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Abstract Early development of the gut ecosystem is crucial for lifelong health. While infant gut bacterial communities have been studied extensively, the infant gut virome remains under-explored. To study the development of the infant gut virome over time and the factors that shape it, we longitudinally assess the composition of gut viruses and their bacterial hosts in 30 women during and after pregnancy and in their 32 infants during their first year of life. Using shotgun metagenomic sequencing applied to dsDNA extracted from Virus-Like Particles (VLPs) and bacteria, we generate 205 VLP metaviromes and 322 total metagenomes. With this data, we show that while the maternal gut virome composition remains stable during late pregnancy and after birth, the infant gut virome is dynamic in the first year of life. Notably, infant gut viromes contain a higher abundance of active temperate phages compared to maternal gut viromes, which decreases over the first year of life. Moreover, we show that the feeding mode and place of delivery influence the gut virome composition of infants. Lastly, we provide evidence of co-transmission of viral and bacterial strains from mothers to infants, demonstrating that infants acquire some of their virome from their mother’s gut.

Abstract Disrupted host-microbe interactions at the mucosal level are key to the pathophysiology of IBD. This study aimed to comprehensively examine crosstalk between mucosal gene expression and microbiota in patients with IBD. To study tissue-specific interactions, we perform transcriptomic (RNA-seq) and microbial (16S-rRNA-seq) profiling of 697 intestinal biopsies (645 derived from 335 patients with IBD and 52 from 16 non-IBD controls). Mucosal gene expression patterns in IBD are mainly determined by tissue location and inflammation, whereas the mucosal microbiota composition shows a high degree of individual specificity. Analysis of transcript-bacteria interactions identifies six distinct groups of inflammation-related pathways that are associated with intestinal microbiota (adjusted P

Emerging evidence suggests the gut microbiome’s potential in predicting response to biologic treatments in patients with inflammatory bowel disease (IBD). In this prospective study, we aimed to predict treatment response to vedolizumab and ustekinumab, integrating clinical data, gut microbiome profiles based on metagenomic sequencing, and untargeted fecal metabolomics. We aimed to identify predictive biomarkers and attempted to replicate microbiome-based signals from previous studies. We found that the predictive utility of the gut microbiome and fecal metabolites for treatment response was marginal compared to clinical features alone. Testing our identified microbial ratios in an external cohort reinforced the lack of predictive power of the microbiome. Additionally, we could not confirm previously published predictive signals observed in similar sized cohorts. Overall, these findings highlight the importance of external validation and larger sample sizes, to better understand the microbiome’s impact on therapy outcomes in the setting of biologicals in IBD before potential clinical implementation.

IntroductionTransparency and traceability are essential for establishing trustworthy artificial intelligence (AI). The lack of transparency in the data preparation process is a significant obstacle in developing reliable AI systems which can lead to issues related to reproducibility, debugging AI models, bias and fairness, and compliance and regulation. We introduce a formal data preparation pipeline specification to improve upon the manual and error-prone data extraction processes used in AI and data analytics applications, with a focus on traceability.MethodsWe propose a declarative language to define the extraction of AI-ready datasets from health data adhering to a common data model, particularly those conforming to HL7 Fast Healthcare Interoperability Resources (FHIR). We utilize the FHIR profiling to develop a common data model tailored to an AI use case to enable the explicit declaration of the needed information such as phenotype and AI feature definitions. In our pipeline model, we convert complex, high-dimensional electronic health records data represented with irregular time series sampling to a flat structure by defining a target population, feature groups and final datasets. Our design considers the requirements of various AI use cases from different projects which lead to implementation of many feature types exhibiting intricate temporal relations.ResultsWe implement a scalable and high-performant feature repository to execute the data preparation pipeline definitions. This software not only ensures reliable, fault-tolerant distributed processing to produce AI-ready datasets and their metadata including many statistics alongside, but also serve as a pluggable component of a decision support application based on a trained AI model during online prediction to automatically prepare feature values of individual entities. We deployed and tested the proposed methodology and the implementation in three different research projects. We present the developed FHIR profiles as a common data model, feature group definitions and feature definitions within a data preparation pipeline while training an AI model for “predicting complications after cardiac surgeries”.DiscussionThrough the implementation across various pilot use cases, it has been demonstrated that our framework possesses the necessary breadth and flexibility to define a diverse array of features, each tailored to specific temporal and contextual criteria.

Abstract Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. Here, we investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR. Multiple bacterial species are associated with lower HRQoL, many of which have previously been associated with adverse health conditions. Gut microbiome distance to the general population is highest among KTR with an impaired physical HRQoL (R = −0.20, P = 2.3 × 10−65) and mental HRQoL (R = −0.14, P = 1.3 × 10−3). Physical and mental HRQoL explain a significant part of variance in the gut microbiome (R 2 = 0.58%, FDR = 5.43 × 10−4 and R 2 = 0.37%, FDR = 1.38 × 10−3, respectively). Additionally, multiple metabolic and neuroactive pathways (gut brain modules) are associated with lower HRQoL. While the observational design of our study does not allow us to analyze causality, we provide a comprehensive overview of the associations between the gut microbiome and HRQoL while controlling for confounders.

Abstract This editorial presents the vision for the newly formed (2022) European 3D Special Interest Group (EU3DSIG) in the landscape of medical 3D printing. There are four areas of work identified by the EU3DSIG in the current landscape, namely: 1) creating and fostering communication channels among researches, clinicians and industry, 2) generating awareness of hospitals point-of-care 3D technologies; 3) knowledge sharing and education; 4) regulation, registry and reimbursement models.

ABSTRACTThe human gut microbiota continues to demonstrate its importance in human health and disease, largely owing to the countless number of studies investigating the fecal microbiota. Underrepresented in these studies, however, is the role played by microbial communities found in the small intestine, which, given the essential function of the small intestine in nutrient absorption, host metabolism, and immunity, is likely highly relevant. This review provides an overview of the methods used to study the microbiota composition and dynamics along different sections of the small intestine. Furthermore, it explores the role of the microbiota in facilitating the small intestine in its physiological functions and discusses how disruption of the microbial equilibrium can influence disease development. The evidence suggests that the small intestinal microbiota is an important regulator of human health and its characterization has the potential to greatly advance gut microbiome research and the development of novel disease diagnostics and therapeutics.

The printing and manufacturing of anatomical 3D models has gained popularity in complex surgical cases for surgical planning, simulation and training, the evaluation of anatomical relations, medical device testing and patient–professional communication. 3D models provide the haptic feedback that Virtual or Augmented Reality (VR/AR) cannot provide. However, there are many technologies and strategies for the production of 3D models. Therefore, the aim of the present study is to show and compare eight different strategies for the manufacture of surgical planning and training prototypes. The eight strategies for creating complex abdominal oncological anatomical models, based on eight common pediatric oncological cases, were developed using four common technologies (stereolithography (SLA), selectie laser sinterning (SLS), fused filament fabrication (FFF) and material jetting (MJ)) along with indirect and hybrid 3D printing methods. Nine materials were selected for their properties, with the final models assessed for application suitability, production time, viscoelastic mechanical properties (shore hardness and elastic modulus) and cost. The manufacturing and post-processing of each strategy is assessed, with times ranging from 12 h (FFF) to 61 h (hybridization of FFF and SLS), as labor times differ significantly. Cost per model variation is also significant, ranging from EUR 80 (FFF) to EUR 600 (MJ). The main limitation is the mimicry of physiological properties. Viscoelastic properties and the combination of materials, colors and textures are also substantially different according to the strategy and the intended use. It was concluded that MJ is the best overall option, although its use in hospitals is limited due to its cost. Consequently, indirect 3D printing could be a solid and cheaper alternative.

Pediatric surgical oncology is a technically challenging field that relies on CT and MRI as the primary imaging tools for surgical planning. However, recent advances in 3D reconstructions, including Cinematic Rendering, Volume Rendering, 3D modeling, Virtual Reality, Augmented Reality, and 3D printing, are increasingly being used to plan complex cases bringing new insights into pediatric tumors to guide therapeutic decisions and prognosis in different pediatric surgical oncology areas and locations including thoracic, brain, urology, and abdominal surgery. Despite this, challenges to their adoption remain, especially in soft tissue-based specialties such as pediatric surgical oncology. This work explores the main innovative imaging reconstruction techniques, 3D modeling technologies (CAD, VR, AR), and 3D printing applications through the analysis of three real cases of the most common and surgically challenging pediatric tumors: abdominal neuroblastoma, thoracic inlet neuroblastoma, and a bilateral Wilms tumor candidate for nephron-sparing surgery. The results demonstrate that these new imaging and modeling techniques offer a promising alternative for planning complex pediatric oncological cases. A comprehensive analysis of the advantages and limitations of each technique has been carried out to assist in choosing the optimal approach.

Pediatric congenital heart disease (CHD) patients are at higher risk of postoperative complications and clinical deterioration either due to their underlying pathology or due to the cardiac surgery, contributing significantly to mortality, morbidity, hospital and family costs, and poor quality of life. In current clinical practice, clinical deterioration is detected, in most of the cases, when it has already occurred. Several early warning scores (EWS) have been proposed to assess children at risk of clinical deterioration using vital signs and risk indicators, in order to intervene in a timely manner to reduce the impact of deterioration and risk of death among children. However, EWS are based on measurements performed at a single time point without incorporating trends nor providing information about patient's risk trajectory. Moreover, some of these measurements rely on subjective assessment making them susceptible to different interpretations. All these limitations could explain why the implementation of EWS in high-resource settings failed to show a significant decrease in hospital mortality. By means of machine learning (ML) based algorithms we could integrate heterogeneous and complex data to predict patient's risk of deterioration. In this perspective article, we provide a brief overview of the potential of ML technologies to improve the identification of pediatric CHD patients at high-risk for clinical deterioration after cardiac surgery, and present the CORTEX traffic light, a ML-based predictive system that Sant Joan de Déu Barcelona Children's Hospital is implementing, as an illustration of the application of an ML-based risk stratification system in a relevant hospital setting.

Inflammatory bowel diseases are heterogeneous, and little is known about how underlying genetic variation can affect their development. Here, the authors report that intestinal inflammation modulates the effect of host genetics on the gut mucosal expression of 190 genes in the context of inflammatory bowel diseases.

Background: Pre-surgical simulation-based training with three-dimensional (3D) models has been intensively developed in complex surgeries in recent years. This is also the case in liver surgery, although with fewer reported examples. The simulation-based training with 3D models represents an alternative to current surgical simulation methods based on animal or ex vivo models or virtual reality (VR), showing reported advantages, which makes the development of realistic 3D-printed models an option. This work presents an innovative, low-cost approach for producing patient-specific 3D anatomical models for hands-on simulation and training. Methods: The article reports three paediatric cases presenting complex liver tumours that were transferred to a major paediatric referral centre for treatment: hepatoblastoma, hepatic hamartoma and biliary tract rhabdomyosarcoma. The complete process of the additively manufactured liver tumour simulators is described, and the different steps for the correct development of each case are explained: (1) medical image acquisition; (2) segmentation; (3) 3D printing; (4) quality control/validation; and (5) cost. A digital workflow for liver cancer surgical planning is proposed. Results: Three hepatic surgeries were planned, with 3D simulators built using 3D printing and silicone moulding techniques. The 3D physical models showed highly accurate replications of the actual condition. Additionally, they proved to be more cost-effective in comparison with other models. Conclusions: It is demonstrated that it is possible to manufacture accurate and cost-effective 3D-printed soft surgical planning simulators for treating liver cancer. The 3D models allowed for proper pre-surgical planning and simulation training in the three cases reported, making it a valuable aid for surgeons.

Gut microbiome alterations have been linked to inflammatory bowel disease (IBD) and obesity. Here, the authors characterize the metagenomes of four large human cohorts and perform co-abundance network analysis showing that dysbiosis in disease is marked by the altered co-abundance relationships, suggesting that pathway coabundance networks are more heterogeneous than species network.

Abstract Food industries seek to incorporate nutritious ingredients as they could bring added value to the final food products. One of the most interesting options is that sea buckthorn contains high concentrations of vitamin C, carotenoids, tocopherols, and other bioactive compounds, in addition to the unique lipid profile in the berry pulp, seed, and peel. This review summarizes the state-of-the-art of potential applications of sea buckthorn within the food and feed industry based on previously described applications. Products such as cheese, yoghurt or beverages already benefit from its application. Moreover, using sea buckthorn in feed products also derives into higher quality final products (e.g. meat quality, egg quality). Poultry, pig, and fish farming have been studied for that purpose. Despite all the accumulated articles depicted in the present review, the use of this fruit in food product formulation is nowadays scarce. New options for food product development with sea buckthorn are herein discussed. Graphical abstract

Here, via a metagenomics analysis of population-based and disease cohorts, Vich Vila et al. study the impact of 41 commonly used medications on the taxonomic structures, metabolic potential and resistome of the gut microbiome, underscoring the importance of correcting for multiple drug use in microbiome studies.

Context: Oesophageal cancer (EC) is among the common causes of illness and death among all cancers worldwide. Advanced EC has a poor prognosis, with worse outcomes observed in low-income settings. Oesophageal squamous cell carcinoma (ESCC) is the most common EC histology reported globally, with the highest ESCC incidence rates in the ‘Asian Belt’ and the African EC corridor. While the aetiology of ESCC is well-documented in the ‘Asian belt’, data for the African EC corridor and the entirety of sub-Saharan Africa (SSA) are fewer. Objective: To help address gaps in ESCC aetiology in SSA, we critically evaluated evidence of lifestyle, environmental, and epigenetic factors associated with ESCC risk and discussed prospects of defining ESCC exposome. Data inclusion: Unlimited English and non-English articles search were made on PubMed Central and Web of Science databases from January 1970 to August 2021. In total, we retrieved 999 articles and considered meta-analyses, case-control, and cohort studies. The quality of individual studies was assessed using the Newcastle–Ottawa scale. Data extraction: Details extracted include the year of publication, country of origin, sample size, comparators, outcomes, study subjects, and designs. Data analysis: Together, we assessed 13 case-control studies and two meta-analyses for the effect of lifestyle or environmental exposures on ESCC risk. Again, we evaluated seven case-control studies and one meta-analysis regarding the role of epigenetics in ESCC tumorigenesis. Results: In general, evidence of ESCC aetiology points to essential contributions of alcohol, tobacco, hot beverages, biomass fuel, and poor oral health/hygiene, although more precise risk characterisation remains necessary. Conclusion: We conclude that ESCC in SSA is a multifactorial disease initiated by several external exposures that may induce aberrant epigenetic changes. The expanding aetiological research in this domain will be enhanced by evidence synthesis from classical and molecular epidemiological studies spanning the external and internal exposome.

No abstract available.

The human gut harbors numerous viruses infecting the human host, microbes, and other inhabitants of the gastrointestinal tract. Most of these viruses remain undiscovered, and their influence on human health is unknown. Here, we characterize viral genomes in gut metagenomic data from 1950 individuals from four population and patient cohorts. We focus on a subset of viruses that is highly abundant in the gut, remains largely uncharacterized, and allows confident complete genome identification—phages that belong to the class Caudoviricetes and possess genome terminal repeats. We detect 1899 species-level units belonging to this subset, 19% of which do not have complete representative genomes in major public gut virome databases. These units display diverse genomic features, are predicted to infect a wide range of microbial hosts, and on average account for 5% of individuals in a cohort). Finally, we find 34 associations between highly prevalent phages and human phenotypes, 24 of which can be explained by the relative abundance of potential hosts.

Aquest treball exposa el disseny, desenvolupament i avaluació del programa educatiu Taller de Meditació i Literatura (TAMELIT), basat en mindfulness (atenció plena) i el model de meditació del ioga i l’advaita, aplicats a la lectura i interpretació de textos literaris. La dispersió mental en la lectura és la problemàtica per a la qual proposem una solució des de la meditació. Partim de la premissa que desenvolupar l’atenció implica afavorir la lectura i comprensió d’un text, i la possibilitat de la seva recreació interior. Es va oferir com a activitat pròpia del Departament de Filologia Catalana i Lingüística General de la Universitat de Barcelona entre 2018 i 2019. Encara que els resultats no mostren canvis estadísticament significatius en el nivell global de mindfulness, l’anàlisi qualitativa sí que reporta millora d’habilitats relacionades. Es discuteixen els resultats i es proposa estandarditzar els protocols d’intervenció i d’avaluació per poder reproduir la investigació i aprofundir en l’abast de les intervencions de mindfulness en l’àmbit educatiu universitari. Paraules clau: Atenció plena, mindfulness, literatura, educació universitària, meditació, comprensió lectora.

Para Gilles Deleuze, el cine de Alfred Hitchcock culminaba el cine clásico (imagen-movimiento) al mismo tiempo que asentaba las bases de la modernidad (imagen-tiempo). ¿Qué ha ocurrido desde entonces? ¿En qué medida el vínculo sensoriomotor a partir del cual Deleuze fundamentaba ambos sistemas sigue siendo un mecanismo figurativo para el cine contemporáneo? El siguiente artículo considera que Mulholland Drive ha sustituido el canon estético que, en el cine moderno, fue representado por Vértigo. La hipótesis de este texto es que el film de David Lynch explora la imagen-cristal deleuziana desde lo que el mismo Deleuze, a partir de la pintura de Bacon, llamó una “lógica de la sensación”. El desbordamiento de los afectos, la autodestrucción, la pérdida de la identidad, el poder subversivo del deseo o la creencia en un mundo que ya no se conforma con la realidad, son algunos de los elementos que transforman la mirada, la acción y la realidad, ejes principales de la teoría del cine de Deleuze.

Faecal sample collection is crucial for gut microbiome research and its clinical applications. However, while patients and healthy volunteers are routinely asked to provide stool samples, their attitudes towards sampling remain largely unknown. Here, we investigate the attitudes of 780 Dutch patients, including participants in a large Inflammatory Bowel Disease (IBD) gut microbiome cohort and population controls, in order to identify barriers to sample collection and provide recommendations for gut microbiome researchers and clinicians. We sent questionnaires to 660 IBD patients and 112 patients with other disorders who had previously been approached to participate in gut microbiome studies. We also conducted 478 brief interviews with participants in our general population cohort who had collected stool samples. Statistical analysis of the data was performed using R. 97.4% of respondents reported that they had willingly participated in stool sample collection for gut microbiome research, and most respondents (82.9%) and interviewees (95.6%) indicated willingness to participate again, with their motivations for participating being mainly altruistic (57.0%). Responses indicated that storing stool samples in the home freezer for a prolonged time was the main barrier to participation (52.6%), but clear explanations of the sampling procedures and their purpose increased participant willingness to collect and freeze samples (P = 0.046, P = 0.003). To account for participant concerns, gut microbiome researchers establishing cohorts and clinicians trying new faecal tests should provide clear instructions, explain the rationale behind their protocol, consider providing a small freezer and inform patients about study outcomes. By assessing the attitudes, motives and barriers surrounding participation in faecal sample collection, we provide important information that will contribute to the success of gut microbiome research and its near-future clinical applications.

Many chronic diseases are associated with decreased abundance of the gut commensal Faecalibacterium prausnitzii. This strict anaerobe can grow on dietary fibers, e.g., prebiotics, and produce high levels of butyrate, often associated to epithelial metabolism and health. However, little is known about other F. prausnitzii metabolites that may affect the colonic epithelium. Here, we analyzed prebiotic cross-feeding between F. prausnitzii and intestinal epithelial (Caco-2) cells in a “Human-oxygen Bacteria-anaerobic” coculture system. Inulin-grown F. prausnitzii enhanced Caco-2 viability and suppressed inflammation- and oxidative stress-marker expression. Inulin-grown F. prausnitzii produced excess butyrate and fructose, but only fructose efficiently promoted Caco-2 growth. Finally, fecal microbial taxonomy analysis (16S sequencing) from healthy volunteers (n = 255) showed the strongest positive correlation for F. prausnitzii abundance and stool fructose levels. We show that fructose, produced and accumulated in a fiber-rich colonic environment, supports colonic epithelium growth, while butyrate does not.

ABSTRACT Inter-individual heterogeneity in drug response is a serious problem that affects the patient’s wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the impact of individual genetic background on drug response variability or drug toxicity, and recently the gut microbiome, which has also been called the second genome, has been recognized as an important player in this respect. Moreover, the microbiome is a very attractive target for improving drug efficacy and safety due to the opportunities to manipulate its composition. Pharmacomicrobiomics is an emerging field that investigates the interplay of microbiome variation and drugs response and disposition (absorption, distribution, metabolism and excretion). In this review, we provide a historical overview and examine current state-of-the-art knowledge on the complex interactions between gut microbiome, host and drugs. We argue that combining pharmacogenomics and pharmacomicrobiomics will provide an important foundation for making major advances in personalized medicine.

Biomonitoring of biological samples arises as an effective tool to evaluate the exposure to mycotoxins in the population. Owing to the wide range of advantages, there is a growing interest in the use of non- and minimally invasive alternative sampling strategies, such as dried blood spot sampling or volumetric absorptive microsampling (VAMS). A VAMS-based multi-mycotoxin method was developed and validated for 24 different mycotoxins. Method validation was based on the Bioanalytical Method Validation Guideline of the Food and Drug Administration from the United States and for most of the studied mycotoxins, the results of the performance characteristics were in agreement with the criteria of the European Commission Decision 2002/657/EC. The recovery for the different mycotoxins was not haematocrit dependent and remained acceptable after storing the VAMS for 7 and 21 days at refrigeration temperature (4 °C) and room temperature, demonstrating that VAMS could be applied to assess mycotoxin exposure in blood in resource-limited areas, where there may be a delay between sampling and analysis. Finally, a comparison between VAMS and a procedure for liquid whole blood analysis, performed on 20 different blood samples, did not result in missed exposed cases for VAMS. Moreover, both methods detected similar levels of ochratoxin A, ochratoxin alpha, zearalenone and aflatoxin B1. Given all the benefits associated with VAMS and the developed method, VAMS sampling may serve as an alternative to conventional venous sampling to evaluate multiple mycotoxin exposure.

The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.

Since the beginning of this century French cinema has founded a unique universe in which, on one hand, new reports are showing an interest in sexuality and intimacy of the body and, on the other hand, the same bodies are willing to accept the sacrifice, rape or death in exchange for getting it wish. From the analysis of numerous films, the following article exposes that the tendency of new generations born in the transfer of a forged desire and realism that transcends into the fantastic. This transfer involves an investment of codes of French tradition while responding to the same reflection on the image that Nouvelle Vague conceived as travel and search for the Other. Depuis le début de ce siècle le cinéma français s’intéresse à un univers narratif singulier dans lequel, d’une part, les nouveaux récits témoignent d’un intérêt pour la sexualité et l’intimité des corps et, d’autre part, ces mêmes corps sont prêts à accepter le sacrifice, le viol ou la mort en échange du désir. À travers l’analyse de nombreux films, cet article démontre que la tendance des nouvelles générations naît dans le transfert d’un désir forgé dans le domaine du réalisme et qui migre vers le fantastique. Ce transfert suppose une inversion des codes de la tradition française, tout en répondant à la même réflexion que la Nouvelle Vague porte sur l’image : ce doit être un voyage, la recherche de l’Autre.

BackgroundGene-microbiome interactions are important in aetiology and pathogenesis of inflammatory bowel disease, a chronic inflammatory disorder of the gastrointestinal tract consisting of Crohn's disease and ulcerative colitis. Scarce studies on gene-microbiome interactions show very little overlap in their results. Therefore, it is of utmost importance that gene-microbiome studies are repeated. We aimed to replicate the association between the SLC39A8 [Thr]391 risk allele and gut microbiome composition in patients with inflammatory bowel disease and healthy controls.MethodsWe collected faecal samples, peripheral blood and extensive phenotype data from 291 patients with inflammatory bowel disease and 476 healthy controls. Carrier status information was obtained from whole exome sequencing data, generated using the Illumina HiSeq. The gut microbiome composition was determined by tag-sequencing the 16S rRNA gene. Associations between carrier status and disease were tested using the Wilcoxon-Mann-Whitney test. Associations between carriers and gut microbiome composition were determined using principal coordinate analyses, variance explained, alpha diversity and additive general linear models in inflammatory bowel disease, healthy controls and all groups combined.ResultsCrohn's disease patients were more often carriers of the missense variant (21/171, 12.3%) than controls (30/476, 6.3%) (OR = 2.1, P = 0.01). We could not identify associations between carrier status and overall gut microbiome composition and microbial richness in all tested groups after correcting for potential confounding factors. We did identify 37 different operational taxonomical units to be associated with carrier status among the tested groups. Two of these 37 were identified before in the discovery study.ConclusionsWe could confirm the genetic association of the SLC39A8 [Thr]391 risk allele with Crohn's disease but we could only limited replicate the association in gut microbiome composition. Independent replication of gene-microbiome studies is warranted to identify true biological mechanisms.

Citrinin (CIT) is a polyketide mycotoxin occurring in a variety of food and feedstuff, among which cereal grains are the most important contaminated source. Pigs and poultry are important livestock animals frequently exposed to mycotoxins, including CIT. Concerns are rising related to the toxic, and especially the potential nephrotoxic, properties of CIT. The purpose of this study was to clarify the histopathological effects on kidneys, liver, jejunum and duodenum of pigs, broiler chickens and laying hens receiving CIT contaminated feed. During 3 weeks, pigs (n = 16) were exposed to feed containing 1 mg CIT/kg feed or to control feed (n = 4), while 2 groups of broiler chickens and laying hens (n = 8 per group) received 0.1 mg CIT/kg feed (lower dose group) and 3 or 3.5 mg CIT/kg feed (higher dose group), respectively, or control feed (n = 4). CIT concentrations were quantified in plasma, kidneys, liver, muscle and eggs using a validated ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Kidneys, liver, duodenum and jejunum were evaluated histologically using light microscopy, while the kidneys were further examined using transmission electron microscopy (TEM). Histopathology did not reveal major abnormalities at the given contamination levels. However, a significant increase of swollen and degenerated mitochondria in renal cortical cells from all test groups were observed (p < 0.05). These observations could be related to oxidative stress, which is the major mechanism of CIT toxicity. Residues of CIT were detected in all collected tissues, except for muscle and egg white from layers in the lowest dose group, and egg white from layers in the highest dose group. CIT concentrations in plasma ranged between 0.1 (laying hens in lower dose group) and 20.8 ng/mL (pigs). In tissues, CIT concentrations ranged from 0.6 (muscle) to 20.3 µg/kg (liver) in pigs, while concentrations in chickens ranged from 0.1 (muscle) to 70.2 µg/kg (liver). Carry-over ratios from feed to edible tissues were between 0.1 and 2% in pigs, and between 0.1 and 6.9% in chickens, suggesting a low contribution of pig and poultry tissue-derived products towards the total dietary CIT intake for humans.

Several studies have shown that binge drinking of alcoholic beverages leads to non-desirable outcomes, which have become a serious threat to public health. However, the bioactive compounds in some alcohol-containing beverages might mitigate the negative effects of alcohol. In beer, the variety and concentration of bioactive compounds in the non-alcoholic fraction suggests that its consumption at moderate levels may not only be harmless but could also positively contribute to an improvement of certain physiological states and be also useful in the prevention of different chronic diseases. The present review focuses on the effects of non-alcoholic components of beer on abdominal fat, osteoporosis, and body hydration in women, conditions selected for their relevance to health and aging. Although beer drinking is commonly believed to cause abdominal fat deposition, the available literature indicates this outcome is inconsistent in women. Additionally, the non-alcoholic beer fraction might improve bone health in postmenopausal women, and the effects of beer on body hydration, although still unconfirmed seem promising. Most of the health benefits of beer are due to its bioactive compounds, mainly polyphenols, which are the most studied. As alcohol-free beer also contains these compounds, it may well offer a healthy alternative to beer consumers.

Deoxynivalenol is one of the most ubiquitous mycotoxins in the Western diet through its presence in cereals and cereal products. A vast amount of studies indicate the worrying level of exposure to this toxin, while even high percentages of the population exceed the tolerable daily intake. To evaluate and assess dietary exposure, analysis of urinary levels of deoxynivalenol and its glucuronides has been proposed as a reliable methodology. An indirect preliminary method was used based on the cleavage of deoxynivalenol glucuronides through the use of enzymes (β-glucuronidase) and subsequent determination of "total deoxynivalenol" (sum of free and released mycotoxins by hydrolysis). Next, a direct procedure for quantification of deoxynivalenol-3-glucuronide and deoxynivalenol-15-glucuronide was developed. As deoxynivalenol glucuronides reference standards are not commercially available, the indirect method is widely applied. However, to not underestimate the total deoxynivalenol exposure in urine, the direct and indirect methodologies need to be compared. Urinary samples (n = 96) with a confirmed presence of deoxynivalenol and/or deoxynivalenol glucuronides were analysed using both approaches. The indirect method clarified that not all deoxynivalenol glucuronides were transformed to free deoxynivalenol during enzymatic treatment, causing an underestimation of total deoxynivalenol. This short communication concludes on the application of direct or indirect assessment of urinary deoxynivalenol.

Zearalenone and alternariol are mycotoxins produced by Fusarium and Alternaria species, respectively, that present estrogenic activity and consequently are classified as endocrine disruptors. To estimate the exposure of the Portuguese population to these two mycotoxins at a national level, a modelling approach, based on data from 94 Portuguese volunteers, was developed considering as inputs: i) the food consumption data generated within the National Food and Physical Activity Survey; and ii) the human biomonitoring data used to assess the exposure to the referred mycotoxins. Six models of association between mycoestrogens urinary levels (zearalenone, total zearalenone and alternariol) and food items (meat, cheese, and fresh-cheese, breakfast cereals, sweets) were established. Applying the obtained models to the consumption data (n = 5811) of the general population, the median estimates of the probable daily intake revealed that a fraction of the Portuguese population might exceed the tolerable daily intake defined for zearalenone. A reference intake value for alternariol is still lacking, thus the characterization of risk due to the exposure to this mycotoxin was not possible to perform. Although the unavoidable uncertainties, these results are important contributions to understand the exposure to endocrine disruptors in Portugal and the potential Public Health consequences.

This article covers the time from 1985 to 1992 in the history of the Swaziland Reformed Church (SRC). In 1985, for the first time in its existence, the SRC had four missionaries working in the four districts of the country. At this stage the SRC formed a presbytery within the synodical region of the Dutch Reformed Church in Africa (DRCA) of Northern Transvaal. In 1989 – at its own request – this church became a regional synod within the DRCA. However, not long thereafter, in 1992, it was forced to become an independent Reformed church, even though it still remained part of the family of Dutch Reformed churches. Making use of original documents, this article records this history of the SRC.

This article covers the time from 1652 onwards when employees of the Dutch East India Company – most of whom were members of the Reformed Church in the Netherlands – arrived at the Cape of Good Hope in present South Africa. With time, a new church, the Dutch Reformed Church, was established in the Cape. In 1836, a number of pioneers moved from the Cape to the east of South Africa and some of them eventually made Swaziland their new home. Although most members of the white Dutch Reformed Church opposed any integration with Christians from other races, there was nevertheless a desire that they should join a Reformed Church. In 1922, the first Dutch Reformed congregation in Swaziland was established in Goedgegun in the southern region of the country, intended for the exclusive use of white, Afrikaans-speaking church members. In 1944, the first Reformed congregation for Swazi members was formed, which later became known as the Swaziland Reformed Church. This article documents the history of this church and concludes with a description of the Swaziland Reformed Church in 1985, with four missionaries from South Africa ministering in the four regions of Swaziland.

Aspergillus flavus is the main producer of carcinogenic aflatoxins in agricultural commodities such as maize. This fungus occurs naturally on crops, and produces aflatoxins when environmental conditions are favorable. The aim of this study is to analyse the genetic variability among 109 A. flavus isolates previously recovered from maize sampled from a known aflatoxin-hotspot (Eastern region, Kenya) and the major maize-growing area in the Rift Valley (Kenya), and to determine their toxigenic potential. DNA analyses of internal transcribed spacer (ITS) regions of ribosomal DNA, partial β-tubulin gene (benA) and calmodulin gene (CaM) sequences were used. The strains were further analyzed for the presence of four aflatoxin-biosynthesis genes in relation to their capability to produce aflatoxins and other metabolites, targeting the regulatory gene aflR and the structural genes aflP, aflD, and aflQ. In addition, the metabolic profile of the fungal strains was unraveled using state-of-the-art LC-MS/MS instrumentation. The three gene-sequence data grouped the isolates into two major clades, A. minisclerotigenes and A. flavus. A. minisclerotigenes was most prevalent in Eastern Kenya, while A. flavus was common in both regions. A. parasiticus was represented by a single isolate collected from Rift Valley. Diversity existed within the A. flavus population, which formed several subclades. An inconsistency in identification of some isolates using the three markers was observed. The calmodulin gene sequences showed wider variation of polymorphisms. The aflatoxin production pattern was not consistent with the presence of aflatoxigenic genes, suggesting an inability of the primers to always detect the genes or presence of genetic mutations. Significant variation was observed in toxin profiles of the isolates. This is the first time that a profound metabolic profiling of A. flavus isolates was done in Kenya. Positive associations were evident for some metabolites, while for others no associations were found and for a few metabolite-pairs negative associations were seen. Additionally, the growth medium influenced the mycotoxin metabolite production. These results confirm the wide variation that exists among the group A. flavus and the need for more insight in clustering the group.

Del héroe de “Cuentos morales” (1963-1972) a la heroína de “Comedias y proverbios” (1981-1987) Éric Rohmer establece el paso de un cine fundado en una lógica de acción a un cine de videncia. De acuerdo con esta idea, a partir de la cual Gilles Deleuze piensa el paso de la imagen-movimiento a la imagen-tiempo, las siguientes páginas retoman el estudio de la primera serie del cineasta para ver en la feminidad abandonada por el héroe (Haydée, Maud, Chloé o Claire) los principios con los que Rohmer concibe sus heroínas posteriores y una nueva lógica de relato. Para ello, por un lado, el artículo revisita los estudios que abordan la puesta en escena de “Cuentos morales” a partir del pensamiento del héroe y de la palabra en particular; por otro lado, propone el deseo y la idea de alteridad como el método que permite pensar la imagen y la palabra en su conjunto, esto es, la mostración y el lenguaje, elementos que, siguiendo las ideas de André Bazin, Rohmer define la naturaleza ambigua del cinematógrafo.

Biomarkers for the determination of the dietary exposure to deoxynivalenol (DON) have been proposed in the past but so far no quantification of their use in humans has been carried out. Following a human intervention study with two mycotoxins, namely DON and deoxynivalenol-3-glucoside (DON3G), the renal excretion of these compounds, including their phase II metabolites, was analysed. The purpose was to develop biokinetic models that can be used to determine: (1) the preferred (set of) urinary biomarker(s), (2) the preferred urinary collection period, and (3) a method to estimate the dietary exposure to these mycotoxins. Twenty adult volunteers were restricted in consuming cereals and cereal-based foods for 4 days. At day 3, a single dose of 1 µg/kg body weight of DON or DON3G was orally administered to 16 volunteers; 4 volunteers served as control. All individual urine discharges were collected during 24 h after administration. The metabolism and renal excretion could be described by a biokinetic model using three physiological compartments (gastrointestinal tract, liver, and kidneys). Kinetic analysis revealed a complete recovery of the renal excretion of total DON (mainly DON and its glucuronides) within 24 h after administration of DON or DON3G. The so-called ‘reverse dosimetry’ factor was used to determine the preferred (set of) biomarker(s) and to estimate the dietary intake of the parent compounds in the future. The fact that DON3G was absorbed and mainly excreted as DON and its glucuronides confirms that DON3G (as well as other modified forms) should be taken into account in the exposure and risk assessment of this group of mycotoxins.

Cincuenta años después del nacimiento de la Nouvelle Vague, sus herencias recibidas en el cine contemporáneo son inevitables. Figuras y motivos visuales; relatos, temas, rostros o lugares comunes; recursos estéticos y de lenguaje. Los ecos se manifiestan de diversos modos, cada filiación implica una relación distinta y por tanto una aproximación dispar para su análisis. Y sin embargo, tanto la academia como la crítica de cine siguen pensando en la Nouvelle Vague como un conjunto, un universo, una corriente o una tendencia estética. Pero, ¿existe una estética nouvellevaguesca? Y, si es así, ¿por qué abordar de nuevo su revisión histórica? A partir de las tesis de Deleuze sobre la imagen-tiempo y de la aseveración de Serge Daney según la cual la Nouvelle Vague contribuyó al paso de un cine del ideal a un cine de la alteridad, el artículo siguiente da respuesta a estas preguntas partiendo de la convicción que los cineastas franceses no crearon un estilo, sino que asentaron un método. Este método consistiría en poner en crisis una relación propia de la narración para hallar una nueva relación en términos de montaje y puesta en escena. En particular, el artículo sostiene que la Nouvelle Vague aboga por esta aproximación haciendo del filme el espacio que permite pensar la visibilidad de la imagen y su figurabilidad a partir de la búsqueda y la pérdida del objeto de deseo en el relato, de lo que resulta una lógica de las imágenes a medio camino entre la representación y la figuración. Para abordar el análisis, el artículo propone una revisión de las primeras obras de François Truffaut, Jean-Luc Godard y Alain Resnais, y el cine de Philippe Garrel como representante de la primera generación francesa después de la Nouvelle Vague.

Hace treinta años Roland Barthes buscaba un tercer nivel de lectura de imágenes que se alejaba de la rígida lectura informativa y simbólica para dejar que fuese el significante quien hablara. Sus análisis llegaron a su mayor notoriedad en el estudio de la fotografía La chambre claire. El artículo siguiente parte de que la hipótesis que Barthes dejó en sus notas sobre el medio fotográfico resuena hoy por un lado en la miniaturización de los recursos y la instantaneidad del soporte de la cámara de vídeo digital y por otro lado, en el principio de modularidad y accesibilidad de los nuevos medios. En una segunda parte, el texto ahonda en la idea de la memoria barthesiana y en el paralelismo que toma junto con las reflexiones que Jean-Luc Godard concedió a través de la imagen electrónica. La aparente arbitrariedad en la selección de las imágenes que integran el estudio sigue el análisis de Barthes, por ello, responde a un criterio de confianza en la espontaneidad y en la memoria del autor.