STING Restricts oHSV Replication and Spread in Resistant MPNSTs but Is Dispensable for Basal IFN-Stimulated Gene Upregulation.

Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive soft-tissue sarcoma amenable only to surgical resection. Oncolytic herpes simplex viruses (oHSVs) are a promising experimental therapy. We previously showed that basal interferon (IFN) and nuclear factor κB (NFκB) signaling upregulate IFN-stimulated gene (ISG) expression and restrict efficient viral infection and cell-to-cell spread in ∼50% of tested MPNSTs. Stimulator of Interferon Genes (STING) integrates DNA sensor activity and mediates downstream IFN signaling in infected cells. We sought to identify STING's role in oHSV resistance and contribution to basal ISG upregulation in MPNSTs. We show that the level of STING activity in human MPNST cell lines is predictive of oHSV sensitivity and that resistant cell lines have intact mechanisms for detection of cytosolic double-stranded DNA (dsDNA). Furthermore, we show that STING downregulation renders MPNSTs more permissive to oHSV infection and cell-to-cell spread. While next-generation viruses can exploit this loss of STING activity, first-generation viruses remain restricted. Finally, STING is not integral to the previously-observed basal ISG upregulation, indicating that other pathways contribute to basal IFN signaling in resistant MPNSTs. These data broaden our understanding of the intrinsic pathways in MPNSTs and their role in oHSV resistance and offer potential targets to potentiate oncolytic virus activity.

Rabies exposures and pre-exposure vaccination practices among individuals with an increased risk of rabies exposure in the United States.

OBJECTIVE To identify knowledge and practices related to rabies vaccination and serologic monitoring among animal care workers in the United States. DESIGN Cross-sectional survey. SAMPLE 2,334 animal care workers (ie, veterinarians, veterinary technicians, animal control workers, and wildlife rehabilitators). PROCEDURES Participants were contacted through relevant professional organizations to participate in an anonymous web-based survey. The survey collected demographic and occupational information, animal handling and potential rabies exposure information, and individual rabies vaccination and serologic monitoring practices. Comparisons of animal bite and rabies exposure rates were made between occupational groups. Multiple logistic regression was used to evaluate factors associated with rabies vaccination status and adherence to serologic monitoring recommendations. RESULTS Respondents reported 0.77 animal bites/person-year or 0.10 bites/1,000 animals handled. The overall rate of postexposure prophylaxis due to an occupational rabies exposure was 1.07/100 person-years. Veterinarians reported the highest rabies vaccination rate (98.7% [367/372]), followed by animal control workers (78.5% [344/438]), wildlife rehabilitators (78.2% [122/156]), and veterinary technicians (69.3% [937/1,352]). Respondents working for employers requiring rabies vaccination and serologic monitoring were 32.16 and 6.14 times, respectively, as likely to be vaccinated or have a current serologic monitoring status as were respondents working for employers without such policies. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, given the high reported rates of animal bites and potential rabies exposures among animal care workers, improvements in rabies vaccination and serologic monitoring practices are needed.

High Mobility Group Box 1 Influences HSV1716 Spread and Acts as an Adjuvant to Chemotherapy.

High Mobility Group Box 1 (HMGB1) is a multifunctional protein that plays various roles in the processes of inflammation, cancer, and other diseases. Many reports document abundant HMGB1 release following infection with oncolytic viruses (OVs). Further, other groups including previous reports from our laboratory highlight the synergistic effects of OVs with chemotherapy drugs. Here, we show that virus-free supernatants have varying cytotoxic potential, and HMGB1 is actively secreted by two established fibroblast cell lines (NIH 3T3 and 3T6-Swiss albino) following HSV1716 infection in vitro. Further, pharmacologic inhibition or genetic knock-down of HMGB1 reveals a role for HMGB1 in viral restriction, the ability to modulate bystander cell proliferation, and drug sensitivity in 3T6 cells. These data further support the multifactorial role of HMGB1, and suggest it could be a target for modulating the efficacy of oncolytic virus therapies alone or in combination with other frontline cancer treatments.

Law Accommodating Nonmotorized Road Users and Pedestrian Fatalities in Florida, 1975 to 2013.

OBJECTIVES: To examine the effect of Florida's adoption of Statute 335.065-a law requiring the routine accommodation of nonmotorized road users (i.e., a "Complete Streets" policy)-on pedestrian fatalities and to identify factors influencing its implementation. METHODS: We used a multimethod design (interrupted time-series quasi-experiment and interviews) to calculate Florida's pedestrian fatality rates from 1975 to 2013-39 quarters before and 117 quarters after adoption of the law. Using statistical models, we compared Florida with regional and national comparison groups. Semistructured interviews were conducted with 10 current and former Florida transportation professionals in 2015. RESULTS: Florida's pedestrian fatality rates decreased significantly-by at least 0.500% more each quarter-after Statute 335.065 was adopted, resulting in more than 3500 lives saved across 29 years. Interviewees described supports and challenges associated with implementing the law. CONCLUSIONS: Florida Statute 335.065 is associated with a 3-decade decrease in pedestrian fatalities. The study also reveals factors that influenced the implementation and effectiveness of the law. Public Health Implications. Transportation policies-particularly Complete Streets policies-can have significant, quantifiable impacts on population health. Multimethod designs are valuable approaches to policy evaluations.

HIV Screening Rates among Medicaid Enrollees Diagnosed with Other Sexually Transmitted Infections.

INTRODUCTION: Approximately 20 million new sexually transmitted infections (STIs) are diagnosed yearly in the United States costing the healthcare system an estimated $16 billion in direct medical expenses. The presence of other STIs increases the risk of HIV transmission. The Centers for Disease Control and Prevention (CDC) has long recommended routine HIV screening for individuals with a diagnosed STI. Unfortunately, HIV screening prevalence among STI diagnosed patients are still sub-optimal in many healthcare settings. OBJECTIVE: To determine the proportion of STI-diagnosed persons in the Medicaid population who are screened for HIV, examine correlates of HIV screening, and to suggest critical intervention points to increase HIV screening in this population. METHODS: A retrospective database analysis was conducted to examine the prevalence and correlates of HIV screening among participants. Participant eligibility was restricted to Medicaid enrollees in 29 states with a primary STI diagnosis (chlamydia, gonorrhea, and syphilis) or pelvic inflammatory disease claim in 2009. HIV-positive persons were excluded from the study. Frequencies and descriptive statistics were conducted to characterize the sample in general and by STI diagnosis. Univariate and multivariate logistic regression were performed to estimate unadjusted odds ratios and adjusted odds ratio respectively and the 95% confidence intervals. Multivariate logistic regression models that included the independent variables (race, STI diagnosis, and healthcare setting) and covariates (gender, residential status, age, and state) were analyzed to examine independent associations with HIV screening. RESULTS: About 43% of all STI-diagnosed study participants were screened for HIV. STI-diagnosed persons that were between 20-24 years, female, residing in a large metropolitan area and with a syphilis diagnosis were more likely to be screened for HIV. Participants who received their STI diagnosis in the emergency department were less likely to be screened for HIV than those diagnosed in a physician's office. CONCLUSION: This study showed that HIV screening prevalence among persons diagnosed with an STI are lower than expected based on the CDC's recommendations. These suboptimal HIV screening prevalence present "missed opportunities" for HIV screening in at-risk populations. Measures and incentives to increase HIV screening among all STI-diagnosed persons are vital to the timely identification of HIV infection, linkage to HIV care, and mitigating further HIV transmission.

U.s. Undergraduate education in public health: hot or not?

OBJECTIVES: Undergraduate public health education has received growing attention in recent years. This includes a Washington Post article referring to undergraduate public health education as a "hot field" for a global generation, the Critical Component Elements of an Undergraduate Major in Public Health developed by the Association of School and Programs in Public Health (ASPPH), and a recent report from the de Beaumont Foundation and ASPPH. To evaluate the demand for the degree and assess the current state of undergraduate public health education, the researchers examined the number and characteristics of publicly reported U.S. baccalaureate public health programs. METHODS: The researchers reviewed three 2013 college directories and the ASPPH website and identified 112 institutions that used the term "public health" in their baccalaureate degree listings that guide prospective students in selecting an academic program. The researchers defined the undergraduate degree in public health as a major leading to a B.S., B.A., or other baccalaureate degree in public health or public health studies that provides students with a strong general background in areas of knowledge basic to public health, or a specialized training in at least one of the five core disciplines of public health. The researchers then compared the degree contents as listed in the directories to the institutions' websites to verify offering a public health curriculum. Carnegie Commission on Higher Education's classifications of colleges and universities were applied to assess the characteristics of institutions offering baccalaureate degrees in public health. RESULTS: Only 54 of the 2,968 U.S. institutions of higher education provided online information meeting the definition of an active undergraduate public health degree program. CONCLUSION: While public health may be a "hot" field in terms of the interest that it generates, the actual number of verified undergraduate programs presently available is relatively modest.

Articulation of undergraduate and graduate education in public health.

The rapid growth of individual undergraduate courses, minors, and baccalaureate degrees in public health presents a new issue for graduate public health education: how does a graduate or professional program address previously completed undergraduate public health course work? A review of college directories found listings for 154 North American baccalaureate degrees in public health, public health education, and public health nursing. This article addresses the purposes of public health undergraduate education as (1) general liberal arts education, (2) education complementary to other non-public health graduate degrees, (3) preprofessional education, and (4) professional education preparing undergraduates for entry-level careers. Following a discussion of reasons to consider articulation of undergraduate and graduate degrees, as well as barriers to articulation, the article presents potential strategies for articulation and future issues to consider in addressing admission of undergraduate public health students to master of public health programs.

The status of national and health administration doctoral education: issues for the 21st century.

Doctoral education is gaining increasing attention as new programs proliferate and enrollment grows. Presently there is no standardization of degrees programs, limited aggregated information about health administration education doctoral programs, and an absence of national policy. The general, doctoral education literature presents a variety of issues and challenges for doctoral health administration education including data trends, supply and demand for doctoral graduates, credential inflation, attrition and degree completion, organizational efforts to improve doctoral education, and strategies for the future. Following the literature review, survey results for a sub-sample of AUPHA affiliated doctoral programs are presented along with related implications.

The Kentucky plan revisited: lessons learned from an innovative doctoral education program.

In the first doctoral education special issue of the Journal of Health Administration Education, the authors presented the University of Kentucky College of Public Health's plans for an innovative new Doctor of Public Health (Dr. P.H.) degree. The degree as designed, prepares graduates for professional practice, and included extensive supervised field experience as part of the academic training linking theory with practice. Based upon the interest that the Kentucky Dr.P.H. degree program received, the authors will share the experience of the degree's initial years of operation through a "lessons learned" paper. As the program evolved there have been many lessons related to trends, curriculum design, admissions, prerequisite requirements, curriculum innovations, scheduling, the comprehensive examination, and attrition. In addition, there are many questions for the future. "In theory, theory and practice are the same. In practice, they are not."-- Lawrence Peter "Yogi" Berra.

Articulation of undergraduate and graduate education in health administration: barriers and strategies for the future.

The initiation of the hospital administration degree at the master's level and not the baccalaureate level was an intentional decision. Unfortunately, during this formative half-decade, the baccalaureate programs developed in a vacuum, isolated from one another and from the long-established graduate programs. While there is not a clear professional consensus that the lack of undergraduate degree articulation with graduate education is a problem, the authors believe this to be the case and believe that many faculty agree. This paper will address the history of health administration education, current academic pathways to careers in health administration, and detailed barriers and strategies to academic degree articulation. The paper concludes that discussion of health administration degree articulation has received modest attention and discussion for more than twenty years, and neither formal relationships nor certification/accreditation has addressed the issue. The authors believe that creation of articulated degrees is desirable and call for AUPHA and CAHME to develop a task force to address barriers and strategies for articulation. Concurrently, while national policy would facilitate more rapid change, we recommend that individual undergraduate and graduate degree programs explore individual relationships as a means to achieve models for the profession as an alternative to the status quo.