A new, brief measure of college students' academic stressors.

Objective: The purpose of this study was to evaluate the psychometric properties of a new measure of academic stressors (the ASM) in college students. Participants: The ASM was given to 677 undergraduate students at three universities along with measures of anxiety/depression, Big Five personality traits, and study skills. Methods: Tests of factorability and an exploratory factor analysis were completed. The internal and test-retest reliability of the measure was also evaluated. Results: The ASM is a concise, valid, and reliable tool for assessing college students' academic stressors. Conclusions: ASM scores predicted anxiety and depression symptoms. Therefore, the ASM can be used by colleges and university to assess students' levels of academic stressors to identify meaningful resources for support.

In Their Own Words: What Do Healthcare Workers Want from Their Organization during the COVID-19 Pandemic?

Pandemics are associated with heightened distress among healthcare workers (HCWs). We report qualitative findings from a two-stage survey administered to HCWs at a large acute care hospital in Ontario during the COVID-19 pandemic to identify their concerns and wellness needs. Responses reflected HCWs' desires to be heard, protected, prepared, supported and cared for by the organization. HCWs' concerns were diverse and dynamic, reflecting the specific circumstances of their work and personal lives as well as the shifting landscape of the pandemic. We discuss implications for organizations seeking to promote and protect HCWs' psychological well-being and resilience during pandemics.

Is it time to reconsider the term "cancer survivor"?

PURPOSE: To improve understanding of how people diagnosed with cancer perceive the term "cancer survivor" and what influences those perceptions. DESIGN: Patients' reactions to the term were surveyed quantitatively and qualitatively. SAMPLE: Women who have primarily experienced breast cancer belonging to The Dr. Susan Love Research Foundation's Army of Women. METHODS: An online survey including fixed-alternative and open-ended questions. CONCLUSIONS: Using the blanket term "survivor" to label a diverse group is problematic; although the term offers a positive identity for some, others reject it or find it offensive, at least for patients like those represented in this study. If cancer patients are going to be labeled, they should choose the one that is most empowering and reflective of their experience. Implications for Psychosocial Providers: Language used in providing care or describing patients is controllable. If evidence exists that a particular term has the potential to inflict psychological harm, why use the term?

Standardization of prophylactic platelet transfusion dosing in a pediatric oncology population: a quality improvement project.

BACKGROUND: Oncology patients are frequent recipients of prophylactic platelet transfusions. Recent studies have demonstrated that lower prophylactic doses of platelets were not associated with a higher incidence of bleeding. At our institution, we found wide variation in platelet dosing due to lack of guidance and support for standardized dosing. STUDY DESIGN AND METHODS: A collaborative process improvement project between oncology, hematology, intensivists, and the transfusion service established guidelines for dosing of prophylactic platelet transfusions in nonbleeding oncology patients: 10 mL/kg or less of apheresis platelets for patients weighing up to 20 kg and 1 unit of apheresis platelets patients weighing 20 kg or more, with our stated goal of standardizing transfusion practice. A graphic data display tool that draws on the electronic medical record to monitor platelet ordering was created, with a target goal of greater than 80% compliance with the dosing guidelines. We implemented decision support for dosing consistent with the guideline, and provided educational materials to prescribers at various levels of training within oncology over multiple plan-do-study-act cycles. RESULTS: We were able to consistently achieve between 85 and 90% compliance of prophylactic platelet transfusion orders without an increase in the number of emergency department visits for bleeding or platelet transfusions or changing the time between platelet transfusions after guideline implementation. CONCLUSION: This project demonstrates that reducing the volume of prophylactic platelet transfusions to doses consistent with published studies was safe and that a process of guideline consensus based on published studies, well-designed decision support for computerized physician order entry, and targeted educational efforts, were effective in changing practice at a large academic hospital.

Myc, Oncogenic Protein Translation, and the Role of Polyamines.

Deregulated protein synthesis is a common feature of cancer cells, with many oncogenic signaling pathways directly augmenting protein translation to support the biomass needs of proliferating tissues. MYC's ability to drive oncogenesis is a consequence of its essential role as a governor linking cell cycle entry with the requisite increase in protein synthetic capacity, among other biomass needs. To date, direct pharmacologic inhibition of MYC has proven difficult, but targeting oncogenic signaling modules downstream of MYC, such as the protein synthetic machinery, may provide a viable therapeutic strategy. Polyamines are essential cations found in nearly all living organisms that have both direct and indirect roles in the control of protein synthesis. Polyamine metabolism is coordinately regulated by MYC to increase polyamines in proliferative tissues, and this is further augmented in the many cancer cells harboring hyperactivated MYC. In this review, we discuss MYC-driven regulation of polyamines and protein synthetic capacity as a key function of its oncogenic output, and how this dependency may be perturbed through direct pharmacologic targeting of components of the protein synthetic machinery, such as the polyamines themselves, the eukaryotic translation initiation factor 4F (eIF4F) complex, and the eukaryotic translation initiation factor 5A (eIF5A).

Evolving paradigms for new agent development in pediatric oncology.

PURPOSE OF REVIEW: To discuss considerations of new paradigms for clinical drug development in pediatric oncology that incorporate our expanding knowledge and complexity of molecular alterations associated with cancer; advances in cancer immunology and cellular therapy; the increasing number of new anticancer drugs, therapeutic approaches, and potential combinations; and recent initiatives by regulatory agencies to improve access to safe and effective therapies. RECENT FINDINGS: Cancer in children and adolescents is a rare event with significant long-term impact on individuals and society. Using multimodality therapy, stratified by patient and disease characteristics, the cure rate for childhood cancer exceeds 80%. Cancer genomics has transformed anticancer drug development. Understanding the genetic basis of pediatric cancers and the use of genomics for risk stratification has changed the focus of drug development from cytotoxic drugs to targeted therapeutic approaches. Advances in cancer immunology, immune checkpoint blockade, and cellular therapy offer novel approaches to harness T cells to treat cancer. To improve the outcome for children and adolescents with cancer and accelerate drug development, understanding drug and target interactions in preclinical models of pediatric cancer should be coupled with efficient clinical trial designs that incorporate biomarker selection, assessment of toxicity and drug exposure, and improved measures of response. SUMMARY: Clinical trials for children and adolescents with cancer evaluate cytotoxic drugs, molecularly target drugs, immunotherapy as well as combination therapies. The framework for oncology clinical trials will continually adapt to improve efficiency of trials and evaluate new therapeutic approaches.

Severe Mucha-Habermann-Like Ulceronecrotic Skin Disease in T-Cell Acute Lymphoblastic Leukemia Responsive to Basiliximab and Stem Cell Transplant.

A 5-year-old girl with T-cell acute lymphoblastic leukemia (T-ALL) developed a progressive eruption of crusted papules and ulcerative plaques involving 80% of her body surface area with histopathology consistent with febrile ulceronecrotic Mucha-Habermann disease (FUMHD), although multiple specimens also contained clonal leukemic cells. Her skin disease was refractory to many classic treatments for FUMHD, including methotrexate, and became so severe that concern about superinfection prevented intensification of chemotherapy for her malignancy. The addition of basiliximab promoted gradual improvement of the skin, allowing for chemotherapy intensification and subsequent bone marrow transplantation, after which the eruption resolved completely. This report describes a severe case of FUMHD-like eruption associated with clonal leukemic cells that improved with basiliximab, suggesting anti-CD25 therapy as a novel treatment for ulceronecrotic skin disease in the setting of high interleukin-2 levels.

Service user and family member perspectives on services for mental health, substance use/addiction, and violence: a qualitative study of their goals, experiences and recommendations.

BACKGROUND: Mental health and substance use disorders (MSD) are significant public health concerns that often co-occur with violence. To improve services that address MSD and violence [MSD(V)], it is critical to understand the perspectives of those most affected, people who have sought help for MSD(V) (i.e., "service users"), especially those with co-occurring issues, as well as their family members. METHODS: We conducted structured interviews with 73 service users and 41 family members of service users in two Ontario communities (one urban, one rural) regarding their goals related to help-seeking, positive and negative experiences, and recommendations for improving systems of care. RESULTS: Overall, participants expressed a need for services that: (1) are respectful, nonjudgmental, and supportive, help service users to feel more 'normal' and include education to reduce stigma; (2) are accessible, varied and publicly funded, thereby meeting individual needs and addressing equity concerns at a systems level; and (3) are coordinated, holistic and inclusive of family members who often support service users. CONCLUSIONS: The findings provide a rich understanding of how service users and their families perceive services for MSD(V) issues and identify key ways to better meet their needs.

The novel PAR2 ligand C391 blocks multiple PAR2 signalling pathways in vitro and in vivo.

BACKGROUND AND PURPOSE: Proteinase-activated receptor-2 (PAR2) is a GPCR linked to diverse pathologies, including acute and chronic pain. PAR2 is one of the four PARs that are activated by proteolytic cleavage of the extracellular amino terminus, resulting in an exposed, tethered peptide agonist. Several peptide and peptidomimetic agonists, with high potency and efficacy, have been developed to probe the functions of PAR2, in vitro and in vivo. However, few similarly potent and effective antagonists have been described. EXPERIMENTAL APPROACH: We modified the peptidomimetic PAR2 agonist, 2-furoyl-LIGRLO-NH2 , to create a novel PAR2 peptidomimetic ligand, C391. C391 was evaluated for PAR2 agonist/antagonist activity to PAR2 across Gq signalling pathways using the naturally expressing PAR2 cell line 16HBE14o-. For antagonist studies, a highly potent and specific peptidomimetic agonist (2-aminothiazo-4-yl-LIGRL-NH2 ) and proteinase agonist (trypsin) were used to activate PAR2. C391 was also evaluated in vivo for reduction of thermal hyperalgesia, mediated by mast cell degranulation, in mice. KEY RESULTS: C391 is a potent and specific peptidomimetic antagonist, blocking multiple signalling pathways (Gq -dependent Ca2+ , MAPK) induced following peptidomimetic or proteinase activation of human PAR2. In a PAR2-dependent behavioural assay in mice, C391 dose-dependently (75 µg maximum effect) blocked the thermal hyperalgesia, mediated by mast cell degranulation. CONCLUSIONS AND IMPLICATIONS: C391 is the first low MW antagonist to block both PAR2 Ca2+ and MAPK signalling pathways activated by peptidomimetics and/or proteinase activation. C391 represents a new molecular structure for PAR2 antagonism and can serve as a basis for further development for this important therapeutic target.

TMPRSS2, a novel membrane-anchored mediator in cancer pain.

More than half of all cancer patients have significant pain during the course of their disease. The strategic localization of TMPRSS2, a membrane-bound serine protease, on the cancer cell surface may allow it to mediate signal transduction between the cancer cell and its extracellular environment. We show that TMPRSS2 expression is not only dramatically increased in the primary cancers of patients but TMPRSS2 immunopositivity is also directly correlated with cancer pain severity in these patients. TMPRSS2 induced proteolytic activity, activated trigeminal neurons, and produced marked mechanical hyperalgesia when administered into the hind paw of wild-type mice but not PAR2-deficient mice. Coculture of human cancer cells with murine trigeminal neurons demonstrated colocalization of TMPRSS2 with PAR2. These results point to a novel role for a cell membrane-anchored mediator in cancer pain, as well as pain in general.

Associations of hair cortisol concentration with self-reported measures of stress and mental health-related factors in a pooled database of diverse community samples.

A pooled database from diverse community samples was used to examine the associations of hair cortisol concentration (HCC) with self-reported stress and stress-linked mental health measures, including depression, anxiety, alcohol and drug use, disability and experiences with aggression. As part of innovative research using a mobile laboratory to study community mental health, data were pooled from five sub-studies: a random sample of the general population (n = 70), people who had received treatment for a mental health and/or substance use problem (n = 78), family members of people treated for mental health and/or substance use problems (n = 49), community volunteers who sometimes felt sad or blue or thought they drank too much (n = 83) and young adults in intimate partner relationships (n = 44). All participants completed a computerized questionnaire including standard measures of perceived stress, chronic stress, depression, anxiety, hazardous drinking, tobacco use, prescription drug use, illicit drug use, disability and intimate partner aggression. HCC was significantly associated with use of antidepressants, hazardous drinking, smoking and disability after adjusting for sub-study and potential confounders (sex, body-mass index, use of glucocorticoids and hair dyed). In addition, preliminary analyses suggest a significant curvilinear relationship between HCC and perceived stress; specifically, HCC increased with higher perceived stress but decreased at the highest level of stress. Overall, HCC was associated with mental health-related variables mainly reflecting substance use or experiencing a disability. The relationship between HCC and self-reported stress is unclear and needs further research.

Linking masculinity to negative drinking consequences: the mediating roles of heavy episodic drinking and alcohol expectancies.

OBJECTIVE: This study extends previous research on masculinity and negative drinking consequences among young men by considering mediating effects of heavy episodic drinking (HED) and alcohol expectancies. We hypothesized that masculinity would have a direct relationship with negative consequences from drinking as well as indirect relationships mediated by HED and alcohol expectancies of courage, risk, and aggression. METHOD: A random sample of 1,436 college and university men ages 19-25 years completed an online survey, including conformity to masculine norms, alcohol-related expectancies, HED, and negative drinking consequences. Regression analyses and structural equation modeling were used. RESULTS: Six of seven dimensions of masculinity and the alcohol expectancy scales were significantly associated with both HED and negative consequences. In multivariate regression models predicting HED and negative consequences, the playboy and violence dimensions of masculinity and the risk/aggression alcohol expectancy remained significant. HED and the risk-taking dimension of masculinity were also significant in the model predicting negative consequences. The structural equation model indicated that masculinity was directly associated with HED and negative consequences but also influenced negative consequences indirectly through HED and alcohol expectancies. CONCLUSIONS: The findings suggest that, among young adult male college and university students, masculinity is an important factor related to both HED and drinking consequences, with the latter effect partly mediated by HED and alcohol expectancies. Addressing male norms about masculinity may help to reduce HED and negative consequences from drinking.

"Blurred lines?" Sexual aggression and barroom culture.

BACKGROUND: Meeting potential sexual/romantic partners for mutual pleasure is one of the main reasons young adults go to bars. However, not all sexual contacts are positive and consensual, and aggression related to sexual advances is a common experience. Sometimes such aggression is related to misperceptions in making and receiving sexual advances while other times aggression reflects intentional harassment or other sexually aggressive acts. This study uses objective observational research to assess quantitatively gender of initiators and targets and the extent that sexual aggression involves intentional aggression by the initiator, the nature of responses by targets, and the role of third parties and intoxication. METHODS: We analyzed 258 aggressive incidents involving sexual advances observed as part of a larger study on aggression in large capacity bars and clubs, using variables collected as part of the original research (gender, intoxication, intent) and variables coded from narrative descriptions (invasiveness, persistence, targets' responses, role of third parties). Hierarchical linear modeling analyses were used to account for nesting of incidents in evening and bars. RESULTS: Ninety percent of incidents involved male initiators and female targets, with almost all incidents involving intentional or probably intentional aggression. Targets mostly responded nonaggressively, usually using evasion. Staff rarely intervened; patron third parties intervened in 21% of incidents, usually to help the target but sometimes to encourage the initiator. initiators' level of invasiveness was related to intoxication of the targets, but not their own intoxication, suggesting intoxicated women were being targeted. CONCLUSIONS: Sexual aggression is a major problem in bars often reflecting intentional sexual invasiveness and unwanted persistence rather than misperceptions in sexual advances. Prevention needs to focus on addressing masculinity norms of male patrons and staff who support sexual aggression and better management of the highly sexualized and sexist environments of most bars.

Physician counseling of overweight patients about preventive health behaviors.

BACKGROUND: Numerous studies show that many primary care physicians (PCPs) do not discuss preventive health behaviors related to diet and exercise with their overweight patients. PURPOSE: To investigate whether certain counseling approaches by PCPs in their clinical encounters with patients are associated with improvements in care and resource utilization. METHODS: A total of 2205 patients in a large HMO were surveyed, during November and December 2010, about their health behaviors and perceptions of their interactions with their PCPs. Survey responses from each patient were matched with 48 months of patient-specific medical claims data, from October 2008 through September 2012, capturing the frequency and monetary costs of health care utilization. A series of regression analyses, completed in June 2013, focused on four dependent variables: patients' intentions to improve diet and activity, patients' satisfaction with their physicians, visits to healthcare providers, and health plan spending on treatment. RESULTS: For each finding, the degree of physician-patient discussion of preventive health behaviors was strengthened when (1) physicians expressed confidence in patients' ability to improve diet and exercise and (2) patients had confidence that their physician could facilitate improvement of these behaviors. CONCLUSIONS: The associations between physician counseling and subsequent key improvements for overweight patients are strengthened by the physician's confidence in the patient's ability to engage in preventive health behaviors and the patient's confidence in the physician's ability to help in implementing these behaviors. Cultivating such mutual confidence is instrumental in optimizing physicians' influence on overweight patients' health behaviors.

The influence of status on group drinking by young adults: a survey of natural drinking groups on their way to and from bars.

BACKGROUND: Young people's social standing among friends and peers has been linked to general levels of drinking and has been shown to influence others' drinking. We extend previous research by examining young adults' status within their natural-occurring drinking groups as a predictor of their subsequent alcohol consumption and encouragement of group members' alcohol consumption during a night out at licensed drinking establishments, a salient context for heavy drinking and alcohol-related risk among young adults. METHODS: We recruited same-sex young adult drinking groups (n = 104 groups; 63 all-male; average group size = 3.4 members; Mage = 21.86) on their way to drinking establishments to complete a survey-containing measures of member-nominated within-group status, likeability, and self-reported alcohol consumption-and a breathalyzer test. At the end of the evening, participants completed the same alcohol consumption measures and were asked to nominate group members who encouraged other members to drink that night. RESULTS: Multilevel analysis revealed that higher-status members engaged in the most alcohol consumption (via both self-report and breathalyzer) but in heavier drinking groups only. Higher-status members also encouraged the most alcohol consumed by others, regardless of levels of group drinking. Further, even though being liked by one's peers was positively related to intoxication that night, it did not account for the significant relationship between within-group status and drinking. CONCLUSIONS: Results suggest that peer-related prevention programs for young adults' problem drinking may benefit from focusing on the structure and dynamic of young people's drinking groups. Also, programs targeting peer norms may be more successful if they incorporate status-related issues.

Development of highly potent protease-activated receptor 2 agonists via synthetic lipid tethering.

Protease-activated receptor-2 (PAR2) is a G-protein coupled receptor (GPCR) associated with a variety of pathologies. However, the therapeutic potential of PAR2 is limited by a lack of potent and specific ligands. Following proteolytic cleavage, PAR2 is activated through a tethered ligand. Hence, we reasoned that lipidation of peptidomimetic ligands could promote membrane targeting and thus significantly improve potency and constructed a series of synthetic tethered ligands (STLs). STLs contained a peptidomimetic PAR2 agonist (2-aminothiazol-4-yl-LIGRL-NH2) bound to a palmitoyl group (Pam) via polyethylene glycol (PEG) linkers. In a high-throughput physiological assay, these STL agonists displayed EC50 values as low as 1.47 nM, representing a ∼200 fold improvement over the untethered parent ligand. Similarly, these STL agonists were potent activators of signaling pathways associated with PAR2: EC50 for Ca(2+) response as low as 3.95 nM; EC50 for MAPK response as low as 9.49 nM. Moreover, STLs demonstrated significant improvement in potency in vivo, evoking mechanical allodynia with an EC50 of 14.4 pmol. STLs failed to elicit responses in PAR2(-/-) cells at agonist concentrations of >300-fold their EC50 values. Our results demonstrate that the STL approach is a powerful tool for increasing ligand potency at PAR2 and represent opportunities for drug development at other protease activated receptors and across GPCRs.

A modified random walk door-to-door recruitment strategy for collecting social and biological data relating to mental health, substance use, addiction, and violence problems in a Canadian community.

AIMS: To describe a modified "random walk" door-to-door recruitment strategy used to obtain a random community sample for participation in a study relating to mental health, substance use, addiction, and violence (MSAV) problems and involving the collection of both self-report and biological (hair and saliva) data. This paper describes study protocols, response rates for the study and for the provision of biological data, and possible further applications for this data collection method. DESIGN: A two-stage cluster sample was derived from the 2006 Canadian census sampling frame for a small Ontario community, based on the random selection of city blocks as the primary sampling units and households as the secondary sampling units. SETTING: A small city in Ontario, Canada. PARTICIPANTS: A general population sample of 92 participants selected randomly from households using Kish tables. MEASURES: A computerized questionnaire was administered to obtain self-report data on MSAV problems. Saliva was collected to study genetic vulnerabilities to MSAV problems, and hair was collected to examine stress levels (via the hormone cortisol) as they relate to MSAV problems. FINDINGS: The study showed a response rate of 50% and a high rate of provision of biological samples (over 95%). CONCLUSIONS: Modified random walk methodologies involving face-to-face recruitment may represent a useful approach for obtaining general population samples for studies of MSAV problems, particularly those involving the collection of biological samples. Further studies are needed to assess whether this approach leads to better response rates and improved estimates compared to other survey methods used in research on substance use.

Community indicators: assessing the impact of alcohol use on communities.

Community indicators are used to assess the impact of alcohol on communities. This article reviews the main data sources for community indicators, discusses their strengths and limitations, and discusses indicators used in reference to four main topics relating to alcohol use and problems at the community level: alcohol use, patterns, and problems; alcohol availability; alcohol-related health outcomes/trauma; and alcohol-related crime and enforcement. It also reviews the challenges associated with collecting community indicator data, along with important innovations in the field that have contributed to better knowledge of how to collect and analyze community-level data on the impact of alcohol.

Does the relationship between depression and intimate partner aggression vary by gender, victim-perpetrator role, and aggression severity?

Research has shown a consistent link between intimate partner violence (IPV) and depression, although this association may vary by gender, role in IPV (victim, perpetrator, or bidirectional), and aggression severity. We evaluated these factors in a telephone survey of 14,063 Canadians. All three factors were found to affect the association of depression with IPV. Specifically, depression was more strongly associated with IPV by a partner (i.e., victimization) for women but with aggression toward a partner (i.e., perpetration) for men. Severity of aggression was associated with increased risk of depression for both one-sided and bidirectional aggression by a partner but more strongly for one-sided aggression toward a partner. These findings suggest that research, prevention, and treatment should focus on all roles in IPV, not just male-to-female aggression.

Lanthanide labeling of a potent protease activated receptor-2 agonist for time-resolved fluorescence analysis.

Protease activated receptor-2 (PAR(2)) is one of four G-protein coupled receptors (GPCRs) that can be activated by exogenous or endogenous proteases, which cleave the extracellular amino-terminus to expose a tethered ligand and subsequent G-protein signaling. Alternatively, PAR(2) can be activated by peptide or peptidomimetic ligands derived from the sequence of the natural tethered ligand. Screening of novel ligands that directly bind to PAR(2) to agonize or antagonize the receptor has been hindered by the lack of a sensitive, high-throughput, affinity binding assay. In this report, we describe the synthesis and use of a modified PAR(2) peptidomimetic agonist, 2-furoyl-LIGRLO-(diethylenetriaminepentaacetic acid)-NH(2) (2-f-LIGRLO-dtpa), designed for lanthanide-based time-resolved fluorescence screening. We first demonstrate that 2-f-LIGRLO-dtpa is a potent and specific PAR(2) agonist across a full spectrum of in vitro assays. We then show that 2-f-LIGRLO-dtpa can be utilized in an affinity binding assay to evaluate the ligand-receptor interactions between known high potency peptidomimetic agonists (2-furoyl-LIGRLO-NH(2), 2-f-LIGRLO; 2-aminothiazol-4-yl-LIGRL-NH(2), 2-at-LIGRL; 6-aminonicotinyl-LIGRL-NH(2), 6-an-LIGRL) and PAR(2). A separate N-terminal peptidomimetic modification (3-indoleacetyl-LIGRL-NH(2), 3-ia-LIGRL) that does not activate PAR(2) signaling was used as a negative control. All three peptidomimetic agonists demonstrated sigmoidal competitive binding curves, with the more potent agonists (2-f-LIGRLO and 2-at-LIGRL) displaying increased competition. In contrast, the control peptide (3-ia-LIGRL) displayed limited competition for PAR(2) binding. In summary, we have developed a europium-containing PAR(2) agonist that can be used in a highly sensitive affinity binding assay to screen novel PAR(2) ligands in a high-throughput format. This ligand can serve as a critical tool in the screening and development of PAR(2) ligands.