Elevated ghrelin alters the behavioral effects of perinatal acetaminophen exposure in rats.

A growing body of evidence links prenatal and early postnatal acetaminophen (APAP) exposure to atypical development of brain and behavior. In adult rodents, APAP is known to produce oxidative stress and lower anxiety-related behavior following acute exposure. In models of early-life exposure, APAP has also been shown to alter anxiety-related and other behaviors. Since the neuropeptide ghrelin has been recently shown to reduce oxidative stress markers and act as a neuroprotectant, we hypothesized that exposure to ghrelin prior to exposure to APAP would mitigate the behavioral effects of APAP exposure. On postnatal day 7, pups were administered doses of either APAP (51.97 mg/kg), ghrelin (1 mg/kg/ml), ghrelin + APAP, or vehicle only. As adults, anxiety-related behavior was assessed in the open field and elevated plus maze. Behavior differed based upon treatment condition. In rats unexposed to ghrelin, APAP treatment resulted in increased exploration (i.e., reduced anxiety) in the open field relative to controls. Rats co-administered APAP and ghrelin did not differ from vehicle-only controls. No significant effects of APAP or interactions between APAP and ghrelin exposures were observed in the elevated plus maze. These results are the first to demonstrate that ghrelin can mitigate the effects of perinatal APAP exposure in rats.

Behavioral effects of postnatal ketamine exposure in rhesus macaque infants are dependent on MAOA-LPR genotype.

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist widely used in pediatric anesthetic and therapeutic practices and veterinary medicine. Previous evidence suggests that exposure to ketamine during sensitive periods of development results in neural apoptosis and atypical behavior. Since monoamine neurotransmitters play important roles in prenatal and early postnatal neural development, and since previous work suggests ketamine can inhibit monoamine transporters, we hypothesized that there would be behavioral consequences of prenatal and early postnatal exposure to ketamine moderated by genotype of the promoter in the monoamine oxidase-A (MAOA) gene. From a large sample of animals (N = 408), we compared groups of rhesus monkeys that had experienced a single exposure to ketamine during prenatal development, an exposure during prenatal development and one postnatal exposure, a postnatal exposure with no prenatal exposure, and no exposures. Animals were classified by putative activity levels for the MAOA genotype and were tested between 3 and 4 months of age on a battery of behavioral tests. Results suggested that animals exposed to ketamine postnatally, at a dose typically used for sedative effects that also had the low-activity variant of MAOA performed poorly on a visual memory test compared to animals with the high-activity variant of the MAOA gene.

Plastic flow anisotropy drives shear fracture.

Fracture of initially crack-free bodies often occurs due to plastic instabilities known as shear bands. Previous computer simulations advanced a myriad of mechanisms to rationalize shear banding. However, they were restricted to planar geometries. We investigate the relevance of anisotropic plasticity by picking an axisymmetric tensile test rig, in which shear localization is rarely observed. The three-dimensional finite-element simulations of shear banding in this type of specimens are the first of their kind. The micromechanical modeling covers a range of competing mechanisms believed to be responsible for such failure. We show that anisotropic plasticity can effectively trigger shear bands thereby causing failure of ductile solids. Our results enable shear fracture to be rationalized in ductile rocks and mitigated against in designing advanced materials.

Biobehavioral consequences of prenatal exposure to a matrilineal overthrow and relocation in captive infant rhesus (Macaca mulatta) monkeys.

There is a general consensus that perinatal experiences help to shape infant behavior; however, relatively little is known about the effects of prenatal experience on postnatal phenotype in non-human primates. The current study sought to take advantage of a naturally occurring incident in a captive population of rhesus monkeys. Following a matrilineal overthrow in an outdoor field cage, pregnant female rhesus macaques were relocated from outdoor to indoor housing. Using data collected from the California National Primate Research Center's Biobehavioral Assessment Program, we assessed infants born to mothers that were in their first or second trimester of pregnancy during the overthrow and relocation, and compared their data with that of animals from two control groups born in the same year: indoor mother raised infants and field cage reared infants. Our results suggest that the experience of an overthrow and relocation during the first trimester elevated postnatal emotional responsiveness, while the same experience in the second trimester resulted in modified HPA axis regulation, elevated glucocorticoid output following maternal separation, and lower hematocrit levels compared to control groups. These data add to a growing body of literature that prenatal experiences represent a significant contribution to postnatal phenotypic variability. Findings such as ours have implications for studies in captive management and the management of captive rhesus monkey populations. Am. J. Primatol. 78:895-903, 2016. © 2016 Wiley Periodicals, Inc.

Elevated yolk progesterone moderates prenatal heart rate and postnatal auditory learning in bobwhite quail (Colinus virginianus).

Previous studies have established that yolk hormones of maternal origin can influence physiology and behavior in birds. However, few studies have examined the effects of maternal gestagens, like progesterone, on chick behavior and physiology. We tested the effects of experimentally elevated egg yolk progesterone on embryonic heart rate and postnatal auditory learning in bobwhite quail hatchlings. Quail chicks were passively exposed to an individual maternal assembly call for 10 min/hr during the 24 hr following hatching. Preference for the familiarized call was tested at 48 hr following hatching in three experimental groups: chicks that received artificially elevated yolk progesterone (P) prior to incubation, vehicle-only controls (V), and non-manipulated controls (C). Resting heart rate of P, V, and C embryos were also measured on prenatal day 17. The resting heart rate of P embryos was significantly higher than both the V and C embryos. Chicks from the P group also showed an enhanced preference for the familiarized bobwhite maternal call when compared to chicks from the C and V groups. Our results indicate that elevated yolk progesterone in pre-incubated bobwhite quail eggs can influence arousal level in bobwhite embryos and postnatal perceptual learning in bobwhite neonates.

Increased yolk progesterone interferes with prenatal auditory learning and elevates emotional reactivity in bobwhite quail (Colinus virginianus) chicks.

Avian eggs contain maternally derived hormones, including testosterone and progesterone. Little is currently known about the effects of these hormones on early behavioral development. We assessed the effects of elevated levels of progesterone levels on prenatal perceptual learning and postnatal emotional reactivity in Northern bobwhite quail. Prior to incubation, eggs received an injection of either progesterone (P) or oil vehicle (V). In P eggs, levels of progesterone were elevated two standard deviations above the mean based on ELISA analysis of progesterone yolk concentrations from a previous study. A third group of eggs served as controls and received no injection (C). Chicks hatched from P eggs displayed elevated levels of emotional reactivity compared to V and C chicks in a tonic immobility task and a hole-in-the-wall emergence task. Chicks from P eggs also failed to demonstrate a preference for a familiarized bobwhite maternal call that had been presented prenatally. In contrast, the V and C chicks demonstrated a significant preference for the familiarized maternal call following hatching, indicating prenatal auditory learning. Our results are consistent with previous findings from precocial birds demonstrating that hormones of maternal origin can influence prenatal perceptual learning as well as emotional reactivity in the period following hatching..

Problematic standard errors and confidence intervals for skewness and kurtosis.

Many statistics packages print skewness and kurtosis statistics with estimates of their standard errors. The function most often used for the standard errors (e.g., in SPSS) assumes that the data are drawn from a normal distribution, an unlikely situation. Some textbooks suggest that if the statistic is more than about 2 standard errors from the hypothesized value (i.e., an approximate value for the critical value from the t distribution for moderate or large sample sizes when α = 5%), the hypothesized value can be rejected. This is an inappropriate practice unless the standard error estimate is accurate and the sampling distribution is approximately normal. We show distributions where the traditional standard errors provided by the function underestimate the actual values, often being 5 times too small, and distributions where the function overestimates the true values. Bootstrap standard errors and confidence intervals are more accurate than the traditional approach, although still imperfect. The reasons for this are discussed. We recommend that if you are using skewness and kurtosis statistics based on the 3rd and 4th moments, bootstrapping should be used to calculate standard errors and confidence intervals, rather than using the traditional standard. Software in the freeware R for this article provides these estimates.

A Comparison of Immune Functionality in Viral versus Non-Viral CFS Subtypes.

Participants with CFS were grouped into viral and non-viral onset fatigue categories and assessed for differential immunological marker expression. Peripheral Blood Mononuclear Cells were assessed for differential phenotypic expression of surface adherence glycoproteins on circulating lymphocytes. The flow cytometric analysis employed fluorescent monoclonal antibody labeling. The viral in comparison to the non-viral group demonstrated significant elevations in several Th1 type subsets including: the percentage and number of CD4+ cells, the percentage and number of CD2+CD26+ cells, the percentage and number of CD2+CD4+CD26+ cells, the percentage and number of CD4+ CD26+ cells, and the percentage of Th2 naïve cells (CD4+ CD45RA+CD62L+). Of the remaining significant findings, the non viral group demonstrated significant elevations in comparison to the viral group for the following Th1 type subsets: the percentage of CD8+ cells, the percentage of T-cytotoxic suppressor cells (CD3+8+), and the percentage and number of Th1 memory cells (CD8+CD45RA-CD62L-). The viral group demonstrated a pattern of activation that differed from that of the group with a non-viral etiology, as evidenced by an elevated and out of range percentage and number of CD4+ cells, the percentage of CD2+CD26+, and the percentage of Th2 naïve cells (CD4+CD45RA+CD62L+). Both groups demonstrated reduced and out of range Natural Killer Cell Cytotoxicity and percentage of B-1 cells (CD5+CD19). In addition, both groups demonstrated an elevated and out of range percentage of CD2+CD8+CD26+, percentage of the Th1 memory subset (CD4+CD45RA-CD62L-), the percentage of Th1 memory and naïve cells (CD8+CD45RA-CD62L-, CD8+CD45RA+CD62L-), the percentage and number of Th2 memory cells (CD4+CD45RA-CD62L+), and the percentage of Th2 memory and naïve cells (CD8+CD45RA-CD62L+, CD8+CD45RA+CD62L+). These findings imply that the homeostatic mechanism responsible for the regulation of the Th1 (cell mediated) and Th2 (humoral) immune responses is disturbed in CFS. The implications of these findings are discussed.

Activity Logs as a Measure of Daily Activity Among Patients with Chronic Fatigue Syndrome.

BACKGROUND: Self-report data collected through interviews has been one of the primary ways of assessing symptoms of patients with chronic fatigue syndrome (CFS). An alternative way to collect data involves activity logs, which involves patients writing down the pattern, intensity, and qualitative nature of activity over several days. AIMS: We examined the associations between activity, evaluation of activity and symptoms. METHODS: Activity log data over a two day period of time were used in the present study using a sample of patients with diagnosed CFS. RESULTS: Findings indicated that the percent of time spent feeling fatigued was positively associated with a higher percent of time in pain and doing activities that were fatiguing. However, time spent in meaningful activities was associated with less fatigue. CONCLUSIONS: These findings and others suggest that activity logs can provide investigators and clinicians with valuable sources of data for understanding patterns of behavior and activity among patients with CFS.