Industry's Giant Leap Into Cellular Therapy: Catalyzing Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy.

PURPOSE OF REVIEW: We describe the significant technological leap from bench to bedside that was achieved through a strong academic-industry collaboration between dedicated clinicians and researchers at the University of Pennsylvania, the Children's Hospital of Philadelphia, and Novartis to commercialize the chimeric antigen receptor T cell (CAR-T) therapy tisagenlecleucel (CTL019; Kymriah®; Novartis Pharma AG, Basel, Switzerland). RECENT FINDINGS: Tisagenlecleucel was the first CAR-T therapy and the first gene therapy to receive US Food and Drug Administration approval in 2017, with an initial indication for pediatric and young adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia, followed by approval in May 2018 for a second indication in adult patients with r/r diffuse large B cell lymphoma. Subsequent approvals in the European Union, Switzerland, and Canada soon followed. The tisagenlecleucel success story represents the development and commercialization of a first-of-its-kind personalized cellular therapy with a manufacturing process that supports commercial production and ongoing global clinical trials in a growing number of countries.

Screening of Lactic Acid Bacteria for Anti-Fusarium Activity and Optimization of Incubation Conditions.

Anti-Fusarium activities of lactic acid bacteria (LAB) Lactobacillus plantarum 299V, L. plantarum NRRL-4496, and Lactobacillus rhamnosus VT1 were determined by a microdilution assay developed in this study against Fusarium graminearum 08/RG/BF/51. A cell-free Lactobacillus culture supernatant (CFLCS) of L. rhamnosus VT1 had the highest anti-Fusarium activity. Response surface methodology was used to optimize the incubation conditions for production of CFLCS. A Box-Behnken factorial design was used to investigate the effects of incubation time, shaking speed, and incubation temperature on the inhibition rate of CFLCS. A model equation was generated to predict the inhibition rate of CFLCS under various incubation conditions. A low probability value (0.0012) and associated F value of 25.10 suggested that the model was highly significant. A high R2 value (0.978) indicated a very satisfactory model performance. Response surface methodology analysis suggested that an incubation temperature at 34°C, a shaking speed at 170 rpm, and an incubation time of 55 h were the best combination for production of CFLCS from L. rhamnosus VT1. Under these incubation conditions, a 10% L. rhamnosus VT1 CFLCS solution was predicted to inhibit the growth of F. graminearum by 75.6% in vitro and inhibited 83.7% of the growth in the validation experiment. Thus, the CFLCS of L. rhamnosus VT1 was an effective anti-Fusarium mixture.

Infestation and Quantification of Ochratoxigenic Fungi in Barley and Wheat Naturally Contaminated with Ochratoxin A.

Cereal grains are a significant source of ochratoxin A (OTA) in the human diet. Multiple ochratoxigenic Aspergillus and Penicillium spp. have been reported as contaminants on various cereal grains around the world, although relatively few species dominate in any given location. Efforts to mitigate the risk of fungal contamination and OTA accumulation can be made pre- and postharvest. Still, a rapid and reliable screening method is sought that can be used to predict the OTA level of a sample and to inform risk assessments prior to processing. In this study, we assessed the efficacy of two OTA-related indices for OTA level prediction. Infestation rates were determined by direct plating for freshly harvested and stored barley, durum, and hard red spring wheat samples (n = 139) with known OTA levels. Presumptive ochratoxigenic isolates were tested for their ability to produce OTA. The nonribosomal peptide synthase (otanpsPN) involved in OTA biosynthesis was used to quantify ochratoxigenic fungi in barley and wheat. Viable Penicillium verrucosum was present in 45% of the samples. In total, 62.7% (n = 110) of the P. verrucosum isolates tested produced OTA on dichloran yeast extract sucrose 18% glycerol agar. Both OTA level and infestation rate (r = 0.30), as well as OTA level and otanpsPN concentration (r = 0.56), were weakly correlated. Neither infestation rate nor otanpsPN concentration is a reliable predictor of OTA level in a sample.

Ochratoxin A in stored U.S. barley and wheat.

Ochratoxin A (OTA) is a mycotoxin of significant health concern that is present in a variety of cereal grains and other foods around the world. Although OTA contamination can occur prior to harvest, it is largely considered a storage issue that can be controlled through the implementation of proper storage practices. Barley, durum, and hard red spring wheat samples that had been stored for various lengths of time were collected (n = 262) over a period of 2 years by multiple commercial grain companies located in the northwestern and northern Great Plains regions of the United States. Samples were analyzed for OTA concentration using high-performance liquid chromatography with fluorescence detection. OTA was detected in 12.2% of the samples, and of those samples, 81.3% had been stored for ≥6 months. One sample of barley and four samples of wheat exceeded 5 ng/g of OTA.

Survey of ochratoxin A in freshly harvested durum and hard red spring wheat in the United States, 2011 and 2012.

Ochratoxin A (OTA) is a toxin produced by some Penicillium and Aspergillus species around the world in a variety of food and feed, especially cereal grains, before harvest but primarily during storage. Durum and hard red spring (HRS) wheat samples were collected right after harvest as part of the U. S. regional crop quality survey in both 2011 (n = 560) and 2012 (n = 654) from the upper Great Plains. All samples were analyzed for OTA contamination using high-performance liquid chromatography with fluorescence detection. Overall, 2.1% of the samples were positive for OTA. In 2011, OTA was detected in 1.0% of the durum wheat samples but was not found in HRS wheat. In 2012, 8.3 and 1.4% of the durum and HRS wheat samples, respectively, were positive for OTA. Of the 25 samples that had detectable OTA, 3 samples (12%), all of which were durum wheat, had OTA that exceeded 5 ng/g.

Multiplex real-time PCR method for detection and quantification of mycotoxigenic fungi belonging to three different genera.

UNLABELLED: Cereal crop plants are colonized by many fungal species such as Aspergillus ochraceus and Penicillium verrucosum, which produce ochratoxins, and Fusarium graminearum, which produces trichothecene mycotoxins. A multiplex real-time PCR method using TaqMan probes was developed to simultaneously detect and quantify these mycotoxigenic Fusarium, Penicillium and Aspergillus species in cereal grains. Primers and probes used in this method were designed targeting the trichothecene synthase (Tri5) gene in trichothecene-producing Fusarium, rRNA gene in Penicillium verrucosum, and polyketide synthase gene (Pks) in Aspergillus ochraceus. The method was highly specific in detecting fungal species containing these genes and was sensitive, detecting up to 3 pg of genomic DNA. These PCR products were detectable over five orders of magnitude (3 pg to 30 ng of genomic DNA). The method was validated by evaluating sixteen barley culture samples for the presence of deoxynivalenol (DON) and ochratoxin A (OTA) producing fungi. Among the barley culture samples tested, 9 were positive for Fusarium spp, 5 tested positive for Penicillium spp, and 2 tested positive for Aspergillus spp. Results were confirmed by traditional microbiological methods. These results indicate that DON- and OTA-producing fungi can be detected and quantified in a single reaction tube using this multiplex real-time PCR method. PRACTICAL APPLICATION: This method would be helpful in detecting and quantifying the mycotoxin producing fungi such as Fusarium, Aspergillus, and Penicillium in cereal grains and cereal-based foods.

Mental health disorders in children of non-drug-abusing parents: a sample from a rural community devastated by methamphetamine.

A representative sample of 58 preschoolers (aged 4 and 5) and 78 school-age children (aged 8 and 9) from methamphetamine-producing (MP) and non-producing (NP) homes was drawn from a rural county in Tennessee, for two separate studies. The researchers assessed the psychological functioning of the children using age appropriate Behavior Assessment System for Children (BASC) forms, and compared the scores of children with NP status with population-based data. The results indicate that in this rural sample, the prevalence of internalizing and externalizing disorders in children from NP homes was higher than in population-based norms. Specifically, the preschoolers showed a higher rate of depression, and the school-age children had higher rates of anxiety, depression, and atypical behaviors than their population-based peers. The results are interpreted in terms of low SES and accessibility to mental health services in rural communities. The authors suggest nurse practitioners include brief psychological screenings in their assessment protocols for this population.

Effect of ozone treatment on the safety and quality of malting barley.

Molds and their mycotoxins are an expensive problem for the malting and brewing industries. Deoxynivalenol (DON) is a mycotoxin that is associated with Fusarium spp. These fungi frequently cause Fusarium head blight in wheat and barley in the midwestern region of the United States; Manitoba, Canada; Europe; and China. Barley growers and malt producers would benefit from a postharvest control method for mold growth and DON production. We evaluated the use of gaseous ozone (O(3)) for preventing Fusarium growth and mycotoxin production while maintaining malt quality characteristics. Micromalting was performed in three replications under standard conditions. Ozone treatment was applied to malting barley during steeping via a submerged gas sparger. Ozone treatment conditions were 26 mg/cm(3) for 120 min after 2 and 6 h of steeping. The effects of gaseous ozone on DON, aerobic plate counts, Fusarium infection, and mold and yeast counts of barley throughout the malting process were measured. Various quality parameters of the malt were measured after kilning. Statistical tools were used to determine the significance of all results. Ozonation of malting barley during steeping did not lead to significant reductions in aerobic plate counts but did lead to a 1.5-log reduction in mold and yeast counts in the final malt. The influence of gaseous ozone on DON concentration was inconclusive because of the low initial concentrations of DON in the barley. Ozone significantly reduced Fusarium infection in germinated barley. Gaseous ozone did not negatively influence any aspect of malt quality and may have subtle beneficial effects on diastatic power and ß-glucan concentrations.

Quantification of Tri5 gene, expression, and deoxynivalenol production during the malting of barley.

Fusarium can survive, grow, and produce mycotoxins during malting. We evaluated the percentage of barley kernels infected with Fusarium (FI) and deoxynivalenol (DON) concentration in three barley treatments (high-quality, naturally infected, and Fusarium graminearum inoculated barley) during various stages of malting. We also applied real-time polymerase chain reaction (real-time PCR) and real-time reverse transcriptase PCR (real-time RT-PCR) methods to quantify trichothecene-producing (Tri5) DNA concentration and expression, respectively. We observed that FI significantly (P<0.05) increased during the germination stage of malting in all barley treatments. Temperatures of 49°C and higher during kilning reduced the FI in high-quality barley treatments, but for inoculated treatments temperatures in excess of 60°C were needed to reduce FI. The Tri5 DNA concentration ranged from non-detectable to 3.9 ng/50mg, 0.1 to 109.8 ng/50mg and 3.4 to 397.5 ng/50 mg in malted high-quality, inoculated and naturally infected barley treatments respectively. Strong gene expression (Tri5) in naturally infected barley treatments was found during the third day of germination, when compared to high-quality and inoculated barley treatments during malting. Deoxynivalenol was present even at high kilning temperatures, as DON is heat stable. The average DON concentration ranged from non-detectable to 0.1 µg/g, non-detectable to 1.1 µg/g, and 1.5 to 45.9 µg/g during various stages of malting in high-quality, inoculated and infected barley and malt samples respectively. Overall, the last 2 days of germination and initial stages of kilning were peak stages for FI, Tri5 gene production, Tri5 gene expression and DON production.

Modified microwave-assisted extraction of ergosterol for measuring fungal biomass in grain cultures.

Ergosterol is a measure for fungal biomass. The recovery rates using a previously described microwave-assisted-extraction (MAE) method for ergosterol analysis tended to be low for grain cultures (pure culture in sterilized 40% moisture content grain) inoculated with Fusarium graminearum . An improved MAE method for measuring ergosterol in grain cultures was developed and compared. Modification to the original MAE included alterations in duration of microwave exposure and extraction solvents. Four autoclaved grains (wheat, rice, barley, and corn) were inoculated with F. graminearum or spiked with ergosterol at concentrations from 0.88 to 100 microg/g and extracted with both methods. The ergosterol recovery rates were significantly different (p < 0.05) for the two methods in assaying both the spiked and grain culture samples. The modified method provided greater recovery rates than the previously reported MAE method for the spiked samples and F. graminearum grain cultures.

The methamphetamine home: psychological impact on preschoolers in rural Tennessee.

CONTEXT: A growing number of children reside with methamphetamine-abusing parents in homes where the illicit drug is produced. Yet, the effects of a methamphetamine environment on psychological child outcome are still unknown. PURPOSE: To examine whether preschoolers who lived in methamphetamine-producing homes are at increased risk for developing psychological problems. METHODS: The participants were 58 white children between the ages of 4 and 5 years; 31 with a history of living in methamphetamine-producing homes and 27 children who live in non-methamphetamine producing homes in rural Tennessee. The groups were similar in age, gender, and socioeconomic background. The groups were compared for behavioral and emotional adjustment using the behavior assessment system for children-parent rating scale-preschool (BASC-PRS-P) form. Biological or custodian parents completed a rating on their preschoolers that provided information about the children's pattern of behavior and feelings. FINDINGS: Preschoolers from the methamphetamine-producing homes showed more externalizing problems than their peers, but were comparable on internalizing problems. On specific behaviors, the data indicate that preschoolers in the methamphetamine group showed higher aggression symptoms than their peers from non-methamphetamine-producing homes. CONCLUSIONS: These findings, if replicated, point to the need for mental health screening when a child is removed from a methamphetamine-producing home.

Effect of hot water treatments on the safety and quality of Fusarium-infected malting barley.

Utilization of Fusarium-infected barley for malting may lead to mycotoxin contamination of malt and decreased malt quality. Hot water treatments may prevent or reduce safety and quality defects and allow use of otherwise good quality barley. We evaluated hot water treatments for preventing Fusarium growth and mycotoxin production while maintaining barley-malt characteristics. Four barley lots with varying deoxynivalenol (DON) concentrations were hot water-treated at 45 or 50 degrees C for 0, 1, 5, 12, and 20 min. Treated barley was malted in a pilot-scale malting unit. Barley and malt were analyzed for Fusarium infection (FI), germinative energy (GE), aerobic plate count (APC), mold and yeast count (MYC), and DON. Malt quality parameters included malt extract, soluble protein, wort color, wort viscosity, free amino nitrogen, alpha-amylase, and diastatic power. Significant decreases in FI occurred within 1 min at both 45 degrees C (41-66%) and 50 degrees C (51-69%) in all barley samples. Significant reductions in APC (1.0-1.8 log) and MYC (1.7-1.8 log) in barley were observed after 5 min at both temperatures. The largest reductions for DON were observed in malts prepared from barley treated with hot water at 45 degrees C (79-93%) and 50 degrees C (84-88%) for 20 min. GE and most of the malt quality parameters were only affected when barley was treated at 50 degrees C for 12 and 20 min. The results suggest that hot water treatments may offer the potential for treating mildly FHB infected malting barley.

Fungistatic activity of flaxseed in potato dextrose agar and a fresh noodle system.

Although numerous researchers have studied flaxseed as a food ingredient for its health benefits, flaxseed (Linum usitatissimum) has never been considered as a food preservative. The objective of this study was to investigate the effect of flaxseed flour (FF) concentration (0, 6, 9, 12, and 15% wt/wt), cultivar ('Omega' and brown) and source (four seed companies located in Minnesota and North Dakota) on flaxseed fungistatic activity. Fungal radial growth was used to assess the fungistatic activity of FF in both potato dextrose agar (PDA) medium and a fresh noodle system. Strains of Penicillium chrysogenum, Aspergillus flavus, Fusarium graminearum, and a Penicillium sp. isolated from molded noodles were used as the test microorganisms. Results showed that growth of F. graminearum was completely inhibited at all FF concentrations in PDA, and the inhibition of the other three test microorganisms increased with increasing FF concentrations. In the model noodle system, FF concentration at 9% or higher significantly reduced the mold count of fresh noodle during storage. In the inoculated noodle system, 6% FF addition was sufficient to significantly inhibit the growth of F. graminearum and A. flavus, whereas 9% FF concentrations showed fungistatic activity against P. chrysogenum and the Penicillium sp. isolate. Differences in the degree of mold inhibition were found among FFs obtained from different sources and cultivars. Results suggested that flaxseed possesses fungistatic activity and could be used as a multifunctional food ingredient.

Mold and mycotoxin problems encountered during malting and brewing.

Fusarium infections in grains can have severe effects on malt and beer. While some degree of Fusarium mycotoxins, such as deoxynivalenol, present in infected barley may be lost during steeping, the Fusarium mold is still capable of growth and mycotoxin production during steeping, germination and kilning. Therefore, detoxification of grain before malting may not be practical unless further growth of the mold is also prevented. Methods to reduce the amount of mold growth during malting are needed. Physical, chemical and biological methods are reviewed. Irradiation looks very promising as a means to prevent Fusarium growth during malting, but the effect on the surviving mold to produce mycotoxins and the effect on malt quality needs further study. Chemical treatments such as ozonation, which would not leave residual chemical in the beer also appear to be promising. Although biological control methods may be desirable, due to the use of "natural" inhibition, the effects of these inhibitors on malt and beer quality requires further investigation. It may also be possible to incorporate detoxifying genes into fermentation yeasts, which would result in detoxification of the wort when mold growth is no longer a problem. Development of these types of technological interventions should help improve the safety of products, such as beer, made from Fusarium infected grain.

Effect of electron-beam irradiation on the safety and quality of Fusarium-infected malting barley.

Utilization of Fusarium-infected barley for malting may lead to mycotoxin production during malting and decreased malt quality. Electron-beam irradiation may prevent safety and quality defects and allow use of otherwise good quality barley. We evaluated electron-beam irradiation for preventing Fusarium growth and mycotoxin production while maintaining barley-malt quality characteristics. Four barley lots with varying deoxynivalenol (DON) concentrations were irradiated at 0, 2, 4, 6, 8, and 10 kGy. Treated barley was malted in a pilot-scale malting unit. Barley and malt were analyzed for Fusarium infection (FI), germinative energy (GE), aerobic plate counts (APC), mold and yeast counts (MYC), and DON. Malt quality parameters included malt extract, soluble protein, wort color, wort viscosity, free amino nitrogen, alpha-amylase, and diastatic power. FI, APC, and MYC decreased in barley with an increase in dosage. The APC and MYC for malts from barley exposed to 8-10 kGy were slightly higher than in other malted samples indicating that irradiation-resistant microflora could flourish during malting. Barley GE significantly decreased (3-15%) at 8-10 kGy. Although irradiation had no effect on DON in raw barley, DON decreased significantly (60-100%) in finished malts prepared from treated barley (6-10 kGy). Malt quality parameters were slightly affected by electron-beam radiation. The results suggest 6-8 kGy may be effective for reducing FI in barley and DON in malt with minimal effects on malt quality.

Evaluation of gaseous ozone and hydrogen peroxide treatments for reducing Fusarium survival in malting barley.

The use of Fusarium-infected barley for malting can lead to mycotoxin production and decreased malt quality. Methods for treatment of Fusarium-infected barley might prevent these safety and quality defects and allow use of otherwise good-quality barley. Gaseous ozone and hydrogen peroxide (HP) were evaluated for effectiveness in reducing Fusarium survival while maintaining germinative energy (GE) in barley. Gaseous ozone treatments (GOT) included concentrations of 11 and 26 mg/g for 0, 15, 30, and 60 min. HP treatments included 0, 5, 10, and 15% concentrations with exposure times of 0, 5, 10, 15, 20, and 30 min. For GOT, in naturally Fusarium-infected barley, a statistically significant (P < 0.05) decrease (24 to 36%) of Fusarium survival occurred within 15 min of exposure at either concentration. GE was significantly (P < 0.05) affected by 30 min at both concentrations in naturally Fusarium-infected barley, but not in sound barley. GOT did not cause any significant (P > 0.05) effect on GE in sound barley at either concentration over the full 30-min exposure time. For HP, Fusarium survival was significantly decreased (50 to 98%) within 5 min of exposure. With the exception of two treatments (10 and 15% HP agitated for 20 min), GE was not statistically significantly different from the control in naturally Fusarium-infected barley. In sound barley, HP had no significant (P > 0.05) effect on GE. The results suggest that GOT and HP might have potential for treatment of Fusarium-infected malting barley.

Microbial loads, mycotoxins, and quality of durum wheat from the 2001 harvest of the northern plains region of the United States.

The 2001 durum wheat crop grown in the Northern Plains was surveyed for microbial loads, mycotoxins, and quality. Correlations among these factors were identified. Effects of cleaning, milling, and pasta processing on microbial loads and deoxynivalenol (DON) concentrations were determined. Aerobic plate counts (APCs), mold and yeast counts (MYCs), internal mold infection (IMI), and internal Fusarium infection (IFI) were lowest in grain samples from Montana and highest in grain from northeastern North Dakota. DON and 15-acetyldeoxynivalenol (15-ADON) were not detected in samples from Montana. Nivalenol was not detected in any samples. DON in North Dakota samples ranged from none detected to 23 micrograms/g. 15-ADON was detected in a few North Dakota samples, with a maximum of 0.8 microgram/g. DON positively correlated with APCs, MYCs, IFI, damaged kernels, total defects, U.S. grade number, and tombstone kernel content and negatively correlated with test weight, vitreous kernel content, and kernel weight. APCs, MYCs, and DON concentrations were lower in semolina than whole grain. Processing semolina into spaghetti did not change DON concentrations. APCs for spaghetti were reduced 2.2 to 4.1 logs from those for semolina, whereas MYCs were reduced 0.1 to 1.7 log. Some APCs in durum flour and semolina were higher than certain industry specifications would allow, although other factors were acceptable. However, microbial loads in the spaghetti were all within specifications found in the available literature.

Evaluation of hot water and electron beam irradiation for reducing Fusarium infection in malting barley.

The use of Fusarium-infected barley for malting may lead to mycotoxin production and decreased product quality. Physical methods for the treatment of Fusarium-infected barley may prevent these safety and quality defects and allow the use of otherwise good quality barley. Hot water and electron beam irradiation were evaluated for their effectiveness in reducing Fusarium infection while maintaining germinative energy in barley samples. Hot-water treatments involved temperatures of 45, 50. 55, and 60 degrees C and treatment times of 0, 1, 5, 10, and 15 min. Electron beam irradiation involved doses ranging from 0 to 11.4 kGy. Treatment with water at 45 degrees C for 15 min resulted in a reduction in Fusarium infection from 32 to 1% after 15 min, with only a very slight reduction in germination. Treatment with water at 50 degrees C for 1 min resulted in a reduction in Fusarium infection from 32 to 2%, and no effect on germination was observed for up to 5 min of treatment. At higher water temperatures. Fusarium infection was essentially eliminated, but germination was also severely reduced. Electron beam irradiation of Fusarium-infected barley reduced Fusarium infection at doses of >4 kGy, and a slight increase in germination for dry samples was observed with doses of 6 to 8 kGy. Doses of >10 kGy significantly decreased germination. Physical methods may have potential for the treatment of Fusarium-infected malting barley.

Evaluation of household sanitizers for reducing levels of Escherichia coli on iceberg lettuce.

Diluted solutions of various household sanitizers (apple cider vinegar, white vinegar, bleach, and a reconstituted lemon juice product) were tested for their effectiveness in reducing counts of inoculated Escherichia coli and naturally present aerobic, mesophilic bacteria on lettuce. Sanitization treatments were carried out at 4 degrees C and at room temperature (ca. 21 degrees C) with and without agitation and at different exposure times (0, 1, 5, and 10 min). Of the sanitizers tested, 35% white vinegar (1.9% acetic acid) was the most effective in reducing E. coli levels (with a 5-log10 reduction after 5 min with agitation and after 10 min without agitation) and in reducing aerobic plate counts (with a >2-log10 reduction after 10 min with agitation). Lettuce samples treated with diluted household sanitizers were analyzed for consumer acceptability by sensory evaluation using a 9-point hedonic scale. The sanitized samples did not differ in acceptability (P > 0.05), except for samples treated with white vinegar. Samples treated with the white vinegar for 10 min were noticeably sour and slightly wilted in appearance. Consumer acceptability was maintained with all sanitization treatments, including those involving 35% white vinegar.

Mycotoxins and fermentation--beer production.

Along with food safety issues due to mycotoxins, the effects of Fusarium infections on malt and beer quality can be disastrous. While some of the Fusarium head blight mycotoxins, such as DON, present in infected barley may be lost during steeping, the Fusarium mold is still capable of growth and mycotoxin production during steeping, germination and kilning. Therefore, detoxification of grain before malting may not be practical unless further growth of the mold is also prevented. Methods for reducing the amount of mold growth during malting are needed. Physical, chemical and biological methods exist for inhibiting mold growth in grain. Irradiation is a promising means for preventing Fusarium growth during malting, but its effects on malt quality and mycotoxin production in surviving mold need to be evaluated in more detail. Chemical treatments such as ozonation, which do not leave chemical residues in beer, also appear to be promising. Although biological control methods may be desirable, the effects of these inhibitors on malt and beer quality require further investigation. In addition, storage studies are needed to determine the effect of biological control on Fusarium viability and malt quality. It may also be possible to incorporate detoxifying genes into fermentation yeasts, which would result in detoxification of mycotoxins present in wort. Development of these types of technological interventions should help improve the safety of products, such as beer, made from Fusarium infected grain.