The effect of exercise on atherosclerosis in the coronary artery and abdominal aorta of mature female swine

Summary This study investigated the effects of chronic exercise on atherosclerosis in the aorta and coronary artery in mature female swine. Preceding and during the exercise training period these animals were fed high fat, (soybean or corn oil) cholesterol-free diets. Sixteen swine were paired according to breed, body weight, and diet. Eight swine were a non-exercise control group while the remaining eight were an experimental group and exercised 4 days per week for 4 months. The exercise training program initially consisted of running at 5.6 km·h⁻¹, zero gradient, for 15 min with increments of 1 min of running time every 2 weeks. The amount of atherosclerosis in the coronary artery and abdominal aorta was determined directly. Plasma lipids, body weight, body potassium, and percent fat were recorded at three intervals during the training program. Four months of exercise had no significant effect on plasma cholesterol, phospholipids, total lipids or triglycerides, although there was a significant effect of test periods on cholesterol. Diet was found to have no influence on plasma lipids. The exercise group did not have larger heart weights, ratio of heart weight to body weight or ratio of heart weight to fat-free body weight. The percent lipid in the lesion area and the lesion surface area of the abdominal aorta was not significantly different between the two groups. The amount of lipid obtained from the intima-media of the coronary artery and the lesion area involvement was not significantly different between the exercise group and the non-exercise group. It is concluded that 4 months of exercise had no effect on plasma lipids, body potassium, body weight, or coronary and aortic atherosclerosis.     

Gene expression changes linked to antimicrobial resistance, oxidative stress, iron depletion and retained motility are observed when Burkholderia cenocepacia grows in cystic fibrosis sputum

Background

Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.

Methods

To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.

Results

We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin.

Conclusion

Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.     

Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase

Tumorigenesis is a multistep process in which oncogenes play a key role in tumor formation, growth, and maintenance. MET was discovered as an oncogene that is activated by its ligand, hepatocyte growth factor. Deregulated signaling in the c-Met pathway has been observed in multiple tumor types. Herein we report the discovery of potent and selective triazolopyridazine small molecules that inhibit c-Met activity.     

Chromosome loss with concomitant duplication and recombination both contribute most to loss of heterozygosity in vitro

Loss of heterozygosity (LOH) plays an important role in the expression of recessive mutations in mammalian cells. To gain insight into the rate and mechanisms of LOH the autosomal HLA-A gene was used as a model system. Spontaneous HLA-A2 mutants originated with a rate of respectively 4.1 × 10⁻⁶ and 6.9 × 10⁻⁶ per cell per generation in TK6 and WI-L2-NS, two isogenic lymphoblastoid cell lines which differ in TP53 status. The rate of loss of HLA-A2 is 10–50 times higher compared to the mutation rate of the X-linked HPRT gene. The homozygous TP53 mutation in WI-L2-NS had no effect on the rate of HLA-A2 loss or the spectrum of these mutations. Microsatellite analysis of most of the HLA-A2 mutants (84%) showed LOH for multiple markers on chromosome arm 6p telomeric of a recombination breakpoint, LOH for all 6p markers, or LOH for markers on both the 6p- and 6q-arms. Cytogenetic analysis showed that these mechanisms gave mutant cells which harbored two intact chromosomes 6 and which were indistinguishable from non-mutant cells. Therefore, loss of HLA-A2 is mainly caused by somatic recombination (33–50%) or chromosome loss with duplication of the remaining chromosome (34–40%). These findings correspond to the mechanisms behind loss of the wild-type RB1 allele in retinoblastoma and suggest that both somatic recombination and chromosome loss followed by duplication contribute to tumorigenesis. Genes Chromosomes Cancer 21:30–38, 1998. © 1998 Wiley-Liss, Inc.     

Smartphone Ownership,Use, and Willingness to Use Smartphones to Provide Peer-Delivered Services: Results from a National Online Survey

Assess certified peer specialists’ smartphone ownership, use, and willingness to use smartphones to provide peer-delivered services. Certified peer specialist from 38 states completed an online survey. The final sample of 267 certified peer specialists included respondents from 38 states. The majority of certified peer specialists were female (73%; n =?195) and Caucasian (79.8%; n =?213), with an average age of 50.9 (SD =?12) years, range from 21 to 77 years. More than half of the certified peer specialists (82.1%; n =?184) were currently working in peer support positions. Of those who reported their mental health diagnoses, 11% reported their diagnosis as schizophrenia spectrum disorder, 22% of respondents reported bipolar disorder, and 23% reported persistent major depressive disorder. Nearly all respondents owned a smartphone (94.8%; n =?253), and everyone indicated that smartphones and tablets could enhance the services they deliver. Certified peer specialists reported substantial ownership and use of smartphones, comparable to existing national data. They are willing to deliver smartphone interventions for mental health and physical health self-management, suggesting that smartphones may be an increasingly useful tool for offering evidence-based care. Without Medicaid mandate, certified peer specialists are naturally trying to enhance peer delivered services with technology. Peer support could act as a mechanism to promote consumer engagement in a smartphone-based intervention. Certified peer specialist own and utilize smartphones, and the majority are willing to deliver technology-based and technology-enhanced interventions using these devices to address medical and psychiatric self-management.