Assessment of the genetic basis of rosacea by genome-wide association study.

Rosacea is a common, chronic skin disease that is currently incurable. Although environmental factors influence rosacea, the genetic basis of rosacea is not established. In this genome-wide association study, a discovery group of 22,952 individuals (2,618 rosacea cases and 20,334 controls) was analyzed, leading to identification of two significant single-nucleotide polymorphisms (SNPs) associated with rosacea, one of which replicated in a new group of 29,481 individuals (3,205 rosacea cases and 26,262 controls). The confirmed SNP, rs763035 (P=8.0 × 10(-11) discovery group; P=0.00031 replication group), is intergenic between HLA-DRA and BTNL2. Exploratory immunohistochemical analysis of HLA-DRA and BTNL2 expression in papulopustular rosacea lesions from six individuals, including one with the rs763035 variant, revealed staining in the perifollicular inflammatory infiltrate of rosacea for both proteins. In addition, three HLA alleles, all MHC class II proteins, were significantly associated with rosacea in the discovery group and confirmed in the replication group: HLA-DRB1*03:01 (P=1.0 × 10(-8) discovery group; P=4.4 × 10(-6) replication group), HLA-DQB1*02:01 (P=1.3 × 10(-8) discovery group; P=7.2 × 10(-6) replication group), and HLA-DQA1*05:01 (P=1.4 × 10(-8) discovery group; P=7.6 × 10(-6) replication group). Collectively, the gene variants identified in this study support the concept of a genetic component for rosacea, and provide candidate targets for future studies to better understand and treat rosacea

Treatment of Acne Vulgaris With Salicylic Acid Chemical Peel and Pulsed Dye Laser: A Split Face, Rater-Blinded, Randomized Controlled Trial

Introduction: Pulsed dye laser (PDL) has been used to treat acne lesions and scar erythema by interrupting superficial vasculature. Salicylic acid chemical peels are employed chiefly due to their lipophilic, comedolytic, and anti-inflammatory properties. Although studies have looked at peels and laser therapy independently in acne management, we examined these treatments in combination. Our primary objective was to evaluate the safety and efficacy of concurrent use of salicylic acid peels with PDL versus salicylic acid peels alone in the treatment of moderate to severe acne vulgaris.Methods: Adult patients with moderate to severe acne were included. Subjects received a total of 3 treatments at 3-week intervals. Per randomized split-face treatment, at week 0, one half of the subject’s face was treated with PDL (595 nm) followed by whole face application of a 30% salicylic acid peel. At weeks 3 and 6, the treatments were repeated. At 0 and 9 weeks, patients were assessed with the Global Evaluation Acne (GEA) scale and Dermatology Life Quality Index (DLQI) questionnaire.Results: Nineteen subjects were enrolled, and 18 completed the study. Significant improvement in acne was seen in both the combined (laser and peel) and chemical peel alone treatment arms (P < .0005 and P = .001). Using the GEA scale score, compared to week 0, the mean difference in acne improvement at week 9 was -1.61 in the combination therapy group versus -1.11 in the peel only group. Based on the GEA scale scoring, a statistically significant greater difference in acne improvement was seen, from week 0 to week 9, in the combination treatment group compared with the peel only group (P = .003).Conclusion: While acne subjects had significant benefit from the salicylic acid peel alone, they experienced greater significant benefit from PDL treatment used in conjunction with salicylic acid peels. The adjunctive utilization of PDL to salicylic acid peel therapy can lead to better outcomes in acne management

Temporal Evolution of Risk Behavior in a Disease Spread Simulation

Human behavior is a dynamic process that evolves with experience. Understanding the evolution of individual's risk propensity is critical to design public health interventions to propitiate the adoption of better biosecurity protocols and thus, prevent the transmission of an infectious disease. Using an experimental game that simulates the spread of a disease in a network of porcine farms, we measure how learning from experience affects the risk aversion of over $1000$ players. We used a fully automated approach to segment the players into 4 categories based on the temporal trends of their game plays and compare the outcomes of their overall game performance. We found that the risk tolerant group is $50\%$ more likely to incur an infection than the risk averse one. We also find that while all individuals decrease the amount of time it takes to make decisions as they become more experienced at the game, we find a group of players with constant decision strategies who rapidly decrease their time to make a decision and a second context-aware decision group that contemplates longer before decisions while presumably performing a real-time risk assessment. The behavioral strategies employed by players in this simulated setting could be used in the future as an early warning signal to identify undesirable biosecurity-related risk aversion preferences, or changes in behavior, which may allow for targeted interventions to help mitigate them.Comment: 12 pages, 1 table, 7 figure

Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus

New World arenaviruses are rodent-transmitted viruses and include a number of pathogens that are responsible for causing severe human disease. This includes Junín virus (JUNV), which is the causative agent of Argentine hemorrhagic fever. The wild nature and mobility of the rodent reservoir host makes it difficult to control the disease, and currently passive immunization with high-titer neutralizing antibody-containing plasma from convalescent patients is the only specific therapy. However, dwindling supplies of naturally available convalescent plasma, and challenges in developing similar resources for other closely related viruses, have made the development of alternative antibody-based therapeutic approaches of critical importance. In this study, we sought to induce a neutralizing antibody response in rabbits against the receptor-binding subunit of the viral glycoprotein, GP1, and the specific peptide sequences in GP1 involved in cellular receptor contacts. While these specific receptor-interacting peptides did not efficiently induce the production of neutralizing antibodies when delivered as a particulate antigen (as part of hepatitis B virus core-like particles), we showed that recombinant JUNV GP1 purified from transfected mammalian cells induced virus-neutralizing antibodies at high titers in rabbits. Further, neutralization was observed across a range of unrelated JUNV strains, a feature that is critical for effectiveness in the field. These results underscore the potential of GP1 alone to induce a potent neutralizing antibody response and highlight the importance of epitope presentation. In addition, effective virus neutralization by rabbit antibodies supports the potential applicability of this species for the future development of immunotherapeutics (e.g., based on humanized monoclonal antibodies). Such information can be applied in the design of vaccines and immunogens for both prevention and specific therapies against this and likely also other closely related pathogenic New World arenaviruses.Fil: Roman Sosa, Gleyder. Ulm University Hospital; AlemaniaFil: Leske, Anne. Friedrich-Loeffler-Institut; AlemaniaFil: Ficht, Xenia. Ulm University Hospital; AlemaniaFil: Dau, Tung Huy. Friedrich-Loeffler-Institut; AlemaniaFil: Holzerland, Julia. Friedrich-Loeffler-Institut; AlemaniaFil: Hoenen, Thomas. Friedrich-Loeffler-Institut; AlemaniaFil: Beer, Martin. Friedrich-Loeffler-Institut; AlemaniaFil: Kammerer, Robert. Friedrich-Loeffler-Institut; AlemaniaFil: Schirmbeck, Reinhold. Friedrich-Loeffler-Institut; AlemaniaFil: Rey, Felix A.. Friedrich-Loeffler-Institut; AlemaniaFil: Cordo, Sandra Myriam. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Groseth, Allison. Friedrich-Loeffler-Institut; Alemani

Updated standardized definitions for efficacy endpoints in adjuvant breast cancer clinical trials: STEEP Version 2.0

Purpose The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed.Methods We conducted systematic searches of ClinicalTrials.gov for adjuvant systemic and local-regional therapy trials for breast cancer to investigate if the primary end points reported met STEEP criteria. On the basis of common STEEP deviations, we performed a series of simulations to evaluate the effect of excluding non-breast cancer deaths and new nonbreast primary cancers from the invasive disease-free survival end point.Results Among 11 phase III breast cancer trials with primary efficacy end points, three had primary end points that followed STEEP criteria, four used STEEP definitions but not the corresponding end point names, and four used end points that were not included in the original STEEP manuscript. Simulation modeling demonstrated that inclusion of second nonbreast primary cancer can increase the probability of incorrect inferences, can decrease power to detect clinically relevant efficacy effects, and may mask differences in recurrence rates, especially when recurrence rates are low.Conclusion We recommend an additional end point, invasive breast cancer-free survival, which includes all invasive disease-free survival events except second nonbreast primary cancers. This end point should be considered for trials in which the toxicities of agents are well-known and where the risk of second primary cancer is small. Additionally, we provide end point recommendations for local therapy trials, low-risk populations, noninferiority trials, and trials incorporating patient-reported outcomes