Associations among impulsivity, adverse childhood experiences, and desirability of first sexual experience on substance use and sexual risk taking in justice-involved male adolescents

Adolescent substance use is a serious public health problem (Johnston et al., 2016). Notably in adolescents, adverse childhood experiences including unwanted sexual experiences (Wills et al., 2001; Negriff, Schneiderman, & Trickett, 2015) and impulsive sensation seeking (impulsivity) (Donohew et al., 2000; Fernández-Artamendi et al., 2016) are linked to adolescent substance use and high-risk sexual behaviors. Research also suggests delinquent youths are particularly vulnerable to substance use disorders and sexually risky behaviors (Pinto et al., 2015). Given the health consequences of both prolonged substance abuse and risky sexual behaviors, identifying additional risk factors is critical to help inform interventions for high-risk youth. Data from 314 males, recruited as part of a randomized clinical trial (N = 460) evaluating a theory-based intervention to reduce sexually risky behaviors among justice-involved adolescents, were used for this analysis. Participants completed assessments of adverse childhood experiences, impulsivity, sociosexuality, substance use histories, alcohol/marijuana problems and dependency, and sexual histories. Structural equational modeling (SEM) was used to examine the influence of impulsivity, adverse childhood experiences, sociosexuality, and desirability of first sexual encounter on sexual risk taking and substance use. The final structural equation model including desirability of first sexual encounter, adverse childhood experiences, and impulsivity as exogenous predictors revealed good model fit, χ2(28) = 37.758, p = 0.1031, RMSEA = .033 (90% CI [.000–.058]), CFI = 0.976, WRMR = 0.678. More adverse childhood experiences were associated with higher levels of substance use (β = 0.206, p = .002), greater desirability of first sexual encounter was associated with more sexual risk taking (β = 0.246, p = .007), and higher impulsivity was associated with higher levels of substance use (β = 0.464, p \u3c .001) and more sexual risk taking (β = 0.336, p = .001). Implications for future research and interventions for this vulnerable population are discussed

Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression

Objectives Tristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP. Methods The expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP. Results TTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation. Conclusions The phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments

Spatiotemporal scaling changes in gait in a progressive model of Parkinson's disease

ObjectiveGait dysfunction is one of the most difficult motor signs to treat in patients with Parkinson's disease (PD). Understanding its pathophysiology and developing more effective therapies for parkinsonian gait dysfunction will require preclinical studies that can quantitatively and objectively assess the spatial and temporal features of gait.DesignWe developed a novel system for measuring volitional, naturalistic gait patterns in non-human primates, and then applied the approach to characterize the progression of parkinsonian gait dysfunction across a sequence of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatments that allowed for intrasubject comparisons across mild, moderate, and severe stages.ResultsParkinsonian gait dysfunction was characterized across treatment levels by a slower stride speed, increased time in both the stance and swing phase of the stride cycle, and decreased cadence that progressively worsened with overall parkinsonian severity. In contrast, decreased stride length occurred most notably in the moderate to severe parkinsonian state.ConclusionThe results suggest that mild parkinsonism in the primate model of PD starts with temporal gait deficits, whereas spatial gait deficits manifest after reaching a more severe parkinsonian state overall. This study provides important context for preclinical studies in non-human primates studying the neurophysiology of and treatments for parkinsonian gait

Nanomaterials for Neural Interfaces

This review focuses on the application of nanomaterials for neural interfacing. The junction between nanotechnology and neural tissues can be particularly worthy of scientific attention for several reasons: (i) Neural cells are electroactive, and the electronic properties of nanostructures can be tailored to match the charge transport requirements of electrical cellular interfacing. (ii) The unique mechanical and chemical properties of nanomaterials are critical for integration with neural tissue as long-term implants. (iii) Solutions to many critical problems in neural biology/medicine are limited by the availability of specialized materials. (iv) Neuronal stimulation is needed for a variety of common and severe health problems. This confluence of need, accumulated expertise, and potential impact on the well-being of people suggests the potential of nanomaterials to revolutionize the field of neural interfacing. In this review, we begin with foundational topics, such as the current status of neural electrode (NE) technology, the key challenges facing the practical utilization of NEs, and the potential advantages of nanostructures as components of chronic implants. After that the detailed account of toxicology and biocompatibility of nanomaterials in respect to neural tissues is given. Next, we cover a variety of specific applications of nanoengineered devices, including drug delivery, imaging, topographic patterning, electrode design, nanoscale transistors for high-resolution neural interfacing, and photoactivated interfaces. We also critically evaluate the specific properties of particular nanomaterials—including nanoparticles, nanowires, and carbon nanotubes—that can be taken advantage of in neuroprosthetic devices. The most promising future areas of research and practical device engineering are discussed as a conclusion to the review.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64336/1/3970_ftp.pd

Differences Between Non-Parental Male and Female Responses to Infant Crying

An article that appeared in JASS, issue 2015The purpose of this study was to determine if there is a difference between how non-parental males and females between the ages of 20 and 24 respond physiologically to an audio recording of a crying infant. Based on previous research that investigated differences in physiological response of mothers and fathers to auditory stimuli of infants in distress, the difference between non-parental male and female physiological responses was studied. It was hypothesized that females would have a greater response in all three physiological variables studied. Within the experiment there were a total of 30 participants; 15 male and 15 female. While participants listened to a 30 second recording of an infant crying, measurements of brain activity, heart rate, and electrodermal activity were taken. Since a large number of studies measuring responses to infant stimuli were conducted using parents as subjects, the present experiment adds a new angle to a widely discussed topic. No significant difference was seen between males and females in any of the physiological variables that were measured

Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression

Objectives Tristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP. Methods The expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP. Results TTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and colocalised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation. Conclusions The phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments.</p