Therapeutic potential of mesenchymal stem cell-derived exosomes for allergic airway inflammation.

Due to their immunomodulatory capacities, mesenchymal stem cells (MSCs) have been extensively used as therapeutic approaches in cell-based therapy for various inflammatory diseases. Several lines of studies have shown that the most beneficial effects of MSCs are associated with MSC-derived exosomes. Exosomes are nanoscale extracellular vesicles that contain important biomolecules such as RNA, microRNAs (miRNAs), DNA, growth factors, enzymes, chemokines, and cytokines that regulate immune cell functions and parenchymal cell survival. Recently, exosomes, especially MSC-derived exosomes, have been shown to have protective effects in allergic airway inflammation. This review focused on the immune-regulatory potential of MSC-derived exosomes as nanoscale delivery systems in the treatment of allergic airway inflammation.

An Interactive Modeling Tool for Projecting the Health and Direct Medical Cost Impact of Changes in the Sexually Transmitted Diseases Prevention Program Budgets.

CONTEXT: Estimating the return on investment for public health services, tailored to the state level, is critical for demonstrating their value and making resource allocation decisions. However, many health departments have limited staff capacity and expertise to conduct economic analyses in-house. PROGRAM: We developed a user-friendly, interactive Excel-based spreadsheet model that health departments can use to estimate the impact of increases or decreases in sexually transmitted infection (STI) prevention funding on the incidence and direct medical costs of chlamydia, gonorrhea, syphilis, and STI-attributable HIV infections. Users tailor results to their jurisdictions by entering the size of their population served; the number of annual STI diagnoses; their prior annual funding amount; and their anticipated new funding amount. The interface was developed using human-centered design principles, including focus groups with 15 model users to collect feedback on an earlier model version and a usability study on the prototype with 6 model users to finalize the interface. IMPLEMENTATION: The STI Prevention Allocation Consequences Estimator ("SPACE Monkey 2.0") model will be publicly available as a free downloadable tool. EVALUATION: In the usability testing of the prototype, participants provided overall positive feedback. They appreciated the clear interpretations, outcomes expressed as direct medical costs, functionalities to interact with the output and copy charts into external applications, visualization designs, and accessible information about the model's assumptions and limitations. Participants provided positive responses to a 10-item usability evaluation survey regarding their experiences with the prototype. DISCUSSION: Modeling tools that synthesize literature-based estimates and are developed with human-centered design principles have the potential to make evidence-based estimates of budget changes widely accessible to health departments.

Evaluating the usability of public health data dashboards as information sources for professionals and the public: Findings from a case study with domain experts.

BACKGROUND: Recently, public health data dashboards have gained popularity as trusted, up-to-date sources of health information. However, their usability and usefulness may be limited. OBJECTIVE: To identify the requirements of usable public health data dashboards through a case study with domain experts. METHODS: Paired-user virtual data collection sessions were conducted with 20 experts in three steps: (1) a monitored use of an existing dashboard to complete tasks and discuss the usability problems, (2) a survey rating user experience, and (3) an interview regarding the users and use cases. Data analysis included quantitative analysis of the survey findings and thematic analysis of the audio transcripts. RESULTS: Analyses yielded several findings: (1) familiar charts with clear legends and labels should be used to focus users' attention on the content; (2) charts should be organized in a simple and consistent layout; (3) contextual information should be provided to help with interpretations; (4) data limitations should be clearly communicated; (5) guidance should be provided to lead user interactions. DISCUSSION: The identified requirements guide health librarians and information professionals in evaluating public health data dashboards. CONCLUSION: Public health data dashboards should be designed based on users' needs to provide useful up-to-date information sources for health information consumers.

Topical anti-TNF-a ssDNA aptamer decreased the imiquimod induced psoriatic inflammation in BALB/c mice.

BACKGROUND: Tumor Necrosis Factor-α (TNF-α) is a pro-inflammatory factor that plays a pivotal role in psoriasis. Due to limitations of monoclonal antibody-based therapies, it is needed to discover new anti-TNF-α factors instead of usual anti-TNF-α monoclonal antibodies. Compared to antibodies, single-stranded DNA or RNA molecules named aptamers, have advantages such as time-saving, less risk for immunogenicity and cost-effectiveness. Therefore, the aim of the present study was to assess the therapeutic effects of T1-T4 dimer anti-TNF-ɑ ssDNA aptamer topical treatment in the imiquimod (IMQ)-induced psoriasis animal model. METHODS: 5% IMQ cream was prescribed on the right ear of BALB/c to induce psoriasis model. The hydrogel-containing anti-TNF-ɑ aptamer or treatment control aptamer (anti- Interleukin (IL)17A) was topically prescribed to the mice's ears 10 min before IMQ cream treatment. The psoriasis area severity index (PASI) score was used to evaluate psoriasis intensity. Histopathology analysis was done for mice ears sections. Mass, size, and cell number of mice spleens were measured. The IL-17 level was determined in culture supernatants of axillary lymph node cells using ELISA. The mRNA expression levels of IL-17A, IL-1ß, STAT3, and S100a9, were evaluated in mice treated ear with quantitative Real Time-PCR. RESULTS: The anti-TNF-ɑ ssDNA aptamer lower doses had significant decrease in IMQ-induced PASI score (p < 0.05). In addition, in these groups, the IL-17A, STAT3, and S100a9 mRNA levels were significantly lower than the IMQ group (p < 0.05). CONCLUSION: According to our findings, this aptamer seems to be a prospective candidate for treating psoriatic inflammation especially in lower concentrations.

Information seeking behaviour differences indicate which US population groups lack information about human papilloma virus and associated cancer risks.

BACKGROUND: The majority of the US population have poor knowledge of cancers related to human papillomavirus (HPV). Identifying best sources for communicating this information can guide strategies to promote HPV vaccination. OBJECTIVES: To assess the relationship between sources of health information and individuals' knowledge of HPV-related cervical and oropharyngeal cancer. METHODS: This study conducts logistic regression on the most recent wave (2019) of the Health Information National Trends Survey. Dependent variables are indicators for self-reported awareness that HPV causes (a) cervical cancer and (b) oropharyngeal cancer. The primary indicator is a variable for different sources of health information: The Internet, professional sources, print materials, friends/family and never looked for health information. RESULTS: Being female, young, non-Hispanic White and having college education is associated with higher odds of knowing about HPV-related cervical cancer. Controlling for demographic factors, individuals using professionals and the Internet are more likely to know that HPV causes cervical cancer (aOR: 2.65, 95% CI: 1.66, 4.25; aOR: 2.47, 95% CI: 1.75, 3.50, respectively) compared to those who have never looked for health information. Similar results were found for HPV-related oropharyngeal cancer. CONCLUSION: Findings provide implications for targeted messaging through effective channels to improve HPV vaccination uptake.

Variation in Patterns of Racial and Ethnic Disparities in Primary and Secondary Syphilis Diagnosis Rates Among Heterosexually Active Women by Region and Age Group in the United States.

BACKGROUND: Syphilis rates have increased substantially over the past decade. Women are an important population because of negative sequalae and adverse maternal outcomes including congenital syphilis. We assessed whether racial and ethnic disparities in primary and secondary (P&S) syphilis among heterosexually active women differ by region and age group. METHODS: We synthesized 4 national surveys to estimate numbers of heterosexually active women in the United States from 2014 to 2018 by region, race and ethnicity, and age group (18-24, 25-29, 30-44, and ≥45 years). We calculated annual P&S syphilis diagnosis rates, assessing disparities with rate differences and rate ratios comparing White, Hispanic, and Black heterosexually active women. RESULTS: Nationally, annual rates were 6.42 and 2.20 times as high among Black and Hispanic than among White heterosexually active women (10.99, 3.77, and 1.71 per 100,000, respectively). Younger women experienced a disproportionate burden of P&S syphilis and the highest disparities. Regionally, the Northeast had the highest Black-White and Hispanic-White disparities using a relative disparity measure (relative rate), and the West had the highest disparities using an absolute disparity measure (rate difference). CONCLUSIONS: To meet the racial and ethnic disparity goals of the Sexually Transmitted Infections National Strategic Plan, tailored local interventions that address the social and structural factors associated with disparities are needed for different age groups.

Integrating human-centered design in public health data dashboards: lessons from the development of a data dashboard of sexually transmitted infections in New York State.

OBJECTIVE: The increased availability of public data and accessible visualization technologies enhanced the popularity of public health data dashboards and broadened their audience from professionals to the general public. However, many dashboards have not achieved their full potential due to design complexities that are not optimized to users' needs. MATERIAL AND METHODS: We used a 4-step human-centered design approach to develop a data dashboard of sexually transmitted infections for the New York State Department of Health: (1) stakeholder requirements gathering, (2) an expert review of existing data dashboards, (3) a user evaluation of existing data dashboards, and (4) an usability evaluation of the prototype dashboard with an embedded experiment about visualizing missing race and ethnicity data. RESULTS: Step 1 uncovered data limitations and software requirements that informed the platform choice and measures included. Step 2 yielded a checklist of general principles for dashboard design. Step 3 revealed user preferences that influenced the chart types and interactive features. Step 4 uncovered usability problems resulting in features such as prompts, data notes, and displaying imputed values for missing race and ethnicity data. DISCUSSION: Our final design was accepted by program stakeholders. Our modifications to traditional human-centered design methodologies to minimize stakeholders' time burden and collect data virtually enabled project success despite barriers to meeting participants in-person and limited public health agency staff capacity during the COVID-19 pandemic. CONCLUSION: Our human-centered design approach and the final data dashboard architecture could serve as a template for designing public health data dashboards elsewhere.

Development of fast-dissolving sublingual nanofibers containing allergen and curcumin for immune response modulation in a mouse model of allergic rhinitis.

Curcumin (CUR) has been considered a potential therapeutic agent for allergic reactions due to its antioxidant and anti-inflammatory activities. Nanofibers have attracted increasing attention in drug delivery. The aim of this study was to investigate the combined therapeutic effects of curcumin and allergen in nanofiber-based treatments in order to increase the effectiveness of sublingual immunotherapy (SLIT) efficacy in a mouse model of allergic rhinitis. Nanofibers containing CUR (1.25% and 2.5%) and ovalbumin 2% (OVA) as an allergen were prepared via electrospinning and characterized. BALB/c mice were sensitized with OVA to the induced allergic rhinitis model. SLIT with free and/or nanofibers was carried out. IL-4, INF-γ, and IgE serum levels were measured using ELISA. Splenocyte proliferation was evaluated by the MTT assay. Lung and nasal histological examinations and nasal lavage fluid (NALF) cell counting were carried out. Nanofibers containing 1.25% CUR and 2% OVA were chosen as the optimal formulations. SLIT treatment with the CUR and OVA nanofiber co-administration led to a significantly decreased serum IgE. Nanofiber containing 2.5 µg of CUR/mouse combined with OVA nanofiber showed a significant decrease in IL-4 and an increase in IFN-γ compared to other groups. NALF assessment showed a significant decrease in specific cell and eosinophil counts in the treated nanofiber groups. The histopathological results of NAL in the optimal formulations were near normal, with diminished cellular infiltration and inflammation. Our findings suggest that co-sublingual administration of allergen and CUR nanofibers can be considered as potential immunomodulatory agents.

An epicutaneous therapeutic pollen-allergen extract delivery system in an allergic rhinitis mouse model: based on allergen loading on DC-specific aptamers conjugated nanogolds.

BACKGROUND: Gold nanoparticles (GNPs) have previously been suggested as appropriate carriers for allergen-specific immunotherapy (AIT). In this study, we assessed efficacy of GNPs and dendritic cells (DC)-specific aptamer-modified GNPs (Apts-GNP) for epicutaneous immunotherapy (EPIT) in the case of pollen allergen extracts containing a variety of allergenic and non-allergenic components. METHODS: BALB/c mice were sensitized to the total protein extract of Platanus orientalis pollen and epicutaneously treated in different groups either with free P. orientalis total pollen extract, naked GNPs, total extract loaded GNPs, and total extract loaded Apts-GNPs with and without skin-penetrating peptides (SPPs). Then, the specific IgE level (sIgE), total IgE concentration (tIgE) in the serum sample, IL-4, IL-17a, IFN-γ, and IL-10 cytokine concentrations in re-stimulated splenocytes with the total extract and mixture of recombinant allergens, nasopharyngeal lavage fluid (NALF) analysis, and histopathological analysis of lung tissue were evaluated. RESULTS: This study indicated the total extract-loaded GNPs, especially Pla. ext (50 µg)-GNPs, significantly decreased sIgE, tIgE, IL-17a, and IL-4 concentrations, immune cells and eosinophils infiltration in NALF, and increased IL-10 and IFN-γ concentrations compared with the PBS-treated group. In addition, the histopathological analysis of lung tissue showed a significant decrease in allergic inflammation and histopathological damage. The DC-targeted group revealed the most significant improvement in allergic-related immune factors with no histopathological damage compared with the same dose without aptamer. CONCLUSION: Loading total protein extract on the GNPs and the Apt-modified GNPs could be an effective approach to improve EPIT efficacy in a pollen-induced allergic mouse model.

Investigating User-Generated Content in an Online Drug Recovery Forum: Lessons for Successful Computer-Mediated Communication of Social Support.

Benefiting from social support in online health communities requires maintaining textual communication. Investigating the process and identifying successful patterns can guide devising interventions to help online support seekers. We propose new methods to investigate the relationship between support-seeking requests and response messages in an online drug recovery forum. We use LIWC2015 text analysis software to quantify the support-seeking messages and apply machine learning algorithms to code the amount of informational and emotional support in the responses. Our work has several findings regarding the language in request messages that would increase or decrease the chances of receiving more informational or emotional support in response. For example, expressions of positive emotions and self-reference in request messages were associated with receiving more emotional support, and messages that used words indicating close relationships received more informational support. These findings contribute to the current understanding of computer-mediated communication of social support in online health communities, identifying strategies to mobilize maximal social resources. Moreover, our proposed methods can be used in other studies to investigate the exchange of social support or similar topics on online platforms.

Development of a usability checklist for public health dashboards to identify violations of usability principles.

OBJECTIVE: To develop a usability checklist for public health dashboards. MATERIALS AND METHODS: This study systematically evaluated all publicly available dashboards for sexually transmitted infections on state health department websites in the United States (N = 13). A set of 11 principles derived from the information visualization literature were used to identify usability problems that violate critical usability principles: spatial organization, information coding, consistency, removal of extraneous ink, recognition rather than recall, minimal action, dataset reduction, flexibility to user experience, understandability of contents, scientific integrity, and readability. Three user groups were considered for public health dashboards: public health practitioners, academic researchers, and the general public. Six reviewers with usability knowledge and diverse domain expertise examined the dashboards using a rubric based on the 11 principles. Data analysis included quantitative analysis of experts' usability scores and qualitative synthesis of their textual comments. RESULTS: The dashboards had varying levels of complexity, and the usability scores were dependent on the dashboards' complexity. Overall, understandability of contents, flexibility, and scientific integrity were the areas with the most major usability problems. The usability problems informed a checklist to improve performance in the 11 areas. DISCUSSION: The varying complexity of the dashboards suggests a diversity of target audiences. However, the identified usability problems suggest that dashboards' effectiveness for different groups of users was limited. CONCLUSIONS: The usability of public health data dashboards can be improved to accommodate different user groups. This checklist can guide the development of future public health dashboards to engage diverse audiences.

Modeling the Potential Impact of Missing Race and Ethnicity Data in Infectious Disease Surveillance Systems on Disparity Measures: Scenario Analysis of Different Imputation Strategies.

BACKGROUND: Monitoring progress toward population health equity goals requires developing robust disparity indicators. However, surveillance data gaps that result in undercounting racial and ethnic minority groups might influence the observed disparity measures. OBJECTIVE: This study aimed to assess the impact of missing race and ethnicity data in surveillance systems on disparity measures. METHODS: We explored variations in missing race and ethnicity information in reported annual chlamydia and gonorrhea diagnoses in the United States from 2007 to 2018 by state, year, reported sex, and infection. For diagnoses with incomplete demographic information in 2018, we estimated disparity measures (relative rate ratio and rate difference) with 5 imputation scenarios compared with the base case (no adjustments). The 5 scenarios used the racial and ethnic distribution of chlamydia or gonorrhea diagnoses in the same state, chlamydia or gonorrhea diagnoses in neighboring states, chlamydia or gonorrhea diagnoses within the geographic region, HIV diagnoses, and syphilis diagnoses. RESULTS: In 2018, a total of 31.93% (560,551/1,755,510) of chlamydia and 22.11% (128,790/582,475) of gonorrhea diagnoses had missing race and ethnicity information. Missingness differed by infection type but not by reported sex. Missing race and ethnicity information varied widely across states and times (range across state-years: from 0.0% to 96.2%). The rate ratio remained similar in the imputation scenarios, although the rate difference differed nationally and in some states. CONCLUSIONS: We found that missing race and ethnicity information affects measured disparities, which is important to consider when interpreting disparity metrics. Addressing missing information in surveillance systems requires system-level solutions, such as collecting more complete laboratory data, improving the linkage of data systems, and designing more efficient data collection procedures. As a short-term solution, local public health agencies can adapt these imputation scenarios to their aggregate data to adjust surveillance data for use in population indicators of health equity.

Industry payments and physicians prescriptions: Effect of a payment restriction policy.

The pharmaceutical industry spends billions of dollars every year for marketing its products to US health care providers. This study investigates the association between industry marketing payments and physicians' prescription in New York and Massachusetts, and examines the effect of the Massachusetts payment restriction policy on this association in comparison with the New York State that has no payment restriction policy. Three panel data models (fixed effects regression (FE), first difference regression (FD), and first difference with lagged independent variable (LFD)) were used to establish the association accounting for unobserved confounders and reverse causality. The main indicator is the total amount of industry payments for meals, drug samples, consulting fees, etc. (excluding research funding, and ownership). Dependent variables are a) yearly days' supply of Medicare Part D prescriptions, b) yearly costs of prescribed prescriptions. Secular time trends, as well as differences between the two states were controlled in all models. All three panel models showed significant positive association between industry payments and physician prescriptions. Particularly, these models show that in the base year (2014), a 1% increase in the annual industry payments was associated with (0.01%-0.04%) increase in days' supply of medication, and (0.01%-0.05%) increase in prescription costs for NYS providers. Moreover, FE and FD models show that compared to NYS physicians, the association of industry payments with days' supply and costs of Medicare Part D prescriptions was (0.01%-0.02%) smaller for MA physicians. Because of the smaller sample size and lower power, the LFD model did not detect a significant difference between the NYS and MA providers. The findings of this study provide additional evidence that industry payments are associated with increases in the volume and cost of Medicare prescriptions. Moreover, these findings provide preliminary evidence that payment restriction policies negatively moderate this association, which calls for further research.

Racial and ethnic disparities in HIV diagnoses among heterosexually active persons in the United States nationally and by state, 2018.

BACKGROUND: Despite declining HIV infection rates, persistent racial and ethnic disparities remain. Appropriate calculations of diagnosis rates by HIV transmission category, race and ethnicity, and geography are needed to monitor progress towards reducing systematic disparities in health outcomes. We estimated the number of heterosexually active adults (HAAs) by sex and state to calculate appropriate HIV diagnosis rates and disparity measures within subnational regions. METHODS: The analysis included all HIV diagnoses attributed to heterosexual transmission in 2018 in the United States, in 50 states and the District of Columbia. Logistic regression models estimated the probability of past-year heterosexual activity among adults in three national health surveys, by sex, age group, race and ethnicity, education category, and marital status. Model-based probabilities were applied to estimated counts of HAAs by state, which were synthesized through meta-analysis. HIV diagnoses were overlaid to calculate racial- and ethnic-specific rates, rate differences (RDs), and rate ratios (RRs) among HAAs by sex and state. RESULTS: Nationally, HAA women have a two-fold higher HIV diagnosis rate than HAA men (rate per 100,000 HAAs, women: 6.57; men: 3.09). Compared to White non-Hispanic HAAs, Black HAAs have a 20-fold higher HIV diagnosis rate (RR, men: 21.28, women: 19.55; RD, men: 15.40, women: 31.78) and Hispanic HAAs have a 4-fold higher HIV diagnosis rate (RR, men: 4.68, RD, women: 4.15; RD, men: 2.79, RD, women: 5.39). Disparities were ubiquitous across regions, with >75% of states in each region having Black-to-White RR ≥10. CONCLUSION: The racial and ethnic disparities across regions suggests a system-wide failure particularly with respect to preventing HIV among Black and Hispanic women. Pervasive disparities emphasize the role for coordinated federal responses such as the current Ending the HIV Epidemic (EHE) initiative.

A Rapid Review of the Impact of Systems-Level Policies and Interventions on Population-Level Outcomes Related to the Opioid Epidemic, United States and Canada, 2014-2018.

OBJECTIVES: In the United States, rising rates of overdose deaths and recent outbreaks of hepatitis C virus and HIV infection are associated with injection drug use. We updated a 2014 review of systems-level opioid policy interventions by focusing on evidence published during 2014-2018 and new and expanded opioid policies. METHODS: We searched the MEDLINE database, consistent with the 2014 review. We included articles that provided original empirical evidence on the effects of systems-level interventions on opioid use, overdose, or death; were from the United States or Canada; had a clear comparison group; and were published from January 1, 2014, through July 19, 2018. Two raters screened articles and extracted full-text data for qualitative synthesis of consistent or contradictory findings across studies. Given the rapidly evolving field, the review was supplemented with a search of additional articles through November 17, 2019, to assess consistency of more recent findings. RESULTS: The keyword search yielded 535 studies, 66 of which met inclusion criteria. The most studied interventions were prescription drug monitoring programs (PDMPs) (59.1%), and the least studied interventions were clinical guideline changes (7.6%). The most common outcome was opioid use (77.3%). Few articles evaluated combination interventions (18.2%). Study findings included the following: PDMP effectiveness depends on policy design, with robust PDMPs needed for impact; health insurer and pharmacy benefit management strategies, pill-mill laws, pain clinic regulations, and patient/health care provider educational interventions reduced inappropriate prescribing; and marijuana laws led to a decrease in adverse opioid-related outcomes. Naloxone distribution programs were understudied, and evidence of their effectiveness was mixed. In the evidence published after our search's 4-year window, findings on opioid guidelines and education were consistent and findings for other policies differed. CONCLUSIONS: Although robust PDMPs and marijuana laws are promising, they do not target all outcomes, and multipronged interventions are needed. Future research should address marijuana laws, harm-reduction interventions, health insurer policies, patient/health care provider education, and the effects of simultaneous interventions on opioid-related outcomes.