Mechanisms linking colorectal cancer to the consumption of (processed) red meat : a review

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. The vast majority of CRC cases have been linked to environmental causes rather than to heritable genetic changes. Over the last decades, epidemiological evidence linking the consumption of red and, more convincingly, of processed red meat to CRC has accumulated. In parallel, hypotheses on carcinogenic mechanisms underlying an association between CRC and the intake of red and processed red meat have been proposed and investigated in biological studies. The hypotheses that have received most attention until now include (1) the presence of polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, two groups of compounds recognized as carcinogenic, (2) the enhancing effect of (nitrosyl)heme on the formation of carcinogenic N-nitroso compounds and lipid peroxidation. However, none of these hypotheses completely explains the link between red and processed red meat intake and the CRC risk. Consequently, scientists have proposed additional mechanisms or refined their hypotheses. This review first briefly summarizes the development of CRC followed by an in-depth overview and critical discussion of the different potential carcinogenic mechanisms underlying the increased CRC risk associated with the consumption of red and processed red meat

Microbial monitoring and degradation of lindane in soil

Lindane (γ-hexachlorocyclohexane, γ-HCH), once the most applied insecticide worldwide, is still considered a serious threat to the environment, due to its persistence in soil and water and to its potential to bioaccumulate in the food chain. Other ubiquitous HCH-isomers, formed as waste products during the production of lindane, also pose a major environmental threat. Because of the widespread pollution by lindane (and other HCH-isomers), there is a need for risk assessment tools to monitor its environmental impact. Monitoring of polluted sites is as yet often restricted to the quantification of the contaminant by means of chemical analyses. In soil the use of microorganisms as indicator tools in monitoring procedures offers many opportunities, because of their ability to respond and rapidly adapt to changes in environmental conditions. As yet, removal of lindane from the environmental compartments has attained the highest priority. A possible approach is bioremediation, the process by which living organisms degrade the contaminant. A technology often used in bioremediation is bioaugmentation, in which specialized microorganisms are introduced into the environment in order to metabolize the targeted compound. Despite its long-term use in bioremediation, bioaugmentation of contaminated sites with microbial cells continues to be a source of controversy within environmental microbiology. This largely results from its notoriously unreliable performance record. In a first part of this research, the applicability of methane oxidation, an important soil function performed by methanotrophic bacteria, was evaluated as a microbial indicator for the monitoring of HCH pollution. The effect of HCH on both the activity and the structure of the methanotrophic community was assessed, using methane oxidation assays and PCR-DGGE (polymerase chain reaction – denaturing gradient gel electrophoresis) respectively. Methane oxidation assays with historically polluted soils revealed that in the long-term methane oxidation was inhibited by HCH pollution. PCR-DGGE and diversity analysis based on Lorenz curves showed that the type I methanotrophic community was less evenly distributed in historically HCH polluted soils compared to less polluted reference soils. Short-term experiments with methane enriched consortia further demonstrated that only γ and δ isomers inhibited methane oxidation. Type I methanotrophs of methane enriched microbial consortia that received γ- or δ-HCH evolved towards higher species richness. Apparently, for historically HCH polluted soils, a narrow community remained after long-term exposure, while in case of short-term exposures, methane enriched consortia were converted into less active, but richer communities when they were stressed by the presence of γ- or δ-HCH. These results demonstrated that methane oxidation activity and structural analysis of type I methanotrophic communities, can be valuable tools in risk assessment studies and the monitoring of HCH pollution. The second part of this doctoral research aimed to develop a promising bioaugmentation technology for the aerobic biodegradation of lindane by surveying microbiological inoculants and by designing a suitable inoculation procedure for their introduction into the environment. The occurrence of HCH degraders was investigated in several contaminated soils. Thirty five enrichment cultures grown on different HCH-isomers yielded 16 cultures in which HCH was removed. HCH-degrading populations were clearly associated with HCH-contaminated soils. Nine HCH-degrading isolates could subsequently be isolated, which were all Sphingomonas spp.. All isolates degraded α- and γ-HCH, while degradation of β- and δ-HCH was highly strain dependent. However, none of the isolates grew on HCH as a sole organic substrate in pure culture. DGGE analyses evaluated whether enrichment of HCH degraders occurred in situ at contaminated sites. Most soils were characterized by diverse bacterial communities, although one soil contained a predominant ribotype, possibly selected by the HCH contamination. However, the latter population was not selected in the enrichment culture from that soil. Furthermore, DGGE analyses indicated that the isolates represented predominant populations in the enrichment cultures, but additional predominant populations, including some Pseudomonas spp., could not be isolated. Isolated strains were subsequently used to assess the feasibility of a slow-release inoculation approach as a bioaugmentation strategy for the degradation of lindane. Slow-release inoculation of Sphingomonas sp. γ1-7 was established in both liquid and soil slurry microcosms, using open ended silicone tubes in which the bacteria are encapsulated in a protective nutrient rich matrix. The capacity of the encapsulated cells to degrade lindane under aerobic conditions was evaluated in comparison with inoculation of free living cells. Encapsulation of cells in silicone tubes caused removal of lindane by adsorption to the silicone tubes, but also ensured prolonged biodegradation activity. Lindane degradation persisted 2.2 and 1.4 times longer, for liquid and soil slurry microcosms respectively, compared to inoculation with free cells. While inoculation of free living cells led to a loss in lindane degrading activity in limited time intervals, encapsulation in these tubes allowed for a more stable actively degrading population. The loss in degrading activity was linked to the loss of the linA gene, encoding γ-HCH dehydrochlorinase (LinA) which is involved in the initial steps of the lindane degradation pathway. Further, the sustained degradation of lindane by Sphingomonas sp. γ1-7 in open ended tubes was evaluated over an extended period of time. It was shown that the slow-release approach by inoculation of encapsulated cells in open ended tubes provided stable lindane degradation for over 4 months, whereas freely inoculated cells could not maintain degradation for longer than one month. Several factors that could possibly regulate this sustained lindane degradation by encapsulated Sphingomonas spp. were systematically assessed in liquid medium. The obtained results indicated that in a relatively nutrient rich medium, nutrient conditions inside the tubes did not influence the rate of lindane degradation. Also, initial cell density inside the tubes only exerted a temporary positive effect on lindane degradation. Quorum sensing regulated gene expression was also assessed, but most likely did not occur. Physical protection from high lindane concentrations or potentially toxic metabolites is likely the prevailing advantage provided by the encapsulation in tubes, although preliminary results also indicate the potential role of increased plasmid stability. In a third and final experimental part of this work, an alternative lindane removal technique was proposed, making use of the catalytic reduction of HCH over a metal catalyst, namely palladium (Pd[0]). Since specific surface area plays an important role in reactivity of catalysts, this study investigated the use of bioPd(0), i.e. nano-scale Pd(0) particles precipitated on the biomass of Shewanella oneidensis, for the removal of lindane. It was demonstrated that bioPd(0) has catalytic activity towards dechlorination of lindane, with the addition of formate as electron donor, and that dechlorination with bioPd(0) was more efficient than with commercial powdered Pd(0). The biodegradable compound benzene was formed as a reaction product and other HCH-isomers could also be dechlorinated. Subsequently, bioPd(0) was implemented in a membrane reactor technology for the treatment of lindane polluted water. In a fed-batch process configuration with formate as electron donor, a removal percentage of 98% of γ-HCH saturated water (10 mg l-1) was achieved within 24 hours. The measured chloride mass balance approached the theoretical value. These results demonstrate, a complete, efficient and fast removal of lindane using catalytic reduction with bioPd(0). In conclusion, this work has shown that in risk assessment and ecotoxicological studies of lindane, the soil methanotrophs represent a sensitive bacterial group, with great potential to be used as indicators for the monitoring of HCH soil pollution. Further research is recommended for the development and validation of methane oxidation bioassays, based on the findings of this research. Slow-release bioaugmentation with encapsulated lindane degrading Sphingomonas spp. in open ended tubes was demonstrated to be a promising tool for soil bioremediation. Although several insights into the mechanisms of the ‘hot spot’ tubes were provided by the present research, more work needs to be done to unravel their true identity. Future research should certainly focus on the further upscaling of this technique for (in situ) soil applications. Finally, the application of an alternative lindane degradation technique - biocatalytic reduction with bioPd(0) - resulted in a complete, efficient and fast removal of lindane, and was demonstrated to be applicable as a membrane based reactor technology

Mechanisms controlling anaemia in Trypanosoma congolense infected mice.

Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia. The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng. The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from haemolysis induced anaemia after infection

An Adaptive Virtual Training System Based on Universal Design

The increasing complexity of manufacturing environments requires effective training systems to prepare the operation personnel for their tasks. Several training systems have been proposed. A common approach is the application of virtual environments to train interactions with an industrial machine in a safe, attractive, and efficient way. However, these training systems cannot adapt to the requirements of an increasingly diversified workforce. This paper introduces an approach for the design of an adaptive virtual training system based on the idea of universal design. The system is based on a two-step approach that consists of an initial adaptation to the user capabilities and real-time adaptations during training based on measurements of the user. The adaptations concern the use of different representations of lessons with different complexity and interaction modalities. The proposed approach provides a flexible training system that can adapt to the needs of a broad group of users

Pollutant exposure and myocardial injury: Protocol and progress report for a toxicological systematic mapping review

An increasing body of evidence identifies pollutant exposure as a risk factor for cardiovascular disease (CVD), while CVD incidence rises steadily with the aging population. Although numerous experimental studies are now available, the mechanisms through which lifetime exposure to environmental pollutants can result in CVD are not fully understood. To comprehensively describe and understand the pathways through which pollutant exposure leads to cardiotoxicity, a systematic mapping review of the available toxicological evidence is needed. This protocol outlines a step-by-step framework for conducting this review. Using the National Toxicology Program (NTP) Health Assessment and Translation (HAT) approach for conducting toxicological systematic reviews, we selected 362 out of 8111 in vitro (17%), in vivo (67%), and combined (16%) studies for 129 potential cardiotoxic environmental pollutants, including heavy metals (29%), air pollutants (16%), pesticides (27%), and other chemicals (28%). The internal validity of included studies is being assessed with HAT and SYRCLE Risk of Bias tools. Tabular templates are being used to extract key study elements regarding study setup, methodology, techniques, and (qualitative and quantitative) outcomes. Subsequent synthesis will consist of an explorative meta-analysis of possible pollutant-related cardiotoxicity. Evidence maps and interactive knowledge graphs will illustrate evidence streams, cardiotoxic effects and associated quality of evidence, helping researchers and regulators to efficiently identify pollutants of interest. The evidence will be integrated in novel Adverse Outcome Pathways to facilitate regulatory acceptance of non-animal methods for cardiotoxicity testing. The current article describes the progress of the steps made in the systematic mapping review process

Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy (CIPN) with Non-Pharmacological Interventions: Clinical Recommendations from a Systematic Scoping Review and an Expert Consensus Process

Background: Most individuals affected by cancer who are treated with certain chemotherapies suffer of CIPN. Therefore, there is a high patient and provider interest in complementary non-pharmacological therapies, but its evidence base has not yet been clearly pointed out in the context of CIPN. Methods: The results of a scoping review overviewing the published clinical evidence on the application of complementary therapies for improving the complex CIPN symptomatology are synthesized with the recommendations of an expert consensus process aiming to draw attention to supportive strategies for CIPN. The scoping review, registered at PROSPERO 2020 (CRD 42020165851), followed the PRISMA-ScR and JBI guidelines. Relevant studies published in Pubmed/MEDLINE, PsycINFO, PEDro, Cochrane CENTRAL, and CINAHL between 2000 and 2021 were included. CASP was used to evaluate the methodologic quality of the studies. Results: Seventy-five studies with mixed study quality met the inclusion criteria. Manipulative therapies (including massage, reflexology, therapeutic touch), rhythmical embrocations, movement and mind–body therapies, acupuncture/acupressure, and TENS/Scrambler therapy were the most frequently analyzed in research and may be effective treatment options for CIPN. The expert panel approved 17 supportive interventions, most of them were phytotherapeutic interventions including external applications and cryotherapy, hydrotherapy, and tactile stimulation. More than two-thirds of the consented interventions were rated with moderate to high perceived clinical effectiveness in therapeutic use. Conclusions: The evidence of both the review and the expert panel supports a variety of complementary procedures regarding the supportive treatment of CIPN; however, the application on patients should be individually weighed in each case. Based on this meta-synthesis, interprofessional healthcare teams may open up a dialogue with patients interested in non-pharmacological treatment options to tailor complementary counselling and treatments to their needs

Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health

Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.The European Partnership for the Assessment of Risks from Chemicals has received funding from the European Union’s Horizon Europe research and innovation program under Grant Agreement No 101057014 and has received co-funding of the authors’ institutions. Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.info:eu-repo/semantics/publishedVersio

Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human health

Enniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA). The tolerable daily intake and maximum levels for ENNs in humans and animals remain unestablished due to key toxicological and toxicokinetic data gaps, preventing full risk assessment. Aiming to find critical data gaps impeding hazard characterization and risk evaluation, this review presents a comprehensive summary of the existing information from in vitro and in vivo studies on toxicokinetic characteristics and cytotoxic, genotoxic, immunotoxic, endocrine, reproductive and developmental effects of the most prevalent ENN analogues (ENN A, A1, B, B1) and BEA. The missing information identified showed that additional studies on ENNs and BEA have to be performed before sufficient data for an in-depth hazard characterisation of these mycotoxins become available.Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human healthpublishedVersio

Prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN) with non-pharmacological interventions : clinical recommendations from a systematic scoping review and an expert consensus process

Background: Most individuals affected by cancer who are treated with certain chemotherapies suffer of CIPN. Therefore, there is a high patient and provider interest in complementary non-pharmacological therapies, but its evidence base has not yet been clearly pointed out in the context of CIPN. Methods: The results of a scoping review overviewing the published clinical evidence on the application of complementary therapies for improving the complex CIPN symptomatology are synthesized with the recommendations of an expert consensus process aiming to draw attention to supportive strategies for CIPN. The scoping review, registered at PROSPERO 2020 (CRD 42020165851), followed the PRISMA-ScR and JBI guidelines. Relevant studies published in Pubmed/MEDLINE, PsycINFO, PEDro, Cochrane CENTRAL, and CINAHL between 2000 and 2021 were included. CASP was used to evaluate the methodologic quality of the studies. Results: Seventy-five studies with mixed study quality met the inclusion criteria. Manipulative therapies (including massage, reflexology, therapeutic touch), rhythmical embrocations, movement and mind-body therapies, acupuncture/acupressure, and TENS/Scrambler therapy were the most frequently analyzed in research and may be effective treatment options for CIPN. The expert panel approved 17 supportive interventions, most of them were phytotherapeutic interventions including external applications and cryotherapy, hydrotherapy, and tactile stimulation. More than two-thirds of the consented interventions were rated with moderate to high perceived clinical effectiveness in therapeutic use. Conclusions: The evidence of both the review and the expert panel supports a variety of complementary procedures regarding the supportive treatment of CIPN; however, the application on patients should be individually weighed in each case. Based on this meta-synthesis, interprofessional healthcare teams may open up a dialogue with patients interested in non-pharmacological treatment options to tailor complementary counselling and treatments to their needs