Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders.

The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions

The Weight of Time: Time influences on overweight and obesity in men

We know that adults’ weight increases with age, at least until around the age of 55 years or older. Recent National Australian surveys show that men and women of all age groups were heavier in 2000 than in 1995 or 1990. These studies also found that a greater proportion of people of all ages were overweight or obese in 2000 than in the previous surveys. These studies also suggested that different generations, also known as ‘birth cohorts’, had different patterns of weight gain. These birth cohort influences mean that the year a person is born and the unique set of experiences people born at that time experience, have an effect on weight gain patterns. People born at other times experience different conditions and have different weight gain patterns. Some birth cohorts or ‘generations’ are well-known, such as the ‘baby boomer’ generation, or pre-war generation. For example, Australians born in the first three decades of the twentieth century experienced World War I and II and the Great Depression during their childhood and early adult life. During these times food was scarce and everyday life required high levels of physical activity. This group overall had lower body weights than more recent generations, meaning they were less at risk of becoming obese. Australians born after 1980 were born into an advanced technological society with greater availability of food, a vastly increased range of food products and increasing serving sizes. At the same time, levels of physical activity in everyday life have been decreasing. Together these factors produce an obesogenic environment. The three National Health surveys, conducted by the Australian Bureau of Statistics for the Australian Institute of Health and Welfare in 1990, 1995 and 2000, produced data which the NSW Centre for Overweight and Obesity has analyzed to find out what effects three time factors -- ageing, the time of the surveys and birth cohort -- have on body mass index (BMI) and the prevalence of overweight and obesity. [Note – BMI used as the indicator of weight status, where BMI = weight (kg)/height2 (M2)] This report provides an overview of key findings of the analyses of the effects of these three time factors on male weight patterns. The complete findings have been published in a comprehensive technical report. The results from the analysis of the effect of birth cohorts have been used to predict the mean body mass index of men in NSW in 2010. The graphs in this report show the results for men but the results for women are available. The overall patterns and implications for women are generally similar to those for men

The Weight of Time: Time influences on overweight and obesity in women

We know that adults’ weight increases with age, at least until around the age of 55 years or older. Recent National Australian surveys show that men and women of all age groups were heavier in 2000 than in 1995 or 1990. These studies also found that a greater proportion of people of all ages were overweight or obese in 2000 than in the previous surveys. These studies also suggested that different generations, also known as ‘birth cohorts’, had different patterns of weight gain. These birth cohort influences mean that the year a person is born and the unique set of experiences people born at that time experience, have an effect on weight gain patterns. People born at other times experience different conditions and have different weight gain patterns. Some birth cohorts or ‘generations’ are well-known, such as the ‘baby boomer’ generation, or pre-war generation. For example, Australians born in the first three decades of the twentieth century experienced World War I and II and the Great Depression during their childhood and early adult life. During these times food was scarce and everyday life required high levels of physical activity. This group overall had lower body weights than more recent generations, meaning they were less at risk of becoming obese. Australians born after 1980 were born into an advanced technological society with greater availability of food, a vastly increased range of food products and increasing serving sizes. At the same time, levels of physical activity in everyday life have been decreasing. Together these factors produce an obesogenic environment. The three National Health surveys, conducted by the Australian Bureau of Statistics for the Australian Institute of Health and Welfare in 1990, 1995 and 2000, produced data which the NSW Centre for Overweight and Obesity has analyzed to find out what effects three time factors -- ageing, the time of the surveys and birth cohort, have on body mass index (BMI) and the prevalence of overweight and obesity. [Note – BMI used as the indicator of weight status, where BMI = weight (kg)/height2 (M2)] This report provides an overview of key findings of the analyses of the effects of these three time factors on female weight patterns. The complete findings have been published in a comprehensive technical report. The results from the analysis of the effect of birth cohorts have been used to predict the mean body mass index of women in NSW in 2010. The graphs in this report show the results for women, and the results for men are available in a separate document. The overall patterns and implications for men are generally similar to those for women. NS

Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism.

Remarkably little is known about the postnatal cellular development of the human amygdala. It plays a central role in mediating emotional behavior and has an unusually protracted development well into adulthood, increasing in size by 40% from youth to adulthood. Variation from this typical neurodevelopmental trajectory could have profound implications on normal emotional development. We report the results of a stereological analysis of the number of neurons in amygdala nuclei of 52 human brains ranging from 2 to 48 years of age [24 neurotypical and 28 autism spectrum disorder (ASD)]. In neurotypical development, the number of mature neurons in the basal and accessory basal nuclei increases from childhood to adulthood, coinciding with a decrease of immature neurons within the paralaminar nucleus. Individuals with ASD, in contrast, show an initial excess of amygdala neurons during childhood, followed by a reduction in adulthood across nuclei. We propose that there is a long-term contribution of mature neurons from the paralaminar nucleus to other nuclei of the neurotypical human amygdala and that this growth trajectory may be altered in ASD, potentially underlying the volumetric changes detected in ASD and other neurodevelopmental or neuropsychiatric disorders

Theoretical He I Emissivities in the Case B Approximation

We calculate the He I case B recombination cascade spectrum using improved radiative and collisional data. We present new emissivities over a range of electron temperatures and densities. The differences between our results and the current standard are large enough to have a significant effect not only on the interpretation of observed spectra of a wide variety of objects but also on determinations of the primordial helium abundance.Comment: Accepted to ApJ

Neuroprotective efficacy of P7C3 compounds in primate hippocampus.

There is a critical need for translating basic science discoveries into new therapeutics for patients suffering from difficult to treat neuropsychiatric and neurodegenerative conditions. Previously, a target-agnostic in vivo screen in mice identified P7C3 aminopropyl carbazole as capable of enhancing the net magnitude of postnatal neurogenesis by protecting young neurons from death. Subsequently, neuroprotective efficacy of P7C3 compounds in a broad spectrum of preclinical rodent models has also been observed. An important next step in translating this work to patients is to determine whether P7C3 compounds exhibit similar efficacy in primates. Adult male rhesus monkeys received daily oral P7C3-A20 or vehicle for 38 weeks. During weeks 2-11, monkeys received weekly injection of 5'-bromo-2-deoxyuridine (BrdU) to label newborn cells, the majority of which would normally die over the following 27 weeks. BrdU+ cells were quantified using unbiased stereology. Separately in mice, the proneurogenic efficacy of P7C3-A20 was compared to that of NSI-189, a proneurogenic drug currently in clinical trials for patients with major depression. Orally-administered P7C3-A20 provided sustained plasma exposure, was well-tolerated, and elevated the survival of hippocampal BrdU+ cells in nonhuman primates without adverse central or peripheral tissue effects. In mice, NSI-189 was shown to be pro-proliferative, and P7C3-A20 elevated the net magnitude of hippocampal neurogenesis to a greater degree than NSI-189 through its distinct mechanism of promoting neuronal survival. This pilot study provides evidence that P7C3-A20 safely protects neurons in nonhuman primates, suggesting that the neuroprotective efficacy of P7C3 compounds is likely to translate to humans as well

Preliminary evidence of increased striatal dopamine in a nonhuman primate model of maternal immune activation.

Women exposed to a variety of viral and bacterial infections during pregnancy have an increased risk of giving birth to a child with autism, schizophrenia or other neurodevelopmental disorders. Preclinical maternal immune activation (MIA) models are powerful translational tools to investigate mechanisms underlying epidemiological links between infection during pregnancy and offspring neurodevelopmental disorders. Our previous studies documenting the emergence of aberrant behavior in rhesus monkey offspring born to MIA-treated dams extends the rodent MIA model into a species more closely related to humans. Here we present novel neuroimaging data from these animals to further explore the translational potential of the nonhuman primate MIA model. Nine male MIA-treated offspring and 4 controls from our original cohort underwent in vivo positron emission tomography (PET) scanning at approximately 3.5-years of age using [18F] fluoro-l-m-tyrosine (FMT) to measure presynaptic dopamine levels in the striatum, which are consistently elevated in individuals with schizophrenia. Analysis of [18F]FMT signal in the striatum of these nonhuman primates showed that MIA animals had significantly higher [18F]FMT index of influx compared to control animals. In spite of the modest sample size, this group difference reflects a large effect size (Cohen's d = 0.998). Nonhuman primates born to MIA-treated dams exhibited increased striatal dopamine in late adolescence-a hallmark molecular biomarker of schizophrenia. These results validate the MIA model in a species more closely related to humans and open up new avenues for understanding the neurodevelopmental biology of schizophrenia and other neurodevelopmental disorders associated with prenatal immune challenge

Creativity out of chaos

Creativity is said to be highly desired in post-modern and post-industrial organizations Creativity and anarchy on the one hand, and managerialism, on the other, can be seen as different forms of knowledge, two opposed ideals. In many organizational as well as societal reforms we currently observe it is the managerialist ideal that wins over the anarchic. In this paper, we wonder if people fear anarchy? We reflect on the possible reasons for the fear, and we also try to explain why we believe that anarchic organizing should not be avoided or feared

Mucinous adenocarcinoma of the bladder associated with long term suprapubic tube: A case report

BACKGROUND: Chronic indwelling catheters may induce histologic changes within the bladder, and these changes are sometimes pre-malignant. There are many documented cases of squamous cell carcinoma associated with indwelling catheters, but only three cases of catheter-associated adenocarcinoma have been reported. In this case report, we present radiographic findings of a case of mucinous adenocarcinoma of the bladder and suprapubic (SP) tract in a quadriplegic patient. CASE PRESENTATION: A 71-year-old male with a history of spinal cord injury presented with hematuria and SP discharge after SP catheterization for 51 years. CT urography was performed and revealed an irregular, infiltrative, and heterogeneous mass arising from the anterior bladder at the level of the suprapubic catheter and extending along the SP tube tract. Cystoscopy and biopsy revealed an adenocarcinoma of the anterior bladder and stoma with extensive associated mucin production and a background of acute and chronic inflammation. Surgical therapy included cystoprostatectomy, abdominal wall resection, ileal conduit creation, and abdominal wall reconstruction. The final diagnosis was a high-grade, T2a/N0/M0 (Stage II) mucinous adenocarcinoma of the bladder. There has been no evidence of tumor recurrence over the previous 5 years. CONCLUSION: Few cases of adenocarcinoma associated with long term indwelling catheter have been reported in the literature, and due to the rarity of this disease process, the prognosis with surgical therapy is not well known. The patient described herein has been free of recurrence for the previous five years, suggesting that surgery is a viable management option for these patients