bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of Risk for Venous and Arterial Thrombosis in Primary Antiphospholipid Syndrome and in Antiphospholipid Syndrome with Systemic Lupus Erythematosus
Authors: DANOWSKI ADRIANA , de AZEVEDO MARIO NEWTON LEITÃO , de SOUZA PAPI JOSE ANGELO , PETRI MICHELLE
Published: May 2009

Objective.

Antiphospholipid syndrome (APS) is characterized by thrombosis (venous and arterial) and pregnancy loss in conjunction with the lupus anticoagulant, IgG or IgM anticardiolipin, or IgG or IgM anti-ß2-glycoprotein I. In most series, only a minority of patients with antiphospholipid antibodies develop a clinical manifestation.

Methods.

A cross-sectional study of consecutive patients in the Hopkins Lupus Center was performed. Interviews were done and records were reviewed for the following variables: gender, ethnicity, hypertension, triglycerides, cholesterol, smoking, diabetes mellitus, homocysteine, cancer, hepatitis C, hormone replacement therapy/oral contraceptives, hereditary thrombophilia, anticardiolipin antibodies IgG, IgM and IgA, and lupus anticoagulant (LAC). Our aim was to identify risk factors associated with thrombosis and pregnancy loss in patients with antiphospholipid antibodies.

Results.

A total of 122 patients (84% female, 74% Caucasian) were studied. Patients were divided into 3 groups: primary APS, APS associated with systemic lupus erythematosus, and patients with systemic lupus erythematosus (SLE) with antiphospholipid antibodies but no thrombosis or pregnancy loss. Venous thrombosis was associated with high triglycerides (p = 0.001), hereditary thrombophilia (p = 0.02), anticardiolipin antibodies IgG > 40 (p = 0.04), and LAC (p = 0.012). Hypertriglyceridemia was associated with a 6.4-fold increase, hereditary thrombophilia with a 7.3-fold increase, and anticardiolipin IgG > 40 GPL with a 2.8-fold increase in the risk of venous thrombosis. Arterial thrombosis was associated with hypertension (p = 0.008) and elevated homocysteine (p = 0.044). Hypertension was associated with a 2.4-fold increase in the risk of arterial thrombosis. No correlations were found for pregnancy loss.

Conclusion.

The frequency of thrombosis and pregnancy loss is greater in APS associated with SLE than in primary APS. Risk factors differ for venous and arterial thrombosis in APS. Treatment of hypertension may be the most important intervention to reduce arterial thrombosis. Elevated triglycerides are a major associate of venous thrombosis, but the benefit of treatment is not known. Hereditary thrombophilia is an associate of venous but not arterial thrombosis, making it cost-effective to investigate only in venous thrombosis.
Poor Validation of Medical Record ICD-9 Diagnoses of Gout in a Veterans Affairs Database
Authors: MALIK AARTI , DINNELLA JANET E. , KWOH C. KENT , SCHUMACHER H. RALPH
Published: May 2009

Objective.

Diagnostic codes based on medical records or claims data have been used to identify patient populations with gout for important epidemiologic and clinical studies. We evaluated whether we can document the accuracy of such diagnoses by review of medical records and then on direct interviews with a subset of patients.

Methods.

Electronic medical records of 289 patients with 2 visits with ICD-9 codes for gout were extensively reviewed to search for documentation of features that would classify patients as having gout by 3 sets of proposed criteria, the American College of Rheumatology (ACR), New York, or Rome criteria. Records of patients who had been seen by rheumatologists were compared with all others. A subset of patients seen in clinic were directly interviewed for comparison with the results from the records.

Results.

Based on medical records review there was documentation of gout by the ACR criteria in only 36%, Rome criteria in 30%, and New York criteria in 33%. Records of patients who had seen rheumatologists had better documentation of classification features. Interview in clinic of 37 patients also improved documentation of the 3 sets of criteria features of gout in 65%–81% of those with ICD-9 codes for gout.

Conclusion.

We found it difficult to confirm ICD-9 coded diagnoses of gout using currently available proposed criteria from details recorded in medical records. This may reflect a problem with available criteria and with documentation. Direct interview of patients may be needed to confirm the presence of typical features when high specificity is desired.
Land-based Exercise for Osteoarthritis of the Knee: A Metaanalysis of Randomized Controlled Trials
Authors: FRANSEN MARLENE , McCONNELL SARA
Published: May 2009

Objective.

To determine if clinical guidelines recommending therapeutic exercise for people with knee osteoarthritis (OA) are supported by rigorous scientific evidence. To explore whether the magnitude of treatment benefit reported in randomized controlled trials (RCT) is associated with exercise dosage or study methodology.

Methods.

We conducted a metaanalysis of RCT comparing some form of land-based therapeutic exercise with a nonexercise group using pain and self-reported physical function outcomes.

Results.

The 32 included studies provided data on almost 3800 participants. Metaanalysis revealed a beneficial treatment effect: standardized mean difference (SMD) 0.40 [95% confidence interval (CI) 0.30 to 0.50] for knee pain; SMD 0.37 (95% CI 0.25 to 0.49) for physical function. While the pooled beneficial effects of the 9 RCT evaluating exercise programs providing fewer than 12 direct supervision occasions or the 9 RCT judged to have a low risk of bias remained significant and clinically relevant, the magnitude of treatment benefit pooled from these RCT was significantly smaller than the comparator group (12 or more supervision occasions, moderate to high risk of bias, respectively). The mode of treatment delivery (individual treatments, exercise classes, home program) was not significantly associated with the magnitude of treatment benefit.

Conclusion.

There is evidence that land-based therapeutic exercise has at least short-term benefit in terms of reduced knee pain and physical disability for people with knee OA. The magnitude of the treatment effect was significantly associated with the number of direct supervision occasions provided and study methodology (assessor blinding, adequate allocation concealment).
Anakinra for Rheumatoid Arthritis: A Systematic Review
Authors: MERTENS MARTY , SINGH JASVINDER A.
Published: May 2009

Objective.

To perform a systematic review of clinical effectiveness and safety of anakinra in rheumatoid arthritis (RA).

Methods.

We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and the reference lists of included articles for randomized controlled trials comparing anakinra to placebo in adults with RA.

Results.

Five trials involving 2846 patients, 781 randomized to placebo and 2065 to anakinra, were included. There was a significant improvement in the number of participants achieving American College of Rheumatology (ACR)20 (38% vs 23%) treated with anakinra 50–150 mg daily versus placebo after 24 weeks. ACR50 (18% vs 7%), ACR70 (7% vs 2%), Health Assessment Questionnaire, visual analog scale for pain, Larsen radiographic scores, and erythrocyte sedimentation rate all demonstrated significant improvement with anakinra versus placebo as well. There were no statistically significant differences noted in the number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). An increase in incidence of serious infections in anakinra versus the placebo group (1.8% vs 0.6%) was noted that may be clinically significant. Injection site reactions were significantly increased, occurring in 71% of anakinra versus 28% of placebo group.

Conclusion.

Anakinra is a relatively safe and modestly efficacious biologic therapy for RA. More studies are needed to evaluate safety and efficacy, especially in comparison to other therapies, and adverse event data for the longterm use of anakinra have yet to be assessed.
Calculation of contaminant distribution in tree and ground nuts
Authors: Toyofuku N. , Schatzki T.
Published: May 2009

A comparison of two different calculational methods is presented to predict the sample distribution P(C;N) of
granular products at any sample size, from an experimental distribution at a single N. The Negative Binomial
density distribution can handle any N that is large with respect to the test size, but is limited to the precision of
two parameter functions. Its application is simple and rapid, particularly at large λ, and useful for obtaining the lot
average concentration, . The non-parametric method can handle any approximation to the experimental data.
It is treated as a sum of Poisson (or multinomial) distributions with varying λl =Np
l , where p
l is the probability of
a kernel containing contaminant in a range of c. This method is currently restricted to λl <2, and is more laborious
than the Negative Binomial. It is ideal for discerning small changes in P(C;N) at small N, indicative of the effects
of production, processing and sorting. These methods were applied to the analysis of contamination in assorted
processed and unprocessed pistachios, almonds, and peanuts. For this paper, the method is illustrated using
aflatoxin contamination of various commodities, but the method can be applied to any contaminant of a granular
commodity. The sparse approximation for distributions (λl <0.1), previously postulated, was verified. P(C;N) at low
C was established in all cases, leading to a much clearer understanding of the source of contamination. The overall
shapes of P(C;N) at low N were alike among tree nuts and among two very different peanut lots. Where available,
test data at widely spaced N were consistent with calculated results. In one pistachio lot, the change of P(C;N) upon
image sorting indicated a hitherto unknown contamination source. The methods show great applicability for risk
analysis and developing sampling protocols.
Aflatoxins evaluation on in-shell and shelled dry Brazil nuts for export analysed by LC-MS/MS - 2006 and 2007 harvests
Authors: Pacheco A. , Scussel V.
Published: May 2009

Dry in-shell and shelled Brazil nuts from two different harvests were evaluated for aflatoxins by LC-tandem mass
spectrometry with atmospheric pressure chemical ionisation in the positive mode. A total of 171 samples of Brazil
nuts for export, comprising 108 in-shell and 63 shelled (large, medium and small sizes) were collected in a factory
located at Manaus city, State of Amazonas, in the Brazilian Amazon. They were collected from big bags (in-shell
nuts) and sorting tables after size classification (shelled nuts), immediately after processing, from April to May of
2006 and 2007. Samples also had their moisture content (mc) and water activity (aw) analysed and the out- and
in-door environmental conditions (relative humidity (RH) and temperature) were monitored during the sampling
period. From all the samples analysed from both harvests, only 8.7% (14) of the nuts contained aflatoxin at levels
>4 µg/kg (EU maximum level). This corresponded to a total number of 11 and 3 for the in-shell and shelled nuts,
respectively. The 2007 harvest nuts had fewer samples with aflatoxin levels higher than 4 mg/kg, with 2 for both
in-shell and shelled nuts each. The analytical method was selective, sensitive and fast (total run time of 7 min). The
RH in the factory ranged from 77.1 to 95.8% (2006) and 76.9 to 91.0% (2007) being the highest RH reached in April.
The data showed that the nuts' aflatoxin levels varied with the year of harvest and cleared up the speculation about
which type of dried nut has aflatoxin levels safe enough for commercialisation.
Ochratoxin A in wine consumers in Italy: dietary profiles
Authors: Gambelli L. , D'Addezio L.
Published: May 2009

The study was carried out on a group of wine consumers, healthy adults, living in one of the areas in Southern
Italy, where the ochratoxin A (OTA) levels in wines were very high. OTA levels in consumed wine ranged from 0.2
to 2 ng/ml for 80% of the samples and from 2.10 to 5.40 ng/ml for the other 20%. OTA values in blood (exposure)
were lower than 0.28 ng/ml for 30% of the subjects, ranged from 0.28 to 0.34 ng/ml for 43% of the subjects, and
reached more than 0.34 ng/ml for 27% of the subjects. Mean OTA measured in urine was 0.43 ng/ml. No significant
correlation was found between OTA concentration in blood and in consumed wine, neither between OTA in
blood and ingestion levels. OTA levels were determined by HPLC. Individual food consumption habits, gathered
in a questionnaire, were studied in association with experimental exposure by means of multiple correspondence
analysis. Subjects consuming one or two glasses of red home-produced wine daily were characterised by medium
exposure, while those consuming three glasses or half a litre per occasion showed a high exposure; low exposure
was associated with weekly consumption of white commercial wine. High quantities of beer and daily consumption
of bread and pasta characterised habitual wine consumers, while weekly consumption of beer, bread and chocolate
characterised moderate wine consumers.
Mycotoxins and skeletal problems in poultry
Authors: Devegowda G. , Ravikiran D.
Published: May 2009

Bone problems are a major threat in meat-type and breeder poultry globally, raising both welfare and economic
concerns. Leg weakness is multifactorial in origin and can be influenced by management, genetics, environment,
nutrition and mycotoxins. Various mycotoxins, singly and severally, are known to exert an adverse effect on bone
metabolism leading to leg weakness. Leg weakness in poultry as caused by mycotoxins and its alleviation is reviewed.
A reappraisal of fungi producing aflatoxins
Authors: Varga J. , Frisvad J. , Samson R.
Published: May 2009

Aflatoxins are decaketide-derived secondary metabolites which are produced by a complex biosynthetic pathway. Aflatoxins are among the economically most important mycotoxins. Aflatoxin B1exhibits hepatocarcinogenic and hepatotoxic properties, and is frequently referred to as the most potent naturally occurring carcinogen. Acute aflatoxicosis epidemics occur in several parts of Asia and Africa leading to the death of several hundred people. Aflatoxin production has incorrectly been claimed for a long list ofAspergillusspecies and also for species assigned to other fungal genera. Recent data indicate that aflatoxins are produced by 13 species assigned to three sections of the genusAspergillus: sectionFlavi(A. flavus, A. pseudotamarii, A. parasiticus, A. nomius, A. bombycis, A. parvisclerotigenus, A. minisclerotigenes, A. arachidicola), sectionNidulantes(Emericella astellata, E. venezuelensis, E. olivicola) and sectionOchraceorosei(A. ochraceoroseus, A. rambellii). Several species claimed to produce aflatoxins have been synonymised with other aflatoxin producers, includingA. toxicarius(=A. parasiticus),A. flavusvar.columnaris(=A. flavus) or A.zhaoqingensis(=A. nomius). Compounds with related structures include sterigmatocystin, an intermediate of aflatoxin biosynthesis produced by several Aspergilli and species assigned to other genera, and dothistromin produced by a range of non-Aspergillusspecies. In this review, we wish to give an overview of aflatoxin production including the list of species incorrectly identified as aflatoxin producers, and provide short descriptions of the 'true' aflatoxin producing species.
Effect of sporidesmin-induced liver damage in ewes before mating on growth of the foetus and placenta
Authors: Oliver M. , Harding J.
Published: May 2009

Sporidesmin is a fungal toxin commonly found in pasture. It causes liver damage in sheep that resembles cholestasis in humans. We determined whether pre-mating sporidesmin-induced liver damage in ewes might provide a useful approach to the experimental induction of intrauterine growth restriction (IUGR). Romney ewes were drenched with sporidesmin extracts. Affected ewes (SP, n=44) and controls (CN, n=42) were mated. Sporidesmin treatment decreased pregnancy rate (non-pregnant; SP 43% vs. CN 12%, twin; SP 23% vs. CN 52%, both P<0.05). SP foetuses were 6% lighter than CN foetuses at 89 days of gestation, but not at 134 days. Increasing maternal plasma gamma glutamyl transferase activities at mating were associated at 89 days with reduced maternal weight (-1.1: -1.9, -0.3 kg/100 U/l, mean effect size: 95% confidence intervals), increased visual liver damage and reduced placentome number (-1.4: -2.7, -0.1/100 U/l) and foetal pancreatic weight (-21: -38, -4 mg/100 U/l). They were also associated at 134 days with reduced weight of the foetal pancreas (-132: -221, -42 mg/100 U/l), spleen (-139: -231, -47 mg/100 U/l) and thyroid (-29: -48, -10 mg/100 U/l) and decreased A-type placentomes (-3.0: -5.0, -1.0/100 U/l). Pre-mating sporidesmin-induced liver damage is not useful for induction of experimental IUGR but does impair the growth of the foetal pancreas, spleen and thyroid and alter placental morphometry.
Ergot alkaloids: extent of human and animal exposure
Authors: Scott P.
Published: May 2009

Ergot alkaloids are formed by Claviceps spp. on grains and grasses and by fungal endophytes such as Neotyphodium
spp. in grasses, notably tall fescue and perennial ryegrass. Ergots from grains and grasses show a wide variation in
alkaloid composition. The main ergot alkaloids are pharmacologically active lysergic acid derivatives – e.g. ergometrine
(ergonovine), ergotamine, ergosine, ergocornine, α-ergocryptine, ergocristine, and ergovaline; derivatives of isolysergic
acid, e.g. ergotaminine; and clavine alkaloids, e.g. agroclavine. Other structurally unrelated toxic alkaloids
such as lolitrems are formed by fungal endophytes in grasses. The present review focuses more on how man and
animals are exposed to ergot alkaloids than on toxicology and methods of analysis. Ergot poisoning in humans, well
known in the Middle Ages, can be of two types: convulsive ergotism and gangrenous ergotism. Since the beginning
of the last century there have been outbreaks in Russia, England, India, France and Ethiopia. The principal route
of human exposure to ergot alkaloids is by consumption of contaminated food; another route is inhalation of grain
dust. Toxicoses in animals due to ergot alkaloids are more common, particularly poisoning of livestock grazing on
endophyte infected grasses. Analyses in Canada, Germany, Switzerland, Sweden and Denmark found ergot alkaloids
in human foods such as wheat and rye flours, bread, and other grain foods, often at levels greater than 1000 µg/kg.
Processing studies have confirmed that the alkaloids survive baking; they also remain to some extent after brewing
of beer. There is little evidence for carryover of ergot alkaloids into animal tissue and milk. As an indication of the
importance of controlling ergot for the health of animals and people, Canada, the European Union, Switzerland,
USA, Japan, Australia and New Zealand have regulations for ergot in grains but only Uruguay and Canada have
regulations for the actual ergot alkaloids in feed.
Biosensors for mycotoxin analysis: recent developments and future prospects
Authors: Maragos C.
Published: May 2009

The toxicity and prevalence of mycotoxins in commodities and foods has necessitated the development of rapid methods in order to ensure the protection of human food and animal feed supplies. Testing for mycotoxins can be accomplished by many techniques that range from determinative tests in which the presence of the toxin is confirmed, to presumptive tests in which the presence of the toxin is inferred from the presence of markers. This review focuses on tests that fall into a third category, namely indirect assays, where the presence of the toxin is established by it's interaction with an intermediary. Such intermediaries include biological materials that bind mycotoxins, such as antibodies, as well as synthetic materials such as polymers and man-made peptides. The diversity of assays within this category is extraordinary and includes assays based upon traditional microwell formats, microbeads, membranes, electrodes, wave-guides, and solution-phase assays. The microbead format includes platforms as diverse as flow injection immunoassays, tandem column immunoassays, and immunoaffinity columns. The membrane-based formats include flow-through as well as lateral-flow assays. The electrode-based formats incorporate miniaturised immunoassays with electrochemical endpoints. The wave-guide-based devices include formats such as surface plasmon resonance, and fluorescence array biosensors, and the solution phase formats include homogeneous assays such as fluorescence polarisation immunoassay. The breadth of technologies brought to bear upon solving the need for rapid, accurate, detection of mycotoxins is impressive and includes technologies currently available commercially and those which appear poised to enter the marketplace.
HT-2 toxin and T-2 toxin in commercial cereal processing in the United Kingdom, 2004-2007
Authors: Scudamore K. , Patel S. , Edwards S.
Published: May 2009

Legislation for mycotoxins in the European Union is being considered for T-2 toxin (T-2) and HT-2 toxin (HT-2). A four-year study on the fate of Fusarium mycotoxins in commercial milling and processing of cereals examined the incidence and concentrations of T-2 and HT-2 in wheat, oats and maize at intake to United Kingdom mills and during subsequent processing. Levels in wheat and maize were low and were not found in maize from Argentina although they did occur in some French consignments of maize. However, every sample of oats was contaminated with levels >20 µg/kg up to 1,600 and >3,000 µg/kg of T-2 and HT-2 respectively, the highest being found in consignments from the United Kingdom and Ireland while levels from Scandinavia were usually lower. Because of the low incidence and concentrations little information could be obtained on their fate during milling and food processing although their distribution in milling streams of wheat and maize was similar to that for other mycotoxins. In oats, most of the mycotoxins were found in the hulls after their removal from the groats so that levels in oats flakes produced from the groats never exceeded 65 and 55 µg/kg respectively. De-hulling of oats thus resulted in a co-product in which mycotoxins were concentrated, >100 µg/kg each of T-2 and HT-2. Two samples analysed for T-2 and 15 for HT-2 contained residues >1000 µg/kg, with maxima of 6,100 and 24,000 µg/kg respectively. Removal of discoloured oat groats by colour sorting reduced mycotoxin levels in the oat flake end product. Manufacture of batches of retail products from wheat and maize resulted in one snack product in which HT-2 at 12 µg/kg was detected. T-2 and HT-2 were undetected in other products. HT-2 was detected in 2 samples of the aqueous liquid drained from cookers during breakfast cereal manufacture.
Biological management of Fusarium head blight and mycotoxin contamination in wheat
Authors: Xue A. , Voldeng H. , Savard M. , Fedak G.
Published: May 2009

Fusarium head blight (FHB), caused by Gibberella zeae is a harmful disease of wheat. To manage FHB and mycotoxin
contamination in wheat, field experiments were conducted from 2007 to 2008 to evaluate a total of 20 selected bioagents
for their ability to inhibit perithecial production of G. zeae and for the control of FHB and deoxynivalenol (DON)
contamination, in comparison with the registered fungicide Folicur (tebuconazole). All 20 bioagents significantly
reduced the perithecial production compared to the untreated control. Clonostachy rosea strain ACM941 was the
most effective treatment, reducing the production of perithecia by 63.7% in 2007 and 67.5% in 2008. These effects
were significantly better than Folicur fungicide, which reduced perithecial production by 30.4% and 20.5%, for 2007
and 2008, respectively. When sprayed on to wheat heads, seven of the 20 bioagents significantly reduced the FHB
index, one reduced Fusarium damaged kernels (FDK), and six reduced DON content in grains in 2007. ACM941 was
the only treatment that significantly reduced FHB index, FDK, and DON, by 46.4%, 29.0% and 28.7%, respectively.
Among the six bioagents and three formulated products evaluated in two separate field trials in 2008, ACM941
and its formulated product ACM941-CU were the only treatments that significantly reduced FHB index, FDK,
and DON. The treatments reduced FHB index by 30.8% and 31.4%, FDK by 17.8% and 43.8%, and DON by 30.8%
and 37.1%, for ACM941 and ACM941-CU, respectively. These effects were less marked than those of the Folicur
fungicide that reduced FHB index by 98.8%, FDK by 94.2%, and DON by 92.1%. Results of this study suggest that
ACM941 is a promising bioagent against G. zeae and may be used as a control measure in organic farming and in
an integrated FHB and DON management program for wheat production.
Development of a European system for identification of emerging mycotoxins in wheat supply chains
Authors: van der Fels-Klerx H. , Kandhai M. , Brynestad S. , Dreyer M. , Börjesson T. , Martins H. , Uiterwijk M. , Morrison E. , Booij C.
Published: May 2009

This paper describes the results of a research project aimed at the conceptual development of an identification system
for emerging mycotoxins in European feed and food supply chains of wheat. Basic requirements for such a system
were addressed, including the selection of indicators, locating information sources, development of underlying
model, and investigation of stakeholders' needs. The selection and ranking of key indicators for identifying emerging
mycotoxins was based on a literature review, followed by a structured expert judgment study. The expert study
was based on the Delphi technique and used a panel of 43 European experts. The Delphi procedure resulted in
a selected set of 12 key indicators for each of three relevant stages of the wheat chain (cultivation; transport and
storage; processing). For wheat cultivation, these were: relative humidity/rainfall, crop rotation, temperature, tillage
practice, water activity in the kernels, crop variety, harvest conditions, changes in fungal populations, fungicide
use, plant health, regional infection pressure and food safety awareness. For the majority of the selected indicators,
information sources were identified in specific European countries. However, most sources are not readily accessible
and particular data is lacking. A theoretical concept for a model underlying the envisioned emerging mycotoxin
identification system has been developed. The model links the key indicators and their information sources to aid
and promote identification of emerging mycotoxins. It manages different types of information sources and levels of
available information. The needs of various stakeholder groups regarding the system were investigated by means of
two empirical elicitation sessions. The results showed that all stakeholders considered that such a system would be
beneficial. One major challenge expected in establishing the system is stakeholder commitment to sharing data and
information. This requires great efforts in improving communication and interaction between the key stakeholders.
What about the 'other' Fusarium mycotoxins?
Authors: Jestoi M. , Kokkonen M. , Uhlig S.
Published: May 2009

Most Fusarium species are capable of producing mycotoxins that may cause adverse effects on human or animal health.
The most commonly studied Fusarium mycotoxins include trichothecenes, zearalenone and fumonisins. However,
it seems that nearly all of the most prevalent Fusarium species infecting grains are also capable of producing other
toxic metabolites. The existing studies, although exiguous, have clearly demonstrated that other toxic metabolites
of Fusarium spp. are also present in our foods and feeds, occasionally at very high levels. It is apparent that since
mycotoxins, including these 'other' metabolites, are natural toxins, they cannot be completely eliminated from food
and feed chains. However, scientific studies are needed to determine their true significance. Thus, the mechanism
and level of toxicity as well as presence and concentration levels will have to be fully clarified. In this paper, we briefly
review the prevalence of the dominant Fusarium species contaminating maize and small-grain cereals worldwide,
and the current knowledge on the biological activity as well as the natural occurrence of their selected less-known
toxic metabolites. Additionally, the significance of these 'other' Fusarium mycotoxins is discussed.
Emerging issues of HT-2 and T-2 toxins in European cereal production
Authors: Edwards S. , Barrier-Guillot B. , Clasen P-E. , Hietaniemi V. , Pettersson H.
Published: May 2009

HT-2 and T-2 toxins are two of the most potent trichothecenes; they have a combined (HT-2+T-2) temporary Tolerable
Daily Intake (TDI) of 0.06 µg/kg body weight/day. The distribution of HT-2 and T-2 appears to be largely restricted
to Europe. Of the cereal species, HT-2 and T-2 usually have higher incidences and concentrations on oats followed by
barley and then wheat, however, this can vary between countries. Survey data from Nordic countries have indicated
that these mycotoxins have increased in recent years, reaching concentrations of >1000 µg/kg HT-2+T-2 in some
samples. HT-2 and T-2 have also been detected in malting barley in France, and in particular in spring sown varieties.
A newly identified species, Fusarium langsethiae, has been implicated as a producer of HT-2 and T-2 in European
cereals. There is limited data available regarding this species' pathogenicity and mycotoxin production. The impact
of agronomy on the concentration of HT-2 and T-2 in cereals has not been clearly identified, but it is evident that
it is different to the impact of agronomy on deoxynivalenol. Processing of cereals can have a major impact on the
HT-2 and T-2 content of cereals. Oats are de-hulled during processing for human consumption; de-hulling reduces
the mycotoxin content of oats by more than 90%. During the malting and brewing of barley the concentration of
HT-2 and T-2 increases and decreases within various stages of the processes and the final mycotoxin load of beers
will depend on the individual processes used by each maltster and brewer. Whether these mycotoxins are an issue
for human health cannot be determined until a full TDI is calculated based on more long-term exposure studies,
and human exposure levels are calculated from surveys of retail products using new, highly sensitive assays.
Dietary glucomannan improves the vaccinal response in pigs exposed to aflatoxin B1 or T-2 toxin
Authors: Meissonnier G. , Raymond I. , Laffitte J. , Cossalter A. , Pinton P. , Benoit E. , Bertin G. , Galtier P. , Oswald I.
Published: May 2009

The aim of the study was to investigate whether dietary supplementation with yeast-derived glucomannan protects pigs against the deleterious effects that exposure to aflatoxin B1(AFB1) or T-2 toxin has on the vaccinal immune response and drug-metabolising enzymes. Three doses of pure mycotoxin (AFB1trial: 482, 968 and 1,912 µg/kg feed; T-2 toxin trial: 593, 1,155 and 2,067 µg/kg feed) with or without dietary glucomannan supplementation (2 g/ kg feed) were tested in weaned pigs for 28 days. At days 4 and 15 pigs were immunised with ovalbumin to study the humoral and cell-mediated antigen-specific immune responses. The effects of AFB1and T-2 toxin intake alone in pigs have already been published. In all parameters investigated no differences were apparent between animals receiving the unsupplemented control diet or the control diet containing glucomannan. In the AFB1trial glucomannan decreased the severity of liver lesions in animals exposed to 968 µg/kg feed. Exposure to both AFB1and T-2 toxin were associated with impaired phase I liver enzyme activities, but glucomannan demonstrated a limited protective effect on these enzymes. With regard to the immune defence system, both toxins modulated the vaccinal immune response; AFB1impaired specific cellular response and T-2 toxin the specific humoral response. Glucomannan supplementation restored the ovalbumin-specific lymphocyte proliferation that was delayed in pigs exposed to AFB1, regardless of dose. In the T-2 toxin trial glucomannan supplementation restored anti-ovalbumin immunoglobulin G production, which was significantly reduced in pigs exposed to both medium and high doses of the toxin. In conclusion, glucomannan dietary supplementation demonstrated no deleterious effects in control animals and protective effects against AFB1and T-2 toxin immunotoxicity during a vaccinal protocol.
Management options, technologies and strategies for minimised mycotoxin contamination of rice
Authors: Gummert M. , Balingbing C. , Barry G. , Estevez L.
Published: May 2009

Ninety percent of the world's rice is produced and consumed in Asia. Millions of rice producers are resource-poor
farmers with a rice area of less than one hectare. Yield increase and the introduction of double-cropping systems
have ensured that rice production has kept up with an increasing demand. However, the increased quantities of
grain and the second harvest, which is often in the wet season, have increased the problems in traditional postharvest
systems. This can be particularly severe in the humid tropics, where post-harvest losses occur because of
outdated management practices and technologies, and delays in post-harvest operations. Fungal infestation of rice
grains can lead to discoloration, which results in price reductions in most markets. This can also result in rice being
contaminated with mycotoxins, which is less visible to consumers. Contamination with ochratoxins, aflatoxins, and
other mycotoxins have occasionally been reported in the literature. In the past, this was not seen as a significant
problem and the focus was on other commodities such as maize and peanuts. However, recent studies and a massive
recall of food products in Japan in September 2008, including sake, shoshu, and rice crackers made from imported
rice from China and Vietnam, which were tested positive for aflatoxins, and also for pesticide residues, have renewed
interest in looking at mycotoxin problems in rice. Exploratory studies in the Philippines compared best practice
post-harvest management with the traditional management practices often used by smallholder farmers and small
processors. It was concluded that synthesis of aflatoxin B1 is very likely in suboptimal post-harvest systems, with
levels far above legislative limits. This indicates that there might be a considerable mycotoxin problem in rice from
smallholder post-harvest operations. Improved post-harvest management options and technologies are available
for diversified small-scale post-harvest systems. Small-scale combine harvesters, affordable and simple mechanical
dryers and hermetic storage systems can help to avoid delays in the post-harvest chain and thus reduce mycotoxin
contamination of rice. The development of strategies to scale out these improved practices and technologies to a
large number of smallholder farmers will continue to be the main challenge.
Fusarium mycotoxins in the food chain: maize-based snack foods
Authors: Scudamore K. , Scriven F. , Patel S.
Published: May 2009

The fate of deoxynivalenol (DON), zearalenone (ZEA) and fumonisins B1 (FB1) and B2 (FB2) were examined in
three representative snack food production methods. Assessing results on an 'as is' basis so as to compare results
with EC legislation showed DON to be the most stable mycotoxin during the manufacture with mean levels in
each finished products >68% of the levels in the starting ingredients. The concentrations of ZEA in the snack food
ingredients during this study were very low but did allow limited studies that showed a mean 52% reduction during
the manufacture of one snack product, but little reduction when producing a tortilla chip. In contrast, fumonisins
were mostly lost (>90%) in two out of the three processes. However in a tortilla chip prepared from maize flour by
extrusion, heating and frying, the amount of FB1 + FB2 remaining in the retail product was reduced on average by
59% which is similar to the 60% difference in the statutory levels for flour (products <500 micron) or 50% difference
for grits (products >500 micron) and retail snack products. Thus the use of maize containing fumonisins in maize
flour at levels just meeting legal limits would present some risk that a proportion of retail products might fail to
meet legislation when the run to run variability is considered. The buyer/processor should thus avoid ingredients
containing mycotoxin levels close to legislatory limits for use in processes where reduction at successive stages in
manufacture are close to or less than those in the legislation. It is suggested that this study provides a useful indication
of these. In commercial operation, there is a reluctance to specify raw materials at anything but the finishing product
levels with implications for availability and cost.
Direct electrochemical detection of trichothecenes in wheat samples using a 96-well electrochemical plate coupled with microwave hydrolysis
Authors: Ricci F. , Pino F. , Abagnale M. , Messia M. , Marconi E. , Volpe G. , Moscone D. , Palleschi G.
Published: May 2009

The use of a 96-well electrochemical plate for the fast and sensitive detection of deoxynivalenol and nivalenol in
wheat samples is shown. Deoxynivalenol and nivalenol are hydrolysed using a microwave hydrolysis procedure (2
min) which leads to the production of electroactive compounds that can be sensitively detected by the use of cheap
screen-printed electrodes. A procedure of extraction with aqueous acetonitrile and a clean-up step was demonstrated
to be suitable for the application with wheat samples providing suitable detection limit (LOD=1.1 µg/g) and working
range (2-20 µg/g) for the determination of deoxynivalenol in cereals for feed consumption.
Transgenic approaches for pre-harvest control of mycotoxin contamination in crop plants
Authors: Cary J. , Rajasekaran K. , Yu J. , Brown R. , Bhatnagar D. , Cleveland T.
Published: May 2009

Mycotoxins are fungal metabolites that can contaminate food and feed crops worldwide and are responsible for toxic effects in animals and humans that consume contaminated commodities. Regulatory guidelines and limits for mycotoxins have been set by the US Food and Drug Administration (FDA) and food safety agencies of other countries for both import and export of affected commodities. Mycotoxin contamination of foods and feeds can also cause serious economic hardships to producers, processors, and the consumer. Therefore, there has been a concerted effort by researchers worldwide to develop strategies for the effective control of mycotoxin contamination of crops, particularly at the pre-harvest stage. Strategies currently being utilised to combat pre-harvest mycotoxin contamination include: (1) use of non-toxigenic biocontrol strains; (2) improved agricultural practices; (3) application of agrochemicals; (4) plant breeding for resistance; and (5) genetic engineering of resistance genes into crop plants. This article highlights research on the genetic engineering of plants for resistance to invasion by mycotoxigenic fungi as well as detoxification of mycotoxins. Emphasis is placed on the most economically relevant fungi and the mycotoxins they produce. These include aflatoxins produced mainly byAspergillus flavusandA. parasiticus, trichothecenes produced mainly byFusarium graminearum, and to a lesser extent, fumonisins produced byF. verticillioides. Information is also presented on the use of genomics and proteomics technologies as a means of identifying genes and proteins that can be utilised in transgenic approaches to control the growth of mycotoxigenic fungi and the mycotoxins that they produce in food and feed crops.
Assessment of oral cytological changes associated with exposure to chemotherapy and/or radiotherapy
Authors: Ahmed Hussain G , Elemirri Dalia AI
Published: May 2009

Background:

Death from cancer is high in Sudan, with low survival rates, as most of the patients present with advanced disease. Most patients receive high and repeated doses of radiotherapy or chemotherapy. The aim of this study was to investigate the feasibility of using cytological evaluation to detect oral epithelial atypia amongst these patients. As a part of the continuous development in cancer therapy, this case control study was conducted in Khartoum, Sudan.

Methods:

Papanicolaou stained oral mucosal cells were obtained from 100 cancer patients receiving radiotherapy and/or chemotherapy (ascertained as cases), 50 cancer patients not exposed to either therapy (control 1), and 50 apparently healthy individuals (control 2).

Statistical analysis:

The data was analyzed by using a computer SPSS program, to obtain the Chi-square test.

Results:

Without prior knowledge of the subjects' group, oral epithelial atypia was detected in 7% of the cases. Inconclusive features of cytological atypia were observed in 13% of the cases. Atypia was not observed in both the control groups. Inflammatory infiltrate and viral cytopathic effects were identified in 32% and 8% of the cases respectively.

Conclusion:

Cytological atypia, viral infections, and inflammatory infiltrates were detected after exposure to radiotherapy and/or chemotherapy.
Cu(II)‐Azabis(oxazoline)‐Complexes Immobilized on Superparamagnetic Magnetite@Silica‐Nanoparticles: A Highly Selective and Recyclable Catalyst for the Kinetic Resolution of 1,2‐Diols
Authors: Schätz Alexander , Hager Markus , Reiser Oliver
Published: May 2009

Two different types of azide functionalized magnetite@silica nanoparticles are synthesized, which are ideally suited as inexpensive supports for catalysts and reagents as demonstrated with the grafting of copper(II)‐azabis(oxazoline) complexes via a copper(I) catalyzed azide/alkyne cycloaddition (CuAAC) reaction. The potential of the immobilized complexes as catalysts is tested in the desymmetrization of racemic 1,2‐diols through asymmetric benzoylation. Compared to azabis(oxazolines) “clicked” to common polymeric supports such as MeOPEG or Merrifield resin, Fe3O4@SiO2 proves to be superior with respect to activity and selectivity, as exemplified by employing the catalysts in up to five runs with consistent high activity and selectivity. Recycling of the catalysts is achieved quantitatively by magnetic decantation.
Improved protein splicing reaction for low solubility protein fragments without insertion of native extein residues
Authors: Kamioka Tetsuya , Tawa Minako , Sohya Shihori , Yamazaki Toshio , Kuroda Yutaka
Published: May 2009

Application of trans protein splicing has been limited both by solubility problems and by the insertion of native extein residues (NERs) at the splicing site. Here, we report two simple methods for overcoming these problems and increasing the yield and activity of the spliced product. First, low solubility was alleviated by adding arginine to the reaction buffer and optimizing the splicing reaction condition. The protocol was demonstrated in the context of a Green Fluorescent Protein variant (GFPuv), and the final yield was increased by 1.9‐fold compared to control experiments performed under the same conditions but without addition of arginine. Second, the insertion of NERs was overcome by mutating, instead of inserting, a minimal number of residues in the target protein to amino acids required for the splicing reaction. We identified optimal splicing sites that conserve as much as possible the prerequisite NERs. As a result, the GFPuv residues 142–146 (EYNYN) were mutated to the reportedly minimal required NERs, EYCFN. GFPs spliced using this strategy had no NERs insertion and a fluorescence activity six times stronger than a control GFPuv with five NERs inserted at the splicing site (residue 145/6). In principle, the present protocol (Sw/oNI) can be applied to any target protein, even when no sequence similarity to NERs is present, though it will introduce up to five mutations at the splicing site. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 465–470, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Mechanistic basis for differential inhibition of the F1Fo‐ATPase by aurovertin
Authors: Johnson Kathryn M. , Swenson Lara , Opipari Anthony W. , Reuter Rolf , Zarrabi Nawid , Fierke Carol A. , Börsch Michael , Glick Gary D.
Published: May 2009

The mitochondrial F1Fo‐ATPase performs the terminal step of oxidative phosphorylation. Small molecules that modulate this enzyme have been invaluable in helping decipher F1Fo‐ATPase structure, function, and mechanism. Aurovertin is an antibiotic that binds to the β subunits in the F1 domain and inhibits F1Fo‐ATPase‐catalyzed ATP synthesis in preference to ATP hydrolysis. Despite extensive study and the existence of crystallographic data, the molecular basis of the differential inhibition and kinetic mechanism of inhibition of ATP synthesis by aurovertin has not been resolved. To address these questions, we conducted a series of experiments in both bovine heart mitochondria and E. coli membrane F1Fo‐ATPase. Aurovertin is a mixed, noncompetitive inhibitor of both ATP hydrolysis and synthesis with lower Ki values for synthesis. At low substrate concentrations, inhibition is cooperative suggesting a stoichiometry of two aurovertin per F1Fo‐ATPase. Furthermore, aurovertin does not completely inhibit the ATP hydrolytic activity at saturating concentrations. Single‐molecule experiments provide evidence that the residual rate of ATP hydrolysis seen in the presence of saturating concentrations of aurovertin results from a decrease in the binding change mechanism by hindering catalytic site interactions. The results from these studies should further the understanding of how the F1Fo‐ATPase catalyzes ATP synthesis and hydrolysis. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 830–840, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
In vitro and in vivo RNA interference mediated suppression of Tn‐caspase‐1 for improved recombinant protein production in High FiveTMcell culture with the baculovirus expression vector system
Authors: Hebert Colin G. , Valdes James J. , Bentley William E.
Published: May 2009

While traditional metabolic engineering generally relies on the augmentation of specific genes and pathways in order to increase the yield of target proteins, the advent of RNA interference (RNAi) as a biological tool has given metabolic engineers another tool capable of rationally altering the host cell's biological landscape in order to achieve a specific goal. Given its broad applicability and potent specificity, RNAi has the ability to suppress genes whose function is contrary to the desired phenotype. In this study, RNAi has been used to increase recombinant protein production in a Trichoplusia ni derived cell line (BTI‐TN‐5B1‐4—High Five™) using the Baculovirus Expression Vector System. The specific target investigated is Tn‐caspase‐1, a protease involved in apoptosis that is likely the principal effector caspase present in T. ni cells. Experiments were first conducted using in vitro synthesized dsRNA to verify silencing of Tn‐capase‐1 and increased protein production as a result. Subsequent experiments were conducted using a cell line stably expressing in vivo RNAi in the form of an inverted repeat that results in a hairpin upon transcription. Using this construct, Tn‐caspase‐1 transcript levels were decreased by 50% and caspase enzymatic activity was decreased by 90%. This cell line, designated dsTncasp‐2, demonstrates superior viability under low nutrient culture conditions and resulted in as much as two times the protein yield when compared to standard High Five cells. Biotechnol. Bioeng. 2009; 104: 390–399 © 2009 Wiley Periodicals, Inc.