Background & Aims Clostridium difficile (C.difficile) is the leading cause of nosocomial infectious diarrhea. Increasing incidence, antibiotic resistance and more virulent strains have dramatically increased the number of C.difficile-related deaths worldwide. The innate host response mechanisms to C.difficile are not resolved; however, we hypothesize that hypoxia-inducible factor (HIF-1) plays an innate protective role in C.difficile colitis. Thus, we assessed the impact of C.difficile toxins on the regulation of HIF-1 and evaluated the role of HIF-1α in C.difficile-mediated injury/inflammation. Methods In vitro studies assessed HIF-1α mRNA, protein levels and DNA binding events in human mucosal biopsies and Caco-2 cells exposed to C.difficile toxins. In vivo studies employed the murine ileal loop model of C.difficile toxin-induced intestinal injury. Mice with targeted deletion of HIF-1α in the intestinal epithelium were used to assess the impact of HIF-1α signaling in response to C.difficile toxin. Results Mucosal biopsies and Caco-2 cells exposed to C.difficile toxin displayed a significant increase in HIF-1α transcription and protein levels. Toxin-induced DNA binding was also observed in Caco-2 cells. Toxin-induced HIF-1α accumulation was attenuated by nitric oxide synthase inhibitors. In vivo, deletion of intestinal epithelial HIF-1α resulted in more severe toxin-induced intestinal injury and inflammation. In contrast, stabilization of HIF-1α, with dimethyloxallyl glycine, attenuated toxin-induced injury and inflammation. This was associated with an induction of HIF-1-regulated protective factors including VEGFa, CD73 and intestinal trefoil factor and down-regulation of proinflammatory molecules TNF and KC. Conclusions Our study is the first to describe the innate protective role for HIF-1α in response to C.difficile toxins. Harnessing the innate protective actions of HIF-1α in response to C.difficile toxins may represent a novel form of therapy for C.difficile-associated disease.

There is a paucity of information surrounding dermatologic care for persons experiencing homelessness (PEH). This scoping review aims to map existing literature and provide a summary of the most common cutaneous manifestations among PEH, risk factors for dermatologic disease, describe any reported interventions, as well as identify research gaps for future studies. Search strategies developed for MEDLINE and hand searching yielded 486 articles. Out of the 486 articles screened, 93 articles met the inclusion criteria. The majority were cohort studies, cross-sectional studies, and case-control studies concentrated in North America and Europe. Excluding the pediatric population, the prevalence of dermatologic conditions ranged from 16.6% to 53.5%. Common skin conditions described in PEH were: acne, psoriasis, seborrheic dermatitis, atopic dermatitis, and lichen simplex chronicus. There were no studies comparing the extent or severity of these cutaneous diseases in PEH and the general population. PEH have a higher prevalence of skin infections and non-melanoma skin cancers. This scoping review has direct implications on public health interventions for PEH and highlights the need for evidence-based interventions to provide optimum and safe dermatologic healthcare for PEH. We propose several recommendations for improved care delivery, including addressing upstream factors and comorbidities impacting skin health, providing trauma informed care, reducing barriers to care, preventing and managing skin conditions, as well as including PEH in the planning and implementation of any proposed intervention.

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Background: Long-term use of immunosuppressive medications by organ transplant recipients (OTRs) leads to an increased risk of non-melanoma skin cancers (NMSCs).The objective of this study was to assess photoprotective knowledge and practices among OTRs and to identify predictors of poor sunscreen adherence and barriers to photoprotection. Methods:A written survey was administered to 300 solid OTRs attending the Southern Alberta Transplant Program. Demographics, transplant and NMSC history, ultraviolet radiation (UVR) exposure, photoprotective knowledge and practices, and barriers to implementing photoprotection were collected. Relevant statistical analyses and univariate and multivariable regression models on sunscreen use were performed. Results:One hundred and seventy-nine of the 300 respondents reported not using sunscreen most days despite 79.3% recalling have received photoprotection education. Of the surveyed OTRs, 45.7% reported no barriers to implementing photoprotective practices. On average, respondents scored 74.5% on a commonly used tool to assess photoprotective knowledge (SD 30.6%). In multivariable analyses, older age, male gender, and lack of post-secondary education were associated with lower rates of self-reported sunscreen use. The most commonly patient-reported barriers to photoprotection were "hassle/time consuming" (16.7%) and "sunscreen is uncomfortable or unpleasant" (10.0%).Conclusions: Despite OTRs self-reporting having received sufficient sun-protective knowledge and demonstrating reasonable recollection of photoprotective education on assessment, implementation of sun protection in the studied OTRs remains suboptimal. K E Y W O R D Seducation, non-melanoma skin cancer, photoprotection, sunscreen, transplantation

Alopecia areata is an autoimmune disease resulting in non-scarring hair loss. Alopecia areata can progress to become alopecia totalis (loss of hair from the entire scalp) or alopecia universalis (loss of hair form the entire body), with the progression estimated to range from 7% to 30%. There are no universally proven therapies that both induce and sustain remission, and furthermore, the course of alopecia areata tends to be unpredictable, with ~80% of patients achieving spontaneous remission within 1 year. We herein present the case of a 61-year-old female who presented with a 20-year history of alopecia universalis, and biopsy confirmed widespread granuloma annulare. Hydroxychloroquine was initiated to treat her granuloma annulare, with subsequent significant hair regrowth on her scalp, eyebrows, eyelashes, and arms. A review of the literature is presented showing that hydroxychloroquine has variable success in treatment of alopecia areata, alopecia totalis, and alopecia universalis.

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Background: Deliberate practice is an important method of skill acquisition and is under-utilized in dermatology training. We delivered a dermatologic morphology training module with immediate feedback for first year medical students. Our goal was to determine whether there are differences in accuracy and learning efficiency between self-regulated and algorithm-regulated groups. Methods: First year medical students at the University of Calgary completed a dermatologic morphology module. We randomly assigned them to either a self-regulated arm (students removed cases from the practice pool at their discretion) or an algorithm-regulated arm (an algorithm determined when a case would be removed). We then administered a pre-survey, pre-test, post-test, and post-survey. Data collected included mean diagnostic accuracy of the practice sessions and tests, and the time spent practicing. The surveys assessed demographic data and student satisfaction. Results: Students in the algorithm-regulated arm completed more cases than the self-regulated arm (52.9 vs. 29.3, p<0.001) and spent twice as much time completing the module than the self-regulated participants (34.3 vs. 17.0 min., p<0.001). Mean scores were equivalent between the algorithm- and self-regulated groups for the pre-test (63% vs. 66%, n = 54) and post-test (90% vs. 86%, n = 10), respectively. Both arms demonstrated statistically significant improvement in the post-test. Conclusion: Both the self-regulated and algorithm-regulated arms improved at post-test. Students spent significantly less time practicing in the self-directed arm, suggesting it was more efficient.

Clostridium difficile (C.diff) is a leading cause of infectious colitis in humans. C.diff toxins disrupt the intestinal epithelial barrier and induce the release of proinflammatory mediators. The hypoxia‐inducible factor‐1 (HIF‐1α) is a stress‐induced transcription factor that mediates mucosal and barrier protective genes. Nitric oxide (NO) and the factor‐inhibiting HIF‐1α (FIH‐1) modulate HIF‐1α expression and signaling, respectively. We hypothesize that NO produced during C.diff toxin‐induced intestinal injury is an important signal to activate HIF‐1α‐mediated protection against C.diff toxin‐induced damage.The in vitro studies analyzed HIF‐1α and FIH‐1 levels during toxin exposure of Caco2 cells. Cells were challenged with both toxin and nitric oxide synthase (NOS) inhibitors to study NO effects on HIF‐1α/FIH‐1 expression. In vivo studies assessed ileal loop tissue from toxin‐treated wild‐type (WT) and inducible NOS knockout (iNOS KO) mice.We have identified that HIF‐1α levels increase at least two‐fold in toxin‐treated cells. FIH‐1 levels also show a 35% decrease in response to toxin. This increase in HIF‐1α protein was suppressed with NOS inhibition. In vivo, serum NO levels increased with toxin exposure; a response which was abrogated in iNOS KO mice.Further study is needed to demonstrate a direct effect of NO on HIF‐1α levels in response to C.diff toxin in vivo. Funding provided by CAG and CIHR.