Lateralization of olfactory cognitive functions: effects of rhinal side of stimulation.

This study investigated differences in olfactory cognitive functions, in 40 healthy young right-handed participants, with respect to side of rhinal stimulation. The targeted functions were: perceived familiarity, episodic recognition memory, free identification and repetition priming in identification. The results showed that odors presented to the right nostril were rated as more familiar than odors presented to the left nostril and also showed significant effects of repetition priming in identification. However, no differences were found between nostrils in episodic recognition memory or free identification. These latter results indicate a rather extensive inter-hemispheric interaction in higher-order cognitive functions.     

Multiple loci contribute to genome-wide recombination levels in male mice

Recent linkage-based studies in humans suggest the presence of loci that affect either genome-wide recombination rates, utilization of recombination hotspots, or both. We have been interested in utilizing cytological methodology to directly assess recombination in mammalian meiocytes and to identify recombination-associated loci. In the present report we summarize studies in which we combined a cytological assay of recombination in mouse pachytene spermatocytes with QTL analyses to identify loci that contribute to genome-wide levels of recombination in male meiosis. Specifically, we analyzed MLH1 foci, a marker of crossovers, in 194 F2 male mice derived from a subspecific cross between CAST/EiJ and C57BL/6J parental strains. We then used these data to uncover loci associated with individual variation in mean MLH1 values. We identified seven recombination-associated loci across the genome (on chromosomes 2, 3, 4, 14, 15, 17, and X), indicating that there are multiple recombination “setting” loci in mammalian male meiosis.     

Long-Term Effects of Sulfadiazine-Trimethoprim Medicated Diet on Cardiac Function,Hematology, and Weight Gain in Hsd:ICR (CD1) and Tac:SW Mice

With the alarming increase in heart disease and heart failure, the need for appropriate and ethical animal models of cardiac dysfunction continues to grow. Currently, many animal models of cardiomyopathy require either invasive procedures or genetic manipulation, both of which require extensive expertise, time, and cost. Serendipitous findings at our institution revealed a possible correlation between sulfadiazine-trimethoprim (SDZ-TMP) medicated diet and the development of cardiomyopathy in IcrTac:ICR mice. We hypothesized that mice fed SDZ-TMP medicated diet continuously for 3 to 6 mo would develop cardiomyocyte degeneration and fibrosis, eventually leading to dilated cardiomyopathy. A total of 44 mice (22 Hsd:ICR (CD1) and 22 Tac:SW) were enrolled in the study. Half of these 44 mice were fed standard rodent diet and the other half were fed SDZ-TMP medicated diet. Baseline samples, including weights, CBCs, select biochemistry parameters, and echocardiography were performed prior to the start of either diet. Weights were obtained monthly and all other parameters were measured at least once during the study, and again at its conclusion. After 42 wk, mice were euthanized, and heart, lung and bone marrow tissue were submitted for histopathologic evaluation. Histologically, hearts were scored for the degree of degeneration, fibrosis, inflammation, and vacuolation. The data showed that SDZ-TMP did not have a significant effect on cardiac function, RBC parameters, biochemistry parameters (ALT, AST, calcium, magnesium, creatine kinase, and creatinine), hematopoiesis, or histologic heart scores. In addition, mice fed the SDZ-TMP medicated diet gained less weight over time. In summary, we were unable to reproduce the previous findings and thus could not use this approach to develop a novel model of cardiomyopathy. However, these results indicate that SDZ-TMP medicated diet containing 1,365 ppm of SDZ and 275 ppm of TMP does not appear to have long-term detrimental effects in mice.

Heart disease is currently the leading cause of death in the United States. The American Heart Association estimates that the prevalence of heart failure will increase to 46% by 2030,⁴ and the cost associated with heart disease is expected to rise from $55 billion in 2016 to $1.2 trillion (US dollars) by 2030.⁴ The existing animal models of heart disease have enhanced our knowledge of its pathophysiology and has led to the development of numerous therapies.^9,30,47,54 However, many animal models of cardiomyopathy require invasive procedures such as aortic constriction,^16,58 left anterior descending artery ligation,^15,31,52 cryogenic injury,^27,57 or renal ischemia⁶⁸ to induce the cardiac changes associated with heart failure. The chemotherapeutic agent doxorubicin has also been used to induce heart failure in mice,^66,69 but a major disadvantage is the risk it poses to workers as a hazardous agent. Genetically engineered mice can replace invasive surgical models of cardiac disease,¹⁴ but they also have significant limitations including cost, time, and failure to express the anticipated phenotype.^3,38,39 Despite advancements in cardiac research, reproducible and economical animal models of heart disease are still needed to further our understanding and explore novel therapeutic solutions.Researchers at the University of Chicago reported that IcrTac:ICR sentinel mice that were accidently fed sulfadiazine trimethoprim (SDZ-TMP) medicated diet for 3 to 6 mo developed cardiomyopathy and subsequently cardiac dysfunction.⁴⁸ Prior to the onset of cardiomyopathy, these animals showed no signs of clinical disease.⁴⁸ SDZ-TMP is a potentiated sulfonamide, and the synergistic activity of sulfadiazine and trimethoprim allows it to not only inhibit folic acid metabolism in bacteria but also in some protozoa and fungi.²⁵ Potentiated sulfonamides are commonly administered to immunocompromised mice to prevent or treat opportunistic infections such as Pneumocystis murina.²⁰ However, SDZ-TMP may have contributed to the development of cardiomyopathy in these mice,⁴⁸ as potentiated sulfonamides are known to have adverse side effects in other animals, such as keratitis sicca, hypothyroidism, anemia, leukopenia, and hypersensitivity reactions.⁵⁰Based on the previous findings,⁴⁸ the goal of this study was to develop a cost-effective, reproducible, and noninvasive animal model of dilated cardiomyopathy. The prior data suggested that this model would have a slow and progressive onset, mimicking many aspects of heart disease and heart failure in humans.⁴⁸ We hypothesized that mice fed SDZ-TMP medicated diet continuously for 3 to 6 mo would develop cardiomyocyte degeneration and fibrosis, eventually progressing to dilated cardiomyopathy. Initial findings were discovered in the outbred stock IcrTac:ICR, but at the time of the present study, live production of this stock had ceased. Therefore, we elected to investigate our hypothesis in 2 readily available outbred stocks. We first attempted to monitor the progression of cardiomyopathy over time via echocardiography in Hsd:ICR (CD1) and Tac:SW mice fed SDZ-TMP medicated diet. In addition to capturing this progression, other objectives of this study were to investigate the long-term effects of SDZ-TMP medicated diet on other health parameters, including CBCs, a subset of biochemistry parameters to assess kidney and liver function, and weight gain. Thus, our goals were to both create an improved animal model of cardiomyopathy and enhance our understanding of prolonged prophylactic antibiotic use and its potential effects on biomedical research models and results.     

The response of the seated human to sinusoidal vibration and impact

Low back pain has been shown to occur more frequently among vehicle drivers than in representative control groups. Thus the response of the human to vibration and impact is of interest. This study investigated the response of the spine to both impact and sinusoidal excitation in either a relaxed or erect seated posture. The sinusoidal testing apparatus used was a resonating system consisting of two parallel wooden beams, simply supported, and the impact testing apparatus a bearing-guided, spring-suspended platform, struck from below. Ten subjects (5 males, 5 females) were evaluated using both methods. Transfer functions were compared at 2-4 Hz, 4-8 Hz and 8-16 Hz intervals using a sign test. Although in 24 comparisons of either test method (vibration or impact) or posture (erect or relaxed) where eleven showed differences significant at the p less than .05 level, only 2 out of 24 comparisons were the differences distinct enough to be significant (at the p less than .01 level). Both of these latter differences were due to test method while the subjects were sitting erect. In those instances where there were no significant differences due to test method, the impact method may be a viable replacement for the vibration test method. Where the levels of significance are higher (p less than .01 or p less than .05), further study of the magnitude of the differences is indicated and may reveal further insight into the seated individual as a system.     

Mounting of the transducers in measurement of segmental motion of the spine

A seated female subject was subjected to sinusoidal whole body vibration at 2, 4, 5 and 6 Hz. Accelerations were measured by accelerometers on pins screwed into the spinous process. The pins were also fitted with light emitting diodes (LED). The displacement of these LEDs were compared to LEDs attached directly to the skin. Substantial differences in measured displacements were noted between surface mounted LEDs and those mounted on pins rigidly attached to the skeleton. These differences were more marked further out from the center line.