Bystander Intoxication and Appraisal of Sexual Assault Risk: A Field Study of Emerging Adult Bargoers.

Emerging adults are especially vulnerable to experiencing alcohol-related sexual assault. While bystanders play a critical role in preventing sexual assault, little is known about how bystander alcohol intoxication affects the intervention process-particularly in naturalistic settings. We recruited 315 emerging adult bargoers ages 21-29 (46% women; 28% non-college attending; 81% White) from a high-density bar area to provide responses to a sexual assault vignette and complete a breath alcohol concentration test. In this field-based study, we found a negative direct association between intoxication and appraisal of risk in the hypothetical sexual assault situation. We also found a negative indirect relation of intoxication on perceptions of personal responsibility to intervene and confidence in the ability to intervene, statistically mediated through reduced risk appraisal. Findings add to the limited literature in laboratory-based settings suggesting that bystander intoxication interferes with sexual assault intervention and help inform effective bystander intervention programming for emerging adults.

Insulin-like growth factor-1 regulates the mechanosensitivity of chondrocytes by modulating TRPV4.

Both mechanical and biochemical stimulation are required for maintaining the integrity of articular cartilage. However, chondrocytes respond differently to mechanical stimuli in osteoarthritic cartilage when biochemical signaling pathways, such as Insulin-like Growth Factor-1 (IGF-1), are altered. The Transient Receptor Potential Vanilloid 4 (TRPV4) channel is central to chondrocyte mechanotransduction and regulation of cartilage homeostasis. Here, we propose that changes in IGF-1 can modulate TRPV4 channel activity. We demonstrate that physiologic levels of IGF-1 suppress hypotonic-induced TRPV4 currents and intracellular calcium flux by increasing apparent cell stiffness that correlates with actin stress fiber formation. Disruption of F-actin following IGF-1 treatment results in the return of the intracellular calcium response to hypotonic swelling. Using point mutations of the TRPV4 channel at the microtubule-associated protein 7 (MAP-7) site shows that regulation of TRPV4 by actin is mediated via the interaction of actin with the MAP-7 domain of TRPV4. We further highlight that ATP release, a down-stream response to mechanical stimulation in chondrocytes, is mediated by TRPV4 during hypotonic challenge. This response is significantly abrogated with IGF-1 treatment. As chondrocyte mechanosensitivity is greatly altered during osteoarthritis progression, IGF-1 presents as a promising candidate for prevention and treatment of articular cartilage damage.

Interpersonal vs. Non-Interpersonal Cumulative Traumas and Psychiatric Symptoms in Treatment-Seeking Incarcerated Women.

Incarcerated women are at elevated risk of lifetime trauma exposure. Prevalence rates of trauma exposure and how these events relate to specific domains of psychiatric symptomology among this group are lacking. This study hypothesized a greater range of diverse cumulative trauma experiences (CTEs) would be positively associated with psychiatric symptoms in general (depression, PTSD, distress tolerance), but that interpersonal CTEs in particular would be uniquely associated with greater symptoms of guilt and shame. A total of 112 women (87% White, Mage = 34 years) seeking treatment for a history of sexual violence victimization participated in the study. Women incarcerated for nonviolent offenses at two minimum-security prisons completed self-report measures of exposure to diverse traumatic events and internalizing symptoms. On average, participants reported a history of experiencing 5.46 traumatic event types. Total CTEs was significantly associated with all psychiatric variables in the expected direction. While both interpersonal and non-interpersonal CTEs were positively associated with levels of PTSD, depression, and distress intolerance, only interpersonal CTEs were significantly associated with guilt and shame. Traumatic experiences that are interpersonal in nature may confer specific risk for psychiatric symptoms in victims.

The Interaction of Rape Myth Acceptance and Alcohol Intoxication on Bystander Intervention.

Bystander interventions for sexual assault promote third-party interference. People who endorse rape myths blame victims more and perpetrators less; consequently, rape myth acceptance (RMA) can impede helping behaviors toward sexual assault victims. Acute alcohol intoxication may exacerbate the effects of RMA on bystander intervention. In this study, we examined the influence of RMA-and potential moderating effect of acute alcohol intoxication-on predictors of bystander intervention. Young adults (N = 128) completed a survey in a lab setting, then consumed either an alcoholic or control beverage, read and listened to a fictional sexual assault scenario, and finally completed a semi-structured interview and postexperiment survey assessing their perceptions of the scenario. Using multivariate analysis of covariance (MANCOVA), we found people with higher RMA blamed the victim more and perpetrator less; they were also less likely to perceive responsibility to intervene for a sexual assault victim. Alcohol intoxication did not exacerbate these effects. That is, alcohol intoxication was not a context in which RMA was expressed more strongly. We recommend bystander programs continue to address RMA, specifically as a barrier to intervening.

Context Matters for the Socially Anxious: Moderating Role of Drinking Context on Alcohol Outcome Expectancies.

Background: Moderating effects of alcohol outcome expectancies (AOE) on the social anxiety (SA)-alcohol misuse relationship are mixed. This may be explained by differential relationships between SA and context-specific AOE. Gender may further moderate these associations, as it influences SA, AOE, and drinking behaviors. Objectives: To examine the moderating role of drinking context (i.e. convivial, negative coping, or personal-intimate) and gender on the relationships between SA and three AOE (i.e. tension reduction, sociability, and sexuality). Methods: Participants (n = 436, Mage=19.32, 72% female, 85.8% White) were 218 undergraduates with elevated SA (high SA group) and a gender-matched low SA group (n = 218) drawn from a larger undergraduate sample (N = 1,015). Participants completed three versions of an AOE measure, differing by drinking context considered. Results: A significant SA group x context x gender interaction was found for tension reduction AOE; compared to men, women in the low SA group reported greater tension reduction AOE in negative coping contexts. Significant SA group and context main effects suggest that sociability and sexuality AOE are endorsed more in the high (vs. low) SA group, and in convivial and personal-intimate compared to negative coping contexts. Conclusions/Importance: Tension reduction AOE vary depending on the drinking context, SA, and gender. Assessment of AOE in specific drinking contexts may help to identify which individuals may be at greatest risk for alcohol misuse and help inform treatment of SA-related problem drinking.

Factor Structure of the Brief Comprehensive Effects of Alcohol Scale in Adolescents.

Alcohol use among adolescents is a public health concern; therefore, it is important that studies that examine factors associated with adolescent drinking behaviors utilize measures that are well-validated for use with this population. The current study examined the factor structure and convergent validity of the Brief Comprehensive Effects of Alcohol scale, a measure of alcohol outcome expectancies and evaluations of expected outcomes, among adolescents ( N = 1,074; 50% girls; Mage = 15.96 years, SD = 1.13, range = 13-18; 74% White) drawn from three independent studies ( nsite 1 = 594; nsite 2 = 97; and nsite 3 = 383). Results yielded support for a four-factor structure for alcohol expectancies and two-factor structure for valuations. Moreover, the factor structure was partially or fully invariant across gender, age, and site. Thus, findings are similar, yet unique, to those identified in college samples. The convergent validity of the modified measure was supported, suggesting that the Brief Comprehensive Effects of Alcohol scale may be useful for assessing adolescents' beliefs about alcohol.

Aneurysmal bone cysts and pathologic fracture associated with supernumerary ring chromosome 6 in two unrelated patients.

Small supernumerary ring chromosome 6 (sSRC[6]) is a rare chromosomal abnormality characterized by a broad clinical phenotype. The spectrum of this disorder can range from phenotypically normal to severe developmental delay and congenital anomalies. We describe two unrelated patients with small SRCs derived from chromosome 6 with a novel bone phenotype. Both patients presented with a complex bone disorder characterized by severe osteopenia, pathologic fractures, and cyst-like lesions within the bone. Imaging revealed decreased bone mineral density, mutiple multiloculated cysts and cortical thinning. Lesion pathology in both patients demonstrated a bland cyst wall with woven dysplastic appearing bone entrapped within it. In patient 1, array comparative genomic hybridization (CGH) detected a tandem duplication of region 6p12.3 to 6q12 per marker chromosome. Cytogenetic analysis further revealed a complex patient of mosaicism with some cell lines displaying either one or two copies of the marker indicative of both tetrasomy and hexasomy of this region. Patient 2 was mosaic for a sSRC that encompassed a 26.8 Mb gain from 6p21.2 to 6q12. We performed an in-depth clinical analysis of a phenotype not previously observed in sSRC(6) patients and discuss the potential influence of genes located within this region on the skeletal presentation observed.

A mutation in TRPV4 results in altered chondrocyte calcium signaling in severe metatropic dysplasia.

Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is a polymodal modulated non-selective cation channel required for normal development and maintenance of bone and cartilage. Heterozygous mutations of this channel cause a variety of channelopathies, including metatropic dysplasia (MD). We analyzed the effect of a novel TRPV4 mutation c.2398G>A, p.Gly800Asp on intracellular calcium ([Ca(2+) ]i ) regulation in chondrocytes and compared this response to chondrocytes with a frequently observed mutation, c.2396C>T, p.Pro799Leu. We observed temperature-dependent [Ca(2+) ]i oscillations in both intact and MD chondrocytes however, MD mutations exhibited increased peak magnitudes of [Ca(2+) ]i during oscillations. We also found increased baseline [Ca(2+) ]i in MD primary cells, as well as increased [Ca(2+) ]i response to either hypotonic swelling or the TRVP4-specific agonist, GSK1016790A. Oscillations and stimulation responses were blocked with the TRPV4-specific antagonist, GSK205. Analysis of [Ca(2+) ]i response kinetics showed that MD chondrocytes had increased frequency of temperature-sensitive oscillations, and the magnitude and duration of [Ca(2+) ]i responses to given stimuli. Duration of the response of the p.Gly800Asp mutation to stimulation was greater than for the p.Pro799Leu mutation. These experiments show that this region of the channel is essential for proper [Ca(2+) ]i regulation. These studies of primary cells from patients show how both mutant and WT TRPV4 channels regulate cartilage and bone development. © 2015 Wiley Periodicals, Inc.

Angiocidin inhibits breast cancer proliferation through activation of epidermal growth factor receptor and nuclear factor kappa (NF-ĸB).

Angiocidin, a tumor-associated peptide, has been previously shown to inhibit tumor progression by blocking angiogenesis. We now show that angiocidin has a direct inhibitory effect on tumor cell proliferation. MDA-MB-231 breast cancer cells were inhibited from proliferating in the presence of epidermal growth factor (EGF) and angiocidin. Angiocidin transfected breast cancer cells also displayed growth inhibition in vitro and failed to develop significant tumors in mice as compared to vector controls. The anti-proliferative effect of angiocidin was reversed by treating the cells with the epidermal growth factor receptor (EGFR) inhibitor 4557W, a potent tyrosine kinase inhibitor. Consistent with these results, we found that treatment of breast cancer cells with angiocidin induced a 2.3 fold increase in EGFR tyrosine 845 phosphorylation while no change in phosphorylation was observed in the remaining 16 phosphorylation sites of EGFR and those of its family members as measured by a human EGFR phosphorylation array. Treatment of breast cancer cells with angiocidin also resulted in the activation of nuclear factor ĸB (Nf-ĸB) and the de novo up-regulation of many down-stream genes transcribed by Nf-ĸB, including cytokines, inflammatory mediators and the cell cycle inhibitor p21(waf1). Therefore, angiocidin is a peptide that not only inhibits tumor angiogenesis but also directly induces inhibition of tumor growth progression through the activation of EGFR and down-stream genes transcribed by Nf-ĸB.