Concerns and opportunities related to discontinuation of treatment in rheumatoid arthritis

In this thesis we describe the concerns and opportunities related to discontinuation of anti rheumatic treatment, in particular, glucocorticoids. We also have focused on treatment of RA patients during a (viral) pandemic (COVID19).Walaeus bibliotheekLUMC / Geneeskund

When the going gets tough, the tough get going: Social identification and individual effort in intergroup competition.

Based on social identity theory, the authors predicted that in ongoing intergroup competition, people’s strength of social identification will have a positive impact on their behavioral efforts on behalf of an ingroup when its current status is low, whereas this will not be the case when its current status is high. In a first experiment, male participants showed the expected pattern of behavior. Female participants, however, tended to display opposite reactions. As a possible explanation, it was argued that the experimental procedure may have inadvertently evoked a gender-based stereotype threat for female participants. In an attempt to obtain more consistent support for their hypothesis, the authors therefore replicated the experiment with modifications to avoid such a threat. These changes proved to be effective in the sense that this time the predicted interaction effect between ingroup identification and current group status was obtained for both male and female participants

Adsorbents for the sequestration of the Pimelea toxin, simplexin

Pimelea poisoning affects cattle grazing arid rangelands of Australia, has no known remedy and significant outbreaks can cost the industry $50 million per annum. Poisoning is attributable to consumption of native Pimelea plants containing the toxin simplexin. Charcoal, bentonite and other adsorbents are currently used by the livestock industry to mitigate the effects of mycotoxins. The efficacy of such adsorbents to mitigate Pimelea poisoning warrants investigation. Through a series of in vitro experiments, different adsorbents were evaluated for their effectiveness to bind simplexin using a simple single concentration, dispersive adsorbent rapid screening method. Initial experiments were conducted in a rumen fluid based medium, with increasing quantities of each adsorbent: sodium bentonite (Trufeed®, Sibelco Australia), biochar (Nutralick®Australia) and Elitox® (Impextraco, Belgium). Data showed the unbound concentration of simplexin decreased with increasing quantities of each adsorbent tested. Sodium bentonite performed best, removing ~95% simplexin at 12 mg/mL. A second experiment using a single amount of adsorbent included two additional adsorbents: calcium bentonite (Bentonite Resources, Australia) and a synthetic adsorbent (Waters, USA). The concentration of simplexin remaining in the solution after 1 h, the amount able to be desorbed off the adsorbent-toxin matrix with replacement fresh fluid, and the amount remaining bound to the adsorbent were measured. All samples containing an adsorbent were statistically different compared to the blank (p < 0.05), indicating some binding activity. Future work will explore the binding mechanisms and behaviour of the toxin-adsorbent complex in the lower gastrointestinal tract

Development of a mixed microbial drench for detoxification of three Leucaena cultivars

The adoption of Leucaena leucocephala in Queensland, as a high protein, leguminous fodder shrub, has been hindered by insect infestation, with psyllids thriving on Leucaena planted in high humidity regions. A psyllid-resistant cultivar of Leucaena has therefore been developed (Redlands). Nonetheless, all Leucaena cultivars contain the non-protein amino acid, mimosine, which in the rumen of cattle can be degraded by many different bacteria to the toxic metabolite 3hydroxy-4-(1H)-pyridone (3,4-DHP). For over 20 years, a mixed microbial drench containing Synergistes jonesii has been produced by DAF to degrade mimosine, 3, 4-DHP and its degradation product 2,3-dihydroxypyridine (2,3-DHP), to reduce any toxic side-effects of feeding Leucaena to cattle (Klieve et al. 2002). This drench is produced in an in-vitro fermentation system supplied with leaf material from the Leucaena cultivar, Cunningham. Previous research found replacing the Cunningham leaf with either psyllid-resistant Redlands or psyllid-tolerant Wondergraze leaf, negatively impacted the mixed bacterial populations’ ability to degrade 3,4-DHP (Ouwerkerk et al. 2019). This study aimed to test how supplying leaf material from a combination of three cultivars, Cunningham, Redlands and Wondergraze of Leucaena (TriMix) to the fermentation system, would affect S. jonesii populations, the ability of the mixed microbial populations to degrade mimosine, 3,4-DHP and 2,3 DHP and if these microbial populations would grow and retain activity, in fermentations supplied leaf from each single Leucaena cultivar

Effects of adsorbents and probiotics in mitigating simplexin poisoning effects in cattle fed Pimelea

Pimelea poisoning of cattle occurs only in arid inland Australia and is caused by the toxin, simplexin found in some native Pimelea plant species. Pimelea-affected cattle show distinctive physical symptoms including subcutaneous oedema under the jaw and brisket, diarrhoea and anaemia. Simplexin was thought to be circulated in the bloodstream to exert its toxic effect, but due to its hydrophobic nature the extent of its blood carriage is unknown. Fletcher et al. (2014) postulated a possible role of rumen microorganisms adapting to detoxify simplexin in cattle fed Pimelea over a prolonged period of time. Anecdotal reports have suggested cattle supplemented with biochar and bentonite showed resistance towards Pimelea poisoning. In this project, a pen trial (QAFFI/QASP/337/20/DAF) was conducted to determine the efficacy of adsorbents (biochar and bentonite) and a bacterial inoculum for reducing the effects of Pimelea poisoning in steers

Do Queensland cattle possess rumen bacteria capable of degrading Leucaena toxins?

Leucaena leucocephala is a leguminous fodder tree used by northern Australian producers to provide protein and boost the weight gains of extensively grazing cattle. There is a range of commercial Leucaena cultivars available which all contain a toxic non-protein amino acid, mimosine. Many rumen bacteria can degrade mimosine to 3,4-dihydroxypyridine (3,4-DHP), which is also toxic to cattle. To enable cattle to safely gain the full benefits of Leucaena, a bacterium, Synergistes jonesii, was isolated that could degrade the toxic metabolites 3,4 DHP and 2,3-hydroxypyridine (2,3-DHP) (Allison et al. 1992). A fermenter-grown mixed bacterial inoculum, containing S. jonesii, has been produced by DAF for over 20 years as an oral drench for cattle to prevent Leucaena toxicity and maximise weight gains (Klieve et al. 2002)

Changes in mixed microbial inoculums to prevent the toxic side-effects in cattle grazing new varieties of Leucaena.

Leucaena leucocephala is a legume fodder crop that grows in tropical and subtropical environments. Leucaena provides a high quality feed for cattle boosting liveweight gain both per animal and per hectare, improving profitability for steer turnover by 121% compared with the base scenario of grazing buffel grass (Bowen and Chudleigh, 2018). A number of commercial leucaena cultivars, Cunningham, Peru, Taramba, El Salvadore, and Wondergraze, are used in Queensland. Leucaena contains a toxic amino acid, mimosine, which many rumen bacteria can degrade to a toxic metabolite 3-hydroxy-4-(1H)-pyridone (DHP). Productivity from leucaena-pasture can be reduced by DHP-induced depressions in intake. A DHP degrading bacterium, Synergistes jonesii was isolated from a mixed bacterial population isolated from a goat from Hawaii (Allison et al., 1992). For over twenty years DAF has provided a mixed bacterial rumen inoculum, containing S. jonesii, for cattle grazing Leucaenapastures, produced in an in vitro fermentation system with Cunningham cultivar as the feed source. All of the commercial cultivars are susceptible to attack by psyllid insects, limiting their use in higher rainfall areas - to address this limitation, a commercial psyllid-resistant cultivar, Redlands, was released in 2019. To assess if the leucaena inoculum is impacted by Redland’s anti-psyllid, chemical characteristics a series of 30 day in vitro anaerobic fermentations were undertaken feeding either Redlands, Cunningham or Wondergraze cultivars. The fermentations were conducted following the method of Klieve et al. (2002). Fermentations were started with either cryopreserved leuceana inoculum from a single day of a production fermentation; or day 30 of a Wondergraze or Redlands fermentation. Daily samples were taken and assays set up on days 10, 15, 20, 25 and 30 to monitor the fermentation’s ability to break down mimosine, 3,4 DHP and 2,3 DHP. Genomic DNA extracted from daily samples was used in a S. jonesii quantitative PCR and for barcoded amplicon sequencing of the 16S rRNA gene V3 –V4 region using the Illumina MiSeq platform

Professionals' preferences in prenatal counseling at the limits of viability: a nationwide qualitative Dutch study

Item does not contain fulltextPrenatal counseling practices at the limits of viability do vary, and constructing a counseling framework based on guidelines, professional and parental preferences, might achieve more homogeneity. We aimed to gain insight into professionals' preferences on three domains of counseling, particularly content, organization, and decision making and their influencing factors. A qualitative, nationwide in-depth exploration among Dutch perinatal professionals by semi-structured interviews in focus groups was performed. Regarding content of prenatal counseling, preparing parents on the short-term situation (delivery room care) and revealing their perspectives on "quality of life" were considered important. Parents should be informed on the kind of decision, on the difficulty of individual outcome predictions, on survival and mortality figures, short- and long-term morbidity, and the burden of hospitalization. For organization, the making of and compliance with agreements between professionals may promote joint counseling by neonatologists and obstetricians. Supportive materials were considered useful but only when up-to-date, in addition to the discussion and with opportunity for personalization. Regarding decision making, it is not always clear to parents that a prenatal decision needs to be made and they can participate, influencing factors could be, e.g., unclear language, directive counseling, overload of information, and an immediate delivery. There is limited familiarity with shared decision making although it is the preferred model. CONCLUSION: This study gained insight into preferred content, organization, and decision making of prenatal counseling at the limits of viability and their influencing factors from a professionals' perspective. What is Known: * Heterogeneity in prenatal counseling at the limits of viability exists * Differences between preferred counseling and actual practice also exists What is New: * Insight into preferred content, organization, and decision making of prenatal periviability counseling and its influencing factors from a professionals' perspective. Results should be taken into account when performing counseling. * Particularly the understanding of true shared decision making needs to be improved. Furthermore, implementation of shared decision making in daily practice needs more attention

Naturally occurring DNA transfer system associated with membrane vesicles in cellulolytic Ruminococcus spp. of ruminal origin

A genetic transformation system with similarities to those reported for gram-negative bacteria was found to be associated with membrane vesicles of the ruminal cellulolytic genus Ruminococcus. Double-stranded DNA was recovered from the subcellular particulate fraction of all the cellulolytic ruminococci examined. Electron microscopy revealed that the only particles present resembled membrane vesicles. The likelihood that the DNA was associated with membrane vesicles (also known to contain cellulosomes) was further supported by the adherence of the particles associated with the subcellular DNA to cellulose powder added to culture filtrates. The particle-associated DNA comprised a population of linear molecules ranging in size from <20 kb to 49 kb (Ruminococcus sp. strain YE73) and from 23 kb to 90 kb (Ruminococcus albus AR67). Particle-associated DNA from R. albus AR67 represented DNA derived from genomic DNA of the host bacterium having an almost identical HindIII digestion pattern and an identical 16S rRNA gene. Paradoxically, particle-associated DNA was refractory to digestion with EcoRI, while the genomic DNA was susceptible to extensive digestion, suggesting that there is differential restriction modification of genomic DNA and DNA exported from the cell. Transformation using the vesicle-containing fraction of culture supernatant of Ruminococcus sp. strain YE71 was able to restore the ability to degrade crystalline cellulose to two mutants that were otherwise unable to do so. The ability was heritable and transferred to subsequent generations. It appears that membrane-associated transformation plays a role in lateral gene transfer in complex microbial ecosystems, such as the rumen