Search

BackgroundClostridioides difficile is a Gram-positive anaerobic bacterium that can produce the toxins TcdA and/or TcdB and is considered an opportunistic pathogen. C. difficile is mainly transmitted as endospores, which germinate to produce the pathogenic vegetative cells under suitable conditions in the gut. To efficiently screen novel therapeutic- interventions against the proliferation of C. difficile within a complex microbial community, platforms are needed that facilitate parallel experimentation. In order to allow for screening of novel interventions a medium-to-high throughput in vitro system is desirable. To this end, we have developed the 96-well CDi-screen platform that employs an adapted simulated ileal effluent medium (CDi-SIEM) and allows for culturing of pathogenic C. difficile.MethodsC. difficile strain ATCC 43599 was inoculated in the form of vegetative cells and spores into the CDi-screen in the presence and absence of a cultured fecal microbiota and incubated for 48h. To demonstrate its utility, we investigated the effect of the human milk oligosaccharide 2’-Fucosyllactose (2’-FL) at 4 and 8 mg/mL on C. difficile outgrowth and toxin production in the CDi-screen. The test conditions were sampled after 24 and 48 hours. C. difficile -specific primers were used to monitor C. difficile growth via qPCR and barcoded 16S rRNA gene amplicon sequencing facilitated the in-depth analysis of gut microbial community dynamics.ResultsC. difficile ATCC 43599 proliferated in CDi-SIEM, both when inoculated as spores and as vegetative cells. The strain reached cell numbers expressed as C. difficile genome equivalents of up to 10 8 cells per mL after 24h of incubation. 2’-FL significantly inhibited the outgrowth of the ATTC 43599 strain within a complex human gut microbial community in the CDi-screen. In addition, a dose-dependent modulation of the gut microbial community composition by 2’-FL supplementation was detected, with a significant increase in the relative abundance of the genus Blautia in the presence of 2’-FL.ConclusionThe CDi-screen is suitable for studying C. difficile proliferation in a complex gut ecosystem and for screening for anti-pathogenic interventions that target C. difficile directly and/or indirectly through interactions with the gut microbiota. Different doses of compounds such as in this study the dose of the human milk oligosaccharide 2’-FL can be screened for efficacy in the inhibition of C. difficile proliferation.

Resumen del póster presentado al International Scientific Association for Probiotics and Prebiotics Annual Meeting (ISAPP), celebrado en Sitges. Barcelona (España) del 15 al 17 de junio de 2022., Carbohydrates entering the complex microbial ecosystem resident in the human gut can be fermented to different degrees by the bacterial species present. Whilst insoluble carbohydrates may be fermented to a low degree, they may still be classed dietary fibres. More extensively fermented carbohydrates frequently display a selectivity towards particular microbial groups; if the end result of this process is an improvement in host health, then we would consider those carbohydrates to be prebiotics. It is a complex task to identify the structural basis of the fermentation selectivity underlying a prebiotic effect. Individuals vary in terms of the diversity of their gut microbiome and in the response of this microbiome to any given carbohydrate. The task is further complicated by the use of varying microbiology techniques across studies. Some generic understanding can be identified: It is clear that low molecular weight carbohydrates of a wide range of structure are very readily metabolised by bifidobacteria and are frequently seen to select for this genus in in vitro studies.. This selectivity is explained by the widespread presence of exo-glycosidase and sugar transport system genes in bifidobacterial genomes. Metabolism of higher molecular weight carbohydrates is dependant of organisms possessing the relevant polysaccharide utilisation genes like the bacteroides, rendering them highly adept at polysaccharide metabolism. To understand the fate of any given carbohydrate in the gut microbiome, however, the presence of cross-feeding networks must be taken into account. We know of some such cross feeding networks likely to operate in the gut but there is much to learn. ILSI Europe has commissioned an expert group to produce an authoritative view of the state of the art in terms of our understanding of structure function relationships in fermented carbohydrates. This presentation will highlight our current understanding of structure function relationships and point to the gaps in knowledge and the questions that arise in this area.

Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetylation in DIPG favors the action of the Bromodomain and Extra-Terminal (BET) protein BRD4, and leads to the reprogramming of the enhancer landscape contributing to the activation of DIPG super enhancer-driven oncogenes. The activity of the acetyltransferase CREB-binding protein (CBP) is enhanced by BRD4 and associated with acetylation of nucleosomes at super enhancers (SE). In addition, CBP contributes to transcriptional activation through its function as a scaffold and protein bridge. Monotherapy with either a CBP (ICG-001) or BET inhibitor (JQ1) led to the reduction of tumor-related characteristics. Interestingly, combined treatment induced strong cytotoxic effects in H3.3K27M-mutated DIPG cell lines. RNA sequencing and chromatin immunoprecipitation revealed that these effects were caused by the inactivation of DIPG SE-controlled tumor-related genes. However, single treatment with ICG-001 or JQ1, respectively, led to activation of a subgroup of detrimental super enhancers. Combinatorial treatment reversed the inadvertent activation of these super enhancers and rescued the effect of ICG-001 and JQ1 single treatment on enhancer-driven oncogenes in H3K27M-mutated DIPG, but not in H3 wild-type pedHGG cells. In conclusion, combinatorial treatment with CBP and BET inhibitors is highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy.

Halogenated natural products (HNPs) show a wide range of interesting biological activities. Chemistry‐guided screening with a software tool dedicated to identifying halogenated compounds in HPLC‐MS data indicated the presence of several uncharacterised HNPs in an extract of the cyanobacterium Fischerella ambigua (Näg.) Gomont 108b. Three new natural products, tjipanazoles K, L, and M, were isolated from this strain together with the known tjipanazoles D and I. Taking into account the structures of all tjipanazole derivatives detected in this strain, reanalysis of the tjipanazole biosynthetic gene cluster allowed us to propose a biosynthetic pathway for the tjipanazoles. As the isolated tjipanazoles show structural similarity to arcyriaflavin A, an inhibitor of the clinically relevant multidrug‐transporter ABCG2 overexpressed by different cancer cell lines, the isolated compounds were tested for ABCG2 inhibitory activity. Only tjipanazole K showed appreciable transporter inhibition, whereas the compounds lacking the pyrrolo[3,4‐c] ring or featuring additional chloro substituents were found to be much less active.

Fragestellung: Klinisch relevant ist bei der operativen Ausräumung von großen Sequestern einseitiger lumbalen Bandscheibenprolaps die Risikoabschätzung, inwieweit bei der vorwiegend mikroskopisch gestützten Manipulation des Sequesters im Rahmen der Extraktion dieser zur kontralateralen[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019)

Fragestellung: Klinisch relevant ist bei der operativen Ausräumung von großen Sequestern einseitiger lumbalen Bandscheibenprolaps die Risikoabschätzung, inwieweit bei der vorwiegend mikroskopisch gestützten Manipulation des Sequesters im Rahmen der Extraktion dieser zur kontralateralen[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018)

33rd European Photovoltaic Solar Energy Conference and Exhibition; 2630-2634, In order to support acceptance and attractivity of building integrated PV (BIPV), there is a rapidly increasing demand for coloured PV modules. Especially, architects and building planners wish an individual colour choice, saturated colors, a homogeneous appearance for all angles of incidence and at the same time a high module efficiency. Furthermore, it is important that glare effects can be suppressed. State of the art concepts offer a restricted choice of colours, show a strong angular dependence, cause a high efficiency loss or do not allow for an efficient industrial production. We overcome these restrictions by using the Morpho butterfly effect, a bionic concept based on 3D photonic structures. Our novel technological realization of these structures is well suited for large scale production.

Increasing activities in Arctic waters bare a risk of oil spills under ice-covered conditions and afford sound understanding of the interplay between sea ice and oil. Towards better knowledge, this study focuses on X-ray- micro computed-tomography (μ-CT) investigations of a laboratory oil- in ice experiment. The 3-dimensional distribution of oil in the porous space of 11- 13 cm columnar ice grown in a laboratory was investigated. Two different oil content measurement methods are discussed. (i) The first method quantifies the oil volume fraction based on μ -CT-scan investigations, allowing spatial oil distribution analysis in the porous space of sea ice. Oil inclusions were mapped manually over the acquired CT-scans with a resolution of 18 μm and 25 μm, respectively. Results give higher oil contents for smaller resolutions. Oil migration of 4 cm was observed. (ii) The second method quantifies the present oil concentration with fluorescent measurements. CT- scans give in comparison to fluorescent measurements a root mean square error of 1.27 % (18 μm) 0.76 % (25 μm), respectively. Bulk salinity determined from melted samples is compared with salinity estimated from μ –CT data. © 2017 Port and Ocean Engineering under Arctic Conditions. Available at http://www.poac.com/PapersOnline.html

33rd European Photovoltaic Solar Energy Conference and Exhibition; 18-22, Bifacial solar cells are known to increase module power and performance. Due to their active rear side additional gains are possible from internal reflections. Existing models to analyze cell-to-module (CTM) gains need to be extended. We analyze reflection within modules with bifacial cells and establish a system and a nomenclature for gains resulting from internal reflection. Transmission through the cell, subsequent reflection on module cover layers and a second absorption of light in the solar cell leads to additional gains in the range of 0.5 – 0.8% for bifacial cells in modules with reflecting rear cover materials (i.e. white backsheets) under STC conditions. We present models to calculate gains and perform measurements on bifacial modules with different backsheets and covers. Cover coupling gains for bifacial cells are higher compared to monofacial cells (20%rel in modules with white backsheets).

Role models have been researched extensively and studies suggest an influence on consumer behaviour. However, limited research is available on direct role models’ influence on the behaviour of young adults. The goal of this research was to utilise Social Cognitive Theory as a guide to understanding how direct role models, such as those of parents influence the consumer and the purchase behaviour of Generation Y (18-35 years old). Non-probability convenience sampling was used and three hundred and sixty-nine respondents completed self-administered questionnaires. The results from structural equation modelling (SEM) support Social Cognitive Theory as parental role model influence (the general perception of parents as role models) affects consumer behaviour, which, in turn, affects purchase behaviour. The consumer and purchase behaviour of the younger (18-25 years old) Generation Y cohort respondents thus reflect parents’ opinions; since the parents were regarded as the role models. These findings emphasise the important role of parents to provide guidance for young adolescence to become skilled consumers and to set good examples in terms of shopping habits. Generation Y consumers should be aware of retailers’ and advertisers’ attempts to capitalise on this influence of parental role models. Reinforcing marketing campaigns, whereby Generation Y consumers are reminded that their parents have been using the specific products or brands as to encourage them to follow suite, is one such an example.

Aim: Adults with intellectual disabilities (ID) are thought to understand less about death, but no comparisons are available to adults without ID. Research involving people with ID is silent on end-oflife planning and fear of death. Method: We compared the responses of 39 adults with mild or moderate ID and 40 disability staff on experience of death, understanding the concept of death, knowledge of and self-determination about end-of-life planning, and fear of death. Results: Adults with ID (95%) and disability staff (100%) reported that they had experienced the death of other people. We found that adults with ID had a significantly poorer understanding of the concept of death, knew much less about and were less selfdetermined about end-of-life planning, but reported greater fear of death. Conclusions: The poorer understanding and lower levels of self-determination we found suggest that future research should develop and evaluate interventions to increase understanding and self-determination about end of life.

Aim: Few self-report instruments about dying and death are available for people with intellectual disability (ID). The Dying to Talk project in Sydney, Australia measured knowledge about death, understanding and self-determination of end-of-life planning, and fear of death. This paper reports on the instruments used. Method: We describe the use, adaptation, piloting and content of these instruments, including development of a new instrument on end-of-life planning. Participants included 39 adults with ID and 40 adults without ID (disability staff).All were assessed by individual interview on all three instruments. A subsample was scored independently by a second rater. Results: Internal consistency and inter-rater agreement were good for each scale. People with ID were willing and able to provide scorable answers for almost all items, with a higher level of non-response on certain fear-ofdeath items. Conclusions: We found the instruments were usable, reliable and valid for people with and without ID. Availability of such instruments will facilitate future research, intervention and practice.

BACKGROUND: Metastatic colorectal cancer (mCRC) that harbours a BRAF V600E mutation (BRAF MT) is associated with poorer outcomes. However, whether this mutation is predictive of treatment benefit from anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is uncertain. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) published up to July 2014 that evaluated the effect of BRAF MT on the treatment benefit from anti-EGFR mAbs for mCRC. RESULTS: Seven RCTs met the inclusion criteria for assessment of overall survival (OS), whereas eight RCTs met the inclusion criteria for assessment of progression-free survival (PFS). For RAS WT/BRAFMT tumours, the hazard ratio for OS benefit with anti-EGFR mAbs was 0.97 (95% CI; 0.67–1.41), whereas the hazard ratio was 0.81 (95% CI; 0.70–0.95) for RAS WT/BRAF WT tumours. However, the test of interaction (P=0.43) was not statistically significant, highlighting that the observed differences in the effect of anti-EGFR mAbs on OS according to the BRAF mutation status may be due to chance alone. Regarding PFS benefit with anti-EGFR mAbs, the hazard ratio was 0.86 (95%CI; 0.61–1.21) for RAS WT/BRAF MT tumours as compared with 0.62 (95% CI; 0.50–0.77) for RASWT/BRAF WT tumours (test of interaction, P=0.07). INTERPRETATION: This meta-analysis demonstrates that there is insufficient evidence to definitively state that RAS WT/BRAF MT individuals attain a different treatment benefit from anti-EGFR mAbs for mCRC compared with RAS WT/BRAF WT individuals. As such, there are insufficient data to justify the exclusion of anti-EGFR mAb therapy for patients with RAS WT/BRAF MT mCRC. Refereed/Peer-reviewed

To succeed, sales managers will need to learn new roles and reinvent others such as applying flexible motivation approaches in working with a multicultural, hybrid, diverse sales force. Many organisations invest a great deal of time and money in designing incentive schemes that are failing to achieve their objective of motivating employees. Large amounts of money are spent on financial incentives, while ignoring non-financial incentives. As companies become increasingly cash-strapped, using non-financial motivators may be the solution. Self-administered questionnaires were completed by a sample of 100 pharmaceutical sales representatives from three South African companies. The questionnaire made use of a four-point Likert scale to rate the importance of various non-financial motivational factors. The respondents indicated that ‘good relationships with customers’ and ‘being well informed’ are the two most important non-financial motivators. The study also showed that demographic groups differ in the importance they attach to non-financial motivators. ‘Having power over other people’ was a more important motivator for sales representatives with a lower educational background. ‘Growth and promotion opportunities’ were more important to males, while differences were found between various age groups and the importance they attached to ‘flexibility of their jobs’. The results of this study could influence the structure of motivational schemes at pharmaceutical companies and enable management to recognise those factors that might lead to increased performance levels.Key words: motivation, sales representatives, non-financial motivators, demographics, reward structures, incentive schemes

Individual consumers are subject to different influences on how they make decisions and what decision-making style they use. Consumer decision-making styles are a mental orientation that characterises a consumer’s approach to making choices. The main purpose of the study is to explore the decision-making styles of South African adult consumers when purchasing general household items. Possible differences in the decision-making styles of adults from different ethnic backgrounds, levels of education, as well as gender and age difference are also investigated. Unlike previous studies, which were confined to students residing mainly in urban areas, this study focuses on adults residing in both urban and township areas. The Consumer Styles Inventory (CSI) that was developed by Sproles and Kendall (1986) has eight factors; and it was used to measure adults’ decision-making styles. Convenience sampling was used, and 344 questionnaires were collected. The results of the study confirmed only six of the eight existing CSI factors, but also identified an additional decision-making style, value consciousness that should be added and explored in the South African context. Significant differences were also found between gender, age and ethnicity and decision-making styles, but respondents’ level of education did not apparently influence their decision-making styles. Decision-making styles are important to marketers because they determine consumer behaviour, are stable over time, and thus are relevant for market segmentation.

Objective: The Piezosurgery device is already well known in the domain of dental and implant surgery. The field of published indications for this tool became larger and larger by time. The main advantages for its use in neurosurgery seem to be the soft tissue protection as well as a more aesthetic outcome[for full text, please go to the a.m. URL], 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Fragestellung: Das Ziel dieser prospektiven Studie ist die Beurteilung der Brustwandbeweglichkeit und der Lungenfunktion bei Patienten nach Brustwandstabilisierung mit einem neuen, schraubenlosen Osteosynthesesystem aus Titan (STRATOS, MedXpert. Germany). Methode: Zwischen 01/2008 und 06/2011[for full text, please go to the a.m. URL], 21. Jahrestagung der Deutschen Gesellschaft für Thoraxchirurgie

The recent identification of genes involved in the production of the potent neurotoxin and keystone metabolite saxitoxin (STX) in marine eukaryotic phytoplankton has allowed us for the first time to develop molecular genetic methods to investigate the chemical ecology of harmful algal blooms in situ. We present a novel method for detecting and quantifying the potential for STX production in marine environmental samples. Our assay detects a domain of the gene sxtA that encodes a unique enzyme putatively involved in the sxt pathway in marine dinoflagellates, sxtA4. A product of the correct size was recovered from nine strains of four species of STX-producing Alexandrium and Gymnodinium catenatum and was not detected in the non-STX-producing Alexandrium species, other dinoflagellate cultures, or an environmental sample that did not contain known STX-producing species. However, sxtA4 was also detected in the non-STX-producing strain of Alexandrium tamarense, Tasmanian ribotype. We investigated the copy number of sxtA4 in three strains of Alexandrium catenella and found it to be relatively constant among strains. Using our novel method, we detected and quantified sxtA4 in three environmental blooms of Alexandrium catenella that led to STX uptake in oysters. We conclude that this method shows promise as an accurate, fast, and cost-effective means of quantifying the potential for STX production in marine samples and will be useful for biological oceanographic research and harmful algal bloom monitoring. © 2011, American Society for Microbiology.

International audience

The method presented here allows high-quality recyclates to be obtained by re-dissolution of mixed, contaminated plastic wastes from composite materials. These recyclates are of virgin quality as regards their processing and usage characteristics. The solvent used is recovered and reused in the process. With slight adaptations, the process presented can also be used for other PVC-containing wastes. The technique has also been applied with some success to other engineering thermoplastics, such as ABS, SMA, PVB and PMMA, taking into account the parameters characteristic of the material. The advantages of the process are especially marked for mixed fractions, composites and wastes with internal contamination. The products from the individual process stages were successfully analysed by thermogravimetric analysis (TGA). In the present study the results obtained by the novel HiRes-TGA proved particularly useful. This analytical technique can also be readily used for characterizing other material systems.

The method presented here allows high-quality recyclates to be obtained by re-dissolution of mixed, contaminated plastic wastes from composite materials. These recyclates are of virgin quality as regards their processing and usage characteristics. The solvent used is recovered and reused in the process. With slight adaptations, the process presented can also be used for other PVC-containing wastes. The technique has also been applied with some success to other engineering thermoplastics, such as ABS, SMA, PVB and PMMA, taking into account the parameters characteristic of the material. The advantages of the process are especially marked for mixed fractions, composites and wastes with internal contamination. The products from the individual process stages were successfully analysed by thermogravimetric analysis (TGA). In the present study the results obtained by the novel HiRes-TGA proved particularly useful. This analytical technique can also be readily used for characterizing other material systems.

1987 wurden 1.928 junge Berufstätige in der DDR zur Jugendorganisation FDJ befragt. Untersuchungschwerpunkte waren: Erwartungen an die FDJ in den Bereichen Interessenvertretung im Betrieb, politisch-ideologische Arbeit und Freizeit, Erfahrungen bei der Teilnahme an Diskussionen und Veranstaltungen, Ausmaß der aktiven Mitarbeit. Als Grundtendenz wird festgestellt: "Die Mehrzahl der jungen Werktätigen identifiziert sich nicht oder nur mit Einschränkungen mit den in der FDJ vorgefundenen politischen Bedingungen der Persönlichkeitsentwicklung." Als entscheidendes praktisches Problem erwies sich das Niveau der innerverbandlichen Demokratie, nur 9% der Jugendlichen ohne Leitungsfunktionen sehen in der FDJ einen engagierten Vertreter ihrer Interessen. 95% der Befragten erwarten in stärkerem Maße, daß sich die FDJ für die Klärung berechtigter Kritik an der betrieblichen Arbeit einsetzen solle. Außerordentlich hoch ist auch das Interesse, "vermittelt über die FDJ ins sozialistische bzw. kapitalistsiche Ausland zu reisen". (psz)

Cotton plants, variety Acala 4-42 family 77 (Gossypium hirsutum L.,), were stem puncture-inoculated with either a defoliating isolate (T9) or a nondefoliating isolate (SS4) of Verticillium albo-atrum (Reinke and Berth.). As symptoms developed, growth regulators were assayed in diseased plants to discern their importance in the disease syndrome.An Avena coleoptile straight growth bioassay demonstrated the presence of several growth-regulatory compounds in cotton tissue extracts. Indoleacetic acid was among the compounds whose effects on coleoptile growth were influenced by disease development. Coleoptile growth due to indoleacetic acid was greater in extracts of diseased stems and leaves than in extracts of comparable healthy tissues. During the defoliation period the T9 and SS4 isolates appeared equally effective in increasing indoleacetic acid and reducing indoleacetic acid decarboxylation. Preceding defoliation, however, in plants showing equivalent symptoms the degradation of auxin was reduced more by infection with T9, the defoliating isolate. The reduced auxin degradation appeared to be releated to concomitant increases in caffeic acid and other indoleacetic acid-oxidase inhibitors in the affected tissues.Abscisic acid in tissue extracts strongly inhibited coleoptile growth. During the defoliation period gas-liquid chromatographic and ultraviolet absorption measurements revealed that abscisic acid levels were approximately doubled in T9-infected leaves but were relatively unaffected in leaves infected with the nondefoliating isolate and in stems infected with either isolate.The onset of epinasty and especially defoliation was also accompanied by increased ethylene production in diseased plants. Ethylene in gas samples taken from jars confining plants infected with SS4 or T9, respectively, was increased 2- and 5-fold over uninoculated controls. Ethylene supplied exogenously to healthy plants in concentrations as low as 0.2 microliter per liter induced both the epinasty and defoliation symptoms characteristic of Verticillium infection. Ethylene treatment did not, however, induce other symptoms of Verticillium infection and did not affect endogenous levels of abscisic acid.Defoliation of T9-but not SS4-infected plants apparently is related to the differential alterations in abscisic acid and ethylene levels induced by each isolate, and perhaps to differential alterations in initial rates of indoleacetic acid decarboxylation. These growth regulator alterations apparently are reflections of altered host metabolism rather than direct contributions of the invading fungus.

Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation, we found that native BRD4 and DOT1L exist in separate protein complexes. Genetic disruption or small-molecule inhibition of BRD4 and DOT1L showed marked synergistic activity against MLL leukemia cell lines, primary human leukemia cells and mouse leukemia models. Mechanistically, we found a previously unrecognized functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in proximity to superenhancers. DOT1L, via dimethylated histone H3 K79, facilitates histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide new insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this disease with poor prognosis.

Helicobacter pylori (H. pylori) infections are usually superficial and clinically asymptomatic, but in approximately 10-20% cases it can be more aggressive and associated with other pathologies. The reason for weak or strong pro-inflammatory responses in gastric mucosa that occur during H. pylori infection is not understood. Combined treatment, including antibiotic therapy with administration of probiotic bacteria along, considerably improves the effectiveness of H. pylori eradication and reduces the relapse rate. Thus, the aim of this study was to analyze the effect of Lactobacillus plantarum (L. plantarum) and/or H. pylori CagA(+) on leucocytes in whole blood cultures. This study revealed how selected strains of H. pylori and L. plantarum modulate expression of chosen membrane markers of monocytes and lymphocytes, and the cytokine synthesis of in vitro cultures. The level of IFN-γ was higher in cultures stimulated with L. plantarum than in combination of this two examinated strains. We also observe the tendency to increase the level of IFN-γ by L. planatrum in relation to cells stimulated by H. pylori. In contrast, both H. pylori alone and in combination with L. plantarum had a strong modulatory effect on the synthesis of interleukin-10. Moreover lymphocytes with higher expression of CD25 and CD58 receptors was observed only in those cultures that were stimulated with L. plantarum strain alone or in combination with H. pylori. Effects exerted on the immune system, both in terms of natural and adaptive response, constitute the only functional criterion of probiotic bacteria. The immunostimulant effects documented in this study suggest that Lactobacillus spp. can restore immune function of mucosal membrane during symptomatic infection with H. pylori.

Background: Current peanut oral immunotherapy is hampered by frequent adverse events. It has been shown that boiling can reduce peanut allergenicity. Hypoallergenic peanut products have the potential to reduce treatment-related reactions during desensitization. Objective: To show that extended boiling (for up to 12 h) can progressively reduce peanut allergenicity while retaining T cell reactivity. Methods: Raw peanuts were boiled for half, 1, 2, 4 and 12 h in deionized water. After dehydration, boiled and raw peanuts were ground, defatted and soluble proteins extracted in PBS and cooking water (leachate) retained. SDS-PAGE, Western blot, inhibition ELISA, mass spectrometry and skin prick test were used to characterize changes to peanut allergens and human IgE reactivity. T cell responses to raw and boiled peanut extracts were determined by proliferation of CD4+/CD25+/CD134+ T cells in peanut-allergic and non-allergic individuals. Results: Extended boiling progressively reduced peanut allergenicity through a combination of leaching of allergens into cooking water, fragmentation of allergens and denaturation of conformational epitopes. Two-hour boiling led to an eightfold reduction in IgE binding capacity of boiled peanuts as determined by inhibition ELISA, while 12-h boiling led to a 19-fold reduction. Mass spectrometry revealed an increasing number of unique allergen peptides with longer boiling times. Raw, 2- and 12-h boiled peanut extracts were equivalent in their ability to stimulate T cell activation and proliferation. Conclusion and Clinical Relevance: Progressive reduction in peanut allergenicity with extended boiling does not affect T cell reactivity. Boiled peanuts may be a candidate for oral immunotherapy. Refereed/Peer-reviewed

Background: Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). Aim: To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. Methods: Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. Results: Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. Conclusion: In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAIDinduced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs. Refereed/Peer-reviewed