Mental health during COVID-19: College students' need for structure.

Objective: College students made the unprecedented shift to remote learning during the COVID-19 pandemic, potentially contributing to escalating anxiety, depression, and suicide. This loss of structure may be a driving factor in students' distress. We examined the relationship between students' mental health, perceived need for structure, and five stressors related to COVID-19. Participants: Students (N = 1319, 76.3% female, 79.8% White) at a southeastern university responded to a survey in spring 2020. Methods: Participants answered questions about global anxiety and depression, suicide, perceived need for structure, and COVID-19 related stressors. Results: Participants reported increased anxiety and depression and elevated suicidality compared to previous studies of student mental health. Findings indicated that the stressors and lack of structure added unique variance toward predicting anxiety and depression. Conclusions: As COVID-19's consequences persist, counseling centers and other stakeholders are urged to work together in providing support for students' mental wellness and stress management.

Phototoxicity─Medicinal Chemistry Strategies for Risk Mitigation in Drug Discovery.

Phototoxicity is a common safety concern encountered by project teams in pharmaceutical research and has the potential to stop progression of an otherwise promising candidate molecule. This perspective aims to provide an overview of the approaches toward mitigation of phototoxicity that medicinal chemists have taken during the lead optimization phase in the context of regulatory standards for photosafety evaluation. Various strategies are laid out based on available literature examples in order to highlight how structural modification can be utilized toward successful mitigation of a phototoxicity liability. A proposed flowchart is presented as a guidance tool to be used by the practicing medicinal chemist when facing a phototoxicity risk. The description of available tools to consider in the drug design process will include an overview of the evolution of in silico methods and their application as well as structure alerts for consideration as potential phototoxicophores.

The role of perceived expertise and trustworthiness in research study and clinical trial recruitment: Perspectives of clinical research coordinators and African American and Black Caribbean patients.

This study investigates the role of source credibility on minority participant recruitment, particularly African American and Black Caribbean patients. A total of nine focus groups (N = 48 participants) were conducted with both patient groups and clinical research coordinators (CRCs). Using the elaboration likelihood model as a guiding framework for analysis, this study found that the credibility of research coordinators (or other professionals who recruit for research studies and clinical trials) was instrumental in shaping attitudes of prospective participants. The perspectives of patients and CRCs aligned closely, with few exceptions. For both groups, professionalism and professional displays (clothing, institutional artifacts) enhanced perceived expertise, a core component of credibility. Trustworthiness, another important component of credibility, was fostered through homophily between recruiter and patient, expressions of goodwill and assuaging anxiety about CRCs' financial motivations for recruitment. Additionally, CRCs believed that credibility was supported when CRCs could emphasize transparency and truthfulness in communication. The importance of these findings for the development of empirically-based training programs to improve communication practices in recruitment contexts is discussed.

Reducing Health Disparities Among African American and Black Caribbean Patients by Improving the Communication Practices of Clinical Research Coordinators.

This manuscript focuses on the communication factors that affect the willingness of African Americans and Black Caribbean patients to participate in clinical trials and research studies. Low rates of research participation by members of communities of color have long been linked to health disparities. While there are many factors that contribute to low rates of accrual of African American and Black patients to clinical trials, a lack of attention to communication factors that enhance or inhibit the recruitment process is central to the problem. In this study, we describe results from the analysis of six focus groups (N = 31) consisting of African American (k = 3) and Black Caribbean (k = 3) participants. Our analyses focus on verbal and nonverbal communication behaviors and how they affect participants' willingness to participate in clinical trials. Specifically, when clinical research coordinators (CRCs) had a professional appearance, made the effort to explain a study in detail, made eye contact, took the time to listen and answer questions patiently, and gave the sense that the CRC was being truthful and transparent, patients felt respected and valued. Additionally, participants emphasized the importance of the process of developing and maintaining a trusting relationship between study participants and CRCs. The results of this study will be used to develop a clinical trial communication training program designed to enhance the communication skills of clinical research coordinators who discuss research participation with African American and Caribbean Black patients.

Discovery of a novel, highly potent and orally bioavailable pyrrolidinone indole series of irreversible Myeloperoxidase (MPO) inhibitors.

Myeloperoxidase (MPO) is a heme-containing peroxidase from phagocytic cells, which plays an important role in the innate immune response. The primary anti-microbial function of MPO is achieved by catalyzing the oxidation of halides by hydrogen peroxide (H2O2). Upon activation of phagocytes, MPO activity is detectable in both phagosomes and extracellularly, where it can remain or transcytose into interstitial compartments. Activated MPO leads to oxidative stress and tissue damage in many inflammatory states, including cardiovascular disease. Starting from a low molecular weight (LMW) high throughput screening (HTS) hit, here we report the discovery of a novel pyrrolidinone indole (IN-4) as a highly potent MPO inhibitor. This compound displays similar in vitro potency across peroxidation, plasma and NETosis assays. In a dilution/dialysis study, <5% of the original MPO activity was detected post-incubation of MPO with IN-4, suggesting irreversible enzyme inhibition. A fast MPO inactivation rate (kinact/Ki) and low partition ratio (k3/k4) make IN-4 kinetic properties attractive for an MPO inhibitor. This compound also displays significant selectivity over the closely related thyroid peroxidase (TPO), and is selective for extracellular MPO over intracellular (neutrophil) MPO. Moreover, IN-4 shows good exposure, low clearance and high oral bioavailability in mice, rats and dogs. The high in vitro MPO activity and high oral exposure observed with IN-4 result in a dose-dependent inhibition of MPO activity in three mouse models of inflammation. In conclusion, IN-4 is a novel, potent, mechanism-based and selective MPO inhibitor, which may be used as superior therapeutic agent to treat multiple inflammatory conditions, including cardiovascular disease.

Developing and evaluating a team development intervention to support interdisciplinary teams.

INTRODUCTION: Incentivizing the development of interdisciplinary scientific teams to address significant societal challenges usually takes the form of pilot funding. However, while pilot funding is likely necessary, it is not sufficient for successful collaborations. Interdisciplinary collaborations are enhanced when team members acquire competencies that support team success. METHODS: We evaluated the impact of a multifaceted team development intervention that included an eight-session workshop spanning two half-days. The workshop employed multiple methods for team development, including lectures on empirically supported best practices, skills-based modules, role plays, hands-on planning sessions, and social interaction within and across teams. We evaluated the impact of the intervention by (1) asking participants to assess each of the workshop sessions and (2) by completing a pre/postquestionnaire that included variables such as readiness to collaborate, goal clarity, process clarity, role ambiguity, and behavioral trust. RESULTS: The content of the team development intervention was very well received, particularly the workshop session focused on psychological safety. Comparison of survey scores before and after the team development intervention indicated that scores on readiness to collaborate and behavioral trust were significantly higher among participants who attended the workshop. Goal clarity, process clarity, and role ambiguity did not differ among those who attended versus those who did not. CONCLUSIONS: Multicomponent team development interventions that focus on key competencies required for interdisciplinary teams can support attitudes and cognitions that the literature on the science of team science indicate are predictive of success. We offer recommendations for the design of future interventions.

Attention control: The missing link between sensory discrimination and intelligence.

Intelligence is correlated with the ability to make fine sensory discriminations. Although this relationship has been known since the beginning of intelligence testing, the mechanisms underlying this relationship are still unknown. In two large-scale structural equation-modelling studies, we investigated whether individual differences in attention control abilities can explain the relationship between sensory discrimination and intelligence. Across these two studies, we replicated the finding that attention control fully mediated the relationships of intelligence/working-memory capacity to sensory discrimination. Our findings show that attention control plays a prominent role in relating sensory discrimination to higher-order cognitive abilities.

Discovery of a novel indole pharmacophore for the irreversible inhibition of myeloperoxidase (MPO).

Myeloperoxidase (MPO) activity and subsequent generation of hypochlorous acid has been associated with the killing of host-invading microorganisms (e.g. bacteria, viruses, and fungi). However, during oxidative stress, high MPO activity can damage host tissue and is linked to several chronic inflammatory conditions. Herein, we describe the development of a novel biaryl, indole-pyrazole series of irreversible mechanism-based inhibitors of MPO. Derived from an indole-containing high-throughput screen hit, optimization efforts resulted in potent and selective 6-substituted indoles with good oral bioavailability and in vivo activity.

The role of maintenance and disengagement in predicting reading comprehension and vocabulary learning.

This study uses a novel framework based on work by Shipstead, Harrison, and Engle (2016) that includes measures of both working memory capacity and fluid intelligence in an attempt to better understand the processes that influence successful reading comprehension at the latent level. Further, we extend this framework to a second educationally relevant ability: second-language vocabulary learning. A large sample of young adults received a battery of working memory, fluid intelligence, language comprehension, and memory updating tasks. The results indicate that individual differences in reading comprehension and vocabulary learning benefit from the ability to maintain active information, as well as to disengage from no longer relevant information. Subsequently, we provide an interpretation of our results based on the maintenance and disengagement framework proposed by Shipstead et al. (2016). (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Successful Strategies for Mitigation of a Preclinical Signal for Phototoxicity in a DGAT1 Inhibitor.

Diacylglycerol O-acyltransferase 1 (DGAT1) inhibitor Pradigastat (1) was shown to be effective at decreasing postprandial triglyceride levels in a patient population with familial chylomicronemia syndrome (FCS). Although pradigastat does not cause photosensitization in humans at the high clinical dose of 40 mg, a positive signal was observed in preclinical models of phototoxicity. Herein, we describe a preclinical phototoxicity mitigation strategy for diarylamine containing molecules utilizing the introduction of an amide or suitable heterocyclic function. This strategy led to the development of two second-generation compounds with low risk of phototoxicity, disparate exposure profiles, and comparable efficacy to 1 in a rodent lipid bolus model for post-prandial plasma triglycerides.

The Invisible Danger of Transferring Toxins with Bunker Gear: A Theory-Based Intervention to Increase Postfire Decontamination to Reduce Cancer Risk in Firefighters.

Studies show significant association between cancer risk and being a firefighter. After exposure to even routine firefighting, firefighters' bunker gear often contains carcinogens that may be absorbed through contact or inhaled through off-gassing, thereby increasing cancer risk. Awareness of increased cancer risk has given rise to policies and practices focused on gear cleaning and decontamination processes to decrease risk; yet, these efforts are in their infancy and tend to be somewhat piecemeal in nature. This study presents a theory-based communication intervention tailored to the unique context of high-reliability organizations (HROs). The intervention focused on increasing postfire decontamination behaviors to reduce exposure to carcinogens among firefighters. Results of the intervention across 14 fire stations from 2 fire departments in South Florida show significant increases in attitudes, norms, and self-efficacy, decreases in perceived barriers, and increased intention to engage in decontamination processes. While the intervention was highly successful in both fire departments, there were significant differences in between organizations; attitudes perceived norms, and barriers to gear cleaning remained significantly different. This highlights the need to examine the specific context of the organization in designing interventions. In line with previous research on HROs, regression models showed that norms and self-efficacy are the strongest predictors of current behavior. However, postintervention, attitudes emerge as the strongest predictor of future behavior. The results of this study provide valuable evidence for utilizing theoretical elements in message design for interventions in HROs, and of the importance of designing communication for specific sites of intervention.

Discovery of 1-((6-Aminopyridin-3-yl)Methyl)-3-(4-Bromophenyl)Urea as a Potent, Irreversible Myeloperoxidase Inhibitor.

Myeloperoxidase (MPO) is a leukocyte-derived redox enzyme that has been linked to oxidative stress and damage in many inflammatory states, including cardiovascular disease. We have discovered aminopyridines that are potent mechanism-based inhibitors of MPO, with significant selectivity over the closely related thyroid peroxidase. 1-((6-Aminopyridin-3-yl)methyl)-3-(4-bromophenyl)urea (Aminopyridine 2) inhibited MPO in human plasma and blocked MPO-dependent vasomotor dysfunction ex vivo in rat aortic rings. Aminopyridine 2 also showed high oral bioavailability and inhibited MPO activity in vivo in a mouse model of peritonitis. Aminopyridine 2 could effectively be administered as a food admixture, making it an important tool for assessing the relative importance of MPO in preclinical models of chronic inflammatory disease.

Safety Gear Decontamination Practices Among Florida Firefighters: Analysis of a Text-Based Survey Methodology.

Despite the National Fire Protection Association (NFPA) 1851 Personal Protective Equipment Care and Maintenance guidelines, little is known about the routine cleaning of firefighter bunker gear. In collaboration with a large Florida firefighter union, a mobile phone text survey was administered, which included eight questions in an item logic format. In total, 250 firefighters participated in the survey of which 65% reported cleaning their bunker gear in the past 12 months. Approximately 32% ( n = 52) indicated that they had above average confidence in gear cleaning procedures. Arriving at a fire incident response was a significant predictor of gear cleaning in the 12 months preceding survey administration. Using mobile phone-based texting for periodic queries on adherence to NFPA cleaning guidelines and safety message distribution may assist firefighters to increase decontamination procedure frequency.

Biphilic Organophosphorus-Catalyzed Intramolecular Csp2-H Amination: Evidence for a Nitrenoid in Catalytic Cadogan Cyclizations.

A small-ring phosphacycloalkane (1,2,2,3,4,4-hexamethylphosphetane, 3) catalyzes intramolecular C-N bond forming heterocyclization of o-nitrobiaryl and -styrenyl derivatives in the presence of a hydrosilane terminal reductant. The method provides scalable access to diverse carbazole and indole compounds under operationally trivial homogeneous organocatalytic conditions, as demonstrated by 17 examples conducted on 1 g scale. In situ NMR reaction monitoring studies support a mechanism involving catalytic PIII/PV═O cycling, where tricoordinate phosphorus compound 3 represents the catalytic resting state. For the catalytic conversion of o-nitrobiphenyl to carbazole, the kinetic reaction order was determined for phosphetane catalyst 3 (first order), substrate (first order), and phenylsilane (zeroth order). For differentially 5-substituted 2-nitrobiphenyls, the transformation is accelerated by electron-withdrawing substituents (Hammett factor ρ = +1.5), consistent with the accrual of negative charge on the nitro substrate in the rate-determining step. DFT modeling of the turnover-limiting deoxygenation event implicates a rate-determining (3 + 1) cheletropic addition between the phosphetane catalyst 3 and 2-nitrobiphenyl substrate to form an unobserved pentacoordinate spiro-bicyclic dioxazaphosphetane, which decomposes via (2 + 2) cycloreversion giving 1 equiv of phosphetane P-oxide 3·[O] and 2-nitrosobiphenyl. Experimental and computational investigations into the C-N bond forming event suggest the involvement of an oxazaphosphirane (2 + 1) adduct between 3 and 2-nitrosobiphenyl, which evolves through loss of phosphetane P-oxide 3·[O] to give the observed carbazole product via C-H insertion in a nitrene-like fashion.

Noncontact measurement of emotional and physiological changes in heart rate from a webcam.

Heart rate, measured in beats per minute, can be used as an index of an individual's physiological state. Each time the heart beats, blood is expelled and travels through the body. This blood flow can be detected in the face using a standard webcam that is able to pick up subtle changes in color that cannot be seen by the naked eye. Due to the light absorption spectrum of blood, we are able to detect differences in the amount of light absorbed by the blood traveling just below the skin (i.e., photoplethysmography). By modulating emotional and physiological stress-that is, viewing arousing images and sitting versus standing, respectively-to elicit changes in heart rate, we explored the feasibility of using a webcam as a psychophysiological measurement of autonomic activity. We found a high level of agreement between established physiological measures, electrocardiogram, and blood pulse oximetry, and heart rate estimates obtained from the webcam. We thus suggest webcams can be used as a noninvasive and readily available method for measuring psychophysiological changes, easily integrated into existing stimulus presentation software and hardware setups.

Firefighter attitudes, norms, beliefs, barriers, and behaviors toward post-fire decontamination processes in an era of increased cancer risk.

Firefighters are exposed to carcinogens such as volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) during fires and from their personal protective equipment (PPE). Recent research has shown that decontamination processes can reduce contamination on both gear and skin. While firefighter cultures that honor dirty gear are changing, little is known about current attitudes and behaviors toward decontamination in the fire service. Four hundred eighty-five firefighters from four departments completed surveys about their attitudes, beliefs, perceived norms, barriers, and behaviors toward post-fire decontamination processes. Overall, firefighters reported positive attitudes, beliefs, and perceived norms about decontamination, but showering after a fire was the only decontamination process that occurred regularly, with field decontamination, use of cleansing wipes, routine gear cleaning, and other behaviors all occurring less frequently. Firefighters reported time and concerns over wet gear as barriers to decontamination.

What item response theory can tell us about the complex span tasks.

Working memory capacity is an important construct in psychology because of its relationship with many higher-order cognitive abilities and psychopathologies. Working memory capacity is often measured using a type of paradigm known as complex span. Some recent work has focused on shortening the administration time of the complex span tasks, resulting in different versions of these tasks being used (Foster et al., 2015; Oswald, McAbee, Redick, & Hambrick, 2015). Variations in the complex span tasks, such as the number of set sizes, can lead to varying power to discriminate individuals at different ability levels. Thus, research findings may be inconsistent across populations due to differing appropriateness for the ability levels. The present study uses a combination of item response theory and correlational analyses to better understand the psychometric properties of the operation span, symmetry span, and rotation span. The findings show that the typical administration of these tasks, particularly the operation span, is not suitable for above average ability samples (Study 1; n = 573). When larger set sizes are added to the tasks (Study 2; n = 351), predictive validity and discriminability is improved for all complex span tasks, however the operation span is still inferior to the spatial tasks. The authors make several conclusions about which tasks and set sizes should be used depending on the intended population, and further suggest avoiding the standard-length operation span for average or higher ability populations. (PsycINFO Database Record

Perceptions of health and cancer risk among newly recruited firefighters in South Florida.

PURPOSE: Despite hazardous exposures to cancer-causing agents in the line of duty, the main health and safety concerns of active firefighters have yet to be studied. We compare the perceptions of health and cancer risks between rookie and experienced firefighters. METHODS: Focus groups were used to investigate potential risk of job exposures, and broad-based concerns regarding work and health. An 18-item demographic survey was also administered. Five focus group sessions were conducted with a total of 57 firefighters. RESULTS: Our findings indicate that both rookie and experienced firefighters have a "high risk, high reward" mindset and identify injury, chronic disease, and stress as main health concerns. Experienced firefighters reported a shift in firefighter culture related to health. CONCLUSION: The perception of health and cancer risk of rookie and experienced firefighters differ in the prioritization of their concerns, however both groups equally report occupational cancer risk as their main health concern.

Firefighter perceptions of cancer risk: Results of a qualitative study.

BACKGROUND: Recent epidemiological research on firefighters indicates an increased incidence of specific types of cancer. Intervention is needed in the fire service yet little is known about how firefighters perceive their cancer risk. METHODS: Participant observation (150 h, n = 100) and focus group (n = 17) data were collected from 15 fire stations in South Florida. Firefighters had at least 3 years of experience, ranks included drivers, captains, lieutenants, and specialty captains, with a median age of 51 years. RESULTS: From the qualitative analysis, two major categories (direct and indirect factors) for cancer risks emerged based on participant notions of cancer risk and cancer prevention behaviors as they relate to firefighting. CONCLUSIONS: Firefighters perceive cancer risks as the result of performing essential job tasks and from indirect job factors related to being a firefighter. The two categories of cancer risks suggest different points of entry for intervention.