Cyclin A/B RxL Macrocyclic Inhibitors to Treat Cancers with High E2F Activity.

Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC).

Salt stress alters the cell wall components and structure in Miscanthus sinensis stems.

Miscanthus is a perennial grass suitable for the production of lignocellulosic biomass on marginal lands. The effects of salt stress on Miscanthus cell wall composition and its consequences on biomass quality have nonetheless received relatively little attention. In this study, we investigated how exposure to moderate (100 mM NaCl) or severe (200 mM NaCl) saline growing conditions altered the composition of both primary and secondary cell wall components in the stems of 15 Miscanthus sinensis genotypes.

Terpenes from Cannabis sativa induce antinociception in a mouse model of chronic neuropathic pain via activation of adenosine A 2A receptors.

Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa . A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies were methodologically limited and few established mechanisms of action.

Predictors of Speech Language Pathology Referral After Pediatric Concussion Using a Speech Language Checklist.

Speech language pathologists have the training to treat pediatric concussion issues in communication; however, they have traditionally not been included in initial concussion treatment. Despite physician understanding of speech language pathologist engagement in traumatic brain injury, speech language pathologist referrals happen only after significant issues in returning to school occurred. Therefore, the purpose of this study was to investigate predictors of physician referral to speech language pathologist using a speech language pathologist screening checklist.

Patient satisfaction with access and continuity of care in a multidisciplinary academic family medicine clinic.

Objective: To determine patient satisfaction with care provided at a family medicine teaching clinic.

Design: Mailed survey.

Setting: Victoria Family Medical Centre in London, Ont.

Surgical culture in transition: gender matters and generation counts.

Background: We sought to study the impact of the change in gender balance and the shift in generational beliefs on the practice of surgery.

Methods: We used in-depth, individual, semistructured interviews to explore the ideas, perceptions and experiences of recently recruited academic surgeons regarding the role of gender and the influence of the changing attitudes of this generation on the work environment. All the interviews were audiotaped and transcribed verbatim.

Effective interventions to facilitate the uptake of breast, cervical and colorectal cancer screening: an implementation guideline.

Background: Appropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. Several high-quality systematic reviews and practice guidelines exist to inform the most effective screening options. However, effective implementation strategies are warranted if the full benefits of screening are to be realized.

What implementation interventions increase cancer screening rates? a systematic review.

Background: Appropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. However, effective implementation strategies are warranted if the full benefits of screening are to be realized. As part of a larger agenda to create an implementation guideline, we conducted a systematic review to evaluate interventions designed to increase the rate of breast, cervical, and colorectal cancer (CRC) screening.

Seeking balance: the complexity of choice-making among academic surgeons.

Purpose: This study describes the experiences of academic surgeons in seeking a balance between their personal and professional lives.

Method: This phenomenological study, conducted in 2009-2010 at the University of Western Ontario, used in-depth individual semistructured interviews to explore the ideas, perceptions, and experiences of 17 recently recruited academic surgeons (nine women/eight men) about seeking balance between their personal and professional lives. All the interviews were audiotaped and transcribed verbatim.

Help-seeking for children with mental health problems: parents' efforts and experiences.

Parents who contacted 1 of 15 children's mental health agencies in Ontario, Canada reported on where and why they were seeking mental health services for their 4- to 17-year-old children. Parents contacted an average of four agencies (± 1.7; range = 1-14) in the previous year.

Pathways of chronic pain in survivors of intimate partner violence.

Objective: To examine the roles of lifetime abuse-related injury, posttraumatic stress disorder (PTSD) symptom severity, and depressive symptom severity in mediating the effects of severity of assaultive intimate partner violence (IPV), psychological IPV, and child abuse on chronic pain severity in women survivors of IPV.

Methods: Structural equation modeling of data from a community sample of 309 women survivors of IPV was used to test partial and full theoretical models of the relationships among the variables of interest.

Results: The full model had good fit and accounted for 40.

Screening for intimate partner violence in health care settings: a randomized trial.

Context: Whether intimate partner violence (IPV) screening reduces violence or improves health outcomes for women is unknown.

Objective: To determine the effectiveness of IPV screening and communication of positive results to clinicians.

Design, Setting, And Participants: Randomized controlled trial conducted in 11 emergency departments, 12 family practices, and 3 obstetrics/gynecology clinics in Ontario, Canada, among 6743 English-speaking female patients aged 18 to 64 years who presented between July 2005 and December 2006, could be seen individually, and were well enough to participate.

Abuse-related injury and symptoms of posttraumatic stress disorder as mechanisms of chronic pain in survivors of intimate partner violence.

Objective: To examine the role of abuse-related injury and posttraumatic stress disorder (PTSD) symptom severity in mediating the effects of assaultive intimate partner violence (IPV) severity, psychological IPV severity, and child abuse severity on chronic pain severity in women survivors of IPV.

Methods: Using data collected from a community sample of 309 women survivors of IPV, structural equation modeling was used to test a theoretical model of the relationships among the key variables.

Results: The theoretical model accounted for almost 38% of the variance in chronic pain severity.

Patterns of medication use among women survivors of intimate partner violence.

Objective: Our objective was to describe patterns of medication use in a convenience sample of 309 women with a history of intimate partner violence (IPV) participating in a study of women's health after leaving an abusive partner (WHES).

Methods: Using data collected through interviews and health assessments, frequencies of past-month use of medications; abuse experienced, health problems and medical diagnoses; and selected demographics were calculated. Associations among abuse history, employment status, health problems, diagnoses, and medications were explored.

Chronic pain in women survivors of intimate partner violence.

Unlabelled: In this descriptive study of chronic pain in a community sample of 292 women who had separated from their abusive partners on average 20 months previously, more than one-third experienced high disability pain as measured by Von Korff's Chronic Pain Grade. Beyond the usual pain locations associated with abuse, 43.2% reported swollen/painful joints.

Approaches to screening for intimate partner violence in health care settings: a randomized trial.

Context: Screening for intimate partner violence (IPV) in health care settings has been recommended by some professional organizations, although there is limited information regarding the accuracy, acceptability, and completeness of different screening methods and instruments.

Objective: To determine the optimal method for IPV screening in health care settings.

Design And Setting: Cluster randomized trial conducted from May 2004 to January 2005 at 2 each of emergency departments, family practices, and women's health clinics in Ontario, Canada.

Women marginalized by poverty and violence. How patient-physician relationships can help.

Objective: To explore the experiences of women relegated to the margins of society by poverty or violence.

Design: Qualitative method of focus groups.

Setting: Shelters and transitional housing in southwestern Ontario.

Integrating knowledge generation with knowledge diffusion and utilization: a case study analysis of the Consortium for Applied Research and Evaluation in Mental Health.

Objective: Knowledge diffusion and utilization (KDU) have become a key focus in the health research community because of the limited success to date of research findings to inform health policies, programs and services. Yet, evidence indicates that successful KDU is often predicated on the early involvement of potential knowledge users in the conceptualization and conduct of the research and on the development of a "partnership culture". This study describes the integration of KDU theory with practice via a case study analysis of the Consortium for Applied Research and Evaluation in Mental Health (CAREMH).