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.

This list of over 300 fiction and non-fiction books on Asian countries is designed as a tool for teachers who desire to select works which will foster in children an interest in Asian nations and a knowledge of customs, daily life and culture of the people. All facets of each country are considered -- the land, people, history, customs, government, religion, education, festivals and holidays, art, and music. More coverage is given to China, India, and Japan because many books on these three countries have been published for children. The majority of the books listed were published in the 1960's. Selective criteria for the books focused on including readable, informative books with acceptable literary quality, authentic content, and quality illustrations and format; availability of books in the United States; books for use in kindergarten through junior high school; and consideration of the reading level ability of children. To help those teachers who wish to expand their own knowledge of a country, a number of books including some of a textbook nature are included. The overall arrangement of the guide is by country. Author entries provide annotations containing complete bibliographic citations and prices. (SJM)

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.

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)

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

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

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.