐Qiang , Wei Hong‐Ping , Deng Jiao‐Yu , Zhang Xian‐En
Published: October 2011

NADH pyrophosphatase (NudC) catalyses the hydrolysis of NAD(H) to AMP and NMN(H) [nicotinamide mononucleotide (reduced form)]. NudC multiple sequence alignment reveals that homologues from most Mycobacterium tuberculosis isolates, but not other mycobacterial species, have a polymorphism at the highly conserved residue 237. To elucidate the functional significance of this polymorphism, comparative analyses were performed using representative NudC isoforms from M. tuberculosis H37Rv (NudCRv) and M. bovis BCG (NudCBCG). Biochemical analysis showed that the P237Q polymorphism prevents dimer formation, and results in a loss of enzymatic activity. Importantly, NudCBCG was found to degrade the active forms of isoniazid (INH), INH‐NAD and ethionamide (ETH), ETH‐NAD. Consequently, overexpression of NudCBCG in Mycobacterium smegmatis mc2155 and M. bovis BCG resulted in a high level of resistance to both INH and ETH. Further genetic studies showed that deletion of the nudC gene in M. smegmatis mc2155 and M. bovis BCG resulted in increased susceptibility to INH and ETH. Moreover, inactivation of NudC in both strains caused a defect in drug tolerance phenotype for both drugs in exposure assays. Taken together, these data suggest that mycobacterial NudC plays an important role in the inactivation of INH and ETH.
Two pathways for RNase E action in Escherichia coli in vivo and bypass of its essentiality in mutants defective for Rho‐dependent transcription termination
Authors: Anupama K. , Leela J. Krishna , Gowrishankar J.
Published: October 2011

The endonuclease RNase E of Escherichia coli is essential for viability, but deletion of its C‐terminal half (CTH) is not lethal. RNase E preferentially acts on 5′‐monophosphorylated RNA whose generation from primary transcripts is catalysed by RppH, but ΔRppH strains are viable. Here we show that the RNase E‐ΔCTH ΔRppH combination is lethal, and that the lethality is suppressed by rho or nusG mutations impairing Rho‐dependent transcription termination. Lethality was correlated with defects in bulk mRNA decay and tRNA processing, which were reversed by the rho suppressor. Lethality suppression was dependent on RNase H1 or the helicase UvsW of phage T4, both of which act to remove RNA–DNA hybrids (R‐loops). The rho and nusG mutations also rescued inviability of a double alteration R169Q (that abolishes 5′‐sensing) with ΔCTH in RNase E, as also that of conditional RNase E deficiency. We suggest that the ΔCTH alteration leads to loss of a second 5′‐end‐independent pathway of RNase E action. We further propose that an increased abundance of R‐loops in the rho and nusG mutants, although ordinarily inimical to growth, contributes to rescue the lethality associated with loss of the two RNase E cleavage pathways by providing an alternative means of RNA degradation.
Low‐grade gliomas as neurodevelopmental disorders: insights from mouse models of neurofibromatosis‐1
Authors: Thangarajh M. , Gutmann D. H.
Published: October 2011

M. Thangarajh and D. H. Gutmann (2012) Neuropathology and Applied Neurobiology38, 241–253

Low‐grade gliomas as neurodevelopmental disorders: insights from mouse models of neurofibromatosis‐1

Over the past few years, the traditional view of brain tumorigenesis has been revolutionized by advances in genomic medicine, molecular biology, stem cell biology and genetically engineered small‐animal modelling. We now appreciate that paediatric brain tumours arise following specific genetic mutations in specialized groups of progenitor cells in concert with permissive changes in the local tumour microenvironment. This interplay between preneoplastic/neoplastic cells and non‐neoplastic stromal cells is nicely illustrated by the neurofibromatosis type 1‐inherited cancer syndrome, in which affected children develop low‐grade astrocytic gliomas. In this review, we will use neurofibromatosis type 1 as a model system to highlight the critical role of growth control pathways, non‐neoplastic cellular elements and brain region‐specific properties in the development of childhood gliomas. The insights derived from examining each of these contributing factors will be instructive in the design of new therapies for gliomas in the paediatric population.
Motivation and experiences of self‐testers regarding tests for cardiovascular risk factors
Authors: Ickenroth Martine H. P. , Grispen Janaica E. J. , Ronda Gaby , Tacken Marloes , Dinant Geert‐Jan , de Vries Nanne K. , van der Weijden Trudy
Published: October 2011

Background  In recent years, self‐tests have become increasingly available to the general public, though their value is still being debated. Because these tests are available, consumers should have access to clear information about self‐testing. Examining experiences of self‐testers could contribute to the development of consumer information.

Objective  Detailed exploration of consumers’ experiences with self‐testing for cardiovascular risk factors.

Methods  Semi‐structured interviews with 20 consumers who had performed a self‐test for glucose, cholesterol or albuminuria. The main topics of the interviews were reasons for self‐testing, performing the self‐test, follow‐up behaviour and perceived need for information on self‐testing. Data were analysed using thematic content analysis.

Results  Regarding the reason for self‐testing, three types of users were distinguished: those who engaged in self‐testing when a test was offered, either with or without previous knowledge about the disease or risk factor, and those who had actively decided to test and had searched for a self‐test themselves. Self‐testers had generally experienced no problems performing the test or interpreting the result and had considerable confidence in the result. They were easily reassured by a normal result, while an abnormal result did not automatically mean they consulted a doctor. Most participants did not feel the need for more information.

Conclusions  Self‐testers often perform tests for reassurance, without considering the disadvantages, such as the absence of professional counselling and the risk of false‐positive or false‐negative results. Consumer information should promote more informed and deliberate choices for self‐testing.
To accept, or not to accept, that is the question: citizen reactions to rationing
Authors: Broqvist Mari , Garpenby Peter
Published: October 2011

Background  The publicly financed health service in Sweden has come under increasing pressure, forcing policy makers to consider restrictions.

Objective  To describe different perceptions of rationing, in particular, what citizens themselves believe influences their acceptance of having to stand aside for others in a public health service.

Design  Qualitative interviews, analysed by phenomenography, describing perceptions by different categories.

Setting and participants  Purposeful sample of 14 Swedish citizens, based on demographic criteria and attitudes towards allocation in health care.

Results  Participants expressed high awareness of limitations in public resources and the necessity of rationing. Acceptance of rationing could increase or decrease, depending on one’s (i) awareness that healthcare resources are limited, (ii) endorsement of universal health care, (iii) knowledge and acceptance of the principles guiding rationing and (iv) knowledge about alternatives to public health services.

Conclusions  This study suggests that decision makers should be more explicit in describing the dilemma of resource limitations in a publicly funded healthcare system. Openness enables citizens to gain the insight to make informed decisions, i.e. to use public services or to ‘opt out’ of the public sector solution if they consider rationing decisions unacceptable.
Doubling the referral rate of monogenic diabetes through a nationwide information campaign – update on glucokinase gene mutations in a Polish cohort
Authors: Borowiec M , Fendler W , Antosik K , Baranowska A , Gnys P , Zmyslowska A , Malecki M , Mlynarski W
Published: October 2011

Borowiec M, Fendler W, Antosik K, Baranowska A, Gnys P, Zmyslowska A, Malecki M, Mlynarski W. Doubling the referral rate of monogenic diabetes through a nationwide information campaign – update on glucokinase gene mutations in a Polish cohort.

In order to improve recruitment efficiency of patients with monogenic diabetes in Poland, in September 2010 a nationwide advertising campaign was launched to inform multiple target groups interested or participating in pediatric diabetologic care. Promotional actions aimed at informing physicians, patients, parents and educators were carried out through nationwide newspapers, medical and patient‐developed websites and educational conference presentations. Recruitment efficiency was compared between September 2010 (publication of the first report on project's results) and the following 12 months. The number of families and patients referred to genetic screening was increased by 92% and 96% respectively nearly reaching the numbers recruited throughout the initial 4 years of the project. Participation of non‐academic centers was also significantly increased from 2.3% to 7.5% (p = 0.0005). DNA sequencing and Multiplex Ligation‐dependant Probe Amplification of the glucokinase gene resulted in finding 50 different mutations. Among those mutations, 19 were novel variants, which included: 17 missense mutations (predicted to be pathogenic according to bioinformatic analysis), 1 nonsense mutation and 1 mutation affecting a consensus intronic splice site. Advertising actions directed at increasing recruitment efficiency are a powerful and possibly neglected tool in screening for rare genetic disorders with a clinically defined phenotype.
Cystic fibrosis mutations for p.F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency
Authors: Sebro R , Levy H , Schneck K , Dimmock D , Raby BA , Cannon CL , Broeckel U , Risch NJ
Published: October 2011

Sebro R, Levy H, Schneck K, Dimmock D, Raby BA, Cannon CL, Broeckel U, Risch NJ. Cystic fibrosis mutations for p.F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency.

Cystic fibrosis (CF) is a monogenetic disease with a complex phenotype. Over 1500 mutations in the CFTR gene have been identified; however, the p.F508del mutation is most common. There has been limited correlation between the CFTR mutation genotype and the disease phenotypes. We evaluated the non‐p.F508del mutation of 108 p.F508del compound heterozygotes using the biological classification method, Grantham and Sorting Intolerant from Tolerant (SIFT) scores to assess whether these scoring systems correlated with sweat chloride levels, pancreatic sufficiency, predicted FEV1, and risk of infection with Pseudomonas aeruginosa in the last year. Mutations predicted to be ‘mild’ by the biological classification method are associated with more normal sweat chloride levels (p < 0.001), pancreatic sufficiency (p < 0.001) and decreased risk of infection with Pseudomonas in the last year (p = 0.014). Lower Grantham scores are associated with more normal sweat chloride levels (p < 0.001), and pancreatic sufficiency (p = 0.014). Higher SIFT scores are associated with more normal sweat chloride levels (p < 0.001) and pancreatic sufficiency (p = 0.011). There was no association between pulmonary function measured by predicted FEV1 and the biological classification (p = 0.98), Grantham (p = 0.28) or SIFT scores (p = 0.62), which suggests the pulmonary disease related to CF may involve other modifier genes and environmental factors.
Underutilization of A2 ABO incompatible kidney transplantation
Authors: Redfield Robert R. , Parsons Ronald F. , Rodriguez Eduardo , Mustafa Moiz , Cassuto James , Vivek Kumar , Noorchashm Hooman , Naji Ali , Levine Matthew H. , Abt Peter L.
Published: October 2011

Redfield RR, Parsons RF, Rodriguez E, Mustafa M, Cassuto J, Vivek K, Noorchashm H, Naji A, Levine MH, Abt PL. Underutilization of A2 ABO incompatible kidney transplantation.  Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01543.x.  © 2011 John Wiley & Sons A/S.

Abstract:  Background:  ABO compatibility creates a disadvantage for O and B renal allograft candidates. A2 ABO incompatible transplant may decrease waiting times and generate equivalent graft survival to an ABO compatible transplant.

Methods:  Death‐censored graft survival was compared between A recipients and O, B, and AB recipients of an A2 allograft with multivariate Cox regression models utilizing data from the United Network of Organ Sharing (UNOS) between 1997 and 2007.

Results:  Eighty‐five percent of A2 kidneys were transplanted into ABO compatible recipients vs. 15% into ABO incompatible recipients. Rates of A2 incompatible kidney transplants did not increase over the study period (14.8% to 14.6%). Mean wait time for A2→O kidneys was 337 vs. 684 d for O→O and for A2→B kidneys, 542 vs. 734 d for B→B. Adjusted relative risk of graft loss at five‐yr was similar between O, B, and AB recipients compared to A recipients of an A2 allograft, corresponding to a five‐yr graft survival of 84%, 86.2%, 86.1%, and 86.1%, respectively.

Conclusion:  A2 incompatible kidney transplantation is underutilized. Graft outcomes are similar among A2 compatible and incompatible recipients. Shorter waiting time and improved access might be achieved if A2 kidneys are considered in all blood groups.
Castleman disease in a pediatric liver transplant recipient: A case report and literature review
Authors: Bonatti Hugo J. R. , Axt Jason , Hunter Ellen Bailey , Lott Sarah Louise , Frangoul Haydar , Gillis Lynette , Correa Hernan , Kelly Beau
Published: October 2011

Bonatti HJR, Axt J, Hunter EB, Lott SL, Frangoul H, Gillis L, Correa H, Kelly B. Castleman disease in a pediatric liver transplant recipient: A case report and literature review.  Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S.

Abstract:  Castleman disease is a rare hematologic disorder, closely linked to the HHV‐8, and most commonly observed in immunocompromised individuals. Thirteen months following a liver transplant for CPS‐1 defect, a 15‐month‐old boy presented with fevers, anemia, and growth retardation. Abdominal CT scan showed splenomegaly and generalized lymphadenopathy. Histology of chest wall lymph nodes revealed a mixed CD3+ T‐cell and CD20+ B‐cell population with atretic germinal centers consistent with multicentric Castleman disease. Qualitative DNA PCR detected HHV‐8 in the resected lymph node and in the blood, supporting the diagnosis. Immunosuppression was tapered, and he was transitioned from tacrolimus to sirolimus. His graft function remained stable, and repeat imaging showed regression of the lymphadenopathy. The child is living one yr after Castleman disease diagnosis with a well‐functioning graft. Castleman disease is a potential complication of solid organ transplant and HHV‐8 infection. Reduction in immunosuppression and switch to sirolimus may be an effective strategy to treat this condition.
Growth discontinuity in males of the deep‐water giant red shrimpAristaeomorpha foliaceain the Mediterranean Sea
Authors: Ragonese Sergio , Vitale Sergio , Dimech Mark , De Santi Alberto
Published: October 2011

The deep‐water giant red shrimp,Aristaeomorpha foliacea(Risso, 1827) (Decapoda, Aristeidae), represents a highly valuable resource for bottom trawling in the Mediterranean Sea. Recent assessments have described both a worsening of the status of the traditionally exploited stocks and low levels of annual‐based instantaneous natural mortality (M 0.4–0.7 year−1) in the unexploited stocks. The mortality (M) figures, however, are in contrast with the longevity (Tmax) of 3–4‐year males and 4–5‐year females, estimated from classical length frequency distribution analysis. Reduced growth (after the onset of sexual maturity) and pile‐up of older individuals in the larger size classes have been considered to be reasonable explanations for the contrast between M and Tmax. We propose that a discontinuity of the growth models could address this contrast. Because a clear discontinuity in sexual maturity is evident only in males, length frequency distribution data for different sets of males collected from the South of Sicily and the Maltese Islands deep bottoms (400–800 m) were fitted with both the classic (c) and double‐phased (d) von Bertalanffy growth formula (VBGF). According to the dVBGF, adult males sharply reduce their growth rate after reaching an age between 1.2 and 1.5 year, which corresponds to the estimates of age at sexual maturity (tmbetween 1 and 1.5 years). The reduction in growth determines a higher Tmax(7.3–9.5 year) and lower M (0.4–0.6 year−1) than previously derived on the basis of cVBGF estimates (Tmax3–4 years and M 1.2 year−1). The dVBGF results suggest that sexual dimorphism and length–sex segregation in giant red shrimps reflect an alternative life history strategy that is based mainly on growth reduction in adult males and it might be adopted for implementing more conservative assessments.
Concomitant presence of endothelial nitric oxide 894T and angiotensin II‐converting enzyme D alleles are associated with diabetic nephropathy in a Kurdish population from Western Iran
Authors: RAHIMI ZOHREH , VAISI‐RAYGANI ASAD , RAHIMI ZIBA , PARSIAN ABBAS
Published: October 2011

Aim:  The present study investigated the influence of insertion (I)/deletion (D) polymorphism of the angiotensin II‐converting enzyme (ACE) gene in combination with endothelial nitric oxide (eNOS) G894T polymorphism on the predisposition to diabetic nephropathy (DN).

Methods:  Using polymerase chain reaction (PCR) and PCR‐restriction fragment length polymorphism (PCR‐RFLP) method, the ACE and eNOS polymorphisms were genotyped in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric type 2 diabetes mellitus (T2DM) patients from Western Iran.

Results:  The presence of eNOS T or ACE D allele was not associated with increased risk of macroalbuminuria (odds ratio (OR) = 1.36, P = 0.27 and OR = 1.6, P = 0.062, respectively). However, in the presence of both alleles there was a trend towards increased risk of macroalbuminuria (fivefold, P = 0.05).

Conclusion:  Our study indicates that the concomitant presence of both ACE D and eNOS T alleles tends to be associated with an elevation risk of macroalbuminuria compared with the presence of each polymorphism alone. This risk could be attributed to the increasing activity of ACE and angiotensin II level in the presence of D allele and decreasing NO production in the presence of T allele accelerating diabetic nephropathy.
Evolution of the biosynthesis of di‐myo‐inositol phosphate, a marker of adaptation to hot marine environments
Authors: Gonçalves Luís G. , Borges Nuno , Serra François , Fernandes Pedro L. , Dopazo Hernán , Santos Helena
Published: October 2011

The synthesis of di‐myo‐inositol phosphate (DIP), a common compatible solute in hyperthermophiles, involves the consecutive actions of inositol‐1‐phosphate cytidylyltransferase (IPCT) and di‐myo‐inositol phosphate phosphate synthase (DIPPS). In most cases, both activities are present in a single gene product, but separate genes are also found in a few organisms. Genes for IPCT and DIPPS were found in the genomes of 33 organisms, all with thermophilic/hyperthermophilic lifestyles. Phylogeny of IPCT/DIPPS revealed an incongruent topology with 16S RNA phylogeny, thus suggesting horizontal gene transfer. The phylogenetic tree of the DIPPS domain was rooted by using phosphatidylinositol phosphate synthase sequences as out‐group. The root locates at the separation of genomes with fused and split genes. We propose that the gene encoding DIPPS was recruited from the biosynthesis of phosphatidylinositol. The last DIP‐synthesizing ancestor harboured separated genes for IPCT and DIPPS and this architecture was maintained in a crenarchaeal lineage, and transferred by horizontal gene transfer to hyperthermophilic marineThermotogaspecies. It is plausible that the driving force for the assembly of those two genes in the early ancestor is related to the acquired advantage of DIP producers to cope with high temperature. This work corroborates the view that Archaea were the first hyperthermophilic organisms.
Novel therapeutics for the management of castration‐resistant prostate cancer (CRPC)
Authors: Lee Daniel J. , Cha Eugene K. , Dubin Justin M. , Beltran Himisha , Chromecki Thomas F. , Fajkovic Harun , Scherr Douglas S. , Tagawa Scott T. , Shariat Shahrokh F.
Published: October 2011

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

Historically, therapies for CRPC have primarily been chemotherapy‐based. A variety of novel therapeutics for CRPC have recently been developed and tested. When evaluating novel therapies for CRPC, there are various different endpoints that can be assessed.

Novel treatments for CRPC to be discussed include docetaxel‐based combinations, new cytotoxic agents, immunotherapeutics, and targeted therapies. We evaluate prostate‐specific antigen, circulating tumour cells, progression‐free survival, overall survival, and other endpoints used in clinical trials.

Androgen‐deprivation therapy is the initial treatment for metastatic prostate cancer. Although highly effective, all men who live long enough will eventually experience disease progression and develop castration resistance. Patients who have castration‐resistant prostate cancer (CRPC) have a median survival of ≈1–3 years.

When evaluating novel therapies for CRPC, one must consider the endpoints measured for determination of response. We will discuss PSA, circulating tumour cells, progression‐free survival, overall survival, and other endpoints used in clinical trials.

Docetaxel and sipuleucel‐T are currently the preferred first‐line treatment options for patients with CRPC; cabazitaxel is a new option for patients after docetaxel failure.

Patients with CRPC historically have very poor survival, underscoring the unmet need for novel therapeutics. Although many agents appear promising, well‐designed randomized phase III trials are necessary to establish their impact on survival and health‐related quality of life.

Promising new therapies include hormonal agents, such as abiraterone and MDV3100, as well as other novel immunotherapeutics and anti‐prostate‐specific membrane antigen therapies. In the future, we anticipate therapies tailored to individual patients' malignancies using various molecular analyses.
The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)
Authors: Gudjónsson Sigurdur , Bläckberg Mats , Chebil Gunilla , Jahnson Staffan , Olsson Hans , Bendahl Pär‐Ola , Månsson Wiking , Liedberg Fredrik
Published: October 2011

Study Type – Diagnostic (case series)

Level of Evidence 4

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

It is well known that CIS is a major risk factor for muscle‐invasive bladder cancer and that this entity can be difficult to diagnose. Taking cold‐cup mapping biopsies from different areas of the bladder (BMAP) is commonly used in patients at risk of harbouring CIS. The diagnostic accuracy of this approach has not been assessed until now.

By using the CIS found in the cystoprostatectomy specimen as an indicator of the true occurrence of CIS and comparing that with the findings of BMAP, it is clear that the sensitivity of BMAP to detect CIS when present is low and that negative findings should be considered unreliable.

OBJECTIVES

To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS).

CIS of the urinary bladder is a flat high‐grade lesion of the mucosa associated with a significant risk of progression to muscle‐invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold‐cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known.

PATIENTS AND METHODS

Male patients with bladder cancer scheduled for cystectomy underwent cold‐cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra.

After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS.

RESULTS

The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (≥2) CIS lesions were found in 30%.

BMAP (cold‐cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold‐cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively.

CONCLUSION

Traditional cold‐cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.
Genetic pathways involved in carcinogenesis of clear cell renal cell carcinoma: genomics towards personalized medicine
Authors: Audenet François , Yates David R. , Cancel‐Tassin Géraldine , Cussenot Olivier , Rouprêt Morgan
Published: October 2011

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

Sporadic clear cell Renal Cell Carcinoma (ccRCC) is dominated by nutations of the VHL gene located on chromosome 3p in up to 90% of cases. This gene plays a critical role in hypoxia response, including stimulation of neoangiogenesis. Since 2006, anti‐angiogenci therapies targeting this pathway are used in metastatic patients with objective response rate as high as 45%. However, these treatments don't target directly the tumour cell, allowing the potential for disease progession despite treatment.

Large scale analysis recently showed that substantial genetic heterogeneity exists in ccRCC. Associated alterations include genes implicated in methylation regulation in 15% of cases, underlying the importance of epigenetic modifications, and truncating mutations in chromatin remodelling complex PRMB1 in 41% of cases. Systematic screening of these tumours is a way to fully determine the somatic genetic architecture of RCC in order to improve tumour classification, to develop prognostic and predictive markers and to target new molecular pathways involved in carcinogenesis.

• A critical review is provided of the recent progress in oncogenetics applied to renal cell carcinoma (RCC) by highlighting our current understanding of the genetic pathways involved in carcinogenesis and its current and future clinical application.

• RCC comprises a model of translational research because an improved understanding of molecular pathways has led to several targeted therapy options for patients with metastatic RCC.

• Alteration of the product of the Von Hippel–Lindau gene/hypoxia inductible factor/vascular endothelial growth factor pathway is well characterized in carcinogenesis and is the target of the current therapies for metastatic RCC.

• However, substantial genetic heterogeneity exists in this cancer and current treatments do not target directly the tumour cell.

• Improving overall survival still remains a challenging objective but, currently, there is a lack of prognostic and predictive biomarkers for response to treatment.

• Further information is awaited from the genomic approach to tumour classification, prognostic markers and predictive indicators of response to the treatment, as well as the personal susceptibility of developing RCC when exposed to risk factors.

• Recent technological developments, such as large‐scale analysis and high‐speed sequencing, will allow the systematic screening of tumours to fully determine the somatic genetic architecture of RCC.
MRI and its role in the evaluation and surgical decision making in patients with challenging IPP presentations: descriptions of MRI findings and algorithm for patient management
Authors: McPhail E. Fred , Nehra Ajay , Bruner Bryan C. , Kawashima Akira , King Bernard F. , Kim Bohyun
Published: October 2011

Study Type – Diagnostic (case series)

Level of Evidence 4

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

It is known that magnetic resonance imaging (MRI) is safe and effective for imaging patients with inflatable penile prostheses (IPPs). Previous series have reported results of MRI for imaging series of patients with IPPs. The impact on management in particular with regard to salvage procedures is not well defined.

This study represents the largest known experience with MRI evaluation of IPPs. This also provides an algorithm that assists with decisions regarding utilization of MRI and treatment planning based on results.

OBJECTIVE

In some patients who undergo placement of an inflatable penile prosthesis (IPP) the device may function inadequately. We describe the use of magnetic resonance imaging (MRI) for anatomical localization and detection of prosthesis malrotation, angulation, displacement and erosion in IPPs with equivocal clinical examination.

PATIENTS AND METHODS

We prospectively performed MRI by a defined protocol including T1‐weighted imaging, and transaxial, sagittal and coronal fat‐saturated fast spin‐echo T2‐weighted imaging in both deflated and inflated states to evaluate patients seen at our referral centre for IPP‐related complaints.

We retrospectively reviewed 32 such MRI studies performed as a supplement to clinical examination between 2000 and 2008.

RESULTS

Of 32 cases, 75% (24/32) underwent surgical intervention. Of these, 45% (11/24) underwent device salvage procedures including cylinder revision in 33% (8/24), cylinder replacement in 8% (2/24) and pump replacement in 4% (1/24).

MRI was most useful for determination of surgical approach in those with abnormal physical examination, and for justification of either surgical or expectant management in those with indeterminate physical examination.

CONCLUSIONS

MRI is safe and effective for imaging genitourinary prostheses.

We found MRI to be a valuable adjunct for evaluation of IPP‐related complaints when clinical examination is equivocal as it detected a variety of prosthetic and corporal abnormalities and impacted management decisions regarding observation, replacement or device salvage procedures.

We provide technique, results and an algorithm that can be beneficial in this complex subset of patients.
Affective prosody labeling in youths with bipolar disorder or severe mood dysregulation
Authors: Deveney Christen M. , Brotman Melissa A. , Decker Ann Marie , Pine Daniel S. , Leibenluft Ellen
Published: October 2011

Background:  Accurate identification of nonverbal emotional cues is essential to successful social interactions, yet most research is limited to emotional face expression labeling. Little research focuses on the processing of emotional prosody, or tone of verbal speech, in clinical populations.

Methods:  Using the Diagnostic Analysis of Nonverbal Accuracy, the current study examined whether youths with pediatric‐onset bipolar disorder (BD) and/or those with chronic and severe irritability (i.e. the severe mood dysregulation phenotype) are impaired in their ability to identify the emotional prosody of a spoken sentence with neutral content.

Results:  Youths with severe mood dysregulation (n = 67) performed more poorly than healthy comparison children (n = 57), even when the sample was limited to unmedicated patients. Medicated BD youths (n = 52) exhibited impairment relative to healthy comparison children. No interactions between group and emotion were observed, suggesting that emotional prosody labeling problems may represent a general deficit in chronically irritable youths and in medicated youths with BD.

Conclusion:  In concert with previously documented facial emotion labeling deficits, difficulties ascertaining the correct emotional tone of a spoken sentence may contribute to emotion dysregulation in chronically irritable children, and possibly also in youths with BD.
Grouping mechanisms in response preparation investigated with event‐related brain potentials
Authors: Sangals Jörg , Dippel Gabriel , Sommer Werner
Published: October 2011

Preliminary information about responses facilitates performance, especially when the information can be grouped into stimulus‐response sets, for example, into fingers belonging to the same hand. Here, we studied the mechanisms of supposedly fast and automatic exogenous as compared to slow and controlled endogenous grouping of same‐hand fingers. As compared to endogenous cuing, exogenous cuing facilitated reaction times and induced larger amplitudes of the contingent negative variation, but did not show any advantage in amplitude or latency of the lateralized readiness potential or in the magnitude of current source density over the motor cortices. Similarly, the stimulus preceding negativity did not seem to be a plausible explanation for the observed effect. Therefore, at least one functional mechanism underlying exogenous stimulus‐response grouping appears to be the facilitation of central response programming.