bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory impact factors: unraveling the transcriptional regulation of complex traits from expression data
Authors: Reverter Antonio , Hudson Nicholas J. , Nagaraj Shivashankar H. , Pérez-Enciso Miguel , Dalrymple Brian P.
Published: February 2010

Motivation: Although transcription factors (TF) play a central regulatory role, their detection from expression data is limited due to their low, and often sparse, expression. In order to fill this gap, we propose a regulatory impact factor (RIF) metric to identify critical TF from gene expression data.

Results: To substantiate the generality of RIF, we explore a set of experiments spanning a wide range of scenarios including breast cancer survival, fat, gonads and sex differentiation. We show that the strength of RIF lies in its ability to simultaneously integrate three sources of information into a single measure: (i) the change in correlation existing between the TF and the differentially expressed (DE) genes; (ii) the amount of differential expression of DE genes; and (iii) the abundance of DE genes. As a result, RIF analysis assigns an extreme score to those TF that are consistently most differentially co-expressed with the highly abundant and highly DE genes (RIF1), and to those TF with the most altered ability to predict the abundance of DE genes (RIF2). We show that RIF analysis alone recovers well-known experimentally validated TF for the processes studied. The TF identified confirm the importance of PPAR signaling in adipose development and the importance of transduction of estrogen signals in breast cancer survival and sexual differentiation. We argue that RIF has universal applicability, and advocate its use as a promising hypotheses generating tool for the systematic identification of novel TF not yet documented as critical.

Contact:  tony.reverter-gomez@csiro.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Inference of RhoGAP/GTPase regulation using single-cell morphological data from a combinatorial RNAi screen
Authors: Nir Oaz , Bakal Chris , Perrimon Norbert , Berger Bonnie
Published: February 2010

Biological networks are highly complex systems, consisting largely of enzymes that act as molecular switches to activate/inhibit downstream targets via post-translational modification. Computational techniques have been developed to perform signaling network inference using some high-throughput data sources, such as those generated from transcriptional and proteomic studies, but comparable methods have not been developed to use high-content morphological data, which are emerging principally from large-scale RNAi screens, to these ends. Here, we describe a systematic computational framework based on a classification model for identifying genetic interactions using high-dimensional single-cell morphological data from genetic screens, apply it to RhoGAP/GTPase regulation in Drosophila, and evaluate its efficacy. Augmented by knowledge of the basic structure of RhoGAP/GTPase signaling, namely, that GAPs act directly upstream of GTPases, we apply our framework for identifying genetic interactions to predict signaling relationships between these proteins. We find that our method makes mediocre predictions using only RhoGAP single-knockdown morphological data, yet achieves vastly improved accuracy by including original data from a double-knockdown RhoGAP genetic screen, which likely reflects the redundant network structure of RhoGAP/GTPase signaling. We consider other possible methods for inference and show that our primary model outperforms the alternatives. This work demonstrates the fundamental fact that high-throughput morphological data can be used in a systematic, successful fashion to identify genetic interactions and, using additional elementary knowledge of network structure, to infer signaling relations.
Bymovirus reverse genetics: requirements for RNA2‐encoded proteins in systemic infection
Authors: YOU YUAN , SHIRAKO YUKIO
Published: February 2010

Barley yellow mosaic virus (BaYMV), the type species of the genus Bymovirus in the family Potyviridae in the picornavirus‐like superfamily, causes a yellow mosaic disease of winter barley with significant yield losses in Europe and East Asia. Until now, infectious in vitro transcripts for the bipartite plus‐sense RNA genome of any bymovirus species have not been available, rendering molecular analyses of bymovirus pathogenicity and the host resistance mechanisms difficult. In this study, we constructed the first cDNA clones of BaYMV RNA1 and RNA2, from which infectious RNA can be transcribed in vitro. Using in vitro transcripts, we showed that RNA1, which encodes eight proteins, including a viral proteinase NIa‐Pro, the RNA‐dependent RNA polymerase NIb, genome‐linked viral protein VPg and the capsid protein CP, replicated autonomously in barley mesophyll protoplasts in the absence of RNA2 optimally at 15 °C, a temperature similar to the optimum for causing disease in barley fields. For systemic infection of barley plants, RNA1 alone was not sufficient and RNA2 was also required. Of the two proteins encoded on RNA2 (P1 with cysteine proteinase activity and P2 with unknown functions), P1 was essential and P2 was dispensable for systemic infectivity. The expression of both P1 and P2, but not the precursor polyprotein, together with RNA1 increased systemic infection and caused mosaic leaf symptoms. The infectious cDNA clones of BaYMV will be vital for future studies of bymovirus–host–vector interactions at the molecular level.
Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome ‐ a randomized, double‐blind, placebo‐controlled study
Authors: WITTMANN T. , PARADOWSKI L. , DUCROTTÉ P. , BUENO L. , ANDRO DELESTRAIN M.‐C.
Published: February 2010

Aliment Pharmacol Ther 31, 615–624

Background  Alverine citrate and simeticone combination has been used for almost 20 years in irritable bowel syndrome (IBS), but supportive scientific evidence of efficacy was limited.

Aim  To evaluate the efficacy of alverine citrate and simeticone combination in patients with IBS‐related abdominal pain/discomfort.

Methods  A total of 412 IBS patients meeting ROME III criteria were included in this double‐blind randomized placebo‐controlled study if their abdominal pain/discomfort intensity was at least 60 mm on a 0–100 mm visual analogue scale (VAS) during a 2‐week run‐in treatment‐free period. Patients were randomly assigned through the use of Interactive Voice Response System to receive either alverine citrate 60 mg with simeticone 300 mg three times daily or matching placebo for 4 weeks.

Results  The full analysis set included 409 patients (71.4% female: mean age: 46.2 ± 13.9 years). At week 4, alverine citrate and simeticone group had lower VAS scores of abdominal pain/discomfort (median: 40 mm vs. 50 mm, P = 0.047) and higher responder rate (46.8% vs. 34.3%, OR = 1.3; P = 0.01) as compared with placebo group. Patient receiving alverine citrate and simeticone reported greater global symptom improvement compared with those receiving placebo (P = 0.0001). Reported adverse events were similar in both groups.

Conclusion  Alverine citrate/simeticone combination was significantly more effective than placebo in relieving abdominal pain/discomfort in patients with IBS.
A pneumatic dilation strategy in achalasia: prospective outcome and effects on oesophageal motor function in the long term
Authors: BRAVI I. , NICITA M. T. , DUCA P. , GRIGOLON A. , CANTÙ P. , CAPARELLO C. , PENAGINI R.
Published: February 2010

Aliment Pharmacol Ther 31, 658–665

Background  Long‐term follow‐up studies of achalasia after pneumatic dilation, mostly retrospective, have shown variable results.

Aim  To examine the outcome of achalasia after pneumatic dilation using a prospective follow‐up programme.

Methods  One or two dilations (first dilation treatment) in 77 patients to achieve stable (>1 year) remission and patients followed up with yearly clinical and manometric assessments. Endoscopy, pH monitoring and barium swallow were also performed.

Results  A total of 69 patients achieved stable remission and were followed up for 5.6 years (3–10.7) [median (IQ range)], whereas six patients underwent cardiomyotomy and two experienced a perforation. Twelve of the 69 patients relapsed after 2.6 years (1.7–5.1): nine of 12 underwent one to two further dilations. Six‐year remission rate (by Kaplan–Meyer estimates) was 82% after first dilation treatment and 96% after all dilations. Continuous antisecretory treatment was clinically needed in 16%, oesophagitis present in 7% and reflux pathological in 28% of the patients. Beneficial effects of dilation on oesophageal motility and on diameter of the oesophageal body at barium swallow were maintained during follow‐up.

Conclusions  A management strategy including sessions of pneumatic dilation until stable remission and a standardized follow‐up is highly successful in the long term. Gastro‐oesophageal reflux is clinically relevant in a minority of patients.
The clinical presentation and prognostic factors for intrahepatic and extrahepatic cholangiocarcinoma in a tertiary care centre
Authors: SINGAL A. G. , RAKOSKI M. O. , SALGIA R. , PELLETIER S. , WELLING T. H. , FONTANA R. J. , LOK A. S. , MARRERO J. A.
Published: February 2010

Aliment Pharmacol Ther 31, 625–633

Background  The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined.

Aim  To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients.

Methods  Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed.

Results  In all, 136 patients had cholangiocarcinoma (79 intra‐ and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months–25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01–1.07), CA 19‐9 levels >100 U/mL (HR 1.90, 95%CI 1.17–3.08) and stage of disease (HR 1.51, 95%CI 1.16–1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26–0.88). There were no significant differences regarding clinical presentation, disease stage (P = 0.98), and survival (P = 0.51) between intra‐ and extrahepatic cholangiocarcinoma.

Conclusions  Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra‐ and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19‐9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables.
Low‐dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease
Authors: ANSARI A. , PATEL N. , SANDERSON J. , O’DONOHUE J. , DULEY J. A. , FLORIN T. H. J.
Published: February 2010

Aliment Pharmacol Ther 31, 640–647

Background  The thiopurine drugs, azathioprine and mercaptopurine (MP), are established treatments for IBD. However, therapeutic failure caused by adverse drug reactions occurs frequently.

Aim  To study combination of allopurinol with reduced‐dose thiopurine in an attempt to avoid adverse drug reactions in the treatment of IBD.

Methods  Patients with drug reactions to full‐dose thiopurines were recruited for combination therapy in two IBD centres in this retrospective study. Dosing was guided by measuring thiopurine methyltransferase (for UK patients) or thioguanine nucleotides and methyl‐6MP (Australian patients). Response was monitored by clinical activity indices.

Results  Of 41 patients, 25 had non‐hepatic and 16 had hepatitic reactions. Clinical remission was achieved in 32 patients (78%) with a median follow‐up of 41 weeks (range 0.5–400). Patients who did not respond to combination therapy tended to fail early with the same adverse reaction. The relative risk of having an adverse reaction with methyl‐6MP in the top interquartile range was 2.7 (1.3–28) times that with methyl‐6MP in the lower three quartiles (95% confidence interval).

Conclusion  The combined experience from our centres is the largest reported experience of this combination therapy strategy in IBD, and the first to provide evidence for benefit in thiopurine and allopurinol co‐therapy to avoid non‐hepatitic adverse drug reactions.
CCR6 identifies lymphoid tissue inducer cells within cryptopatches
Authors: Lügering A , Ross M , Sieker M , Heidemann J , Williams I R , Domschke W , Kucharzik T
Published: February 2010

The chemokine receptor CCR6 is expressed by dendritic cells, B and T cells predominantly within the organized structures of the gut-associated lymphatic tissue. Its ligand CCL20 is synthesized by the follicle-associated epithelium and is crucial for the development of M cells within Peyer's patches. In addition, lineage-negative c-kit positive lymphocytes within cryptopatches (CP) express CCR6. CCR6-deficient mice exhibit an altered intestinal immune system containing increased amounts of intraepithelial lymphocytes and show smaller Peyer's patches, while progression of cryptopatches to mature isolated lymphoid follicles (ILF) is inhibited. In this report, we show that lin- c-kit+ lymphocytes express a variety of different chemokine receptors and that CCR6 identifies those cells located within CP. In contrast, cells found outside CP are positive for CXCR3 and exhibit a different surface marker profile, suggesting that at least two different populations of lin- c-kit+ cells are present. The presence of CCR6 does not influence the expression of Notch molecules on lin- c-kit+ cells, nor does it influence Notch ligand expression on bone marrow-derived dendritic cells. In the human gut, CCR6 identifies clusters of lymphocytes resembling murine CP. CCR6 seems to have an important role for lin- c-kit+ cells inside CP, is expressed in a regulated manner and identifies potential human CP.
Interleukin-10 inhibitsMycobacterium bovisbacillus Calmette–Guérin (BCG)-induced macrophage cytotoxicity against bladder cancer cells
Authors: Luo Y , Han R , Evanoff D P , Chen X
Published: February 2010

The mechanisms underlying bacillus Calmette–Guérin (BCG) immunotherapy of bladder cancer currently remain elusive. Previously, we demonstrated that macrophages were cytotoxic to bladder cancer cells upon BCG stimulation in vitro. However, macrophages from C57BL/6 mice were less potent than those from C3H/HeN mice for the killing of bladder cancer cells. This study was to determine whether interleukin (IL)-10 produced by macrophages in response to BCG is a causative factor for the reduced cytotoxicity in BCG-stimulated C57BL/6 macrophages. Thioglycollate-elicited peritoneal macrophages were prepared and analysed for the BCG induction of cytotoxicity, cytokines and nitric oxide (NO) in vitro. Compared to BCG-stimulated C3H/HeN macrophages, BCG-stimulated C57BL/6 macrophages exhibited reduced killing of bladder cancer MBT-2 cells and MB49 cells. Studies demonstrated further that BCG-stimulated C57BL/6 macrophages produced a high level of IL-10, which correlated with reduced production of tumour necrosis factor (TNF)-α, IL-6 and NO. Neutralizing endogenous IL-10 during BCG stimulation increased C57BL/6 macrophage cytotoxicity against MB49 cells by 3·2-fold, along with increased production of TNF-α by 6·4-fold and NO by 3·6-fold, respectively. Macrophages from C57BL/6 IL-10−/− mice also exhibited increased killing of MB49 cells and production of TNF-α and NO upon BCG stimulation. In addition, supplementation of exogenous recombinant IL-10 reduced BCG-induced C3H/HeN macrophage cytotoxicity against both MBT-2 cells and MB49 cells in a dose-dependent manner. These results reveal the inhibitory role of IL-10 in BCG-induced macrophage cytotoxicity, suggesting that blockage of IL-10 may potentially enhance the effect of BCG in the treatment of bladder cancer patients.
Association of FcGRIIa with Graves’ disease: a potential role for dysregulated autoantibody clearance in disease onset/progression
Authors: Yesmin Kadija , Hargreaves Chantal , Newby Paul R. , Brand Oliver J. , Heward Joanne M. , Franklyn Jayne A. , Gough Stephen C. L. , Simmonds Matthew J.
Published: February 2010

Objective  Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves’ disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region.

Design  A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region.

Patients  A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort.

Measurements  We used the χ2‐test to investigate association between the Tag SNPs and GD.

Results  Association between the rs1801274 (P = 0·003, OR = 1·12 [95% CI = 1·03–1·22] and rs6427598 (P = 0·012, OR = 0·90 [95% CI = 0·83‐0·98]) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes.

Conclusions  This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general.
Influence of parental origin of the X chromosome on physical phenotypes and GH responsiveness of patients with Turner syndrome
Authors: Ko Jung Min , Kim Jae‐Min , Kim Gu‐Hwan , Lee Beom Hee , Yoo Han‐Wook
Published: February 2010

Objective  Previous studies have reported the effects of parental origin of the X chromosome on specific phenotypic and cognitive profiles in Turner syndrome (TS). Here, we investigate the possible parent‐of‐origin effects on physical phenotypes and responsiveness to GH in Korean patients with TS.

Design and patients  Thirty‐three patients with TS with nonmosaic karyotype and their parents participated in this study. The parental origin of the normal X chromosome was determined by comparing parental DNA polymorphisms using nine highly polymorphic microsatellite markers on the X chromosome. For the evaluation of parent‐of‐origin effects, typical phenotypic traits, including congenital malformations, auxological and endocrinological profiles, were compared.

Results  The retained X chromosome was of maternal (Xm) origin in 60·6% patients and paternal (Xp) origin in 39·4% patients. No significant parent‐of‐origin effects on stature, body mass index, cardiac, renal, skeletal, lymphatic, hearing or ocular systems were evident. We observed no differences in height gain after GH treatment. In patients with the 45,X karyotype, patient height was positively correlated with maternal height in the Xm group (r = 0·60, P = 0·04). Moreover, patient height was more significantly correlated with maternal than paternal height, irrespective of the parental origin of the retained X chromosome.

Conclusion  While we observed no significant impact of parental origin of the X chromosome on several phenotypic traits in patients with TS, a maternal imprinting effect on stature was suggested at least in patients with 45,X. Further studies on a larger number of patients with TS are essential to define the potential imprinting effects of undetermined genes on the X chromosome.
What to do for moderate‐to‐severe and active Graves’ orbitopathy if glucocorticoids fail?
Authors: Bartalena Luigi
Published: February 2010

Treatment of Graves’ orbitopathy (GO) is a major challenge, and the outcome of medical therapy is unsatisfactory in about one‐third of cases. Glucocorticoids are the first‐line therapy for moderate‐to‐severe and active GO, more commonly given through the intravenous route. Uncertainty remains as to the best therapeutic approach when the initial glucocorticoid treatment provides an incomplete response or no response. The choice largely depends on personal experience because of the limited evidence in this field. In the author’s view, if a first course of glucocorticoids provides a suboptimal response, a second course of intravenous (or oral) glucocorticoids associated with orbital radiotherapy should be given. An alternative might be represented by oral glucocorticoids associated with cyclosporine. The use of biological agents, the most promising being rituximab, is for the time being experimental and warrants support from randomized clinical trials.
ORIGINAL ARTICLE: Effects of rosiglitazone on bone mineral density and remodelling parameters in Postmenopausal diabetic women: a 2‐year follow‐up study
Authors: Berberoglu Zehra , Yazici Ayse C. , Demirag Nilgun G.
Published: February 2010

Objective  To evaluate the effect of rosiglitazone on bone metabolism and bone density.

Design  An open‐label, randomized, controlled trial of 24‐month duration.

Patients and measurements  Obese, postmenopausal women with newly diagnosed diabetes were studied. Before and after the intervention, metabolic bone markers and bone density were assessed.

Results  Twenty‐six patients received rosiglitazone (4 mg/day), and 23 remained on diet alone. Serum bone‐specific alkaline phosphatase and osteocalcin levels decreased by 17% (P < 0·001 vs control group) and 26% (P < 0·01 vs control group), respectively, in the rosiglitazone group. There were no significant changes in the deoxypyridinoline levels between the two groups. Annual bone loss at the trochanter and at the lumbar spine associated with each year of rosiglitazone use was 2·56% (P = 0·01 vs control group) and 2·18% (P < 0·01 vs control group), respectively. Femoral neck and total hip bone density declined significantly in both groups (P < 0·01, and P = 0·01, respectively) but was not significantly different between the two groups.

Conclusions  Rosiglitazone treatment adversely affects bone formation over a 2‐year period. It increases bone loss at the lumbar spine and trochanter in postmenopausal, type 2 diabetic women. However, bone loss at the total hip did not differ with use of this agent.
Thyroid dysfunction in a UK hepatitis C population treated with interferon‐α and ribavirin combination therapy
Authors: Costelloe Seán J. , Wassef Nancy , Schulz Josephine , Vaghijiani Tina , Morris Catherine , Whiting Stephen , Thomas Michael , Dusheiko Geoffrey , Jacobs Michael , Vanderpump Mark P. J.
Published: February 2010

Objective  To assess the incidence of thyroid dysfunction (TD) in a UK cohort of patients with hepatitis C virus (HCV) infection treated with interferon‐α (IFNα) and ribavirin combination therapy (IFN/RBV).

Design, patients and measurements  A retrospective study of 288 patients who received IFN/RBV for HCV during a 2‐year period from January 2006 was performed. Thyroid function was assessed during a 24‐week or 48‐week course of IFN/RBV. If serum thyrotrophin (TSH) became undetectable (<0.01 mU/l) and serum free thyroxine (T4) was raised, a diagnostic thyroid isotope scan was performed.

Results  Full medical records were examined for 260 patients (172 men, 88 women) included in the study, of whom 22.3% (16.9% of men, 33.0% of women) developed TD during IFN/RBV. In total, 10.4% developed a suppressed serum TSH (0.8% Graves’ disease, 9.6% transient thyroiditis) while 11.9% developed an elevated serum TSH with 1.5% becoming permanently hypothyroid and requiring levothyroxine therapy. Women had a relative risk (RR) for developing TD of 1.96 (CI: 1.75–3.03, P = 0.004). A serum TSH ≥1.75 mU/l and a positive thyroid peroxidase (TPO) antibody titre pretherapy were associated with RRs for progression to TD of 6.02 (CI: 2.95–12.78, P < 0.0001) and 4.35 (CI: 2.58–6.52; P < 0.0001), respectively, while combination of baseline TSH and TPO antibody data predicted progression to TD with a sensitivity of 94.7%.

Conclusions  Although TD was common in this cohort, just 2.3% developed TD that required ongoing therapy. Pre‐IFN/RBV serum TSH and TPO antibody titre were found to predict progression to TD in this group of patients.
Migration for velocity and attenuation perturbations
Authors: Hak Bobby , Mulder Wim A.
Published: February 2010

Migration maps seismic data to reflectors in the Earth. Reflections are not only caused by small‐scale variations of the velocity and density but also of the quality factor that describes attenuation. We investigated scattering due to velocity and attenuation perturbations by computing the resolution function or point‐spread function in a homogeneous background model. The resolution function is the migration image of seismic reflection data generated by a point scatterer. We found that the resolution function mixes velocity and attenuation parameter perturbations to the extent that they cannot be reconstructed independently. This is true for a typical seismic setting with sources and receivers at the surface and a buried scatterer. As a result, it will be impossible to simultaneously invert for velocity and attenuation perturbations in the scattering approach, also known as the Born approximation.

We proceeded to investigate other acquisition geometries that may resolve the ambiguity between velocity and attenuation perturbations. With sources and receivers on a circle around the scatterer, in 2D, the ambiguity disappears. It still shows up in a cross‐well setting, although the mixing of velocity and attenuation parameters is less severe than in the surface‐to‐surface case. We also consider illumination of the target by diving waves in a background model that has velocity increasing linearly with depth. The improvement in illumination is, however, still insufficient to remove the ambiguity.
Alarmingly high prevalence of obesity in haemophilia in the state of Mississippi
Authors: MAJUMDAR S. , MORRIS A. , GORDON C. , KERMODE J. C. , FORSYTHE A. , HERRINGTON B. , MEGASON G. C. , IYER R.
Published: February 2010

Summary.  The state of Mississippi has consistently been ranked as the state with most number of obese people in the United States with prevalence rates of >30%. Our aims in this study were to estimate the prevalence of overweight and obesity in children and adults diagnosed with haemophilia in Mississippi, and to assess whether race/ethnicity and the severity of haemophilia are important risk factors. A retrospective chart review was performed for all haemophilic patients seen at the Mississippi Hemophilia Treatment Center. Patients were classified into two major age groups: age 2–19.9 years and ≥20 years. Body mass index (BMI) was calculated from the height and weight in kg m−2 from the last clinic visit. Out of a total of 132 haemophilic patients, 61% were white and 37% were African American. Overall, 51% of the haemophilic patients were either obese or overweight. The prevalence of obesity in the  adult (≥20 years old) haemophilic patients was 36% and an additional 32% were overweight. A significantly greater proportion of patients >20 years old were overweight or obese as compared with the patients in the 2–19.9 year age range (P < 0.002). However, race/ethnicity and severity of haemophilia were not significant risk factors for overweight and obesity. There is a very high prevalence of obesity in the Mississippi haemophilic population, especially in adults. Particular attention at clinic visits should be paid to the BMI in order to identify patients that are overweight or obese to allow for early and appropriate intervention.
Mortality and causes of death in Italian persons with haemophilia, 1990–2007
Authors: TAGLIAFERRI A. , RIVOLTA G. F. , IORIO A. , OLIOVECCHIO E. , MANCUSO M. E. , MORFINI M. , ROCINO A. , MAZZUCCONI M. G. , FRANCHINI M. ,   ON BEHALF OF THE ITALIAN ASSOCIATION OF HEMOPHILIA CENTERS
Published: February 2010

Summary. Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co‐morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate. The mortality rate ratio standardized to the male Italian population (SMR) was reduced during the periods 1990–1999 and 2000–2007 such that during the latter, death rate overlapped that of the general population (SMR 1990–1999: 1.98 95% CI 1.54–2.51; SMR 2000–2007: 1.08 95% CI 0.83–1.40). Similarly, life expectancy in the whole haemophilic population increased in the same period (71.2 years in 2000–2007 vs. 64.0 in 1990–1999), approaching that of the general male population. While human immunodeficiency virus infection was the main cause of death (45%), 13% of deaths were caused by hepatitis C‐associated complications. The results of this retrospective study show that in Italian PWH improvements in the quality of treatment and global medical care provided by specialized haemophilia centres resulted in a significantly increased life expectancy.
Thrombin generation in haemophilia A patients with mutations causing factor VIII assay discrepancy
Authors: GILMORE R. , HARMON S. , GANNON C. , BYRNE M. , O’DONNELL J. S. , JENKINS P. V.
Published: February 2010

Summary.  Up to 40% of patients with mild haemophilia A have a discrepancy whereby factor VIII (FVIII) measurements by a two‐stage chromogenic assay (FVIII:CCH) are disproportionately reduced compared with the FVIII one‐stage clotting value (FVIII:C). Which assay best reflects the coagulation potential and clinical phenotype in this patient group is of clinical significance, yet remains unclear. We have assessed the global coagulant ability of haemophilia patients with FVIII assay discrepancy using calibrated automated thrombography (CAT). A total of 18 patients with mutations Arg531His/Cys or Arg698Trp causing FVIII discrepancy were investigated, together with 12 haemophilia patients with concordant FVIII values and 15 normal controls. Factor VIII levels in all patients and controls were measured using both one‐stage clotting assay and two‐stage chromogenic assay. Thrombin generation was assessed in platelet‐poor plasma by CAT using a low tissue factor concentration (1 pm). FVIII:CCH values were below normal in all patients, and in the discrepant group were between 1.5‐ and 8‐fold lower than FVIII:C values. CAT parameters were affected in all haemophilia patients. The endogenous thrombin potential (ETP) was reduced to 58–67% of the mean normal value (1301 nm min−1), whereas peak thrombin was further reduced to 27–30% of the mean normal value (178 nm) in both discrepant and concordant patient groups. Analysis of the discrepant patient group showed the most significant correlation between the one‐stage FVIII:C assay and ETP (r2 = 0.44) and peak thrombin parameters (r2 = 0.27).
Radioisotope synoviorthesis with Holmium‐166‐chitosan complex in haemophilic arthropathy
Authors: CHO Y. J. , KIM K. I. , CHUN Y. S. , RHYU K. H. , KWON B. K. , KIM D. Y. , YOO M. C.
Published: February 2010

Summary.  Radiosynoviorthesis is a safe and easy method for synovectomy in haemophilic arthropathy. Various agents have been used in radiosynoviorthesis, especially newly developed agent Holmium‐166‐chitosan complex has good clinical outcome. This study analysed clinical results and radiologic evaluation of radioisotope synoviorthesis using Holmium‐166‐chitosan complex in haemophilic arthropathy. From March 2001 to December 2003, 58 radiosynoviorthesis were performed in 53 haemophiliacs. The average age at procedure was 13.8 years. The Arnold and Hilgartner stage of the patients was from I to IV. Holmium‐166‐chitosan complex was injected in 31 ankle joints, 19 elbow joints and 8 knee joints. Average follow‐up was 33 months since primary procedure. The range of motion of each joint, frequency of intra‐articular bleeding and factor dose used were analysed for clinical assessment. There was no significant improvement of range of motion in affected joints. After procedure, the average frequency of bleeding of the elbow joint has decreased from 3.76 to 0.47 times per month, the knee joint from 5.87 to 1.12 times per month, and the ankle joint from 3.62 to 0.73 times per month respectively (P < 0.05). After treatment, the average coagulation factor dose injected was significantly decreased to 779.3 units per month from 2814.8 units per month before treatment (P < 0.001). Radioisotope synoviorthesis with Holmium‐166‐chitosan complex in haemophilic arthropathy is a very safe and simple procedure with the expectation of a satisfactory outcome without serious complication. It has excellent bleeding control effect on target joint and the need for substitution of coagulation factor concentrate can be reduced.
Storage temperature and packaging condition affect the total phenolic content and antioxidant activity of black soybeans and koji
Authors: Huang Ru‐Yue , Wang Yen‐Ju , Sheen Lee‐Yan , Chou Cheng‐Chun
Published: February 2010

In this study, powders of steamed black soybeans and the Aspergillus awamori‐fermented black soybeans (koji) were subjected to storage at 4 °C and 25 °C with or without deoxidant and desiccant for 120 days. It was found that total phenolic content and the antioxidant activity including the DPPH radicals scavenging effect, Fe2+‐chelating ability and reducing activity of the methanol extracts from black soybeans and koji decreased as the storage period was extended. Furthermore, storage temperature and packaging condition affected the antioxidant activity of the methanol extracts of black soybeans and koji. After 120‐day storage, extract from black soybeans holding at 4 °C with deoxidant and desiccant exhibited the highest residual of DPPH radicals scavenging effect, Fe2+‐chelating ability and reducing activity of 71.78%, 72.66% and 70.04%, respectively. Meanwhile, the highest residual of 77.78%, 81.71% and 85.05% respectively, was noted with extract from koji held at 25 °C with deoxidant and desiccant.
Oxidative stability of camelina oil in salad dressings, mayonnaises and during frying
Authors: Eidhin Deirdre Ní , O’Beirne David
Published: February 2010

Oxidative stability of omega‐3 rich camelina oil in food products and during frying was evaluated and compared with sunflower oil. Camelina oil‐based salad dressings were of similar oxidative stability to those prepared with sunflower oil, as indicated by predominantly insignificant (P > 0.05) differences in peroxide values (PV), ρ‐anisidine values (AV), total oxidation values (TOTOX), conjugated diene levels (CD) and conjugated triene levels (CT). However, thiobarbituric acid reactive substances (TBARS) were significantly higher (P < 0.05) for camelina oil and salad dressings throughout storage. Camelina and sunflower oils, alone and in salad dressings or mayonnaises, were acceptable to a sensory analysis panel with slightly lower scores for camelina oil. PV, AV and TOTOX values were similar for camelina and sunflower oil during deep frying but while PVs remained low (<10 meq kg−1), AV and TOTOX values increased quickly. TBARS values were significantly higher in deep‐frying camelina oil and ‘fishy’ odours were observed.
Screening of Bifidobacterium spp. based on in vitro growth responses to bovine lactoferrin
Authors: Morshedur Rahman Md. , Kim Woan‐Sub , Kumura Haruto , Shimazaki Kei‐ichi
Published: February 2010

In the present study, we investigated the in vitro growth responses of fourteen strains of four Bifidobacterium spp. (Bifidobacterium infantis, B. breve, B. bifidum, B. longum) against bovine lactoferrin (bLf) at various concentrations. Bacterial strains were grown in deMan, Rogosa and Sharpe (MRS) broth with or without bLf, and growth was monitored by measuring absorbance at 660 nm. A dose‐dependent and strain‐dependent growth response was observed. Bifidobacterium spp. were ranked into high, medium and low according to their calculated relative growth response levels against lactoferrin (Lf). Strains showed better growth responses against holo‐type Lf. However, no inhibitory effects at high concentrations (4 mg mL−1) or with apo‐type Lf were observed. These results strongly suggest that the growth response of Bifidobacterium spp. against bLf may be a selection criterion for their use in fermented products. In addition, use of holo‐type Lf in fermented food products may be more effective for probiotic growth, and could also be used as a source of iron to the host.
A study of the physicochemical and sensory properties of organic and conventional potatoes (Solanum tuberosum) before and after baking
Authors: Gilsenan Clare , Burke Róisín M. , Barry‐Ryan Catherine
Published: February 2010

The objective of this study was to investigate if there were any differences in the physicochemical and sensory properties of organic and conventional potatoes (cv. Orla). The conventional potatoes had a lower dry matter content (P ≤ 0.05) and a slightly softer texture (P ≤ 0.05) than the organic potatoes. The trained panel perceived the conventional baked potato to be slightly softer, less adhesive and wetter than the organic baked potato (P ≤ 0.05). However, the consumer panel found no significant difference between the organic and conventional baked potato samples for the sensory attributes of appearance, aroma, texture and taste acceptability.
Effects of mineral oil coating on internal quality of chicken eggs under refrigerated storage
Authors: Jirangrat Wannita , Torrico Damir Dennis , No June , No Hong Kyoon , Prinyawiwatkul Witoon
Published: February 2010

The selected internal qualities (weight loss, Haugh unit, yolk index, and albumen pH) of noncoated and mineral oil‐coated chicken eggs during 15 weeks of storage at 4 °C and/or during 5 weeks of storage at 25 °C were evaluated. Results indicated that, without refrigeration, the noncoated and mineral oil‐coated eggs rapidly changed from AA to C and B grades as measured by Haugh unit, respectively, after 5 weeks of storage. However, the AA quality of the noncoated eggs could be maintained under refrigerated storage (4 °C) for at least 5 weeks. The mineral oil coating and refrigerated storage (4 °C) synergistically minimised weight loss and preserved the albumen and yolk qualities of chicken eggs during a long‐term storage. At 4 °C, the mineral oil‐coated eggs preserved the initial AA grade for at least 15 weeks with l.19% weight loss.
Proteolysis and texture changes of a Spanish soft cheese (‘Torta del Casar’) manufactured with raw ewe milk and vegetable rennet during ripening
Authors: Francisco‐José Delgado , Joaquín Rodríguez‐Pinilla , José González‐Crespo , Ramírez Rosario , Isidro Roa
Published: February 2010

Proteolysis and textural changes of the Spanish ewe raw milk soft cheese of the Protected Designation of Origin Torta del Casar were studied in four different stages of ripening, with 1, 30, 60 and 90 days. In general, proteolysis in Torta del Casar cheese was weak at 1 and 30 days and it was more intense between the 30–60 days of ripening. Soluble nitrogen non‐protein nitrogen, polypeptide N and free amino acids values significantly increased during cheese ripening. Protein and casein nitrogen decreased significantly after 60 days of ripening resulting in the increase of the other nitrogen fractions measured. Caseins changes determined by capillary zone electrophoresis showed that proteolysis of β‐casein occurred faster than αs1‐casein but the latter suffered higher proteolytic degradation at the end of ripening (day 90). This pattern of degradation of caseins is reversed in other cheeses made with animal rennet. Texture analysis showed that firmness and consistency decreased along ripening while adhesiveness increased. Highly significant correlations were found between textural parameters, residual caseins levels and nitrogen fractions during maturation, which shows the importance of proteolytic changes for an optimal texture formation.
Characterisation of Argentinean honeys and evaluation of its inhibitory action on Escherichia coli growth
Authors: Fangio Maria Florencia , Iurlina Miriam Ofelia , Fritz Rosalia
Published: February 2010

The aim of this work was to evaluate the physicochemical, sensory and Escherichia coli growth inhibitory characteristics of honey of different botanical sources from two geographic origin of Argentina. Honeys were obtained from apiaries located in two zones. The floral identification of honeys allowed to clustered them as monofloral, mixed and polyfloral honeys. The study of the physicochemical parameters such as colour, free acidity, pH and moisture showed that the last one reflected significant differences between honeys. These differences were markedly reflected in the average values of moisture content for each zone, being 18.96% and 14.29% to centre and east zone, respectively. In general, honeys evaluated presented an inhibitory effect on the E. coli growth at different periods of time (bacteriostatic action). Only, two of the samples would show a bactericide action against E. coli at 48 h of incubation. Honeys with higher non‐hydrogen peroxide activity, were collected from a same geographic place at the same season of year, showing a relationship between the antimicrobial activity and the geographic origin, which could be associated with the typical flora of the place.
Enzymatically modified tea seed oil as cocoa butter replacer in dark chocolate
Authors: Zarringhalami Soheila , Sahari Mohammad Ali , Barzegar Mohsen , Hamidi‐Esfehani Zohreh
Published: February 2010

Cocoa butter replacer (CBR) was prepared by enzymatic interesterification of hydrogenated and solid fraction (SF) of tea seed oil at weight percent ratio of 30:70, using sn‐1,3 specific lipase from Thermomyces lanuginosus. Dark chocolate samples were then prepared with the prepared CBR as a replacement for 5%, 10%, 15% and 20% of cocoa butter (CB) and the effect of the replacement on hardness (as a key quality factor in chocolate) of the chocolate samples was investigated. Results showed that chocolate samples containing 5% and 10% of interesterified sample (EIS), had the closer texture to that of CB chocolate than other samples. The solid fat content (SFC) profiles also revealed that blending 10% of EIS with CB in chocolate formulation dose not affect the sharp melting point of CB. Based on the results taken from bloom formation, polymorphic structure and sensory evaluation, adding up to 10% of EIS in chocolate formulation reduces the bloom development without adverse affecting the desirable β crystal formation and sensory qualities in the chocolate samples.
Desorption isotherms and thermodynamic properties of sweet corn cultivars (Zea mays L.)
Authors: De Oliveira Gabriel Henrique Horta , Corrêa Paulo Cesar , Araújo Eduardo Fontes , Valente Domingos Sárvio Magalhães , Botelho Fernando Mendes
Published: February 2010

The desorption isotherms and thermodynamic properties of two cultivars of sweet corn were obtained during the drying process of these products. The isotherms were determined by a dynamic method for various temperature and humidity conditions. Equilibrium moisture content (Xeq) data were correlated by the Guggenheim–Anderson–de Boer model and an artificial neural network (ANN) model. These models were fitted to the experimental data. The Xeq for corn grain increased with an increase in the relative humidity at fixed temperature and decreased with an increase in temperature at a constant relative humidity. The experimental data were analysed by a thermodynamic approach to obtain the isosteric heat of desorption (ΔH), differential entropy (ΔS), activation energy (Ea) and Gibbs free energy (ΔG). The ΔH and ΔS increased with a decrease in moisture content, while ΔG decreased exponentially with an increase in Xeq. The Arrhenius equation was used to obtain Ea values, with Supersweet corn having higher Ea.
Antioxidant activity of two yeasts and their attenuation effect on 4‐nitroquinoline 1‐oxide induced in vitro lipid peroxidation
Authors: Chen Li‐Shui , Ma Ying , Chen Li‐Jun , Zhao Chang‐Hui , Maubois Jean‐Louis , Jiang Tie‐Ming , Li Hai‐Mei , He Sheng‐Hua
Published: February 2010

To obtain functional yeast with antioxidant ability for food industry, the antioxidant activity of intact cell and intracellular cell‐free extract of Pichia fermentans BY5 and Issatchenkia orientalis BY10 was investigated. Both intact cell and extract of them demonstrated antioxidant activity ranged from 49% to 68%. The ability to scavenge 1, 1‐diphenyl‐2‐picrylhydrazyl free radicals were 12–41%. Furthermore, the reducing activity, Fe2+‐chelating ability, scavenging of reactive oxygen species of extracts illuminated these two isolates had excellent antioxidant ability. And then, the attenuated effect of cell‐free extracts from these two strains was evaluated using 4‐nitroquiunoline 1‐oxide (4‐NQO) as an inducing reagent. The results indicated that the addition of extraction inhibit the lipid peroxidation induced by 4‐NQO, which mainly caused by the protective intracellular protein rather than the polysaccharides. Therefore, these two yeast strains have potential to be utilised for production of functional foods.
Enzymatic production of bioactive protein hydrolysates from tuna liver: effects of enzymes and molecular weight on bioactivity
Authors: Ahn Chang‐Bum , Lee Ka‐Hwa , Je Jae‐Young
Published: February 2010

Tuna liver is fish by‐product, which is normally discarded and/or used as fish meal and animal feed because of poor functionality. In this study, we attempt to recover functional peptides from tuna liver protein by enzymatic hydrolysis using various proteases, and further hydrolysates were fractionated into four categories base on their molecular weight (MW) by ultrafiltration membranes. All fractionated hydrolysates produced by Alcalase, Neutrase and Protamex following Flavourzyme hydrolysis showed excellent antioxidant activities against DPPH, hydrogen peroxide and hydroxyl radical scavenging, and reducing power. Their bioactivity was dependent on treated enzymes, and antioxidant activities of fractions dependent on employing bioassay. Moreover, they confirmed antioxidant ability toward the protection effects on hydroxyl radical‐induced DNA damage by the measuring the conversion of supercoiled pBR322 plasmid DNA to the open circular form. In addition, all fractionated hydrolysates inhibited acetylcholinesterase activity, which is involved in Alzheimer’s diseases, and high MW fractions showed high AChE inhibition activity than those of low MW fractions.
Volatile composition of functional ‘a la Piedra’turrón with propolis
Authors: Narbona Elena , García‐García Elena , Vázquez‐Araújo Laura , Carbonell‐Barrachina Ángel A.
Published: February 2010

‘A la piedra’turrón is the simplest version of turrón and was used as model matrix to add a functional ingredient: bee propolis (0.05%). Propolis possesses antibacterial, antifungal and antiviral properties; however, its flavour is quite intense and not expected in confections. The aroma profiles of control and functional ‘a la piedra’ (ALP) turrón were studied. A total of fifty‐nine compounds were detected, including mainly terpenes (twenty‐one), terpenoids (fourteen) and aldehydes (eight). Most of these compounds come from lemon peel (thirty‐four out of fifty‐nine). However, descriptive sensory analysis proved that other attributes, such as toasted, nutty, cinnamon, sweet and aftertaste, were also of importance. The addition of propolis at the selected ratio did not changed neither the instrumental aroma profile nor the descriptive sensory profile of this confection but will improve its health benefits by incorporating into the consumers’ diet 50 mg propolis per 100 g of functional ALP turrón.