The effect of some injurious agents on the biochemistry of brain development and a study of some characteristics of synaptic membrane acetylcholinesterase

The effects of maternal hyperthermia on the state of development of newborn guinea-pig brain have been studied with particular regard to DNA content and the activities of brain plasma membrane marker enzymes. Hyperthermia of about 4 C applied to pregnant guinea-pigs daily between the l8th and 25th days of gestation resulted in newborn exhibiting a high degree of microencephaly, but with no other obvious abnormalities. Microencephalic animals were also found to have reduced brain DNA content. However, the reduction in brain weight and DNA content were localised primarily to the cerebral hemispheres, as no such effects were detected for cerebellar tissue. The protein specific activities of plasma membrane marker enzymes from synaptic and microsomal membrane fractions from the brains of microencephalic newborn were found to be similar to those from control animals. On the other hand, the activities of these enzymes in homogenates of microencephalic guinea-pig cerebral tissue, when expressed as a function of DNA content, have been shown to be higher than such values for control cerebral tissue. These results have been discussed in terms of current models of brain development, and it is suggested that heat damage in the earliest stages of brain development can influence the subsequent differentiation of brain cells. In this case it is suggested that hyperthermia indirectly brings about more elaborate dendritic development in surviving brain cells. The effects of hypothyroidism on the development of the specific activities of synaptic membrane enzymes in the rat brain has also been investigated. In control rats the specific activities of synaptic plasma membrane ATPases and acetylcholinesterase increased in the immediate postnatal period. The rates of increase in the activities of these enzymes in membrane preparations from hypothyroid rat brain were lower than for control preparations after about the 10th or 12th days of gestation, and did not attain normal adult values by 44 days post parturn. These lower enzyme activity values have been shown not to be due to an increase in the 'latent' enzyme fraction hidden within membrane vesicles. This description of qualitative changes in the development of synapses in rat brain has been discussed in terms of current models of brain dysfunction in hypothyroid rat brain which ascribe significance only to quantitative reduction in brain cell growth. Some characteristics of synaptic membrane acetylcholinesterase from normal rat brain have also been examined in order to evaluate the possible role for lipid in the properties of this enzyme. Non-linear Arrhenius temperature-activity plots, usually associated with lipid dependent enzymes, have been found for acetylcholinesterase. The effects of membrane association, detergents and other lipophilic agents on the activity and kinetic properties of acetylcholinesterase have been evaluated. These data have been interpreted as evidence for a lipoprotein structure for acetylcholinesterase and for the involvement of lipid in the properties of this enzyme, particularly in the maintenance of a low activation energy state at physiological temperatures. This lipid has been tentatively identified as cardiolipin (diphosphatidylglycerol) as a phospholipid extracted from partially purified acetylcholinesterase in high salt conditions migrated on two dimensional thin-layer chromatography plates in a similar fashion to a commercial cardiolipin standard. The low-ionic strength soluble and membrane-bound fractions of synaptic membrane acetylcholinesterase were further examined in order to assess the role of the membrane in enzyme properties. The membrane-enzyme was shown to be much more stable to irreversible thermal inactivation than the soluble. However, this difference was also observed in Lubrol detergent solubilized preparations. The difference in stability of these fractions has in this case been attributed not to membrane association, but to differences in the oligomeric nature of soluble and membrane- bound acetylcholinesterase. These properties of acetylcholinesterase have been discussed in terms of a potential model for lipid-protein interactions in general

Olanzapine Attenuates Cue-elicited Craving for Tobacco

Rationale: Recent biological conceptualizations of craving and addiction have implicated mesolimbic dopamine activity as a central feature of the process of addiction. Imaging, and pharmacological studies have supported a role for dopaminergic structures in cue-elicited craving for tobacco. Objective: If mesolimbic dopamine activity is associated with cue-elicited craving for tobacco, a dopamine antagonist should attenuate cueelicited craving for tobacco. Thus, the aim of the present study was to determine whether an atypical antipsychotic (olanzapine, 5 mg) decreased cue-elicited craving for tobacco. Method: Participants were randomly assigned to 5 days of pretreatment with olanzapine (5 mg; n=31) or were randomly assigned to 5 days of a matching placebo (n=28). Approximately 8 h after the last dose, participants were exposed to a control cue (pencil) followed by exposure to smoking cues. Participants subsequently smoked either nicotine cigarettes or de-nicotinized cigarettes. Results: Olanzapine attenuated cue-elicited craving for tobacco but did not moderate the subjective effects of smoking. Discussion: This study represents one of the first investigations of the effect of atypical antipsychotics on cue-elicited craving for tobacco. The results suggest that medications with similar profiles may reduce cue-elicited craving, which in turn, may partially explain recent observations that atypical antipsychotics may reduce substance use

Use of Saltmarsh by Dragonflies (Odonata) in the Baie des Chaleurs Region of Quebec and New Brunswick in Late Summer and Autumn

During late summer and autumn, in the Baie des Chaleurs region of Quebec, 18 species of adult dragonflies were recorded during one or more visits of at least 2 hours each to 14 saltmarshes. Three species, Aeshna canadensis, Sympetrum danae and S. internum, were present in more than half of the sites. The most abundant species was S. internum with over 100 seen at some locations. Adults of several species, including Aeshna canadensis, A. umbrosa, Enallagma civile, E. hageni, Ischnura verticalis, Lestes disjunctus, Libellula quadrimaculata, Sympetrum danae, S. internum and S. obtrusum, occurred in relatively high frequencies in both Baie des Chaleurs saltmarshes and in those elsewhere in Acadia. Within Baie des Chaleurs observations of emergence and/or presence of larvae, as well as regional abundance, were recorded for Aeshna canadensis, A. umbrosa, Ischnura verticalis, Sympetrum costiferum, S. internum and S. vicinum. Oviposition in saltmarsh pools was recorded for Aeshna canadensis, Enallagma civile, E, hageni, Ischnura verticalis, Lestes congener and Sympetrum danae. The saltmarsh dragonfly fauna of Baie des Chaleurs is significantly different from that of the rest of Acadia based on frequencies predicted from the latter region. To a large extent this difference is a result of significantly increased use of saltmarsh habitat by adults of six species including Lestes congener, Sympetrum danae, Aeshna canadensis, Sympetrum costiferum, Lestes disjunctus, and Sympetrum internum (in order of decreasing significance) in Baie des Chaleurs in comparison with saltmarshes elsewhere in Acadia. Local amelioration of salty conditions in certain saltmarshes, superimposed on regional amelioration as a result of protection from storms and saltwater dilution in the Baie des Chaleurs estuary, may contribute to an environment where adaptation can occur or where already tolerant species can exist. Dragonflies use saltmarsh habitat on the northeast coast of North America more extensively than is currently documented

Low-intensity educational interventions supporting self-management to improve outcomes related to chronic breathlessness: a systematic review

Chronic breathlessness is debilitating and frightening, often resulting in emergency department presentations with acute-on-chronic breathlessness. Self-management is complex, involving 14 components as identified by the Practical Systematic Review in Self-Management Support (PRISMS). Low-intensity educational interventions that support breathlessness self-management through written/visual educational materials, alongside limited health professional support, are available. Our aim was to describe components of low-intensity educational interventions that support and improve self-management for adults with chronic breathlessness and evaluate their efficacy for improving breathlessness-related outcomes. A systematic review was conducted, including RCTs that compared these interventions with usual care in adults with chronic disease. Synthesis took a narrative approach utilizing the PRISMS taxonomy and Template for Intervention Description and Replication (TIDieR) checklist. Of the 1948 articles identified, 7 met criteria reporting 7 RCTs using 6 interventions. Studies utilized 12 out of 14 PRISMS components, the most frequent being training/rehearsal for psychological strategies. Evidence for effectiveness was inconsistent and attempts to identify beneficial components were confounded by intervention complexity and heterogeneity. The optimal content and delivery of low-intensity educational interventions that support self-management to improve chronic breathlessness-related outcomes in adults cannot be defined from current published literature. Future research should incorporate more detailed, standardized reporting to enable comparison and meta-analysis

Successful renal transplantation following prior bone marrow transplantation in pediatric patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72010/1/j.1399-3046.2004.00208.x.pd

An algorithm for computing the centered Hausdorff measure of self-similar sets

We provide an algorithm for computing the centered Hausdorff measure of self-similar sets satisfying the strong separation condition. We prove the convergence of the algorithm and test its utility on some examples

Ethical, legal, and social implications of learning health systems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141917/1/lrh210051-sup-0001-Supplementary_info.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141917/2/lrh210051.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141917/3/lrh210051_am.pd

Use of Saltmarsh by Dragonflies (Odonata) in the Baie des Chaleurs Region of Quebec and New Brunswick in Late Summer and Autumn

During late summer and autumn, in the Baie des Chaleurs region of Quebec, 18 species of adult dragonflies were recorded during one or more visits of at least 2 hours each to 14 saltmarshes. Three species, Aeshna canadensis, Sympetrum danae and S. internum, were present in more than half of the sites. The most abundant species was S. internum with over 100 seen at some locations. Adults of several species, including Aeshna canadensis, A. umbrosa, Enallagma civile, E. hageni, Ischnura verticalis, Lestes disjunctus, Libellula quadrimaculata, Sympetrum danae, S. internum and S. obtrusum, occurred in relatively high frequencies in both Baie des Chaleurs saltmarshes and in those elsewhere in Acadia. Within Baie des Chaleurs observations of emergence and/or presence of larvae, as well as regional abundance, were recorded for Aeshna canadensis, A. umbrosa, Ischnura verticalis, Sympetrum costiferum, S. internum and S. vicinum. Oviposition in saltmarsh pools was recorded for Aeshna canadensis, Enallagma civile, E, hageni, Ischnura verticalis, Lestes congener and Sympetrum danae. The saltmarsh dragonfly fauna of Baie des Chaleurs is significantly different from that of the rest of Acadia based on frequencies predicted from the latter region. To a large extent this difference is a result of significantly increased use of saltmarsh habitat by adults of six species including Lestes congener, Sympetrum danae, Aeshna canadensis, Sympetrum costiferum, Lestes disjunctus, and Sympetrum internum (in order of decreasing significance) in Baie des Chaleurs in comparison with saltmarshes elsewhere in Acadia. Local amelioration of salty conditions in certain saltmarshes, superimposed on regional amelioration as a result of protection from storms and saltwater dilution in the Baie des Chaleurs estuary, may contribute to an environment where adaptation can occur or where already tolerant species can exist. Dragonflies use saltmarsh habitat on the northeast coast of North America more extensively than is currently documented

Using Research Metrics to Improve Timelines: Proceedings from the 2nd Annual CTSA Clinical Research Management Workshop

The Clinical and Translational Science Award (CTSA) Consortium Workshop was conceived as a venue to foster communication among Academic Medical Centers (AMCs) in the development of methods to improve clinical research management. The consortium, comprised of 46 awardee sites as of 2009, many with multiple AMCs, is expected to expand to 60 sites when fully implemented. At the 2nd Annual CTSA Clinical Research Management Workshop held on June 22 nd and 23 rd , 2009, on the National Institutes of Health (NIH) campus, consortium members and potential CTSA sites gathered with stakeholders from private industry, the NIH, the Food and Drug Administration, and private research organizations, to formulate a plan to address challenges in clinical research management. Specific aims included improving protocol processing and sharing process improvement initiatives in the expectation that best practices will be implemented and improvements will be measured and reported. The findings presented at this workshop indicated significant variance in Institutional Review Board approval of protocols and contract execution by AMC and CTSA sites. Most represented marked delays compared to non-AMC sites and that, as a likely consequence, AMCs were later to enroll patients and/or meet enrollment targets compared to dedicated or professional sites. Clin Trans Sci 2010; Volume 3: 305–308Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79218/1/j.1752-8062.2010.00246.x.pd