Australian healthy retail policies in hospital settings - a policy analysis and scoping review of potential impacts on dietary behaviours.

Objectives and importance of study: This study analyses Australian healthy hospital retail policies to identify the similarities and differences in the policies and policy implementation processes. The potential impact of the different policy components on dietary behaviours were examined via a scoping review. STUDY TYPE: Policy analysis and scoping review. METHODS: Healthy retail policy documents and policy implementation guidelines were identified via a grey literature search on Department of Health websites of all Australian jurisdictions. Policy components and policy implementation processes were extracted and analysed for similarities and differences. The potential effectiveness of the different policy components on purchasing and/or dietary behaviour were identified via a scoping review of the academic literature, conducted in March 2023 across seven electronic databases and Google Scholar. The scoping review included studies reporting the impacts of healthy food retail interventions implemented in hospitals. No timeframe restriction was applied for both the grey literature search and the scoping review. RESULTS: All Australian jurisdictions, except Tasmania, have implemented jurisdiction specific healthy retail policies in public hospital settings. There are similarities and difference in the policy components and implementation design across the jurisdictions. Similarities included the policy scope, use of a traffic light system to classify the nutritional healthiness of food and beverages for sale, and the standards used to determine the mix of healthy and unhealthy food availability. These similarities allowed sharing of resources across some jurisdictions. There is limited evaluation of policy impacts on purchase and/or consumption behaviours. Twenty of 27 studies identified via the scoping literature review examined interventions similar to the Australian policies and showed that these policies could result in increased purchase of healthier products among staff and visitors. Key implementation success factors include strong support for the policy from all stakeholders, practical implementation support resources, and impacts on retailer profitability. CONCLUSIONS: The healthy hospital retail policies implemented across Australian jurisdictions could encourage healthier food and beverage purchases among staff and visitors. Evaluation of the policies could facilitate further refinement to enhance effectiveness and translation of learnings to international contexts.

How much is invested in obesity prevention in Australia? An analysis of major research and Federal Government funding, 2013-2022.

Objective and importance of study: Overweight and obesity are the second leading risk factors for death and non-communicable disease in Australia. This study aimed to examine the Australian Federal Government funding landscape for population-level obesity prevention from 2013 to 2022. STUDY TYPE: A retrospective analysis and narrative synthesis of publicly available data on obesity prevention funding from the Federal Government and major federally funded Australian research organisations. METHODS: Searches were conducted of Australian Federal Government Budget documents and funding announcements from the National Health and Medical Research Council (NHMRC), Australian Research Council (ARC) and Medical Research Future Fund (MRFF). Funding allocations targeting obesity prevention, or the prevention of risk factors associated with obesity, were included. These were determined by the presence of keywords related to obesity, unhealthy diet, physical activity and sedentary behaviour. Data were extracted verbatim, coded and narratively synthesised by funding source. RESULTS: From 2013 to 2022, 186 funding allocations for obesity prevention in Australia were identified, totalling approximately A$778 million. The proportion of funding allocated to obesity prevention compared to the total annual budget of each funding source was relatively low: NHMRC = 1.1%; ARC = 0.2%; MRFF = 0.8%; Federal Government = 0.1% (of health budget). Funding for obesity prevention initiatives fluctuated over time. CONCLUSIONS: Findings underscore the need for strategic and ongoing funding allocation to support obesity prevention research, implementation and sustainment of evidence-based obesity prevention initiatives in Australia.

Suppression of TCF4 promotes a ZC3H12A-mediated self-sustaining inflammatory feedback cycle involving IL-17RA/IL-17RE epidermal signaling.

IL-17C is an epithelial cell-derived proinflammatory cytokine whose transcriptional regulation remains unclear. Analysis of the IL17C promoter region identified TCF4 as putative regulator, and siRNA knockdown of TCF4 in human keratinocytes (KCs) increased IL17C. IL-17C stimulation of KCs (along with IL-17A and TNF-α stimulation) decreased TCF4 and increased NFKBIZ and ZC3H12A expression in an IL-17RA/RE-dependent manner, thus creating a feedback loop. ZC3H12A (MCPIP1/Regnase-1), a transcriptional immune-response regulator, also increased following TCF4 siRNA knockdown, and siRNA knockdown of ZC3H12A decreased NFKBIZ, IL1B, IL36G, CCL20, and CXCL1, revealing a proinflammatory role for ZC3H12A. Examination of lesional skin from the KC-Tie2 inflammatory dermatitis mouse model identified decreases in TCF4 protein concomitant with increases in IL-17C and Zc3h12a that reversed following the genetic elimination of Il17c, Il17ra, and Il17re and improvement in the skin phenotype. Conversely, interference with Tcf4 in KC-Tie2 mouse skin increased Il17c and exacerbated the inflammatory skin phenotype. Together, these findings identify a role for TCF4 in the negative regulation of IL-17C, which, alone and with TNF-α and IL-17A, feed back to decrease TCF4 in an IL-17RA/RE-dependent manner. This loop is further amplified by IL-17C-TCF4 autocrine regulation of ZC3H12A and IL-17C regulation of NFKBIZ to promote self-sustaining skin inflammation.

Detection of evoked resonant neural activity in Parkinson's disease.

Objective. This study investigated a machine-learning approach to detect the presence of evoked resonant neural activity (ERNA) recorded during deep brain stimulation (DBS) of the subthalamic nucleus (STN) in people with Parkinson's disease.Approach. Seven binary classifiers were trained to distinguish ERNA from the background neural activity using eight different time-domain signal features.Main results. Nested cross-validation revealed a strong classification performance of 99.1% accuracy, with 99.6% specificity and 98.7% sensitivity to detect ERNA. Using a semi-simulated ERNA dataset, the results show that a signal-to-noise ratio of 15 dB is required to maintain a 90% classifier sensitivity. ERNA detection is feasible with an appropriate combination of signal processing, feature extraction and classifier. Future work should consider reducing the computational complexity for use in real-time applications.Significance. The presence of ERNA can be used to indicate the location of a DBS electrode array during implantation surgery. The confidence score of the detector could be useful for assisting clinicians to adjust the position of the DBS electrode array inside/outside the STN.

Retrospective pharmacogenetic study of psoriasis highlights the role of KLK7 in tumour necrosis factor signalling.

BACKGROUND: Multiple treatment options are available for the management of psoriasis, but clinical response varies among individual patients and no biomarkers are available to facilitate treatment selection for improved patient outcomes. OBJECTIVES: To utilize retrospective data to conduct a pharmacogenetic study to explore the potential genetic pathways associated with drug response in the treatment of psoriasis. METHODS: We conducted a retrospective pharmacogenetic study using self-evaluated treatment response from 1942 genotyped patients with psoriasis. We examined 6 502 658 genetic markers to model their associations with response to six treatment options using linear regression, adjusting for cohort variables and demographic features. We further utilized an integrative approach incorporating epigenomics, transcriptomics and a longitudinal clinical cohort to provide biological implications for the topmost signals associated with drug response. RESULTS: Two novel markers were revealed to be associated with treatment response: rs1991820 (P = 1.30 × 10-6) for anti-tumour necrosis factor (TNF) biologics; and rs62264137 (P = 2.94 × 10-6) for methotrexate, which was also associated with cutaneous mRNA expression levels of two known psoriasis-related genes KLK7 (P = 1.0 × 10-12) and CD200 (P = 5.4 × 10-6). We demonstrated that KLK7 expression was increased in the psoriatic epidermis, as shown by immunohistochemistry, as well as single-cell RNA sequencing, and its responsiveness to anti-TNF treatment was highlighted. By inhibiting the expression of KLK7, we further illustrated that keratinocytes have decreased proinflammatory responses to TNF. CONCLUSIONS: Our study implicates the genetic regulation of cytokine responses in predicting clinical drug response and supports the association between pharmacogenetic loci and anti-TNF response, as shown here for KLK7.

Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis.

The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occur within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2+ fibroblasts in psoriasis contribute to amplification of the immune network through transition to a pro-inflammatory state. The SFRP2+ fibroblast communication network involves production of CCL13, CCL19 and CXCL12, connected by ligand-receptor interactions to other spatially proximate cell types: CCR2+ myeloid cells, CCR7+ LAMP3+ dendritic cells, and CXCR4 expressed on both CD8+ Tc17 cells and keratinocytes, respectively. The SFRP2+ fibroblasts also express cathepsin S, further amplifying inflammatory responses by activating IL-36G in keratinocytes. These data provide an in-depth view of psoriasis pathogenesis, which expands our understanding of the critical cellular participants to include inflammatory fibroblasts and their cellular interactions.

Attitudes and beliefs towards COVID-19 and COVID-19 vaccination among rheumatology patients in a Los Angeles County safety net clinic.

BACKGROUND: The novel Coronavirus disease (COVID-19) pandemic has represented an evolving global threat with high morbidity and mortality. Patients with autoimmune rheumatic diseases and on immune-suppressing medications may be at increased risk to more severe disease, hospitalization, and death. Vaccines are essential to combat the COVID-19 pandemic and curb the spread of infection. Rheumatology patients may be more fearful to receive the vaccine compared to the general population. The Los Angeles County rheumatology patients are primarily Hispanic and represent a unique and possibly particularly vulnerable cohort warranting further exploration into barriers to receive the COVID-19 vaccine. We aimed to explore the willingness of COVID-19 vaccine acceptance among patients with rheumatic disease. METHODS: We conducted a cross-sectional survey to assess the perceptions and barriers to COVID-19 vaccine acceptance in our Los Angeles County rheumatology clinics between July 2021 to September 2021 and received responses from 116 patients. RESULTS: The majority of respondents were female (83.9%), 41-60 years of age (59.8%), Hispanic (89.2%), with high school or lower level of education (68.7%), and had Rheumatoid Arthritis (56.9%). We found most (88.4%) patients received at least one dose of the COVID-19 vaccine. We identified no differences in vaccine acceptance related to age, education, race, and ethnicity. Most respondents agreed that their health condition puts them at high risk of COVID-19 complications. In addition, individuals reported that they valued being engaged by their rheumatologists in discussions of the risk and benefits of the vaccine prior to receiving it. CONCLUSION: We found that the majority of patients were already vaccinated or willing to be vaccinated, at higher levels than general United States population and that a conversation initiated by a rheumatologist can have positive effect on patients' health behaviors related to COVID-19.

YBX1-interacting small RNAs and RUNX2 can be blocked in primary bone cancer using CADD522.

Primary bone cancer (PBC) comprises several subtypes each underpinned by distinctive genetic drivers. This driver diversity produces novel morphological features and clinical behaviour that serendipitously makes PBC an excellent metastasis model. Here, we report that some transfer RNA-derived small RNAs termed tRNA fragments (tRFs) perform as a constitutive tumour suppressor mechanism by blunting a potential pro-metastatic protein-RNA interaction. This mechanism is reduced in PBC progression with a gradual loss of tRNAGlyTCC cleavage into 5' end tRF-GlyTCC when comparing low-grade, intermediate-grade and high-grade patient tumours. We detected recurrent activation of miR-140 leading to upregulated RUNX2 expression in high-grade patient tumours. Both tRF-GlyTCC and RUNX2 share a sequence motif in their 3' ends that matches the YBX1 recognition site known to stabilise pro-metastatic mRNAs. Investigating some aspects of this interaction network, gain- and loss-of-function experiments using small RNA mimics and antisense LNAs, respectively, showed that ectopic tRF-GlyTCC reduced RUNX2 expression and dispersed 3D micromass architecture in vitro. iCLIP sequencing revealed YBX1 physical binding to the 3' UTR of RUNX2. The interaction between YBX1, tRF-GlyTCC and RUNX2 led to the development of the RUNX2 inhibitor CADD522 as a PBC treatment. CADD522 assessment in vitro revealed significant effects on PBC cell behaviour. In xenograft mouse models, CADD522 as a single agent without surgery significantly reduced tumour volume, increased overall and metastasis-free survival and reduced cancer-induced bone disease. Our results provide insight into PBC molecular abnormalities that have led to the identification of new targets and a new therapeutic.

Interprofessional Naloxone Student Training to Manage Suspected Opioid Overdose.

PURPOSE: The study purpose was to examine the effect of interprofessional naloxone training on students' knowledge, confidence, and interprofessional collaboration competency. The overarching goal was to decrease mortality related to opioid overdoses. DESIGN/METHODS: A training session for interprofessional students consisted of a lecture presentation, demonstration, and hands-on practice regarding appropriate administration of naloxone for suspected opioid overdose. A questionnaire elicited baseline and change in knowledge, confidence, and interprofessional collaboration competency scores at pretraining and posttraining. In addition, changes in knowledge and confidence were also measured 3 weeks after the training. Thematic analysis explored training components that students perceived as valuable or needing improvement. RESULTS: Participants (N = 100) were nursing (n = 33), physician assistant (n = 37), and pharmacy (n = 30) students. Pretraining and posttraining comparison demonstrated increased knowledge (P < .001), confidence (P < .001), and collaboration scores (P < .001). At 3 weeks, knowledge and confidence remained higher than pretraining (P < .001). Knowledge was trending downward compared with posttraining (P = .09). Thematic analysis identified 4 themes: (a) indications for administration of different naloxone types, (b) learning modalities, (c) knowledge application, and (d) improvements. CONCLUSIONS: An interprofessional naloxone administration training resulted in increased knowledge, confidence, and interprofessional teamwork. Educators can adapt this training for a variety of future or current healthcare professionals to improve immediate intervention and outcomes in suspected opioid overdoses.

IL-17-induced dimerization of IL-17RA drives the formation of the IL-17 signalosome to potentiate signaling.

Signaling through innate immune receptors such as the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily proceeds via the assembly of large membrane-proximal complexes or "signalosomes." Although structurally distinct, the IL-17 receptor family triggers cellular responses that are typical of innate immune receptors. The IL-17RA receptor subunit is shared by several members of the IL-17 family. Using a combination of crystallographic, biophysical, and mutational studies, we show that IL-17A, IL-17F, and IL-17A/F induce IL-17RA dimerization. X-ray analysis of the heteromeric IL-17A complex with the extracellular domains of the IL-17RA and IL-17RC receptors reveals that cytokine-induced IL-17RA dimerization leads to the formation of a 2:2:2 hexameric signaling assembly. Furthermore, we demonstrate that the formation of the IL-17 signalosome potentiates IL-17-induced IL-36γ and CXCL1 mRNA expression in human keratinocytes, compared with a dimerization-defective IL-17RA variant.

Remote Virtual Simulation With Prelicensure Nursing Students During Rapid Course Transition.

ABSTRACT: The advent of COVID-19 required educational programs to rapidly transition courses to the remote environment. A postpartum hemorrhage simulation used within a traditional prelicensure bachelor of science in nursing program was rapidly transitioned to the remote virtual format to meet required social distancing guidelines. This quasi-experimental study examined student knowledge before and after participation in a remote virtual simulation (RVS) with a postanalysis of student confidence and satisfaction. RVS can increase student knowledge and provide adequate student satisfaction. However, hands-on learning appears to result in higher student confidence and satisfaction compared to RVS.

Challenges of caring for homeless patients with inflammatory arthritis: 12-month follow-up observations and identification of certain barriers to care.

Homelessness is a public health crisis and there is a paucity of information about patients with rheumatic disease experiencing homelessness. We sought to develop approaches to improve care for this unique patient population. We previously reported observations on 17 homeless patients with inflammatory arthritis (15 rheumatoid arthritis (RA), 2 psoriatic arthritis (PsA)). We obtained follow-up information from our original 17 patients and compared this to data summarized and published about them from 12 months previously. We also created and administered a 100-question needs assessment survey. Follow-up 12-month clinical information was available from 13/17 homeless and 13/17 non-homeless controls. Homeless patients remained less well with more disease than non-homeless patients-poorer access to clinic appointments (80% vs 91%, p < 0.05), more emergency services use (20 vs 5 ED visits), less DMARDs use (43% vs 100%, p < 0.01), and more steroid use (29% vs 0%, p < 0.01). Homeless patients also had higher inflammatory markers than non-homeless patients (ESR 32 vs 26 mm/h and CRP 17 vs 5 mg/L), although these findings were not statistically significantly different. Seventy-eight percent of homeless patients were stable, 14% improved, and 7% worse; 21% had stable controlled and 57% stable active disease vs 62% and 0% of non-homeless (p < 0.01). Among the homeless, 6 (4 RA, 2 PsA) completed the survey, 2 declined, and 9 could not be reached. All 6 had found housing although all still had housing insecurity; 4 (67%) were homeless in the past. Three out of six (50%) obtained housing from social assistance during hospitalization following disease exacerbation while homeless. The average monthly income was $873. 5/6 (83.3%), were unable to work due to health, and were in considerable pain that adversely impacted their physical and mental health and ability to perform ADLs. Their perceived "greatest need" included dental care, physical therapy, knee surgery, employment, socialization secondary to isolation, and stable housing. Our understanding of the unique challenges of patients with rheumatic disease experiencing homelessness is improved, but not complete. Strengthened collaboration between street medicine providers and rheumatologists is necessary to improve care for homeless patients, especially given poorer outcomes compared with non-homeless counterparts. Key Points • We report 12-month follow-up information from our original 17 homeless patients with inflammatory arthritis (related in this journal in 2021) and their responses to an extensive needs assessment survey designed to identify barriers to care. • Homeless patients with inflammatory arthritis continued to have worse disease outcomes, use more corticosteroids and less DMARDs, and be seen less often in rheumatology clinics and more frequently in emergency departments than their non-homeless counterparts. • Survey data indicated that social assistance during hospitalization was a key area where healthcare providers could intervene to provide housing security for homeless patients and improve outcomes. Patients perceived "greatest needs" went beyond housing and rheumatological care and critically included access to social/specialty services. • Street medicine is the direct delivery of healthcare to people experiencing homelessness wherever they reside. Our observations, obtained in collaboration with street medicine colleagues, suggest important and salutary opportunities for this partnership to improve care for these particular patients.

Dissecting cellulitis of the scalp associated with peripheral and axial spondyloarthritis: report of a case and review of the literature.

Dissecting cellulitis of the scalp (DCS) is a rare, primary neutrophilic cicatricial alopecia of unknown etiology. The disease follows a chronic, relapsing, and remitting course which may ultimately lead to scar formation and alopecia. The association of seronegative peripheral and/or axial spondyloarthritis in patients with hidradenitis suppurativa (HS) and acne conglobata (AC) is well established. However, the occurrence of spondyloarthropathy in patients with either isolated or combined DCS is relatively rare and therefore underrecognized by clinicians. We report a patient with DCS with inflammatory peripheral arthritis and asymptomatic radiographic sacroiliitis. Using PubMed, Ovid, and Google scholar, we searched for case reports of inflammatory arthritis in HS, AC, and DCS in the English literature from 1982 to present. We identified 12 patients with DCS who had associated spondyloarthropathy with adequate clinical details for a systematic analysis. We outline key clinical features, radiographic findings, and treatment utilized for these patients. Seronegative axial and peripheral spondyloarthritis may occur in the setting of isolated DCS as well with concomitant HS and AC. The inflammatory arthritis often develops during acute flares of the cutaneous disease. Choosing optimal drug therapy may be challenging. Current options include anti-TNF-α medications, which have been reported to be effective for both the cutaneous lesions and the associated spondyloarthritis. The complex pathophysiology of the conditions that comprise the follicular occlusion triad warrants further research into the potential role of additional biologic agents.

Skin codelivery of contact sensitizers and neurokinin-1 receptor antagonists integrated in microneedle arrays suppresses allergic contact dermatitis.

BACKGROUND: Allergic contact dermatitis (CD) is a chronic inflammatory skin disease caused by type 1 biased adaptive immunity for which there is an unmet need for antigen (Ag)-specific immunotherapies. Exposure to skin sensitizers stimulates secretion of the proinflammatory neuropeptides substance P and hemokinin 1, which signal via the neurokinin-1 receptor (NK1R) to promote the innate and adaptive immune responses of CD. Accordingly, mice lacking the NK1R develop impaired CD. Nonetheless, the role and therapeutic opportunities of targeting the NK1R in CD remain to be elucidated. OBJECTIVE: We sought to develop an Ag-specific immunosuppressive approach to treat CD by skin codelivery of hapten and NK1R antagonists integrated in dissolvable microneedle arrays (MNA). METHODS: In vivo mouse models of contact hypersensitivity and ex vivo models of human skin were used to delineate the effects and mechanisms of NK1R signaling and the immunosuppressive effects of the contact sensitizer NK1R antagonist MNA in CD. RESULTS: We demonstrated in mice that CD requires NK1R signaling by substance P and hemokinin 1. Specific deletion of the NK1R in keratinocytes and dendritic cells, but not in mast cells, prevented CD. Skin codelivery of hapten or Ag MNA inhibited neuropeptide-mediated skin inflammation in mouse and human skin, promoted deletion of Ag-specific effector T cells, and increased regulatory T cells, which prevented CD onset and relapses locally and systemically in an Ag-specific manner. CONCLUSIONS: Immunoregulation by engineering localized skin neuroimmune networks can be used to treat cutaneous diseases that like CD are caused by type 1 immunity.

Motherhood Together: Effects of an Adapted Prenatal Curriculum on Mother and Infant Outcomes.

Background: Research shows that pregnant women experiencing housing insecurity are more likely to face barriers to prenatal care that can lead to negative health outcomes for both mother and infant. Previous studies have also shown that prenatal education programs provide pregnant mothers with the knowledge and resources that increase the likelihood of positive health outcomes. An interprofessional healthcare team in Central Arkansas modified an existing prenatal education program to create Motherhood Together, a program specifically tailored for pregnant women facing house insecurity. Methods: The purpose of this initial evaluation of the Motherhood Together program was to identify the feasibility of the program and preliminary outcomes. This evaluation sought to better understand the demographic composition of the population participating in Motherhood Together (n = 19), as well as the effect of the program on infant outcomes, health literacy, and maternal self-care. The overall participant experience and feedback to enhance the program was also obtained. Results: The average age of participants was 24.6 years old and 77.8% reported high school as their highest level of educational attainment. The majority of participants identified as Black/African American (77.8%) and 22.2% identified as White. Participants scored the experience of Motherhood Together sessions positively with an overall score of 3.75/4.00. Participants reported an average gestational age at delivery being 36.9 weeks with 25% reporting preterm births following the program. Multivitamins were reported as being taken by 100% of participants following participation. Conclusion: Tailoring the pre-existing educational program to create the Motherhood Together program was clearly feasible and continues to serve as a critical resource for improving equity in infant and maternal outcomes in central Arkansas.

An efficient miRNA knockout approach using CRISPR-Cas9 in Xenopus.

In recent years CRISPR-Cas9 knockouts (KO) have become increasingly ultilised to study gene function. MicroRNAs (miRNAs) are short non-coding RNAs, 20-22 nucleotides long, which affect gene expression through post-transcriptional repression. We previously identified miRNAs-196a and -219 as implicated in the development of Xenopus neural crest (NC). The NC is a multipotent stem-cell population, specified during early neurulation. Following EMT, NC cells migrate to various points in the developing embryo where they give rise to a number of tissues including parts of the peripheral nervous system, pigment cells and craniofacial skeleton. Dysregulation of NC development results in many diseases grouped under the term neurocristopathies. As miRNAs are so small, it is difficult to design CRISPR sgRNAs that reproducibly lead to a KO. We have therefore designed a novel approach using two guide RNAs to effectively 'drop out' a miRNA. We have knocked out miR-196a and miR-219 and compared the results to morpholino knockdowns (KD) of the same miRNAs. Validation of efficient CRISPR miRNA KO and phenotype analysis included use of whole-mount in situ hybridization of key NC and neural plate border markers such as Pax3, Xhe2, Sox10 and Snail2, q-RT-PCR and Sanger sequencing. To show specificity we have also rescued the knockout phenotype using miRNA mimics. MiRNA-219 and miR-196a KO's both show loss of NC, altered neural plate and hatching gland phenotypes. Tadpoles show gross craniofacial and pigment phenotypes.

Mouse Models of Psoriasis: A Comprehensive Review.

The use of preclinical animal models of psoriasis has significantly increased over the last three decades, with each model having unique strengths and limitations. Some models translate better to human disease, and many have provided unique insight into psoriasis disease pathogenesis. In this comprehensive review, we present a comparative description and discussion of genetic mouse models, xenograft approaches, and elicited methods using cytokine injections into and topical imiquimod onto mice. We provide an inclusive list of genetically modified animals that have had imiquimod applied to or cytokines injected into their skin and describe the outcomes of these manipulations. This review will provide a valuable resource for those interested in working with psoriasis animal models.

Cardiac Manifestations of Systemic Lupus Erythematous: An Overview of the Incidence, Risk Factors, Diagnostic Criteria, Pathophysiology and Treatment Options.

Systemic lupus erythematosus (SLE) is a complex connective tissue disease that can potentially affect every organ of the human body. In some cases, SLE may present with diverse cardiac manifestations including pericarditis, myocarditis, valvular disease, atherosclerosis, thrombosis, and arrhythmias. Heart disease in SLE is associated with increased morbidity and mortality. It is unclear whether traditional treatments for coronary artery disease significantly impact mortality in this population. Current therapeutic agents for SLE include glucocorticoids, hydroxychloroquine, mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, and B cell-directed therapies. This article will provide a comprehensive review and update on this important disease state.

IFN-κ Is a Rheostat for Development of Psoriasiform Inflammation.

Psoriasis is a common, inflammatory autoimmune skin disease. Early detection of an IFN-1 signature occurs in many psoriasis lesions, but the source of IFN production remains debated. IFN-κ is an important source of IFN-1 production in the epidermis. We identified a correlation between IFN-regulated and psoriasis-associated genes in human lesional skin. We thus wanted to explore the effects of IFN-κ in psoriasis using the well-characterized imiquimod psoriasis model. Three mouse strains aged 10 weeks were used: wild-type C57Bl/6, C57Bl/6 that overexpress Ifnk in the epidermis (i.e., transgenic), and total body Ifnk-/- (i.e., knockout) strain. Psoriasis was induced by topical application of imiquimod on both ears for 8 consecutive days. Notably, the severity of skin lesions and inflammatory cell infiltration was more significantly increased in transgenic than in wild-type than in knockout mice. Gene expression analysis identified greater upregulation of Mxa, Il1b, Tnfa, Il6, Il12, Il23, Il17, and Ifng in transgenic compared to wild-type compared to knockout mice after imiquimod treatment. Furthermore, imiquimod increased CD8+ and CD4+ T-cell infiltration more in transgenic than in wild-type than in knockout mice. In summary, we identified IFN-κ as a rheostat for initiation of psoriasiform inflammation. This suggests that targeting IFN-1s early in the disease may be an effective way of controlling psoriatic inflammation.