Renal Failure in a Depressed Adolescent on Escitalopram

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63252/1/cap.2008.1842.pd

Development of a New in vitro System for Cystic Fibrosis Research

poster abstractIndividuals with cystic fibrosis (CF) have a life expectancy of 40 years and require daily treatments to mitigate the effects of the disease. CF impacts organs throughout the body, especially the lungs, where thick mucus builds up, impairs breathing, and provides an environment for bacterial growth. Chronic lung infection is the leading cause of mortality in CF. The majority of CF lung infections are caused by Pseudomonas aeruginosa, a common bacterium which typically does not cause disease in healthy individuals. In the CF lung, however, P. aeruginosa burrows into the thick mucus layer, evades the immune system, and resists antibiotic therapy by encasing itself in a protective matrix called a biofilm. Laboratory methods for studying biofilm are not true replicas of the CF lung environment, leaving a knowledge gap between how bacteria grow in a test tube (in vitro) and how they grow in the lungs of a person with CF. The focus of this work is to develop an improved laboratory model which combines artificial sputum (as a surrogate for mucus in the CF lung) and cultured CF airway epithelial cells. To assess the potential of this model, we have performed experiments to compare P. aeruginosa in artificial sputum versus standard laboratory media. Results demonstrate that P. aeruginosa in artificial sputum exhibits differences in growth, biofilm formation, toxin production, cytotoxicity, and protein expression, compared to results in standard media. These data suggest that our model system can contribute new information to the understanding of CF airway infection. The aim of future studies is to use this system to identify sputum components and bacterial proteins which have not been recognized previously by standard methods. It is our ultimate goal to contribute knowledge leading to improved longevity and quality of life for people with CF

DOES LOW MAGNESIUM IN CYSTIC FIBROSIS CONTRIBUTE TO BACTERIAL PATHOGENICITY?

poster abstractCystic fibrosis (CF) is a genetic disease for which there is currently no cure. Individuals with CF are plagued by myriad symptoms, including chronic pneumonia, which diminishes quality of life and reduces life expectancy to 40 years. The most common bacterium in CF patients’ lungs is Pseudomonas aeruginosa, a highly adaptable organism capable of surviving robust antibi-otic treatment. At the heart of developing improved treatments for CF pa-tients is the need to better understand P. aeruginosa pathogenicity. To this end, we have been studying the role of magnesium, which is often found at below normal levels in CF patients. Magnesium is an essential element in numerous cellular functions in both bacteria and humans. In previous re-search, we developed a P. aeruginosa strain with a deletion of the magnesi-um transport protein MgtE, as well as 16 plasmids carrying different muta-tions of the mgtE gene. Experiments with these constructs demonstrated a relationship between magnesium transport and bacterial toxin production. In the research presented here, we hypothesize that lower levels of magnesium may trigger a bacterial response, causing a change in P. aeruginosa patho-genicity. Changes may include differential growth, toxin release, and for-mation of biofilms, which are surface-adhered, antibiotic tolerant bacterial communities in a protective polysaccharide matrix. Using various magnesi-um levels, we have measured P. aeruginosa growth rates, motility, biofilm formation, and cytotoxicity toward cultured cells derived from the CF bron-chial epithelium. Preliminary results suggest that lower magnesium contrib-utes to changes in the bacterium that favor persistence in the CF lung. On-going studies include the effect of long-term growth of P. aeruginosa in low magnesium and how this impacts a number of virulence factors. We antici-pate that our research will elucidate the relationship between magnesium and P. aeruginosa pathogenicity and potentially lead to improved treatments for CF patients

Classical and quantum magnetisation reversal studied in single nanometer-sized particles and clusters using micro-SQUIDs

Recent progress in experiment on quantum tunnelling of the magnetic moment in mesoscopic systems will be reviewed. The emphasis will be made on measurements of individual nanoparticles. These nanomagnets allow one to test the border between classical and quantum behaviour. Using the micro-SQUID magnetometer, waiting time, switching field and telegraph noise measurements show unambiguously that the magnetisation reversal of small enough single crystalline nanoparticles is described by a model of thermal activation over a single-energy barrier. Results on insulating BaFeO nanoparticles show strong deviations from this model below 0.4 K which agree with the theory of macroscopic quantum tunnelling in the low dissipation regime.Comment: 6 pages, 2 figures, conference proceedings of LT22-Helsink

Targeting Siglec-7 and Siglec-9 with Sialic Acid Coated Nanoparticles

Systemic Lupus Erythematosus (SLE) is an autoimmune disease which is well characterized by the over production of proinflammatory cytokines such as type I interferons (IFN) and TNFα, downstream of the pathogen recognition toll-like receptors, TLR-7 and TLR-9. Sialic Acid Immunoglobulin-Like Lectins (Siglecs) are cell surface receptors that have previously shown to be negative regulators of type I IFNs. Murine Siglec-E is one such negative regulator that has the ability to inhibit TLR driven IFN production. PLGA nanoparticles conjugated to the sialic acid ligand of Siglec-E (Sia NPs) were observed to inhibit production of the pro-inflammatory cytokine, TNFα in murine peritoneal macrophages. Biodistribution analysis in mice showed that fluorescently labeled- Sia NPs localized to areas known to have high levels of Siglec-E expression. The aim of this study was to evaluate the capability of these nanoparticles to activate the human orthologues of Siglec-E, Siglec-7 and Siglec-9, in human peripheral blood mononuclear cells in order to investigate their potential as a therapeutic modality in SLE patients. Expression analysis demonstrated that SLE patients display lower levels of Siglec-7 and Siglec-9 expression in resting immune cells compared to healthy controls. Following stimulation, Siglec-7 is upregulated in peripheral blood mononuclear cells. Unexpectedly however, addition of Sia NPs resulted in exacerbation of the proinflammatory response as measured by TNF-α and RANTES expression suggesting that Siglec-7, while it possesses an inhibitory motif, may in fact be acting in a pro- inflammatory manner. Screening of other potential ligands identified sialic acid GD3 as an inhibitor of TLR and immune complex driven cytokine production in immune cells. Whether this is mediated by Siglec 7 however was not determined. Further investigation into the role of Siglec-7 in SLE patient monocytes and immune cells is required before it can be determined to be a good target for activation with sialic acid coated nanoparticles

Utility Measurement: Configural-Weight Theory and the Judge\u27s Point of View

Subjects judged the values of lotteries from 3 points of view: the highest price that a buyer should pay, the lowest price that a seller should accept, and the “fair” price. The rank order of judgments changed as a function of point of view. Data also showed violations of branch independence and monotonicity (dominance). These findings pose difficulties for nonconfigural theories of decision making, such as subjective expected utility theory, but can be described by configural-weight theory. Configural weighting is similar to rank-dependent utility theory, except that the weight of the lowest outcome in a gamble depends on the viewpoint, and 0-valued outcomes receive differential weighting. Configural-weight theory predicted the effect of viewpoint, the violations of branch independence, and the violations of monotonicity, using a single scale of utility that is independent of the lottery and the point of view

A functional learning resource center for an elementary school

"January 1971, College of Education and University Extension Division cooperating."One of the important dimensions of the current revolution in elementary education is the individualization of instruction-a dimension which forces the teacher to change his role from being primarily a dispenser of information to one of diagnostician and prescriber. Individualized instruction can be labeled as one of the fastest moving innovations in elementary education today. At least many educators are giving lip service to it, and many are eagerly attempting to put the concept into practice. As I work with educators in Missouri and other states, I find there is a sincere desire to implement a program of individualization. Two factors which I feel are essential in the initiation of a program on individualized learning are: (1) a set of guidelines stated so that skills to be developed are definitely defined and (2) an abundance and variety of supplementary materials. To accomplish the first factor, teachers must decide on the behavioral objectives for each academic subject from ·kindergarten through sixth grade. To fulfill the second, they must select from supplementary texts, pamphlets, records, films, and tapes the materials which meet these objectives on all levels for varying learning and study styles. A trend is to house these materials in a Leaming Resource Center (LRC) so they are readily available to all students of the school. It is my observation that establishment of a Learning Resource Center is one of the first steps in individualizing instruction. After the teacher has made an accurate diagnosis and has written an appropriate prescription for the individual the materials are then easily accessible. In my work as an elementary specialist for continuing professional education, I have found a limited number of Learning Resource Centers in operation. Educators know the value of these centers and they desire help in establishing and administrating one. The Learning Resource Center must have financing and backing of the school district if it is to function efficiently. The Board of Education of Clayton, Mo., granted funds to McMorrow Elementary School to develop a Learning Resource Center. In the following pages George Fairgrieve, Principal; Jane Coffey, Learning Resource Center Director; and Barbara Lehman, Primary Teacher; describe the functional Learning Resource Center at McMorrow Elementary School. As I edited this material, I knew it would be a beneficial document and tool of reference for you in establishing your LRC. Probably you will not need to utilize nor will you agree with all of the material as stated. However, you should find much of it adaptable to your school situation. It is my recommendation that as you read this monograph you note what appears usable and modify it into a functional plan for your school. Then you will have made an excellent beginning.--Introduction.Includes bibliographical reference

Vascular changes in diabetic retinopathy-a longitudinal study in the Nile rat.

Diabetic retinopathy is the most common microvascular complication of diabetes and is a major cause of blindness, but an understanding of the pathogenesis of the disease has been hampered by a lack of accurate animal models. Here, we explore the dynamics of retinal cellular changes in the Nile rat (Arvicanthis niloticus), a carbohydrate-sensitive model for type 2 diabetes. The early retinal changes in diabetic Nile rats included increased acellular capillaries and loss of pericytes that correlated linearly with the duration of diabetes. These vascular changes occurred in the presence of microglial infiltration but in the absence of retinal ganglion cell loss. After a prolonged duration of diabetes, the Nile rat also exhibits a spectrum of retinal lesions commonly seen in the human condition including vascular leakage, capillary non-perfusion, and neovascularization. Our longitudinal study documents a range and progression of retinal lesions in the diabetic Nile rat remarkably similar to those observed in human diabetic retinopathy, and suggests that this model will be valuable in identifying new therapeutic strategies

Aripiprazole in children and adolescents with Tourette's disorder: an open-label safety and tolerability study

The aim of this study was to conduct a prospective safety and tolerability study of aripiprazole for the treatment of tics in children and adolescents with Tourette's disorder (TD).Eleven subjects (10 males) with TD (age 9-19 years, mean 13.36, standard deviation [SD] 3.33) who did not respond or were unable to tolerate previous tic medication were treated with aripiprazole in an open-label, flexible-dosing study over 10 weeks. Tic severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impressions Scale for tics (CGI-Tics) at baseline and at follow-up.The mean (+/-SD) daily dose for aripiprazole was 4.5 +/- 3.0 mg. Mean (+/-SD) YGTSS Global Severity scores reduced from 61.82 +/- 13.49 at baseline to 33.73 +/- 15.18 at end point; mean YGTSS total tic scores reduced from 28.18 +/- 7.74 at baseline to 16.73 +/- 7.54 at end point. Mean (+/-SD) CGI-Tic severity scores reduced from 4.45 +/- 0.52 (moderate-marked) at baseline to 3.18 +/- 0.60 (mild) at end point. On the CGI-Tic improvement scale, 10 (91%) subjects achieved 1 ("very much improved") or 2 ("much improved") at end point. Most common adverse effects included appetite increase and weight gain in 5 subjects, mild extrapyramidal effects in 7 subjects, and headaches and tiredness/fatigue in 7 subjects; 1 subject experienced akathisia and muscle cramps.Aripiprazole appears to be a safe and tolerable treatment in children and adolescents with TD that appears to reduce tics; it should be further investigated as a treatment option in controlled trials