Assessing the Functional Accessibility, Actionability, and Quality of Patient Education Materials from Canadian Cancer Agencies.

Patient education materials (PEM)s were extracted from provincial cancer agencies to determine their organizational health literacy by evaluating the quality, actionability, and functional accessibility (e.g., readability and understandability) of their PEMs. PEMs from 10 provincial agencies were assessed for their grade reading level (GRL), using eight numerical and two graphical readability scales, and underwent a difficult word analysis. The agencies were assessed for PEM quality using two methods (JAMA benchmarks and DISCERN), while actionability and understandability were assessed using the Patient Education Materials Assessment Tool (PEMAT). Seven hundred and eighty-six PEMs were analyzed. The overall average GRL was 9.3 ± 2.1, which is above the recommended 7th GRL for health information. The difficult word analysis showed that 15.4% ± 5.1% of texts contained complex words, 35.8% ± 6.8% of texts contained long words, and 24.2% ± 6.6% of texts contained unfamiliar words. Additionally, there was high overlap between the most frequently identified difficult words in the PEMs and the most frequently misunderstood words by cancer patients identified in the literature. Regarding quality indicators, no agency displayed all four indicators according to the JAMA benchmarks and DISCERN scores ranged between 38 (poor) to 66 (excellent). PEMAT scores ranged between 68% to 88% for understandability and 57% to 88% for actionability. PEMs continue to be written at a level above the recommended GRL across all provinces, and there was overall high variability in the quality, understandability, and actionability of PEMs among provincial agencies. This represents an opportunity to optimize materials, thus ensuring understanding by a wider audience and improving health literacy among Canadian cancer patients.

Development and Implementation of a Medical Respite Program for People Experiencing Homelessness: An Analysis of a Cross-sectoral Partnership.

People with lived experience of homelessness (PWLEH) undergo worse health outcomes despite frequent acute care use, often because their functional and social needs remain unmet. In response, a homeless shelter and the provincial health authority formed a partnership to implement a medical respite program. We describe this collaboration by conducting a qualitative study, interviewing people involved in planning and implementing the program (n=25). Thematic analysis was performed. Stakeholders were motivated by a common desire to address the health inequities experienced by PWLEH, and frontline service providers felt a sense of teamwork. However, due to logistical limitations, an evolution of partnerships, and lack of role clarity, there was no singular program vision, resulting in lack of stakeholder support and conflicts between partner organizations. Health care for PWLEH must be multidisciplinary and cross-sectoral. The synergies and challenges described shed light on how future partnerships can be navigated.

Interventions Associated With Reduced Loneliness and Social Isolation in Older Adults: A Systematic Review and Meta-analysis.

Importance: Loneliness and social isolation are public health concerns faced by older adults due to physical, cognitive, and psychosocial changes that develop with aging. Loneliness and social isolation are associated with increased morbidity and mortality. Objective: To evaluate interventions, targeting older adults, associated with a reduction in loneliness and social isolation. Data Sources: OVID, CINAHL, CENTRAL, Embase, PsychINFO, Web of Science, and Scopus were searched from inception to March 2020. Study Selection: Peer-reviewed randomized clinical trials measuring loneliness and social isolation or support in adults aged 65 years or older. Only English language articles were included. Data Extraction and Synthesis: Two independent reviewers screened studies, extracted data, and assessed risk of bias. Random-effects models were performed to pool the overall effect size by intervention. Statistical heterogeneity was evaluated with the I2 statistic and by estimating prediction intervals. Data were analyzed from November 2021 to September 2022. Main Outcomes and Measures: Quantitative measures of loneliness, social isolation, or social support based on an effect size of standardized mean differences. Results: Seventy studies were included in the systematic review (8259 participants); 44 studies were included in the loneliness meta-analysis (33 in the community with 3535 participants; 11 in long-term care with 1057 participants), with participants' ages ranging from 55 to 100 years. Study sizes ranged from 8 to 741 participants. Interventions included animal therapy, psychotherapy or cognitive behavioral therapy, multicomponent, counseling, exercise, music therapy, occupational therapy, reminiscence therapy, social interventions, and technological interventions. Most interventions had a small effect size. Animal therapy in long-term care, when accounting for studies with no active controls, had the largest effect size on loneliness reduction (-1.86; 95% CI, -3.14 to -0.59; I2 = 86%) followed by technological interventions (videoconferencing) in long-term care (-1.40; 95% CI, -2.37 to -0.44; I2 = 70%). Conclusions and Relevance: In this study, animal therapy and technology in long-term care had large effect sizes, but also high heterogeneity, so the effect size's magnitude should be interpreted with caution. The small number of studies per intervention limits conclusions on sources of heterogeneity. Overall quality of evidence was very low. Future studies should consider measures of social isolation in long-term care and identify the contextual components that are associated with a reduction in loneliness.

Assessment of the Readability and Quality of Online Patient Education Material for Chronic Medical Conditions.

Patient education materials (PEMs) were assessed from chronic health condition associations to determine their quality and if they were above the 6th grade reading level (GRL) recommended by the Centers for Disease Control and National Institutes of Health. PEMs from 55 associations were assessed for their GRL using ten readability scales and underwent a difficult word analysis. The associations had their quality assessed using two methods: the Journal of the American Medical Association (JAMA) Benchmarks and Health on the Net Foundation Code of Conduct certification (HONCode). Two thousand five hundred and ninety PEMs, collected between June and November 2021, were analyzed. The overall GRL average was 10.8 ± 2.8, with a range of 0 to 19. Difficult word analysis showed that 15.8% ± 4.8 contained complex words of 3 or more syllables and 25.7% ± 6.3 contained words which were unfamiliar. No association displayed all four indicators of quality according to JAMA Benchmarks or held an up-to-date HONCode certification. The PEM readability continues to be written at a level above the recommended GRL. Additionally, the lack of quality indicators from the associations' websites may make it difficult for older adults to identify the sources as credible. This represents an opportunity to optimize materials that would be understood by a wider audience.

A Qualitative and Quantitative Analysis of the Geriatrics Update: Clinical Pearls Course.

BACKGROUND: The University of Calgary Cumming School of Medicine Annual Geriatrics Update: Clinical Pearls Course (Geriatrics Update) is a one-day, continuing medical education (CME) course designed to enhance geriatrics competency for family physicians (FPs), given increasing population age and complexity. We aimed to evaluate how the course meets FPs' perceived learning needs and identify modifications that may better support FPs. METHODS: Descriptive data from 2018-2019 course evaluation surveys including demographic data, evaluations, and narrative feedback from participating FPs. Semi-structured phone and video-conferenced interviews with FPs were thematically analyzed each year. RESULTS: Evaluation surveys had high response rates of FPs (52 or 61% in 2018; 39 or 58% in 2019). Most FP respondents (84% in 2018 and 82% in 2019) intended to make practice changes. FPs were significantly (p=.001) more confident on course objectives after the course in both years. All interviewees (n=20) described fulfilled perceived and unperceived learning needs and planned to return. The Geriatrics Update course is the primary source of Geriatrics CME for 60% of interviewees. CONCLUSIONS: Iterative evaluation of Geriatrics Update identified that the course is well received, and often FPs primary source of geriatric CME. Interviews provided additional context and descriptive feedback to improve course delivery and better meet FP learning needs.

IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses.

Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent phase of allergic contact hypersensitivity (CHS). However, the cytokines driving maintenance and survival of pathogenic T cells during and following CHS remain mostly unknown. Upon epicutaneous allergen challenge, we here report that macrophages produce IL-27 which then induces IL-15 production from epidermal keratinocytes and dermal myeloid cells within leukocyte clusters. In agreement with the known role of IL-15 as a T cell survival factor and growth cytokine, this signaling axis enhances BCL2 and survival of skin T cells. Genetic depletion or pharmacological blockade of IL-27 in CHS mice leads to abrogated epidermal IL-15 production resulting in a decrease in BCL2 expression in T cells and a decline in dermal CD8+ T cells and T cell cluster numbers. These findings suggest that the IL-27 pathway is an important cytokine for regulating cutaneous T cell immunity.

Evaluation of an Intergenerational and Technological Intervention for Loneliness: Protocol for a Feasibility Randomized Controlled Trial.

BACKGROUND: Social integration and mental health are vital aspects of healthy aging. However, close to half of Canadians older than 80 years report feeling socially isolated. Research has shown that social isolation leads to increased mortality and morbidity, and various interventions have been studied to alleviate loneliness among older adults. This proposal presents an evaluation of an intervention that provides one-on-one coaching, is intergenerational, provides both educational and socialization experiences, and increases technology literacy of older adults to overcome loneliness. OBJECTIVE: This paper describes the protocol of a randomized, mixed-methods study that will take place in Ontario, Canada. The purpose of this study is to evaluate if an intergenerational technology literacy program can reduce social isolation and depression in older adults via quantitative and qualitative outcome measures. METHODS: This study is a randomized, mixed-methods, feasibility trial with 2 conditions. Older adults in the intervention condition will receive 1 hour of weekly technological assistance to send an email to a family member, for 8 weeks, with the assistance of a volunteer. Participants in the control condition will not receive any intervention. The primary outcomes are loneliness, measured using the University of California, Los Angeles Loneliness Scale, and depression, measured using the Center for Epidemiologic Studies Depression scale, both of which are measured weekly. Secondary outcomes are quality of life, as assessed using the Older People's Quality of Life-Brief version, and technological literacy, evaluated using the Computer Proficiency Questionnaire-12, both of which will be administered before and after the intervention. Semistructured interviews will be completed before and after the intervention to assess participants' social connectedness, familiarity with technology, and their experience with the intervention. The study will be completed in a long-term care facility in Southwestern Ontario, Canada. Significance was set at P<.05. RESULTS: This study was funded in April 2019 and ethical approval was obtained in August 2019. Recruitment for the study started in November 2019. The intervention began in February 2020 but was halted due to the COVID-19 pandemic. The trial will be restarted when safe. As of March 2020, 8 participants were recruited. CONCLUSIONS: Information and communication technology interventions have shown varying results in reducing loneliness and improving mental health among older adults. Few studies have examined the role of one-on-one coaching for older adults in addition to technology education in such interventions. Data from this study may have the potential to provide evidence for other groups to disseminate similar interventions in their respective communities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23767.

Health Services: A Mixed Methods Assessment of Canadian Cancer Patient Education Materials Related to the 2019 Novel Coronavirus.

The 2019 novel coronavirus (COVID-19) pandemic has prompted the reorganization in the scheduling and method of care for many patients, including patients diagnosed with cancer. Cancer patients, who have an immunocompromised status, may be at a higher risk of severe symptoms from infection with COVID-19. While information is rapidly evolving regarding COVID-19, Canada, both nationally and provincially, has been conveying new information to patients online. We assessed the content and readability of COVID-19-related online Canadian patient education material (PEM) for cancer patients to determine if the content of the material was written at a grade reading level that the majority of Canadians can understand. PEMs were extracted from provincial cancer agencies and the national Canadian Cancer Society, evaluated using 10 readability scales, qualitatively analyzed to identify their themes and difficult word content. Thirty-eight PEMs from both national and provincial cancers associations were, on average, written above the recommended 7th grade level. Each of the associations' average grade levels were: BC Cancer (11.00 95% confidence interval [CI] 8.27-13.38), CancerControl Alberta (10.46 95% CI 8.29-12.62), Saskatchewan Cancer Agency (11.08 95% CI 9.37-12.80), Cancer Care Manitoba (9.55 95% CI 6.02-13.01), Cancer Care Ontario (9.35 95% CI 6.80-11.90), Cancer Care Nova Scotia (10.95 95% CI 9.86-12.04), Cancer Care Eastern Health Newfoundland and Labrador (10.14 95% CI 6.87-13.41), and the Canadian Cancer Society (10.06 95% CI 8.07-12.05). Thematic analysis identified 4 themes: public health strategy, information about COVID-19, patient instructions during COVID-19, and resources. Fifty-three percent of the complex words identified were medical jargon. This represents an opportunity to improve PEM readability, to allow for greater comprehension amongst a wider target audience.

Assessment of the Readability of Online Patient Education Material from Major Geriatric Associations.

BACKGROUND/OBJECTIVES: An increasing number of patients are using the internet to supplement information provided by medical professionals. Online geriatric patient education materials (PEMs) should be written at or below a 6th grade reading level (GRL) that takes into account barriers unique to the geriatric population. The objectives of the study are to assess PEMs of geriatric associations' websites and determine whether they are above the GRL recommended by the Centers for Disease Control and National Institutes of Health. DESIGN: Descriptive and correlational methodology. PEMs from 10 major geriatric associations were assessed for their GRL using 10 scales. Eight of the scales provide a numerical GRL while two of the scales provide a visual representation of the GRLs. Analysis was conducted using Readability Studio 2019.3. SETTING: Analysis was conducted February 2020. PARTICIPANTS: Identified 10 geriatric associations and 884 PEMs. MEASUREMENTS: GRLs were measured by 10 validated readability indices: the Degrees of Reading Power and Grade Equivalent test, Flesch-Kincaid grade level, Simple Measure of Gobbledygook test, Coleman-Liau Index, Gunning Fog Index, New Fog Count, New Dale-Chall readability formula, Ford, Caylor, Sticht scale, Raygor readability estimate graph, and Fry readability graph. RESULTS: The mean of all PEMs using the numerical scales was 11.1 ± 2.4. Ninety-nine percent of PEMs are above the 6th GRL. PEMs ranged from a grade 3.0 to 19.0 reading level. Analysis of variance demonstrated a significant difference between associations (P < .0001), and multiple comparison analysis identified the National Institute on Aging as the content easiest to read (9.5 ± 1.6). CONCLUSION: PEMs from geriatric association websites are written above the recommended 6th GRL. As patients increasingly look toward online supplementary health information during COVID-19, there is an opportunity for improving PEMs to enable greater comprehension by the target population.

A comparison of electronically-delivered and face to face cognitive behavioural therapies in depressive disorders: A systematic review and meta-analysis.

BACKGROUND: Cognitive behavioural therapy (CBT) is a widely used treatment for depression. However, limited resource availability poses several barriers to patients seeking access to care, including lengthy wait times and geographical limitations. This has prompted health care services to introduce electronically delivered CBT (eCBT) to facilitate access. Although previous reviews have compared the effects of eCBT to face-to-face CBT, there is an overall lack of adequately powered and up-to-date evidence in the literature to provide a reliable comparison between the two modes of administration. The purpose of this study is to evaluate the effects of eCBT compared to face-to-face CBT through a systematic review of the literature. METHODS: To be eligible for this review, studies needed to be randomized controlled trials evaluating the clinical effectiveness of any form of eCBT compared to face-to-face CBT. These encompassed studies evaluating a wide range of outcomes including severity of symptoms, adverse outcomes, clinically relevant outcomes, global functionality, participant satisfaction, quality of life, and affordability. There were no restrictions on participant age or sex.We searched MEDLINE, EMBASE, Psych Info, Cochrane CENTRAL and CINAHL databases from inception to February 20th, 2020 using a comprehensive search strategy. All stages of literature screening and data extraction were completed independently in duplicate. Data extraction and risk of bias analyses, including GRADE ratings, were conducted on studies meeting inclusion criteria. Qualitative measures are reported in a narrative summary. We pooled quantitative data in meta-analyses to provide an estimated summary effect. This review adheres to PRISMA reporting guidelines. FINDINGS: In total, we included 17 studies in our analyses. Our results demonstrated that eCBT was more effective than face-to-face CBT at reducing depression symptom severity (Standardized mean difference [SMD]: -1.73; 95% confidence interval [CI]: -2.72, -0.74; GRADE: moderate quality of evidence). There were no significant differences between the two interventions on participant satisfaction (SMD 0.13 95%; CI -0.32, 0.59; GRADE: low quality of evidence). One RCT reported eCBT to be less costly than face-to-face CBT (GRADE: low quality of evidence). Results did not differ when stratified by subgroups such as participant age and study location. INTERPRETATION: Although we found eCBT to have moderate evidence of effectiveness in reducing symptoms of depression, high heterogeneity among studies precludes definitive conclusions for all outcomes. With the current reliance and accessibility of technology to increasing number of people worldwide, serious consideration in utilizing technology should be given to maximize accessibility for depression treatments. Our results found eCBT is at least as effective as face to face CBT, thus eCBT should be offered if preferred by patients and therapists. FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.

In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27-mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus.

Examining the Feasibility of a Mindfulness Intervention for the Prevention of Falls: A Pilot Study.

This pilot study was designed to assess the feasibility of implementing a mindfulness intervention in the prevention of falls. We employed a quasi-experimental design consisting of 22 participants from two retirement homes in Ontario partaking in the regional falls prevention class. Participants were assigned to either an eight-week intervention, comprising mindfulness exercises incorporated into the standard falls prevention class, or to the standard falls prevention class. Participants were assessed using the Tinetti Balance and Gait Scale and the Timed Up and Go (TUG) test. The mindfulness intervention showed no significant effect on TUG or balance scores; however, there was a significant effect on assessments of gait. Given the ease of implementation of mindfulness-based interventions, further research may be warranted in mindfulness as a potential modality for falls prevention.

Demonstration of 99mTc-MDP Uptake in a Mobile Urinary Bladder Calculus on SPECT/CT.

We report a large mobile bladder calculus with intense Tc-MDP uptake demonstrated on both whole-body bone scintigraphy and SPECT/CT images in a patient with complicated chronic history of urolithiasis and urinary tract infection. Bone tracer uptake in bladder calculus is a rare phenomenon and might be related to the composition and matrix of calculus, direct exposure to excreted radiotracer, and bacterial colonization on the surface of calculus.

Percutaneous Gastrostomy Tube Placement: Recognizing When Things Go Wrong.

Percutaneous radiologic gastrostomy is a commonly performed, minimally invasive procedure for long-term enteral access in patients with a variety of conditions. Compared with other methods, it is less invasive, less costly, and safe, with a high technical success rate. The risk of complications is low, and most require only conservative management. Early, accurate diagnosis of more severe complication is crucial, as these may require prompt intervention. Therefore, radiologists should understand the imaging features, clinical presentation, and management of gastrostomy-related complications. This article will review the indications for long-term enteral access, discuss the available methods, summarize the percutaneous radiologic technique, and highlight the associated complications from gastrostomy placement.

Free Emergency Manual Books Improve Actual Clinical Use During Crisis in China.

Introduction Emergency manuals (EM) are widely implemented and effective tools for anesthesiologists and perioperative teams to manage patients during critical events. Team simulation studies have shown that the use of training aids and checklists decreases human error. Previous research has examined the use of EM at hospitals in the United States, but few studies have explored its impact in an international setting. In this paper, we conduct a nationwide survey in China to assess the implementation and effectiveness of EM in clinical settings. Methods Based on the known benefits of using these training aids, we hypothesize that introducing EM will improve team response and reduce errors during crisis management. Copies of the translated Stanford University Operating Room Emergency Handbook were distributed free of charge to hospital anesthesiology departments across China. A survey was then sent out to members of the New Youth Anesthesia Forum, a social networking group of over 100,000 anesthesiologists. Results Respondents (n = 818) were separated based on whether or not they received the free EM (yes = 410; no = 408). Our study found that groups who received the manuals demonstrated significantly higher levels of self-review, group study, simulation training participation, and usage during critical events than groups that did not receive the free books (respectively; p < 0.001). Conclusions These findings strengthen prior evidence suggesting that implementing EM can contribute to the effective management of acute events in a hospital and preoperative setting. Overall, EM can minimize preventable patient risk and benefit anesthesiologists in their clinical practice. These findings indicate that free books can enhance the implementation of emergency manual and actual emergency manual use during critical events.

A comparative histomorphological and micro computed tomography study of the primary stability and the osseointegration of The Sydney Mini Screw; a qualitative pilot animal study in New Zealand rabbits.

OBJECTIVE: The aim of this study was to assess the potential of improving orthodontic miniscrews' (MSs) primary stability in vivo by evaluating the dispersion capacity of an injectable bone graft substitute (iBGS) through a newly designed hollow MS [The Sydney Mini Screw (SMS)] and its integration with the cortical and trabecular bone by using the femur and tibia in a New Zealand rabbit animal model. METHODS: In total, 24 MSs were randomly placed in each proximal tibia and femur of 6 New Zealand rabbits with an open surgery process. Aarhus MSs were used as controls and the effect of injection of iBGS was studied by implanting SMSs with and without iBGS injection. The dispersion of iBGS and the integration of the SMS were studied by using micro Computed Tomography (µCT) and histochemical analysis at two time points, 0 day and 8 weeks post-implantation. RESULTS: iBGS was successfully injected through the SMS and hardened in situ. After 8 weeks, µCT results revealed that the iBGS particles were resorbed and bone tissue was formed around the SMS and within its lateral exit holes. CONCLUSIONS: This pilot animal study showed the high potential of the combined use of iBGS and SMS as a newly developed technique to promote the primary stability of MSs.

Folding of the silver aptamer in a DNAzyme probed by 2-aminopurine fluorescence.

The RNA-cleaving Ag10c DNAzyme was recently isolated via in vitro selection and it can bind two Ag+ ions for activity. The Ag10c contains a well-defined Ag+ binding aptamer as indicated by DMS footprinting. Since aptamer binding is often accompanied with conformational changes, we herein used 2-aminopurine (2AP) to probe its folding in the presence of Ag+. The Ag10c was respectively labeled with 2AP at three different positions, both in the substrate strand and in the enzyme strand, one at a time. Ag+-induced folding was observed at the substrate cleavage junction and the A9 position of the enzyme strand, consistent with aptamer binding. The measured Kd at the A9 position was 18 µM Ag+ with a Hill coefficient of 2.17, similar to those obtained from the previous cleavage activity based assays. However, labeling a 2AP at the A2 position inhibited the activity and folding. Compared to other metal ions, Ag+ has a unique sigmoidal folding profile indicative of multiple silver binding cooperatively. This suggests that Ag+ can induce a local folding in the enzyme loop and this folding is important for activity. This study provides important biophysical insights into this new DNAzyme, suggesting the possibility of designing folding-based biosensors for Ag+.

Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.

Breast cancer is the most common malignancy diagnosed among women and represents a heterogeneous group of subtypes. Radiation therapy is a critical component of treatment for breast cancer patients. However, little is known about radiation response among these intrinsic subtypes. In previous studies, we identified a significant induction of FAS after irradiation in biologically favorable breast cancer patients and breast cancer cell lines. Here, we expanded our study and investigated radiation response in a mouse model of breast cancer. MCF7 (luminal), HCC1954 (HER2+) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of nude mice. These mice were then treated with different doses of radiation to assess tumor growth control. We further investigated the therapeutic effect of FAS modulation by silencing FAS in radiation-responsive tumors and injecting FAS agonist antibody into radiation-resistant tumors. Exposure to radiation inhibited MCF7, and to a lesser extent HCC1954 tumor growth in a dose-dependent manner. In contrast, SUM159 tumors were resistant to radiation. The estimated TCD50 values were 19.3 Gy for MCF7 and 44.9 Gy for SUM159. Radiation induced FAS expression in MCF7 tumors, but not SUM159 tumors. We found that silencing of FAS did not negatively impact radiation response in MCF7 tumors, possibly due to compensation by other apoptotic pathways. On the other hand, FAS activating antibody in combination with radiation treatment delayed SUM159 and HCC1954 tumor growth. However, it did not reach statistical significance compared to radiation treatment alone. Our results suggest that there is intrinsic variation in radiation response among breast cancer subtypes. FAS activation concurrent with radiation slows tumor growth in the radiation-resistant subtypes, but the effect was not significant. Alternative subtype-specific modulators of radiation response are under investigation.

Pathogenesis of Thromboembolism and Endovascular Management.

Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted.

IL-27 Facilitates Skin Wound Healing through Induction of Epidermal Proliferation and Host Defense.

Skin wound repair requires a coordinated program of epithelial cell proliferation and differentiation as well as resistance to invading microbes. However, the factors that trigger epithelial cell proliferation in this inflammatory process are incompletely understood. In this study, we demonstrate that IL-27 is rapidly and transiently produced by CD301b+ cells in the skin after injury. The functional role of IL-27 and CD301b+ cells is demonstrated by the finding that CD301b-depleted mice exhibit delayed wound closure in vivo, which could be rescued by topical IL-27 treatment. Furthermore, genetic ablation of the IL-27 receptor (Il27Ra-/-) attenuates wound healing, suggesting an essential role for IL-27 signaling in skin regeneration in vivo. Mechanistically, IL-27 feeds back on keratinocytes to stimulate cell proliferation and re-epithelialization in the skin, whereas IL-27 leads to suppression of keratinocyte terminal differentiation. Finally, we identify that IL-27 potently increases expression of the antiviral oligoadenylate synthetase 2, but does not affect expression of antibacterial human beta defensin 2 or regenerating islet-derived protein 3-alpha. Together, our data suggest a previously unrecognized role for IL-27 in regulating epithelial cell proliferation and antiviral host defense during the normal wound healing response.