Analysis of data on the certificate of advanced graduate specialization program as collected by means of questionnaire

Thesis (Ed.M.)--Boston Universit

Biotransformation of 2,4,6-trinitrotoluene by ruminal organisms

2,4,6-Trinitrotoluene (TNT) has been the common munitions used in the world and is an environmental contaminant that is amendable to reductive transformation reactions. The rumen is an extremely reductive environment containing diverse microbial populations. There are 21 pure culture ruminal bacteria species in culture collection, these were tested for the ability to degrade TNT. Of the 21 bacterial strains tested, 12 showed > 90% degradation of TNT, 5 strains showed 80-90% degradation, 3 strains only had low TNT degrading ability and one organism was completely inhibited by TNT concentrations of 100 mg/l. Of the 12 strains able to transform >90% of the TNT, 7 showed evidence of degradation of aminodinitrotoluene (ADNTs) and were subsequently tested for the ability to degrade ADNTs and diaminonitrotoluene (DANTs). Four were able to completely transform all these compounds, one was able to degrade all but 2,4-diaminonitrotoluene and the remaining two were able to degrade the ADNTs but were unable to transform the DANTs at a concentration of 50 mg/l. Degradation constants ranged from 0.31-11.39 h⁻¹ and the Michaelis-Menten constant ranged from 20-739 mg/l. Inhibition was detected for two of the organisms tested at levels of TNT higher than 50 mg/l. In order to determine the effect of TNT on rumen bacterial populations, rumen fluid was collected from three sheep before and after feeding TNT at a dose of 35.5 mg/day and compared to a control animal. Clone libraries were constructed for each rumen fluid sample and compared for changes in microbial populations. Several clones from the pre-TNT clustered with clones from the end of the experiment. The diversity and richness indices reveal that the number of clones sequenced were not enough to completely describe the populations found in the rumen. A limited number of shifts in populations between the pre- and post-treatment were detected within animals. However, there was no pattern in population fluxes detected in relationship to TNT treatment. These results indicate that a broad range of ruminal bacteria can degrade TNT and that feeding TNT at levels found in plant material to sheep does not affect the bacterial populations

Metabolism of ergot alkaloids by sheep

The digestion responses and degradation of ergovaline and production of lysergic acid in the rumen of sheep offered Neotyphodium coenophialum-infected tall fescue straw at two ergovaline levels was investigated. Six crossbred wethers (56 +1- 3 kg BW) were randomly assigned to one of two treatment groups in a cross-over design. Each experimental period consisted of 28 d feeding periods with a 14 d wash-out between periods. During the wash-out period all animals received a diet containing <10 ppb ergovaline. Treatments were 1) < 10 ppb ergovaline (E-) and 2) 500 ppb ergovaline (E+). Ergovaline levels were achieved with a combination of tall fescue straw (35Oppb ergovaline) plus Neotyphodium coenophialum-infected tall fescue seed (3,300 ppb ergovaline). Diets were isonitrogenous. Rumen fluid was sampled three times (d 0, 3, 28) during the 28- day experimental period for ergovaline and lysergic acid. Samples were collected at time 0 (prior to feeding), 6, and 12 h post feeding. Total fecal and urine collection commenced on d 21 and continued till d 25 of the experimental period. Rumen ammonia, rumen pH, and rectal temperature were not influenced by ergovaline concentration (P > 0.10). Digestion of DM, ADF and CP were not different between treatments (P > 0.10). Feed intake and body weight were different between treatments (P> 0.10). Water intake was reduced by ergovaline intake (P <0.05). Serum prolactin was reduced by 27% with ergovaline intake (P <0.05). Ergovaline concentration in rumen fluid expressed as a percent of intake increased over sampling time and sampling day (P < 0.05). Lysergic acid concentration in rumen fluid expressed as a percent of intake increased over time from dO to d3 (P < 0.05) but was not different between d3 and d28 at any time point (P> 0.10). The feces contained an average of 0.41 tmo1/day ergovaline and 0.87 μmol/day lysergic acid. Urine contained no detectable ergovaline; lysergic acid concentration was 1.05 μmol/day The appearance of lysergic acid in the feces, urine and rumen fluid is likely from the degradation of ergovaline in the rumen due to microbial degradation and further break down in the lower digestive tract. In order to determine if the increased tolerance sheep display to fescue toxicosis is due to ruminal bacteria five major sheep ruminal bacteria were monitored during the adaptation to Neotyphodium coenophialum -infected tall fescue straw. This increased tolerance supports the belief that there are microorganisms in the rumen of sheep capable of detoxifying the alkaloids found in infected tall fescue. Rectal temperatures and serum prolactin levels were monitored as an indication of toxicosis. Daily rectal temperatures were not influenced by alkaloid concentration (38.4°C E- vs. 38.4 °C E+, SE 0.0615; p = 0.40). Serum prolactin was decreased to 6.4 ng/ml for E+ from 22.9 ng/ml for Etreatment (SE 5.19; p = 0.023), indicating subclinical but not clinical fescue toxicosis. A period effect was detected for most primers used, indicating change in microbial populations due to adaptation to the fescue straw. Prevotella bryantii B14 was detected in low levels through the entire feeding period and levels were approximately the same (95% B- and 89% E+ of day 0 on day 28) from day 0 to 28 but no difference was detected between treatment groups (90% E- vs. 93% E+; p = 0.45). The Streptococcus group (S. bovis, S. caprinus, S. equines) was detected in low levels through the entire feeding period and E+ treatment tended to lower the concentration of 16S gene but no statistical difference was detected between treatment groups (89% E- vs. 94% E+; p = 0.39). Selenomas ruminantium- Mitsuokella multiacida JCM6582 was the most abundant organism found in the samples and levels were approximately the same (97% E- and 105% E+ of day 0 on day 28) from day 0 to 28 but no difference was detected between treatment groups (92% E- vs. 106% E+; p = 0.52). Eubacterium ruminatium (ATCC 17233) was undetectable in most samples over all periods. Ruminococcus flavefaciens (ATCC 19208T) sequence was detected in moderate levels through the entire feeding period and levels were approximately the same (97% E- and 99% E+ of day 0 on day 28) from day 0 to 28 but no difference was detected between treatment groups (91% E- vs. 92% E+; p = 0.28). Ruminococcus albus was detected in low levels through the entire feeding period and levels were approximately the same (95% E- and 83% E+ of day 0 on day 28) from day 0 to 28 but no difference was detected between treatment groups (87% E- vs. 89% E+; p = 0.33). These results imply that none of the five bacteria monitored in this study is responsible for the metabolism of ergot alkaloids

Pharmacological Evaluation of the Long-Term Effects of Xanomeline on the M1 Muscarinic Acetylcholine Receptor

Xanomeline is a unique agonist of muscarinic receptors that possesses functional selectivity at the M1 and M4 receptor subtypes. It also exhibits wash-resistant binding to and activation of the receptor. In the present work we investigated the consequences of this type of binding of xanomeline on the binding characteristics and function of the M1 muscarinic receptor. Pretreatment of CHO cells that stably express the M1 receptor for 1 hr with increasing concentrations of xanomeline followed by washing and waiting for an additional 23 hr in control culture media transformed xanomeline-induced inhibition of [3H]NMS binding from monophasic to biphasic. The high-affinity xanomeline binding site exhibited three orders of magnitude higher affinity than in the case of xanomeline added directly to the binding assay medium containing control cells. These effects were associated with a marked decrease in maximal radioligand binding and attenuation of agonist-induced increase in PI hydrolysis and were qualitatively similar to those caused by continuous incubation of cells with xanomeline for 24 hr. Attenuation of agonist-induced PI hydrolysis by persistently-bound xanomeline developed with a time course that parallels the return of receptor activation by prebound xanomeline towards basal levels. Additional data indicated that blockade of the receptor orthosteric site or the use of a non-functional receptor mutant reversed the long-term effects of xanomeline, but not its persistent binding at an allosteric site. Furthermore, the long-term effects of xanomeline on the receptor are mainly due to receptor down-regulation rather than internalization

Suppression of ovarian hormones in adolescent rats has no effect on anxiety-like behaviour or c-fos activation in the amygdala

Support was provided the British Society for Neuroendocrinology, Carnegie Trust for the Universities of Scotland and School of Psychology & Neuroscience, University of St Andrews.In humans, sex differences in mood disorders emerge during adolescence, with prevalence rates being consistently higher in females than males. It has been hypothesised that exposure to endogenous ovarian hormones during adolescence enhances the susceptibility of females to mood disorders from this stage of life onwards. However, experimental evidence in favour of this hypothesis is lacking. In the present study, we examined the long‐term effects of suppressing adolescent gonadal hormone levels in a group of female Lister‐hooded rats via administration of a gonadotrophin‐releasing hormone antagonist (Antide; administered on postnatal day [PND] 28 and 42) compared to control females and males (n = 14 per group). We predicted that, in adulthood, Antide‐treated female rats would exhibit more male‐like behaviour than control females in novel environments (elevated‐plus maze, open field and light‐dark box), in response to novel objects and novel social partners, and in an acoustic startle task. Progesterone and luteinising hormone assays (which were conducted on blood samples collected on PND 55/56 and 69/70) confirmed that the hypothalamic‐pituitary‐gonadal axis was temporarily suppressed by Antide treatment. In addition, Antide‐treated females were found to exhibit a modest pubertal delay, as measured by vaginal opening, which was comparable in length to the pubertal delay that has been induced by adolescent exposure to alcohol or stress in previous studies of female rats. However, Antide‐treated females did not substantially differ from control females on any of the behavioural tests, despite the evidence for predicted sex differences in some measures. Following the acoustic startle response task, all subjects were culled and perfused, and c‐Fos staining was conducted in the medial and basolateral amygdala, with the results showing no significant differences in cell counts between the groups. These findings suggest that ovarian hormone exposure during adolescence does not have long‐term effects on anxiety‐related responses in female rats.Publisher PDFPeer reviewe

Potential unique causes of burnout for chiropractic professionals

Objective The objective of this narrative review is to discuss the potential for burnout in chiropractic practitioners. This discussion is grounded in the job demands-resource model, the conservation of resources model, the unique profession-specific stressors experienced by chiropractors, and information from similar health care professions. Methods A search using both the indexed (PubMed and PsychLit) and nonindexed psychosocial literature was used. Other resources included the Cochrane Library, articles from governing bodies of the chiropractic profession, trade magazines, and research conferences and symposium proceedings. Articles were analyzed following the grounded theory principles: open coding and memos for conceptual labeling, axial coding and memos for category building, and selective coding for model building. Results Potential stressors unique to doctors of chiropractic include factors associated with physical workload, role stress, and mental and emotional demands. Conclusions There are unique chiropractic-specific occupational characteristics that possibly contribute to burnout in the chiropractic professionals. These findings emphasize the need for assessing and measuring burnout and attrition within the chiropractic profession