Mechanistic insights into medulloblastoma relapse.

Pediatric brain tumors are the leading cause of cancer-related deaths in children, with medulloblastoma (MB) being the most common type. A better understanding of these malignancies has led to their classification into four major molecular subgroups. This classification not only facilitates the stratification of clinical trials, but also the development of more effective therapies. Despite recent progress, approximately 30% of children diagnosed with MB experience tumor relapse. Recurrent disease in MB is often metastatic and responds poorly to current therapies. As a result, only a small subset of patients with recurrent MB survive beyond one year. Due to its dismal prognosis, novel therapeutic strategies aimed at preventing or managing recurrent disease are urgently needed. In this review, we summarize recent advances in our understanding of the molecular mechanisms behind treatment failure in MB, as well as those characterizing recurrent cases. We also propose avenues for how these findings can be used to better inform personalized medicine approaches for the treatment of newly diagnosed and recurrent MB. Lastly, we discuss the treatments currently being evaluated for MB patients, with special emphasis on those targeting MB by subgroup at diagnosis and relapse.

Triptolide and its pro-drug Minnelide target high-risk MYC amplified medulloblastoma in preclinical models.

Most children with medulloblastoma (MB) achieve remission, but some face very aggressive metastatic tumors. Their dismal outcome highlights the critical need to advance therapeutic approaches that benefit such high-risk patients. Minnelide, a clinically relevant analog of the natural product triptolide, has oncostatic activity in both preclinical and early clinical settings. Despite its efficacy and tolerable toxicity, this compound has not been evaluated in MB. Utilizing a bioinformatic dataset that integrates cellular drug response data with gene expression, we predicted that Group 3 (G3) MB, which has a poor five-year survival, would be sensitive to triptolide/Minnelide. We subsequently showed that both triptolide and Minnelide attenuate the viability of G3 MB cells ex vivo. Transcriptomic analyses identified MYC signaling, a pathologically relevant driver of G3 MB, as a downstream target of this class of drugs. We validated this MYC dependency in G3 MB cells and showed that triptolide exerts its efficacy by reducing both MYC transcription and MYC protein stability. Importantly, Minnelide acted on MYC to reduce tumor growth and leptomeningeal spread, which resulted in improved survival of G3 MB animal models. Moreover, Minnelide improved the efficacy of adjuvant chemotherapy, further highlighting its potential for the treatment of MYC-driven G3 MB patients.

Downloading and Analysis of Metabolomic and Lipidomic Data from Metabolomics Workbench Using MetaboAnalyst 5.0.

Advances in computational and data processing technology have enabled the development of many novel tools for analyzing metabolomic and lipidomic data. These advances involved the catalyst for the creation of publicly accessible complex web-based databases such as the Metabolomics Workbench. Open Source internet-based software packages such as MetaboAnalyst 5.0 enable researchers to perform a wide range of analyte identification and statistical analyses of their own and other researchers' data in order to identify biomarkers and classify compounds. In this paper, we set forth a protocol for obtaining experimental data of interest from a public data repository (Metabolomics Workbench), converting the data into a format suitable for submission to MetaboAnalyst 5.0, and then uploading the data to the MetaboAnalyst server for identification and statistical analysis.

A revisit to staining reagents for neuronal tissues.

In the early days of deciphering the injured neuronal tissues led to the realization that contrast is necessary to discern the parts of the recovering tissues from the damaged ones. Early attempts relied on available (and often naturally occurring) staining substances. Incidentally, the active ingredients of most of them were small molecules. With the advent of time, the knowledge of chemistry helped identify compounds and conditions for staining. The staining reagents were even found to enhance the visibility of the organelles. Silver impregnation identification of Golgi bodies was discovered in owl optic nerve. Staining reagents since the late 1800s were widely used across all disciplines and for nerve tissue and became a key contributor to advancement in nerve-related research. The use of these reagents provided insight into the organization of the neuronal tissues and helped distinguish nerve degeneration from regeneration. The neuronal staining reagents have played a fundamental role in the clinical research facilitating the identification of biological mechanisms underlying eye and neuropsychiatric diseases. We found a lack of systematic description of all staining reagents, whether they had been used historically or currently used. There is a lack of readily available information for optimal staining of different neuronal tissues for a given purpose. We present here a grouping of the reagents based on their target location: (I) the central nervous system (CNS), (II) the peripheral nervous system (PNS), or (III) both. The biochemical reactions of most of the staining reagents is based on acidic or basic pH and specific reaction partners such as organelle or biomolecules that exists within the given tissue type. We present here a summary of the chemical composition, optimal staining condition, use for given neuronal tissue and, where possible, historic usage. Several biomolecules such as lipids and metabolites lack specific antibodies. Despite being non-specific the reagents enhance contrast and provide corroboration about the microenvironment. In future, these reagents in combination with emerging techniques such as imaging mass spectrometry and kinetic histochemistry will validate or expand our understanding of localization of molecules within tissues or cells that are important for ophthalmology and vision science.

Association of age with survival in older patients with cutaneous melanoma treated with immune checkpoint inhibitors.

INTRODUCTION: Several types of immune checkpoint inhibitors (ICIs) are approved to treat advanced melanoma, but their effectiveness has not been compared in older patients treated outside of a clinical trial. Moreover, evidence suggests that a patient's response to ICI therapy may vary by age and type of ICI. The purpose of this study was to compare survival by ICI type in older patients with melanoma and to investigate treatment effect modification by age. MATERIALS AND METHODS: Using the SEER-Medicare database, we identified patients with cutaneous melanoma (2012-2015) treated with an ICI (CTLA-4, PD-1, or combination CTLA-4 + PD-1 inhibitors). Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for ICI types. We used an interaction term and stratified models to test for treatment effect modification by age. RESULTS: Of the 1435 patients included in our analysis, 790 (55.1%) received CTLA-4 inhibitors, 512 (35.7%) received PD-1 inhibitors, and 133 (9.3%) were treated with combination ICIs. Median survival ranged from 13.4 months (95%CI: 10.7-16.3) for CTLA-4 inhibitors to 23.5 months (95%CI: 16.2-30.0) for combination ICIs. In multivariable models, the risk of death was lower with PD-1 inhibitors compared to CTLA-4 inhibitors (HR = 0.78, 95%CI: 0.68-0.89). An age*ICI type interaction term was significant (p < 0.001), and survival gains were greater the older age group (≥80) compared to the younger group (65-79). DISCUSSION: In a population-based setting, we identified important differences in survival by ICI type in older patients with melanoma treated with ICIs, with prolonged survival associated with PD-1 inhibitors compared to CTLA-4 inhibitors.

Immune checkpoint inhibitors retain effectiveness in older patients with cutaneous metastatic melanoma.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have dramatically changed the treatment landscape for advanced melanoma, but their use in older patients remains understudied. An age-related decline in immune function is of concern when treating older patients because host immune factors can influence clinical outcomes with immunotherapy. Therefore, we aimed to evaluate the effectiveness of ICIs in patients 65 years and older. METHODS: Using the SEER-Medicare data, we evaluated survival by first systemic treatment type in a retrospective cohort study of patients aged 65 years and older who were diagnosed with stage IV cutaneous melanoma between 2012 and 2015. Cox proportional hazards regression was used to estimate hazard ratios (HR) and their corresponding 95% confidence intervals. RESULTS: A total of 541 patients were included in this study. Median survival differed significantly between groups (p < 0.0001) and was longest in patients treated with PD-1 inhibitors (34.0 months), followed by CTLA-4 inhibitors (16.8 months), targeted therapy (9.7 months), chemotherapy (7.1 months), and no systemic therapy (3.6 months). The ICI survival benefit persisted after adjusting for age, sex, comorbidities, M stage, the presence of brain metastases, and evaluation at an NCI-designated cancer center. Hazard ratios comparing ICIs to no systemic therapy were 0.35 (95% CI: 0.24-0.52) for PD-1 inhibitors and 0.48 (95% CI: 0.37-0.63) for CTLA-4 inhibitors. We did not observe a difference in ICI effectiveness by age group (65-74 vs ≥75). CONCLUSIONS: In a nationally representative cohort of patients with advanced melanoma, ICI therapy delivered in a real world setting significantly improved survival in patients aged 65 years and older.

Diagnostic Accuracy of Technology-based Eye Care Services: The Technology-based Eye Care Services Compare Trial Part I.

PURPOSE: Ophthalmologic telemedicine has the ability to provide eye care for patients remotely, and many countries have used screening tele-ophthalmology programs for several years. One such initiative at the Veterans Affairs (VA) Healthcare System is Technology-based Eye Care Services (TECS). The TECS services are located in primary care clinics and provide basic screening eye care, including vision, refraction, and retinal photography. Eye care providers ("readers") review the clinical data and recommend appropriate follow-up. One of the most common referrals from TECS has been for glaucoma, and this study was powered for glaucoma/glaucoma suspect detection. The current study was undertaken to identify aspects of the protocol that could be refined to enhance accuracy. DESIGN: Prospective comparison between the standard TECS protocol versus a face-to-face (FTF) examination on 256 patients, all of whom had no known history of significant ocular disease. PARTICIPANTS: Patients with no known ocular disease who were scheduled for an in-person eye appointment at the Atlanta VA. Patients underwent screening through the TECS protocol and received an FTF examination on the same day (gold standard). The TECS readers were masked to the results of the FTF examination. MAIN OUTCOME MEASURES: Percent agreement, kappa, sensitivity, and specificity were calculated for the TECS readers' interpretations versus the FTF examination. RESULTS: The TECS readers showed substantial agreement for cataract (κ ≥ 0.71) and diabetic retinopathy (κ ≥ 0.61) and moderate to substantial agreement for glaucoma/glaucoma suspect (κ ≥ 0.52) compared with an FTF examination. Age-related macular degeneration (AMD) showed moderate agreement (κ ≥ 0.34). Percent agreement with the TECS protocol was high (84.3%-98.4%) for each of the disease categories. Overall sensitivity and specificity were ≥75% and ≥55%, respectively, for any diagnosis resulting in referral. Inter-reader and intra-reader agreement was substantial for most diagnoses (κ > 0.61) with percent agreements ranging from 66% to 99%. CONCLUSIONS: Our results indicate that the standard TECS protocol is accurate when compared with an FTF examination for the detection of common eye diseases. The inclusion of additional testing such as OCT could further enhance diagnostic capability.

The Impact of OCT on Diagnostic Accuracy of the Technology-Based Eye Care Services Protocol: Part II of the Technology-Based Eye Care Services Compare Trial.

PURPOSE: Ophthalmologic telemedicine programs help to address the growing demand for eye care and lessen healthcare disparities for patients. One example is Technology-Based Eye Care Services (TECS), implemented in the Veteran Affairs Healthcare System in 2015. Accuracy and quality data for TECS both have been reported, and data suggest that although the TECS examination is comparable with an in-person examination, sensitivity for glaucoma and glaucoma suspect detection is less than that for other diseases, such as macular degeneration. Several articles suggest that OCT can improve disease detection for glaucoma. Therefore, this study was undertaken to test the impact of OCT on the accuracy of the TECS protocol. This article reports the data from part II of the TECS Compare trial; results from part I are discussed in a previous article. DESIGN: Prospective comparison between the TECS protocol with OCT versus a face-to-face (FTF) examination for 256 patients. PARTICIPANTS: An eligible patient was defined as a patient with no known ocular disease who desired a routine eye examination. METHODS: Patient underwent the TECS protocol workup and OCT nerve, OCT macula, and FTF examination on the same day. MAIN OUTCOME MEASURES: Percent agreement, κ values, sensitivity, and specificity were calculated for nonexpert readers after OCT interpretation of the TECS protocol using the FTF examination as the clinical gold standard. RESULTS: OCT did not improve the diagnostic accuracy of the TECS protocol when compared with an FTF examination. In most cases, OCT had no impact, and in the case of reader 2, OCT actually reduced the κ value from moderate agreement to agreement equal to chance while lowering the percent agreement by 10%. OCT also did not impact inter- or intrareader variability parameters. CONCLUSIONS: In this study, OCT did not seem to improve the accuracy of glaucoma or retinal disease detection when added to the standard TECS protocol. In one case, OCT worsened the agreement of the reader compared with the FTF. Further study is necessary to confirm these findings, and results may change if the readers are glaucoma or retina specialists instead of nonexpert OCT readers, comprehensive and anterior segment specialists.

"Fear guides the eyes of the beholder": Assessing gaze avoidance in social anxiety disorder via covert eye tracking of dynamic social stimuli.

Gaze avoidance is an important feature of social anxiety disorder (SAD) and may serve as a biobehavioral marker of SAD. The purpose of the present study was to replicate and extend findings on gaze avoidance in SAD via eye tracking during a computerized social simulation. Patients with SAD (n = 27) and a (sub)sample of demographically-matched healthy controls (HC; n = 22) completed a computerized, dynamic social simulation task involving video clips of actors giving positive and negative social feedback to the participant. All participants were unknowingly eye tracked during the simulation, and post-study consent was obtained to examine responses. Consistent with the bivalent fear of evaluation (BFOE) model of social anxiety, fear of positive evaluation related systematically to state anxiety in response to positive social feedback, and fear of negative evaluation related systematically to state anxiety in response to negative social feedback. Moreover, compared to HCs, SAD patients exhibited significantly greater global gaze avoidance in response to both the positive and negative video clips. Our results provide strong additional support for gaze avoidance as a biobehavioral marker of SAD, as well as additional support for the BFOE model. Implications for the assessment and treatment of SAD are discussed.

Temporal Trends in Cardiovascular Hospital Discharges Following a Mass Chlorine Exposure Event in Graniteville, South Carolina.

Background: On January 6, 2005, a train derailed in Graniteville, South Carolina, releasing nearly 60,000 kg of toxic chlorine gas. The disaster left nine people dead and was responsible for hundreds of hospitalizations and outpatient visits in the subsequent weeks. While chlorine gas primarily affects the respiratory tract, a growing body of evidence suggests that acute exposure may also cause vascular injury and cardiac toxicity. Here, we describe the incidence of cardiovascular hospitalizations among residents of the zip codes most affected by the chlorine gas plume, and compare the incidence of cardiovascular discharges in the years leading up to the event (2000-2004) to the incidence in the years following the event (2005-2014). Methods: De-identified hospital discharge information was collected from the South Carolina Revenue and Fiscal Affairs Office for individuals residing in the selected zip codes for the years 2000 to 2014. A quasi-experimental study design was utilized with a population-level interrupted time series model to examine hospital discharge rates for Graniteville-area residents for three cardiovascular diagnoses: hypertension (HTN), acute myocardial infarction (AMI), and coronary heart disease (CHD). We used linear regression with autoregressive error correction to compare slopes for pre- and post-spill time periods. Data from the 2000 and 2010 censuses were used to calculate rates and to provide information on potential demographic shifts over the course of the study. Results: A significant increase in hypertension-related hospital discharge rates was observed for the years following the Graniteville chlorine spill (slope 8.2, p < 0.001). Concurrent changes to CHD and AMI hospital discharge rates were in the opposite direction (slopes -3.2 and -0.3, p < 0.01 and 0.14, respectively). Importantly, the observed trend cannot be attributed to an aging population. Conclusions: An unusual increase in hypertension-related hospital discharge rates in the area affected by the Graniteville chlorine spill contrasts with national and state-level trends. A number of factors related to the spill may be contributing the observation: disaster-induced hypertension, healthcare services access issues, and, possibly, chlorine-induced susceptibility to vascular pathologies. Due to the limitations of our data, we cannot determine whether the individuals who visited the hospital were the ones exposed to chlorine gas, however, the finding warrants additional research. Future studies are needed to determine the etiology of the increase and whether individuals exposed to chlorine are at a heightened risk for hypertensive heart disease.

Intolerance of uncertainty moderates the relations among religiosity and motives for religion, depression, and social evaluation fears.

OBJECTIVES: Intolerance of uncertainty (IU) underlies several psychological disorders, and religion may help some individuals cope with IU and/or protect against psychological symptoms. It was hypothesized that IU would moderate the relations between coping motives for being religious, as well as religiosity, and common psychological disorder symptoms: Depression and social evaluation fears. METHODS: Study 1 included 473 self-reporting community members (M age = 48, 48% female, 80% Protestant/Catholic). Study 2 included 412 self-reporting undergraduates ( M age = 19, 71% female, 76% Protestant/Catholic). RESULTS: For Study 1, coping-based motives related to greater depression for young adults with above-average IU and to lower depression for young adults with below-average IU. For Study 2, religiosity related to lower depression and fear of negative evaluation for individuals with above-average IU and to greater fear of positive evaluation for individuals with below-average IU. CONCLUSION: IU may be an important mechanism between aspects of religion and psychological disorder symptoms.

Web-based CBT for the prevention of anxiety symptoms among medical and health science graduate students.

Medical and health science graduate students report greater anxiety problems than the general population, but they are less likely to seek treatment due to cultural and logistical barriers. One preventative approach that overcomes these barriers is web-based cognitive behavioral therapy (webCBT). It is unknown whether webCBT is effective for preventing anxiety escalation within this population. A randomized controlled trial was conducted, comparing the effects of webCBT versus a control group (CG). Medical university students (n=594; Mage=27; 67% female; 80% Caucasian) completed online baseline measures and four assigned online activities. Measures were re-administered after approximately three months. There was a small interaction effect between time of assessment and treatment condition. Anxiety severity was lower in the webCBT (M[SD]=2.88[3.36]) versus CG condition (M[SD]=3.69 [3.35]) at follow-up. This effect was moderate for students with mild, versus minimal, anxiety at baseline. The proportion of students with possible anxiety disorder was lower in the webCBT (4.5%) versus CG (8.5%) condition, and the proportion of mildly anxious students with a clinically significant increase in symptoms was lower in the webCBT (10%) versus CG (20%) condition. WebCBT may aid in preventing anxiety escalation in this population, particularly for at-risk students who report mild anxiety symptoms.

Preliminary evidence for differential olfactory and trigeminal processing in combat veterans with and without PTSD.

Structural and functional changes in the olfactory system are increasingly implicated in the expression of PTSD. Still, very little is known about the neurobiological networks of trauma-related odor sensitivity or how they relate to other objective and subjective measures of olfaction and PTSD. The purpose of this study was to replicate prior findings and further characterize olfactory function in trauma-exposed combat veterans with and without PTSD. We also sought to extend this area of research by exploring the effects of time since the combat-related index trauma (TST) on post-trauma olfactory function, as well as by correlating odor-elicited brain activity to general olfactory ability and odor-elicited PTSD symptoms. Participants included combat veterans with PTSD (CV+PTSD; n = 21) or without any psychiatric disorder (CV-PTSD; n = 27). TST was coded as greater (n = 24) or less (n = 24) than 5 years. There were main effects and/or interaction for PTSD-status and TST across several parameters of olfactory function: odor detection, odor identification, ratings for trauma-related odor intensity and triggered PTSD symptoms, and trauma odor-elicited brain activation. Overall, results suggest olfactory impairment in chronic PTSD, but not necessarily in the earlier stages of the disorder, although some early-stage olfactory findings may be predictive of later olfactory impairment. Results also suggest that trauma-exposed individuals who never develop PTSD may demonstrate olfactory resiliency. Finally, results highlight a potentially unique role of trigeminal odor properties in the olfactory-PTSD relationship.

The vulnerability of self-reported disability measures to malingering: a simulated ADHD study.

OBJECTIVE: Making diagnostic and accommodation decisions for potential Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is difficult, as the assessor often relies more on self-reported symptoms and functional disability than in childhood evaluations. Malingering of ADHD occurs frequently in the educational setting and for a variety of reasons, including the potential benefits of access to stimulant medications and academic accommodations. METHOD: The present study utilized a simulation design to examine the potential for malingering of self-reported functional disability on the World Health Organization Disability Schedule 2.0 (WHODAS). Participants were 167 students from two Midwestern universities. Thirty-six self-reported a previous diagnosis of ADHD, and the remaining 131 students were randomly assigned to one of three conditions: best effort, malingering for the purpose of receiving stimulant medication, or malingering for the purpose of receiving extra time accommodations. RESULTS: Individuals in both malingering groups reported higher levels of disability on all domains of the WHODAS compared to healthy controls and individuals with ADHD. There were no significant differences between malingering groups. CONCLUSIONS: Results suggest the WHODAS is susceptible to non-credible responses and should not be relied upon solely as a measure of disability in the context of ADHD evaluations.

Effects of gender role self-discrepancies and self-perceived attractiveness on social anxiety for women across social situations.

BACKGROUND AND OBJECTIVES: Psychosocial factors, such as gender role norms, may impact how social anxiety disorder (SAD) is experienced and expressed in different social contexts for women. However to date, these factors have not been examined via experimental methodology. DESIGN: This was a cross-sectional, quasi-experimental controlled study. METHODS: The current study included 48 highly socially anxious (HSA) women (70.9% meeting criteria for SAD) and examined the relationships among psychosocial factors (i.e. gender role self-discrepancies and self-perceived physical attractiveness), self-perceived social performance, and state anxiety, across two in vivo social tasks (i.e. conversation and opinion speech). RESULTS: On average, participants reported belief that they ought to be less feminine for the speech task and more masculine for both the conversation and speech tasks. Also, for the conversation task, only lower self-rated attractiveness predicted poorer self-perceived performance and greater post-task state anxiety, above gender role self-discrepancies and confederate gender. For the speech task, only greater self-discrepancy in prototypical masculine traits predicted poorer performance ratings, and it was related to greater state anxiety in anticipation of the task. CONCLUSION: For HSA women, psychosocial factors may play different roles in social anxiety across social contexts.

Relations among Social Anxiety, Eye Contact Avoidance, State Anxiety, and Perception of Interaction Performance during a Live Conversation.

There is building evidence that highly socially anxious (HSA) individuals frequently avoid making eye contact, which may contribute to less meaningful social interactions and maintenance of social anxiety symptoms. However, research to date is lacking in ecological validity due to the usage of either static or pre-recorded facial stimuli or subjective coding of eye contact. The current study examined the relationships among trait social anxiety, eye contact avoidance, state anxiety, and participants' self-perceptions of interaction performance during a live, four-minute conversation with a confederate via webcam, and while being covertly eye-tracked. Participants included undergraduate women who conversed with same-sex confederates. Results indicated that trait social anxiety was inversely related to eye contact duration and frequency averaged across the four minutes, and positively related to state social anxiety and negative self-ratings. In addition, greater anticipatory state anxiety was associated with reduced eye contact throughout the first minute of the conversation. Eye contact was not related to post-task state anxiety or self-perception of poor performance; although, trends emerged in which these relations may be positive for HSA individuals. The current findings provide enhanced support for the notion that eye contact avoidance is an important feature of social anxiety.

Fear of positive evaluation and alcohol use problems among college students: the unique impact of drinking motives.

BACKGROUND AND OBJECTIVES: There is strong empirical support that individuals with elevated social anxiety are at risk for alcohol-related impairment. Because social anxiety is a multifaceted construct, it is important to consider which specific facets contribute to alcohol problem vulnerability. For example, although social anxiety has traditionally been conceptualized as a fear of negative evaluation (FNE), emerging data suggest that fear of positive evaluation (FPE) is also an important factor in pathological social anxiety. The current manuscript reports novel findings regarding FPE, alcohol use motives, and reported alcohol use problems. DESIGN AND METHODS: Participants included undergraduates from two American universities (n = 351) who completed a battery of measures assessing fears of evaluation, drinking motives, and alcohol usage related problems. RESULTS: FPE significantly predicted alcohol use problems, above and beyond FNE. Also, coping and conformity motives for drinking, but not social or enhancement motives, each uniquely mediated the relationship between FPE and alcohol use problems. CONCLUSIONS: FPE may be an important cognitive-affective vulnerability factor. With additional clinical research, FPE could serve as a meaningful therapeutic target in interventions designed to decrease problem drinking among highly socially anxious patients.

Psychometric evaluation of the Concerns of Social Reprisal Scale: Further explicating the roots of fear of positive evaluation.

Fear of positive evaluation (FPE) has been proposed to be an important feature of social anxiety disorder (SAD) and to be rooted, at least partly, in concerns of social reprisal due to positive impressions. In order to formally test this hypothesis, the Concerns of Social Reprisal Scale (CSRS) was developed. The purpose of the present series of studies was to examine the psychometric profile of the CSRS across several independent samples including: a large (n=981) undergraduate sample; a clinical sample of individuals diagnosed with social anxiety disorder (n=27), and a demographically-matched subsample of healthy control participants (n=24). The factorial validity, internal consistency, and construct validity of the CSRS were examined. Results across both studies provided support for the psychometric profile of the CSRS. The implications of concerns of social reprisal for the assessment of social anxiety symptoms, theoretical models of fear of evaluation and SAD, and their potential clinical utility with regard to treating SAD are discussed.

Culture of honour theory and social anxiety: Cross-regional and sex differences in relationships among honour-concerns, social anxiety and reactive aggression.

Consistent with the "flight or fight" model of anxiety, social anxiety may incite withdrawal or attack; yet, it is unclear why some socially anxious individuals are vulnerable to aggress. It may be that culture impacts tendencies to "fight" or "flee" from social threat. Honour cultures, including the American South, permit or even promote aggression in response to honour-threats. Thus, social anxiety in the South may be more associated with aggression than in non-honour cultures. In the current sample, region moderated the relation between social anxiety and aggression; social anxiety related positively to reactive (but not proactive) aggression among Southerners (n = 285), but not Midwesterners (n = 258). Participant sex further moderated the relationship, such that it was significant only for Southern women. Also, for Southerners, prototypically masculine honour-concerns mediated the relationship between social anxiety and reactive aggression. Cultural factors may play key roles in aggressive behaviour among some socially anxious individuals.

Poly(anhydride-esters) comprised exclusively of naturally occurring antimicrobials and EDTA: antioxidant and antibacterial activities.

Carvacrol, thymol, and eugenol are naturally occurring phenolic compounds known to possess antimicrobial activity against a range of bacteria, as well as antioxidant activity. Biodegradable poly(anhydride-esters) composed of an ethylenediaminetetraacetic acid (EDTA) backbone and antimicrobial pendant groups (i.e., carvacrol, thymol, or eugenol) were synthesized via solution polymerization. The resulting polymers were characterized to confirm their chemical composition and understand their thermal properties and molecular weight. In vitro release studies demonstrated that polymer hydrolytic degradation was complete after 16 days, resulting in the release of free antimicrobials and EDTA. Antioxidant and antibacterial assays determined that polymer release media exhibited bioactivity similar to that of free compound, demonstrating that polymer incorporation and subsequent release had no effect on activity. These polymers completely degrade into components that are biologically relevant and have the capability to promote preservation of consumer products in the food and personal care industries via antimicrobial and antioxidant pathways.