Dengue NS1 antibodies are associated with clearance of viral NS1.

BACKGROUND: Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. METHODS: Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. RESULTS: Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. DISCUSSION: The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

International time trends and differences in topical actinic keratosis therapy utilization.

Background: Actinic Keratoses (AK) are precancerous lesions that can lead to Squamous Cell Carcinoma. International differences in the utilization of topical medications to treat AK are not well described. Objectives: To describe international differences in topical AK medication utilization, including associations of countries' economic status with AK medication utilization. Methods: We used IQVIA MIDAS pharmaceutical sales data for 65 countries (42 high-income, 24 middle-income) from April 2011 to December 2021. We calculated each country's quarterly utilization of medications in grams per 1000 population. We used univariable linear regression to assess the association between country economic status and AK medication utilization. Results: High-income countries used 15.37 more grams per 1000 population of 5-fluorouracil (95% CI: 9.68, 21.05), 4.64 more grams per 1000 population of imiquimod (95% CI: 3.45, 5.83), and 0.32 more grams per 1000 population of ingenol mebutate (95% CI: 0.05, 0.60). Limitations: Missing medication utilization data for some countries. Conclusion: High-income countries use more topical AK therapies than middle-income countries.

Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.

Novel Insights into the Cardioprotective Effects of the Peptides of the Counter-Regulatory Renin-Angiotensin System.

Currently, cardiovascular diseases are a major contributor to morbidity and mortality worldwide, having a significant negative impact on both the economy and public health. The renin-angiotensin system contributes to a high spectrum of cardiovascular disorders and is essential for maintaining normal cardiovascular homeostasis. Overactivation of the classical renin-angiotensin system is one of the most important pathophysiological mechanisms in the progression of cardiovascular diseases. The counter-regulatory renin-angiotensin system is an alternate pathway which favors the synthesis of different peptides, including Angiotensin-(1-7), Angiotensin-(1-9), and Alamandine. These peptides, via the angiotensin type 2 receptor (AT2R), MasR, and MrgD, initiate multiple downstream signaling pathways that culminate in the activation of various cardioprotective mechanisms, such as decreased cardiac fibrosis, decreased myocardial hypertrophy, vasodilation, decreased blood pressure, natriuresis, and nitric oxide synthesis. These cardioprotective effects position them as therapeutic alternatives for reducing the progression of cardiovascular diseases. This review aims to show the latest findings on the cardioprotective effects of the main peptides of the counter-regulatory renin-angiotensin system.

Association between psoriasis and cardiometabolic comorbidities in a racially and ethnically diverse low-income primary care population.

Psoriasis is associated with cardiometabolic comorbidities, including obesity, diabetes, hyperlipidaemia and hypertension. Many studies that established these associations originated from primarily White and/or relatively affluent populations. To evaluate whether there is a differential risk for cardiometabolic comorbidities in racial/ethnic minorities, we performed a cross-sectional analysis comparing cardiometabolic comorbidities between those with and without psoriasis in a racially and ethnically diverse population of 56 987 low-income patients, stratified by race/ethnicity, and assessed whether race/ethnicity acts as an effect modifier for cardiometabolic comorbidities. We found that psoriasis was statistically significantly associated with obesity, diabetes, hyperlipidaemia and hypertension. The association of psoriasis with comorbidities did not differ significantly by race/ethnicity; thus, we did not find evidence of effect modification. However, our diverse, low-income population had an extremely high baseline prevalence of cardiometabolic comorbidities compared with previous populations studied. Our results suggest education and intervention regarding modifiable risk factors are particularly important among vulnerable populations.

Patient Perspectives on Social Risk Screening and Documentation in a Dermatology Clinic.

Importance: Providing person-centered dermatologic care includes consideration of social risk factors, such as housing instability and unreliable transportation, that may affect clinical management. Patients' perspectives on social risk screening and documentation in dermatology clinics have not yet been evaluated. Objective: To understand patients' perspectives on social risk screening and documentation in a dermatology clinic. Design, Setting, and Participants: This mixed-methods study used a survey and semistructured interviews and was conducted in a general dermatology clinic at a large urban public hospital. Patients at the clinic were eligible to complete the survey if they were 18 years or older; able to speak and read English, Spanish, or Cantonese; and comfortable using a computer tablet. Survey participants who preferred to use English were eligible for interviews. The survey included social risk screening questions, measures of acceptability, and questions on social risk factors associated with patient acceptability. Semistructured interviews were conducted to explore attitudes and beliefs about social risk screening and documentation. Survey and interview findings were integrated during data analysis through development of themes and joint display. Data were analyzed from December 2021 to April 2023. Main Outcomes and Measures: There were 2 outcome measures of acceptability: appropriateness of screening in a dermatology clinic and comfort with documentation of social risk in the electronic health record (EHR). Results: A total of 135 participants (including 73 males [54.1%]) answered both measures of acceptability in the survey. Of these participants, 116 (85.9%) reported that social risk screening in their dermatology clinic was very or somewhat appropriate and 85 (63.0%) reported being completely or somewhat comfortable with having their social risks documented in the EHR. Themes that were developed from surveys and interviews were the (1) role of interpersonal factors in willingness to disclose social risks, (2) implications of institutional trust for willingness to disclose and comfort with documentation, and (3) relevance of screening in a dermatology clinic. Conclusions and Relevance: Results of this study showed that most participants found social risk screening to be appropriate in a dermatology clinic, although a smaller proportion of participants were comfortable with EHR documentation of their social risks. Optimizing patients' trust in their physicians and the medical system, while addressing privacy and discrimination concerns, may help facilitate disclosure of social risks.

Effects of Metformin on Ischemia/Reperfusion Injury: New Evidence and Mechanisms.

The search for new drugs with the potential to ensure therapeutic success in the treatment of cardiovascular diseases has become an essential pathway to follow for health organizations and committees around the world. In June 2021, the World Health Organization listed cardiovascular diseases as one of the main causes of death worldwide, representing 32% of them. The most common is coronary artery disease, which causes the death of cardiomyocytes, the cells responsible for cardiac contractility, through ischemia and subsequent reperfusion, which leads to heart failure in the medium and short term. Metformin is one of the most-used drugs for the control of diabetes, which has shown effects beyond the control of hyperglycemia. Some of these effects are mediated by the regulation of cellular energy metabolism, inhibiting apoptosis, reduction of cell death through regulation of autophagy and reduction of mitochondrial dysfunction with further reduction of oxidative stress. This suggests that metformin may attenuate left ventricular dysfunction induced by myocardial ischemia; preclinical and clinical trials have shown promising results, particularly in the setting of acute myocardial infarction. This is a review of the molecular and pharmacological mechanisms of the cardioprotective effects of metformin during myocardial ischemia-reperfusion injury.

Effects of rIL2/anti-IL2 antibody complex on chikungunya virus-induced chronic arthritis in a mouse model.

Chikungunya virus (CHIKV) is characterized by disabling joint pain that can cause persistent arthritis in approximately one-fourth of patients. Currently, no standard treatments are available for chronic CHIKV arthritis. Our preliminary data suggest that decreases in interleukin-2 (IL2) levels and regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Low-dose IL2-based therapies for autoimmune diseases have been shown to up-regulate Tregs, and complexing IL2 with anti-IL2 antibodies can prolong the half-life of IL2. A mouse model for post-CHIKV arthritis was used to test the effects of recombinant IL2 (rIL2), an anti-IL2 monoclonal antibody (mAb), and the complex on tarsal joint inflammation, peripheral IL2 levels, Tregs, CD4 + effector T cells (Teff), and histological disease scoring. The complex treatment resulted in the highest levels of IL2 and Tregs, but also increased Teffs, and therefore did not significantly reduce inflammation or disease scores. However, the antibody group, which had moderately increased levels of IL2 and activated Tregs, resulted in a decreased average disease score. These results suggest the rIL2/anti-IL2 complex stimulates both Tregs and Teffs in post-CHIKV arthritis, while the anti-IL2 mAb increases IL2 availability enough to shift the immune environment towards a tolerogenic one.

The Social Determinants of Health and Their Impact on Dermatologic Health, Part 1: The Social Determinants of Health and Their Dermatologic Implications.

The social determinants of health (SDoH) have significant influences on health and lead to health disparities in a variety of complex and intersecting ways. They are the nonmedical factors that must be addressed to improve health outcomes and achieve greater health equity. They are shaped by the structural determinants of health and impact individual socioeconomic status as well as the health of entire communities. Part 1 of this 2-part review aims to shed light on how the SDoH impact health and their specific implications on dermatologic health disparities.

The Social Determinants of Health and Their Impact on Dermatologic Health, Part 2: Taking Action to Address the Social Determinants of Health.

The social determinants of health (SDoH) impact health and lead to health disparities in a variety of complex and intersecting ways. They are the nonmedical factors that must be addressed to improve health outcomes and achieve greater health equity. The SDoH contribute to dermatologic health disparities and decreasing these disparities requires multilevel action. Part 2 of this 2-part review offers a framework that dermatologists can use to help address the SDoH both at the point of care and in the health care system at large.

Effects of IL2/anti-IL2 antibody complex on chikungunya virus-induced arthritis in a mouse model.

Chikungunya virus (CHIKV) is characterized by disabling joint pain that can cause persistent arthritis in approximately one-fourth of patients. Currently, no standard treatments are available for chronic CHIKV arthritis. Our preliminary data suggest that decreases in interleukin-2 (IL2) levels and regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Low-dose IL2-based therapies for autoimmune diseases have been shown to up-regulate Tregs, and complexing IL2 with anti-IL2 antibodies can prolong the half-life of IL2. A mouse model for post-CHIKV arthritis was used to test the effects of IL-2, an anti-IL2 monoclonal antibody (mAb), and the complex on tarsal joint inflammation, peripheral IL2 levels, Tregs, effector (Teff) T cells, and histological disease scoring. The complex treatment resulted in the highest levels of IL2 and Tregs, but also increased Teffs, and therefore did not significantly reduce inflammation or disease scores. However, the antibody group, which had moderately increased levels of IL2 and activated Tregs, resulted in a decreased average disease score. These results suggest the IL2/anti-IL2 complex stimulates both Tregs and Teffs in post-CHIKV arthritis, while the anti-IL2 mAb increases IL2 availability enough to shift the immune environment towards a tolerogenic one.

Regulatory T-cells and GARP expression are decreased in exercise-associated chikungunya viral arthritis flares.

Objective: Chikungunya virus (CHIKV) causes persistent arthritis, and our prior study showed that approximately one third of CHIKV arthritis patients had exacerbated arthritis associated with exercise. The underlying mechanism of exercise-associated chikungunya arthritis flare (EACAF) is unknown, and this analysis aimed to examine the regulatory T-cell immune response related to CHIKV arthritis flares. Methods: In our study, 124 Colombian patients with a history of CHIKV infection four years prior were enrolled and 113 cases with serologically confirmed CHIKV IgG were used in this analysis. Patient information was gathered via questionnaires, and blood samples were taken to identify total live peripheral blood mononuclear cells, CD4+ cells, T regulatory cells, and their immune markers. We compared outcomes in CHIKV patients with (n = 38) vs. without (n = 75) EACAF using t-tests to assess means and the Fisher's exact test, chi-squared to evaluate categorical variables, and Kruskal-Wallis tests in the setting of skewed distributions (SAS 9.3). Results: 33.6% of CHIKV cases reported worsening arthritis with exercise. EACAF patients reported higher global assessments of arthritis disease ranging from 0-100 (71.2 ± 19.7 vs. 59.9 ± 28.0, p=0.03). EACAF patients had lower ratios of T regulatory (Treg)/CD4+ T-cells (1.95 ± 0.73 vs. 2.4 ± 1.29, p = 0.04) and lower percentage of GARP (glycoprotein-A repetitions predominant) expression per Treg (0.13 ± 0.0.33 vs. 0.16 ± 0.24 p= 0.020). Conclusion: These findings suggest relative decreases in GARP expression may indicate a decreased level of immune suppression. Treg populations in patients with CHIKV arthritis may contribute to arthritis flares during exercise, though current research is conflicting.

Evaluation of a pilot forensic dermatology curriculum in the USA.

Physician participation in asylum medicine through forensic medical evaluations increases the likelihood that asylum seekers are granted legal status. Based on a review of existing literature and input from content experts, we designed and implemented a forensic dermatology curriculum for dermatology residents at University of California, San Francisco. Our pilot curriculum led to improvements in learners' attitudes regarding physician participation in asylum medicine and their confidence in describing skin findings of torture or abuse.