Impact of Environmental Conditions on the Concentrations of Trichothecenes, Their Glucosides, and Emerging Fusarium Toxins in Naturally Contaminated, Irradiated, and Fusarium langsethiae Inoculated Oats.

Trichothecenes produced by Fusarium species are commonly detected in oats. However, the ratios of the concentrations of free trichothecenes and their conjugates and how they are impacted by different interacting environmental conditions are not well documented. This study aims to examine the effect of water activity (0.95 and 0.98 aw) and temperature (20 and 25 °C) stress on the production of T-2 and HT-2 toxins, deoxynivalenol and their conjugates, as well as diacetoxyscirpenol (DAS). Multiple mycotoxins were detected using liquid chromatography-tandem mass spectrometry from 64 contaminated oat samples. The highest concentrations of HT-2-glucoside (HT-2-Glc) were observed at 0.98 aw and 20 °C, and were higher than other type A trichothecenes in the natural oats' treatments. However, no statistical differences were found between the mean concentrations of HT-2-Glc and HT-2 toxins in all storage conditions analysed. DAS concentrations were generally low and highest at 0.95 aw and 20 °C, while deoxynivalenol-3-glucoside levels were highest at 0.98 aw and 20 °C in the naturally contaminated oats. Emerging mycotoxins such as beauvericin, moniliformin, and enniatins mostly increased with a rise in water activity and temperature in the naturally contaminated oats treatment. This study reinforces the importance of storage aw and temperature conditions in the high risk of free and modified toxin contamination of small cereal grains.

Biocontrol activities of yeasts or lactic acid bacteria isolated from Robusta coffee against Aspergillus carbonarius growth and ochratoxin A production in vitro.

Biocontrol Agents (BCAs) can be an eco-friendly alternative to fungicides to reduce the contamination with mycotoxigenic fungi on coffee. In the present study, different strains of bacteria and yeasts were isolated from Ivorian Robusta coffee. Their ability to reduce fungal growth and Ochratoxin A (OTA) production during their confrontation against Aspergillus carbonarius was screened on solid media. Some strains were able to reduce growth and OTA production by 85 % and 90 % and were molecularly identified as two yeasts, Rhodosporidiobolus ruineniae and Meyerozyma caribbica. Subsequent tests on liquid media with A. carbonarius or solely with OTA revealed adhesion of R. ruineniae to the mycelium of A. carbonarius through Scanning Electron Microscopy, and an OTA adsorption efficiency of 50 %. For M. caribbica potential degradation of OTA after 24 h incubation was observed. Both yeasts could be potential BCAs good candidates for Ivorian Robusta coffee protection against A. carbonarius and OTA contamination.

Impact of predicted climate change environmental conditions on the growth of Fusarium asiaticum strains and mycotoxins production on a wheat-based matrix.

Fusarium asiaticum is a predominant fungal pathogen causing Fusarium Head Blight (FHB) in wheat and barley in China and is associated with approximately £201 million in annual losses due to grains contaminated with mycotoxins. F. asiaticum produces deoxynivalenol and zearalenone whose maximum limits in cereals and cereals-derived products have been established in different countries including the EU. Few studies are available on the ecophysiological behaviour of this fungal pathogen, but nothing is known about the impact of projected climate change scenarios on its growth and mycotoxin production. Therefore, this study aimed to examine the interacting effect of i) current and increased temperature (25 vs 30 °C), ii) drought stress variation (0.98 vs 0.95 water activity; aw) and iii) existing and predicted CO2 concentrations (400 vs 1000 ppm) on fungal growth and mycotoxin production (type B trichothecenes and zearalenone) by three F. asiaticum strains (CH024b, 82, 0982) on a wheat-based matrix after 10 days of incubation. The results showed that, when exposed to increased CO2 concentration (1000 ppm) there was a significant reduction of fungal growth compared to current concentration (400 ppm) both at 25 and 30 °C, especially at 0.95 aw. The multi-mycotoxin analysis performed by LC-MS/MS qTRAP showed a significant increase of deoxynivalenol and 15-acetyldeoxynivalenol production when the CH024b strain was exposed to elevated CO2 compared to current CO2 levels. Zearalenone production by the strain 0982 was significantly stimulated by mild water stress (0.95 aw) and increased CO2 concentration (1000 ppm) regardless of the temperature. Such results highlight that intraspecies variability exist among F. asiaticum strains with some mycotoxins likely to exceed current EU legislative limits under prospected climate change conditions.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Efectividad de la colecistectomía laparoscópica de puerto único asistida con imanes bajo anestesia espinal

Objetivo: Determinar la efectividad de la colecistectomía laparoscópica de puerto único asistida por imanes bajo anestesia espinal en el tratamiento quirúrgico de la colecistopatía litiásica crónica. Material y Métodos: Estudio prospectivo de cohorte en 51 pacientes entre octubre de 2019 y febrero de 2021. 17 pacientes fueron sometidos a colecistectomía laparoscópica de puerto único asistida por imanes y 34 a colecistectomía laparoscópica convencional por un mismo equipo quirúrgico. Se aplicó la técnica quirúrgica descrita por Dominguez et al y SAGES, bajo anestesia espinal. Se realizó estadística descriptiva e inferencial, analizando el dolor postoperatorio a las 3, 6, 12, 24 y 72 h y la satisfacción de los pacientes. Resultados: Se encontró diferencia significativa en el dolor postoperatorio en el grupo de estudio a las 6 h (p = 0,022), 12 h (p = 0,039), 24 h (p = 0,025) y 72 h (p < 0,001). En la satisfacción se encuentra un RR de 3 (p = 0,001), sin diferencia significativa en el tiempo operatorio y horas de hospitalización postquirúrgicas. Conclusiones: La colecistectomía laparoscópica de puerto único asistida por imanes, bajo anestesia espinal, ha demostrado efectividad en la reducción importante del dolor postoperatorio a partir de las 6 h, y en la superación de las expectativas en los intervenidos, sin aumento significativo de tiempo operatorio ni estancia hospitalaria.

Aim: To determine the effectiveness of magnet-assisted single-port laparoscopic cholecystectomy under spinal anesthesia in surgical treatment of chronic lithiasic cholecystopathy. Materials and Method: Prospective cohort study in 51 patients between October 2019 and February 2021. 17 patients underwent magnet-assisted single-port laparoscopic cholecystectomy and 34 underwent conventional laparoscopic cholecystectomy by the same surgical team. The surgical technique described by Dominguez and SAGES was used, under spinal anesthesia. Descriptive and inferential statistics were performed, analyzing postoperative pain at 3, 6, 12, 24 and 72 hours and patient satisfaction. Results: A significant difference in postoperative pain was found in the study group at 6 h (p = 0.022), 12 h (p = 0.039), 24 h (p = 0.025) and 72 h (p < 0.001). In satisfaction, there is an RR of 3 (p = 0.001), with no significant difference in operative time and postoperative hospitalization hours. Conclusions: Magnet-assisted single-port laparoscopic cholecystectomy under spinal anesthesia has shown effectiveness in significantly reducing postoperative pain after 6h, associated with significantly exceeding expectations in those operated on, without a significant increase in operative time or hospital stay.

Acclimatisation of Fusarium langsethiae, F. poae and F. sporotrichioides to elevated CO2: Impact on fungal growth and mycotoxin production on oat-based media.

Oats are highly susceptible to infection by Fusarium species, especially F. langsethiae, F. poae and F. sporotrichioides which contaminate the grain with mycotoxins. Climate change is expected to affect fungal colonisation and associated mycotoxin production. The objective of this study was to examine the effect of acclimatisation to elevated CO2 on the growth and mycotoxin production capacity of these fungal species. Strains of F. langsethiae (FL; seven strains), F. poae (FP; two strains) and F. sporotrichioides (FS; one strain) were acclimatised by sub-culturing for 10 generations at either 400 or 1000 ppm CO2 under diurnal temperature conditions. At each sub-culturing, the effect of acclimatisation to elevated CO2 on (a) lag phase prior to growth, (b) growth rate on oat-based media was assessed. Additionally, the production of type A trichothecenes and related toxic secondary metabolites of sub-cultures after 1, 7 and 10 generations were assessed using LC-MS/MS qTRAP. The results showed that Fusarium strains had an increased lag time and growth rate in response to the combined effect of sub-culturing and elevated CO2 levels. T-2 + HT-2 production was affected by elevated CO2 in strain FL4 (7.1-fold increase) and a decrease in strain FL1 (2.0-fold decrease) at the first sub-culturing and FS (1.3-fold decrease) after 7 sub-cultures compared to ambient conditions. The effect of sub-culturing on T-2 + HT-2 production varied depending on the fungal strain. For strain FL4, significantly less T-2 + HT-2 toxins were produced after 10 generations (4.4-fold decrease) as compared to that under elevated CO2 conditions after one sub-culture, and no change was observed under ambient conditions. The FS strain showed significant stimulation of T-2 + HT-2 toxin production after 10 sub-cultured generations (1.1-fold increase) compared to the initial sub-culture of this strain under elevated CO2 conditions. The production of other toxic secondary metabolites was generally not impacted by elevated CO2 conditions or by sub-culture for 10 generations, with the exceptions of FL1 and FP1. FL1 produced significantly more neosolaniol after 10 generations, when compared to those after 1 and 7, regardless of the CO2 conditions. For FP1, elevated CO2 significantly triggered beauvericin production after an initial sub-culture when compared to ambient conditions at the same sub-culture stage (29-fold). FP1 acclimatisation to elevated CO2 led to a decrease of beauvericin production after 10 generations when compared to 1 (6-fold). In contrast, sub-culturing for 10 generations compared to 1 under ambient CO2 conditions resulted in an increase in this toxin (12-fold).

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease.

Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson's Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 × 10 -5 ; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4 . We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.

Business intelligence for the visualization and data analysis of Telepharmacy activity indicators in a hospital pharmacy service scorecard.

OBJECTIVE: The consolidation of Telepharmacy during the COVID-19 pandemic  has raised the need for managing large volumes of real-time activity data  through data analysis. The aim of this project was to design a dynamic, user- friendly, customizable scorecard in a hospital pharmacy service for the  visualization and analysis of Telepharmacy activity indicators through the use  of advanced business intelligence technology. METHOD: The software tool was developed by a multidisciplinary team between  April and May 2021, driven from the hospital pharmacy service. Once the Telepharmacy indicators of interest were established,  datasets were extracted from raw databases (administrative databases,  Telepharmacy database, outpatient dispensing software, drug catalogues)  through data analysis. The different data sources were integrated in a  scorecard using PowerBI®. The criteria for processing missing and duplicated  data were defined, and data pre-processing, normalization and transformation were performed. Once the pilot scorecard was validated by  different profiles of users, the structure was designed for the panels to  automatically update as databases were updated. RESULTS: Design and implementation of a scorecard of Telepharmacy activity:  general descriptive panel (demographic profile of patients, count and delivery  conditions, program and medical service); geolocation of destination;  pharmacological profile; relative analysis of patients involved in the  Telepharmacy program with respect to the total of outpatients. In the last  updating as of January 2022, data from 16,000 dispensations to more than  4,000 patients had been collected. This means that 21.93% of outpatients had  benefited at some time point from the Telepharmacy service. Filters enable the  visualization of timeline progress and patient characterization, and  measure Telepharmacy activity by program. CONCLUSIONS: The processing of large Telemedicine datasets from various  sources through Business Intelligence in a hospital pharmacy service makes it  possible to synthesize information, generate customized reports, and visualize  information in a dynamic and attractive format. The application of this new  technology will help us improve strategic clinical and management decision  making.

OBJETIVO: La consolidación de la Telefarmacia en el contexto de la pandemia por la COVID-19 exige manejar a tiempo real un gran volumen de datos de actividad mediante análisis de datos. El objetivo de este trabajo fue diseñar un cuadro de mando ágil, personalizable y dinámico para la visualización y análisis de indicadores de actividad en Telefarmacia en un servicio de farmacia de hospital, mediante el empleo de herramientas  avanzadas de inteligencia empresarial (business intelligence).Método: Un equipo de trabajo multidisciplinar desarrolló una herramienta de  software entre abril y mayo de 2021 impulsado desde el servicio de farmacia  de hospital. Una vez consensuados los indicadores de interés en Telefarmacia,  se extrajeron los datos a partir de bases de datos brutas (base de datos de  Telefarmacia, programa de dispensación de pacientes externos, bases de datos  administrativas, catálogos de fármacos) mediante análisis de datos. La  integración de las diferentes fuentes de datos en el cuadro de mando se realizó mediante PowerBI®. Se definió el manejo de los datos perdidos y duplicados y  se aplicó preprocesamiento, normalización y transformación de los datos. Una  vez  validado el piloto por diferentes tipos de usuarios, se diseñó la estructura para actualización automática de los paneles con las sucesivas actualizaciones de las fuentes de datos. RESULTADOS: Diseño e implementación de un cuadro de mando de la actividad  en Telefarmacia: panel descriptivo general (perfil demográfico de pacientes,  recuento y condiciones de envíos, programa y servicio médico); geolocalización  de destino; perfil farmacológico; análisis relativo de los  pacientes beneficiarios de Telefarmacia respecto del total de pacientes  externos. En el último corte, a enero de 2022, se habían incluido datos de  16.000 dispensaciones con entrega informada a más de 4.000 pacientes, lo  que supone que el 21,93% de los pacientes externos han estado en algún momento en el programa de Telefarmacia. La aplicación de filtros permite  visualizar la evolución temporal, caracterizar grupos de pacientes y  dimensionar la actividad por programas. CONCLUSIONES: El procesamiento de paquetes de datos de Telemedicina, de  gran volumen, difícil manejo y procedentes de diversas fuentes relativas a Telefarmacia mediante inteligencia empresarial, en un servicio de farmacia  de hospital, permite sintetizar la información y proporcionar informes  personalizados y visualizaciones dinámicas y atractivas. La aplicación de estas  nuevas tecnologías puede ayudarnos a mejorar la toma de decisiones  estratégicas, tanto clínicas como de gestión.

Inteligencia empresarial para la visualización y análisis de datos de indicadores de actividad de Telefarmacia en un cuadro de mando de un servicio de farmacia de hospital / Business intelligence for the visualization and data analysis of Telepharmacy activity indicators in a hospital pharmacy service scorecard

Objetivo: La consolidación de la Telefarmacia en el contexto de la pandemia por la COVID-19 exige manejar a tiempo real un gran volumen dedatos de actividad mediante análisis de datos. El objetivo de este trabajofue diseñar un cuadro de mando ágil, personalizable y dinámico para lavisualización y análisis de indicadores de actividad en Telefarmacia en unservicio de farmacia de hospital, mediante el empleo de herramientas avanzadas de inteligencia empresarial (business intelligence).Método: Un equipo de trabajo multidisciplinar desarrolló una herramienta de software entre abril y mayo de 2021 impulsado desde el servicio de farmacia de hospital. Una vez consensuados los indicadoresde interés en Telefarmacia, se extrajeron los datos a partir de bases dedatos brutas (base de datos de Telefarmacia, programa de dispensación de pacientes externos, bases de datos administrativas, catálogosde fármacos) mediante análisis de datos. La integración de las diferentesfuentes de datos en el cuadro de mando se realizó mediante PowerBI®.Se definió el manejo de los datos perdidos y duplicados y se aplicópreprocesamiento, normalización y transformación de los datos. Una vez validado el piloto por diferentes tipos de usuarios, se diseñó la estructurapara actualización automática de los paneles con las sucesivas actualizaciones de las fuentes de datos.Resultados: Diseño e implementación de un cuadro de mando de laactividad en Telefarmacia: panel descriptivo general (perfil demográficode pacientes, recuento y condiciones de envíos, programa y serviciomédico); geolocalización de destino; perfil farmacológico; análisis relativo de los pacientes beneficiarios de Telefarmacia respecto del totalde pacientes externos. En el último corte, a enero de 2022, se habíanincluido datos de 16.000 dispensaciones con entrega informada a másde 4.000 pacientes, lo que supone que el 21,93% de los pacientes externos han estado en algún momento en el programa de Telefarmacia. (AU)

Objective: The consolidation of Telepharmacy during the COVID-19pandemic has raised the need for managing large volumes of real-timeactivity data through data analysis. The aim of this project was to designa dynamic, user-friendly, customizable scorecard in a hospital pharmacyservice for the visualization and analysis of Telepharmacy activity indicators through the use of advanced business intelligence technology.Method: The software tool was developed by a multidisciplinary teambetween April and May 2021, driven from the hospital pharmacy service.Once the Telepharmacy indicators of interest were established, datasetswere extracted from raw databases (administrative databases, Telepharmacy database, outpatient dispensing software, drug catalogues) throughdata analysis. The different data sources were integrated in a scorecardusing PowerBI®. The criteria for processing missing and duplicated datawere defined, and data pre-processing, normalization and transformationwere performed. Once the pilot scorecard was validated by differentprofiles of users, the structure was designed for the panels to automaticallyupdate as databases were updated. Results: Design and implementation of a scorecard of Telepharmacyactivity: general descriptive panel (demographic profile of patients, countand delivery conditions, program and medical service); geolocation ofdestination; pharmacological profile; relative analysis of patients involvedin the Telepharmacy program with respect to the total of outpatients. Inthe last updating as of January 2022, data from 16,000 dispensations tomore than 4,000 patients had been collected. This means that 21.93%of outpatients had benefited at some time point from the Telepharmacyservice. (AU)

May Measurement Month 2017-2019: an analysis of blood pressure screening results from Dominican Republic.

Arterial hypertension is the main risk factor that contributes to cardiovascular disease and represents a leading cause of morbidity and mortality globally. May Measurement Month (MMM) is a global screening campaign with the aim of improving awareness of hypertension at the individual and population level, an initiative that has been supported in the Dominican Republic (DR) since 2017. Adults (≥18 years) were recruited by sampling in different places in the DR, three blood pressure (BP) readings were performed per participant, and data on risk factors and comorbidities were collected. Hypertension was defined as systolic BP ≥140 mm Hg, diastolic BP ≥ 90 mm Hg (mean of second and third readings), and/or taking antihypertensive medication. Multiple imputation was used to estimate participants' mean BP when three readings were not available. Of 3693 participants, 2134 (57.8%) had hypertension, of whom 1646 (77.1%) were taking medication, but only 38.6% of those on treatment had their BP under control(<140/90 mmHg). The remaining 61.4% of the participants received inadequate treatment. A total of 66% of treated patients were taking a single antihypertensive drug. MMM provides an important platform for the standardized compilation of BP data and the creation of awareness of hypertension in the DR and other nations of the world. The data generated from the 2017-2019 MMM campaigns highlight the importance of adequate detection, knowledge, and control of BP.

Searching for the Fusarium spp. Which Are Responsible for Trichothecene Contamination in Oats Using Metataxonomy to Compare the Distribution of Toxigenic Species in Fields from Spain and the UK.

The contamination of oats with Fusarium toxins poses a high risk for food safety. Among them, trichothecenes are the most frequently reported in European oats, especially in northern countries. The environmental conditions related to the climate change scenario might favour a distribution shift in Fusarium species and the presence of these toxins in Southern European countries. In this paper, we present an ambitious work to determine the species responsible for trichothecene contamination in Spanish oats and to compare the results in the United Kingdom (UK) using a metataxonomic approach applied to both oat grains and soil samples collected from both countries. Regarding T-2 and HT-2 toxin producers, F. langsethiae was detected in 38% and 25% of the oat samples from the UK and Spain, respectively, and to the best of our knowledge, this is the first report of the detection of this fungus in oats from Spain. The relevant type B trichothecene producer, F. poae, was the most frequently detected Fusarium species in oats from both origins. Other important trichothecene producers, such as the Fusarium tricinctum species complex or Fusarium cerealis, were also frequently detected in oat fields. Many Fusarium toxins, including T-2 and HT-2 toxins, deoxynivalenol, or nivalenol, were detected in oat samples. The results obtained in this work revealed a clear change in the distribution of trichothecene producers and the necessity to establish the potential of these species to colonize oats and their ability to produce mycotoxins.

Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson's disease cohort.

BACKGROUND: Large-scale Parkinson's disease (PD) genome-wide association studies (GWAS) have, until recently, only been conducted on subjects with European-ancestry. Consequently, polygenic risk scores (PRS) constructed using PD GWAS data are likely to be less predictive when applied to non-European cohorts. METHODS: Using GWAS data from the largest study to date, we constructed a PD PRS for a Latino PD cohort (1497 subjects from LARGE-PD) and tested it for association with PD status and age at onset. We validated the PRS performance by testing it in an independent Latino cohort (448 subjects) and by repeating the analysis in LARGE-PD with the addition of 440 external Peruvian controls. We also tested SNCA haplotypes for association with PD risk in LARGE-PD and a European-ancestry PD cohort. RESULTS: The GWAS-significant PD PRS had an area under the receiver-operator curve (AUC) of 0.668 (95% CI: 0.640-0.695) in LARGE-PD. The inclusion of external Peruvian controls mitigated this result, dropping the AUC 0.632 (95% CI: 0.607-0.657). At the SNCA locus, haplotypes differ by ancestry. Ancestry-specific SNCA haplotypes were associated with PD status in both LARGE-PD and the European-ancestry cohort (p-value < 0.05). These haplotypes both include the rs356182 G-allele, but only share 14% of their variants overall. CONCLUSION: The PD PRS has potential for PD risk prediction in Latinos, but variability caused by admixture patterns and bias in a European-ancestry PD PRS data limits its utility. The inclusion of diverse subjects can help elucidate PD risk loci and improve risk prediction in non-European cohorts.

Impacts of Gaseous Ozone (O3) on Germination, Mycelial Growth, and Aflatoxin B1 Production In Vitro and In Situ Contamination of Stored Pistachio Nuts.

Pistachio nuts can become colonized by mycotoxigenic fungi, especially Aspergillus flavus, resulting in contamination with aflatoxins (AFs). We examined the effect of gaseous O3 (50-200 ppm; 30 min; 6 L/min) on (a) in vitro germination, (b) mycelial growth, and (c) aflatoxin B1 (AFB1) production on a milled pistachio nut-based medium at different water activity (aw) levels and at 30 °C. This was complimented with in situ studies exposing raw pistachio nuts to 50-200 ppm of O3. Exposure of conidia to gaseous O3 initially resulted in lower germination percentages at different aw levels. However, 12 h after treatment, conidial viability recovered with 100% germination after 24-48 h. Growth rates of mycelial colonies were slightly decreased with the increase of the O3 dose, with significant inhibition only at 0.98 aw. The production of AFB1 after O3 treatment and storage for 10 days was stimulated in A. flavus colonies at 0.98 aw. Raw pistachio nuts inoculated with A. flavus conidia prior to O3 exposure showed a significant decrease in population after 20 days of storage. However, AFB1 contamination was stimulated in most O3 treatments. The relationship between exposure concentration, time and prevailing aw levels on toxin control needs to be better understood for these nuts.

Interacting Environmental Stress Factors Affect Metabolomics Profiles in Stored Naturally Contaminated Maize.

There is interest in understanding the relationship between naturally contaminated commodities and the potential for the production of different useful and toxic secondary metabolites (SMs). This study examined the impact of interacting abiotic stress parameters of water availability and temperature of stored naturally contaminated maize on the SM production profiles. Thus, the effect of steady-state storage water activity (aw; 0.80−0.95) and temperature (20−35 °C) conditions on SM production patterns in naturally contaminated maize was examined. The samples were analysed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) to evaluate (a) the total number of known SMs, (b) their concentrations, and (c) changes under two-way interacting environmental stress conditions. A total of 151 metabolites were quantified. These included those produced by species of the Aspergillus, Fusarium and Penicillium genera and other unspecified ones by other fungi or bacteria. There were significant differences in the numbers of SMs produced under different sets of interacting environmental conditions. The highest total number of SMs (80+) were present in maize stored at 20−25 °C and 0.95 aw. In addition, there was a gradation of SM production with the least number of SMs (20−30) produced under the driest conditions of 0.80 aw at 20−30 °C. The only exception was at 35 °C, where different production patterns occurred. There were a total of 38 Aspergillus-related SMs, with most detected at >0.85 aw, regardless of the temperature in the 50−500 ng/g range. For Fusarium-related SMs, the pattern was different, with approx. 10−12 SMs detected under all aw × temperature conditions with >50% produced at 500 ng/g. A total of 40−45 Penicillium-related SMs (50−500 ng/g) were detected in the stored maize but predominantly at 20−25 °C and 0.95 aw. Fewer numbers of SMs were found under marginal interacting abiotic stress storage conditions in naturally contaminated maize. There were approx. eight other known fungal SM present, predominantly in low concentrations (<50 ng/g), regardless of interacting abiotic conditions. Other unspecified SMs present consisted of <20 in low concentrations. The effect of interacting abiotic stress factors for the production of different suites of SMs to take account of the different ecological niches of fungal genera may be beneficial for identifying biotechnologically useful SMs.

De novo genome assembly and functional annotation for Fusarium langsethiae.

BACKGROUND: Fusarium langsethiae is a T-2 and HT-2 mycotoxins producing species firstly characterised in 2004. It is commonly isolated from oats in Northern Europe. T-2 and HT-2 mycotoxins exhibit immunological and haemotological effects in animal health mainly through inhibition of protein, RNA and DNA synthesis. The development of a high-quality and comprehensively annotated assembly for this species is therefore essential in providing the molecular understanding and the mechanism of T-2 and HT-2 biosynthesis in F. langsethiae to help develop effective control strategies. RESULTS: The F. langsethiae assembly was produced using PacBio long reads, which were then assembled independently using Canu, SMARTdenovo and Flye. A total of 19,336 coding genes were identified using RNA-Seq informed ab-initio gene prediction. Finally, predicting genes were annotated using the basic local alignment search tool (BLAST) against the NCBI non-redundant (NR) genome database and protein hits were annotated using InterProScan. Genes with blast hits were functionally annotated with Gene Ontology. CONCLUSIONS: We developed a high-quality genome assembly of a total length of 59 Mb and N50 of 3.51 Mb. Raw sequence reads and assembled genome is publicly available and can be downloaded from: GenBank under the accession JAFFKB000000000. All commands used to generate this assembly are accessible via GitHub: https://github.com/FadyMohareb/fusarium_langsethiae .

Comparison of multiple mycotoxins in harvested maize samples in three years (2018-2020) in four continents.

This study has examined the pattern of mycotoxin contamination of maize destined for animal feed in different global regions over a period of 3 years (2018-2020) with up to 1000+ samples analysed in each year. Overall, >75% of samples in each of the survey years were contaminated with multiple mycotoxins regardless of the global region (Europe, Africa, Asia, South Americas countries). Using LC-MS/MS, it was possible to quantify the relative contamination present in the samples in each year from the different regions of eight different mycotoxins including aflatoxin B1 (AFB1), ochratoxin A (OTA) deoxynivalenol (DON), fumonisin B1 (FB1) and B2, zearalenone (ZEA), T-2 and HT-2 toxins. The trends in mycotoxin contamination showed that there was a consistent contamination with DON in the 3 sampling years in all four regions. Interestingly, AFB1 contamination was prevalent in all regions in 2018, but more predominant in Europe and in 2019. In contrast, in 2020 it was found to be the major contaminant in Africa only. However, FB1 contamination of maize which was prevalent in Europe in 2018, became more prevalent in Asia and LATAM countries in 2019 and even in African maize in 2020. Comparisons of contamination with different mycotoxins in each of the years globally showed significant differences for AFB1, FB1, DON and ZEA between the different years. These results are discussed in relation to the trends of contamination of maize with mixtures of mycotoxins and the implication for their control in this key commodity used as an important ingredient in animal feed.

Comparison of growth and aflatoxin B1 production profiles of Aspergillus flavus strains on conventional and isogenic GM-maize-based nutritional matrices.

Maize grown in both North and South America are now predominantly genetically modified (GM) cultivars with some resistance to herbicide, pesticide, or both. There is little information on the relative colonisation and aflatoxin B1 (AFB1) production with maize meal-based nutritional matrices based on kernels of non-GM maize and isogenic GM-ones by strains of Aspergillus flavus. The objectives were to examine the effect of interacting conditions of temperature (25-35 °C) and water availability (0.99-0.90 water activity, aw) on (a) mycelial growth, (b) AFB1 production and (c) develop contour maps of optimum and marginal conditions of these parameters for four strains of A. flavus on three different non-GM and isogenic GM-maize based nutritional media. The growth of the four strains of A. flavus (three aflatoxigenic; one non-aflatoxigenic) was relatively similar in relation to the temperature × aw conditions examined on both non-GM and GM-based matrices. Optimum growth overall was at 30-35 °C and 0.99 aw for all four strains. Under water stress (0.90 aw) growth was optimum at 35 °C. Statistically: non-GM, GM cultivars, temperature and aw all significantly affected growth rates. For AFB1 production, all single and interacting factors were statistically significant except for non-GM × GM cultivar. In conclusion, colonisation of GM- and non-GM nutritional sources was similar for the different A. flavus strains examined. The contour maps will be very useful for understanding the ecological niches for both toxigenic and non-toxigenic strains in the context of the competitive exclusion of those producing aflatoxins.

Characterizing the Genetic Architecture of Parkinson's Disease in Latinos.

OBJECTIVE: This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. METHODS: We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value <1 × 10-5 were tested in a replication cohort of 1,234 self-reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc. We also performed an admixture mapping analysis where local ancestry blocks were tested for association with PD status. RESULTS: One locus, SNCA, achieved genome-wide significance (p-value <5 × 10-8 ); rs356182 achieved genome-wide significance in both the discovery and the replication cohorts (discovery, G allele: 1.58 OR, 95% CI 1.35-1.86, p-value 2.48 × 10-8 ; 23andMe, G allele: 1.26 OR, 95% CI 1.16-1.37, p-value 4.55 × 10-8 ). In our admixture mapping analysis, a locus on chromosome 14, containing the gene STXBP6, achieved significance in a joint test of ancestries and in the Native American single-ancestry test (p-value <5 × 10-5 ). A second locus on chromosome 6, containing the gene RPS6KA2, achieved significance in the African single-ancestry test (p-value <5 × 10-5 ). INTERPRETATION: This study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study. ANN NEUROL 2021;90:353-365.

Impacts of Climate Change Interacting Abiotic Factors on Growth, aflD and aflR Gene Expression and Aflatoxin B1 Production by Aspergillus flavus Strains In Vitro and on Pistachio Nuts.

Pistachio nuts are an important economic tree nut crop which is used directly or processed for many food-related activities. They can become colonized by mycotoxigenic spoilage fungi, especially Aspergillus flavus, mainly resulting in contamination with aflatoxins (AFs), especially aflatoxin B1 (AFB1). The prevailing climate in which these crops are grown changes as temperature and atmospheric CO2 levels increase, and episodes of extreme wet/dry cycles occur due to human industrial activity. The objectives of this study were to evaluate the effect of interacting Climate Change (CC)-related abiotic factors of temperature (35 vs. 37 °C), CO2 (400 vs. 1000 ppm), and water stress (0.98-0.93 water activity, aw) on (a) growth (b) aflD and aflR biosynthetic gene expression and (c) AFB1 production by two strains A. flavus (AB3, AB10) in vitro on milled pistachio-based media and when colonizing layers of shelled raw pistachio nuts. The A. flavus strains were resilient in terms of growth on pistachio-based media and the colonisation of pistachio nuts with no significant difference when exposed to the interacting three-way climate-related abiotic factors. However, in vitro studies showed that AFB1 production was significantly stimulated (p < 0.05), especially when exposed to 1000 ppm CO2 at 0.98-0.95 aw and 35 °C, and sometimes in the 37 °C treatment group at 0.98 aw. The relative expression of the structural aflD gene involved in AFB1 biosynthesis was decreased or only slightly increased, relative to the control conditions at elevated CO, regardless of the aw level examined. For the regulatory aflR gene expression, there was a significant (p < 0.05) increase in 1000 ppm CO2 and 37 °C for both strains, especially at 0.95 aw. The in situ colonization of pistachio nuts resulted in a significant (p < 0.05) stimulation of AFB1 production at 35 °C and 1000 ppm CO2 for both strains, especially at 0.98 aw. At 37 °C, AFB1 production was either decreased, in strain AB3, or remained similar, as in strain AB10, when exposed to 1000 ppm CO2. This suggests that CC factors may have a differential effect, depending on the interacting conditions of temperature, exposure to CO2 and the level of water stress on AFB1 production.

Comparative Growth Inhibition of Bread Spoilage Fungi by Different Preservative Concentrations Using a Rapid Turbidimetric Assay System.

Bread and intermediate moisture bakery products are mainly spoiled by yeasts and filamentous fungi. The inoculum load and preservation system used determines their shelf life. To extend the shelf life of such commodities, the use of chemical preservatives is the most common way to try and control the initiation of mold spoilage of bread. This study has utilized a rapid turbidimetric assay system (Bioscreen C) to examine the temporal efficacy of calcium propionate (CP) and potassium sorbate (PS) for controlling the growth of important bread spoilage fungi. The objectives were to compare the temporal growth of strains of three important spoilage fungi Hyphopichia burtonii (HB17), Paecilomyces variotii (PV11), and Penicillium roqueforti (PR06) isolated from visibly molded bread to (a) different concentrations of CP and PS (0-128 mM), (b) temperatures (25°C, 30°C), (c) water activity (aw; 0.95, 0.97), and (d) pH (5.0, 5.5). All three abiotic factors, pH, aw, and temperature, and preservative concentrations influenced the relative growth of the species examined. In general, PS was more effective than CP in inhibiting the growth of the strains of these three species. In addition, the Time to Detection (TTD) for the efficacy of the preservatives under the interacting abiotic factors was compared. The strain of Paecilomyces variotii (PV10) was the most tolerant to the preservatives, with the shortest TTD values for both preservatives. P. roqueforti was the most sensitive with the longest TTD values under all conditions examined. These results are discussed in the context of the evolution of resistance to food-grade preservatives by such spoilage fungi in bakery products.