Different immortalized keratinocyte cell lines display distinct capabilities to differentiate and reconstitute an epidermis in vitro.

Dermatological research relies on the availability of suitable models that most accurately reflect the in vivo situation. Primary keratinocytes obtained from skin reduction surgeries are not only limited by availability but have a short lifespan and show donor-specific variations, which hamper the understanding of general mechanisms. The spontaneously immortalized keratinocyte cell line HaCaT displays chromosomal aberrations and is known to differentiate in an abnormal manner. To overcome these issues, we validated different engineered immortalized cell lines created from primary human keratinocytes (NHK) as model systems to study epidermal function. Cell lines either immortalized by the expression of SV40 large T antigen and hTERT (NHK-SV/TERT) or by transduction with HPV E6/E7 (NHK-E6/E7) were analysed for their growth and differentiation behaviour using 2D and 3D culture systems and compared to primary keratinocytes. Both cell lines displayed a robust proliferative behaviour but were still sensitive to contact inhibition. NHK-E6/E7 could be driven into differentiation by Ca2+ switch, while NHK-SV/TERT needed withdrawal from any proliferative signal to initiate a delayed onset of differentiation. In 3D epidermal models both cell lines were able to reconstitute a stratified epidermis and functional epidermal barrier. However, only NHK-E6/E7 showed a degree of epidermal maturation and stratification that was comparable to primary keratinocytes.

Socio-cultural power of social media on orthorexia nervosa: An empirical investigation on the mediating role of thin-ideal and muscular internalization, appearance comparison, and body dissatisfaction.

As social media continues to penetrate users' daily lives, concerns about its negative impact on body image issues and eating disorders are becoming focuses of research. It remains unclear whether social media should be held responsible for promoting orthorexia nervosa-a problematic and extreme fixation on healthy eating. The present study draws on socio-cultural theory and tests a social media-based model in the context of orthorexia nervosa to enhance knowledge of social media's influence on body image issues and orthorectic eating tendencies. The socio-cultural model was tested using structural equation modeling based on responses from a German-speaking sample (n = 647). The results indicate that social media users' involvement with health and fitness accounts is associated with higher orthorectic eating tendencies. Thin-ideal and muscular internalizations mediated this relationship. Interestingly, body dissatisfaction and appearance comparison were not mediators, which can be attributed to the characteristics of orthorexia nervosa. Higher involvement with health and fitness accounts on social media was also related to higher appearance comparisons. The results highlight the powerful influence of social media on orthorexia nervosa and the relevance of socio-cultural models in investigating the mechanisms underlying this influence.

Exploring the Dunning-Kruger Effect in Health Communication: How Perceived Food and Media Literacy and Actual Knowledge Drift Apart When Evaluating Misleading Food Advertising.

Marketers often advertise products high in sugar, fat or calories as healthy products. With this potentially misleading information, they can influence eating decisions with negative consequences for human health. Consumers need the ability to uncover misleading food advertising. However, individuals' perceived knowledge and their actual objective abilities often drift apart - a phenomenon which has come to be known as the Dunning-Kruger Effect. Thus, this study set out to uncover the phenomenon's potential existence in health communication, more precisely in the area of food and media literacy. In a quantitative survey representative of the Austrian population (n = 1000) the Dunning-Kruger Effect (DKE) could be detected: Individuals who were most knowledgeable underestimated their food and media literacy, but - on the positive side - they acted as opinion leaders. Individuals who were least knowledgeable about advertising strategies used to market an unhealthy product as healthy and about the actual nutrition score of the advertised product were most likely to overestimate their own food and media literacy. Worryingly, further concerning consequences emerged, especially for least knowledgeable individuals. The study's results provide important implications for public health campaigns.

Mechanism of anti-inflammatory effects of rifampicin in an ex vivo culture system of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the hair follicles leading to painful lesions, associated with increased levels of pro-inflammatory cytokines. Numerous guidelines recommend antibiotics like clindamycin and rifampicin in combination, as first-line systemic therapy in moderate-to-severe forms of inflammation. HS has been proposed to be mainly an auto-inflammatory disease associated with but not initially provoked by bacteria. Therefore, it has to be assumed that the pro-inflammatory milieu previously observed in HS skin is not solely dampened by the bacteriostatic inhibition of DNA-dependent RNA polymerase. To further clarify the mechanism of anti-inflammatory effects of rifampicin, ex vivo explants of lesional HS from 8 HS patients were treated with rifampicin, and its effect on cytokine production, immune cells as well as the expression of Toll-like receptor 2 (TLR2) were investigated. Analysis of cell culture medium of rifampicin-treated HS explants revealed an anti-inflammatory effect of rifampicin that significantly inhibiting interleukin (IL)-1ß, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α production. Immunohistochemistry of the rifampicin-treated explants suggested a tendency for it to reduce the expression of TLR2 while not affecting the number of immune cells.

Toward Optimal Communication About HPV Vaccination for Preteens and Their Parents: Evaluation of an Online Training for Pediatric and Family Medicine Health Care Providers.

OBJECTIVE: Health care provider recommendation is a key determinant of human papillomavirus (HPV) vaccination. We developed an online training program for providers that addressed vaccine guidelines, hesitancy to strongly recommend the vaccine, and reluctance to discuss HPV infection as a sexually transmitted infection. DESIGN: Single-group evaluation with 3 waves. Providers completed a 29-item electronic survey with closed and open-ended response options after course completion. SETTING: Pediatric and family medicine practices in North Carolina. PARTICIPANTS: Prescribing clinicians (MD, DO, family nurse practitioner, physician assistant) who serve preteens aged 11 to 12 years. In wave 3, we expanded our communities to include nursing and medical staff. INTERVENTION: An asynchronous online course to promote preteen HPV vaccination. Topics included HPV epidemiology, vaccine recommendations from the Advisory Committee on Immunization Practices (ACIP), preteen-provider-parent communication, topics about hesitancy to seek vaccination, subjects related to sexual health, and practice-level strategies to increase vaccination rates. The course, approved for 12 CME and CNE credits, was live for 4 weeks and available on-demand for 3 additional months. MAIN OUTCOME MEASURES: Provider-reported change in vaccine communication, perceptions of course content in improving practice, and satisfaction with materials. RESULTS: A total of 113 providers from 25 practices enrolled in the course and 69 (61%) completed an evaluation. Providers spent an average of 6.3 hours on the course and rated the CDC (Centers for Disease Control and Prevention)-ACIP Web site and multiple resources on hesitancy and communication about sexually transmitted infection vaccines most highly of all materials across the 3 waves. Almost all (96%) agreed the course will improve their practice. About half of all participants said they were either "much more likely" (28%) or "more likely" (19%) to recommend the vaccine after course participation. CONCLUSIONS: An online format offers a highly adaptable and acceptable educational tool that promotes interpersonal communication and practice-related changes known to improve providers' vaccine uptake by their patients.

The use of advertising appeals in breast cancer detection messages: a web content analysis.

We explored the use of different advertising appeals in breast cancer detection messages. We analyzed the extent to which emotional appeals were applied in advertisements that promoted two forms of breast cancer detection behaviors: breast self-examination (BSE) and mammographic screening. Findings of a content analysis of 456 breast cancer-related advertisements gathered in February 2016 indicated that textual fear appeals, humor appeals and erotic appeals were more likely to be featured in BSE-promoting advertisements than in breast cancer-related advertisements with other message purposes. While shame-guilt appeals were more likely to be used in mammography-promoting messages, humor and erotic appeals were less likely to be applied. Regarding hybrid message appeals, combinations of humor appeals with erotic, fear and shame-guilt appeals, as well as combined erotic-fear appeals were found more in BSE-promotion messages. Mammography-promoting messages made less use of hybrid messages with a humorous touch as compared to breast cancer advertisements with other message purposes. The results are in contrast to research findings on the effectiveness of message appeals and thus allow to some extent the evaluation of whether scientific findings on the effectiveness of message appeals are reflected in the current advertising practice.

Blocking mTOR Signalling with Rapamycin Ameliorates Imiquimod-induced Psoriasis in Mice.

The mTOR (mechanistic target of rapamycin) inhibitor rapamycin has long been known for its immune suppressive properties, but it has shown limited therapeutic success when given systemically to patients with psoriasis. Recent data have shown that the mTOR pathway is hyperactivated in lesional psoriatic skin, which probably contributes to the disease by interfering with maturation of keratinocytes. This study investigated the effect of topical rapamycin treatment in an imiquimod-induced psoriatic mouse model. The disease was less severe if the mice had received rapamycin treatment. Immunohistological analysis revealed that rapamycin not only prevented the activation of mTOR signalling (P-mTOR and P-S6 levels), but almost normalized the expression of epidermal differentiation markers. In addition, the influx of innate immune cells into the draining lymph nodes was partially reduced by rapamycin treatment. These data emphasize the role of mTOR signalling in the pathogenesis of psoriasis, and support the investigation of topical mTOR inhibition as a novel anti-psoriatic strategy.

Assessing Opportunities to Enhance Comprehensive Health Promotion and Wellness Programming in a State Community College System.

BACKGROUND North Carolina has the third largest community college system in the nation and reaches residents in all 100 counties. Few studies have focused on the health of employees who work at these institutions. We assessed the current status of and interest in supporting health promotion efforts among North Carolina Community College System members.METHODS North Carolina Community College System presidents completed a brief 15-item survey assessing support for and interest in offering health promotion programs. Wellness coordinators completed a 60-item questionnaire assessing current health promotion programming and organizational, environmental, and policy supports for health promotion efforts. Onsite interviews with a sub-sample of Wellness coordinators offered insights into important implementation considerations. We examined differences by campus size with Fisher's exact test.RESULTS All 58 presidents (100%) and 51 wellness coordinators (88%) completed surveys. Ten percent of colleges offered comprehensive employee health promotion programming. Most offered physical activity (70.6%), tobacco cessation (51.0%), weight loss/management (49.0%), and/or nutrition counseling (47.1%). Larger colleges were more likely to offer programming and environmental support. Nearly all presidents (89.7%) believed it is "very" or "extremely" important to offer health promotion programs to employees, and most (84%) were interested in promoting health through a university partnership.LIMITATIONS Despite very high survey response rates from presidents and wellness coordinators at each community college, onsite interviews were only done at select campuses, limiting the generalizability and scope of conclusions derived from interview data.CONCLUSION Community colleges in North Carolina are promising settings for promoting employee health. Findings identify resources, barriers, and technical assistance that could facilitate greater adoption and implementation of programs.

Evidence for Eight-Node Mixed-Symmetry Superconductivity in a Correlated Organic Metal.

We report on a combined theoretical and experimental investigation of the superconducting state in the quasi-two-dimensional organic superconductor κ-(ET)_{2}Cu[N(CN)_{2}]Br. Applying spin-fluctuation theory to a low-energy, material-specific Hamiltonian derived from ab initio density functional theory we calculate the quasiparticle density of states in the superconducting state. We find a distinct three-peak structure that results from a strongly anisotropic mixed-symmetry superconducting gap with eight nodes and twofold rotational symmetry. This theoretical prediction is supported by low-temperature scanning tunneling spectroscopy on in situ cleaved single crystals of κ-(ET)_{2}Cu[N(CN)_{2}]Br with the tunneling direction parallel to the layered structure.

Insulin Resistance May Contribute to Upregulation of Adhesion Molecules on Endothelial Cells in Psoriatic Plaques.

Psoriasis primarily affects the skin, but also has a systemic dimension and is associated with severe comorbidities. Since endothelial cells play an important role in psoriasis as well as in the development of cardiovascular comorbidities, we investigated whether a common mechanism, namely cytokine-induced insulin resistance, underlies both pathologies. Activation of the insulin pathway was studied in psoriatic skin and dermal endothelial cells. Expression of adhesion molecules was assessed by flow cytometry, as well as their biological function in flow chamber experiments. The phosphorylation status of Akt, a central kinase in the insulin pathway, suggests that endothelial cells within psoriatic plaques are rendered insulin resistant by pro-inflammatory cytokines. Insulin counteracts the expression of adhesion molecules, but has limited effects on interactions between T cells and endothelial cells. Pro-inflammatory cytokines induce insulin resistance in endothelial cells, which may contribute to the development of the inflammatory infiltrate in psoriasis.

Bridging Research, Practice, and Policy: The "Evidence Academy" Conference Model.

Innovative models to facilitate more rapid uptake of research findings into practice are urgently needed. Community members who engage in research can accelerate this process by acting as adoption agents. We implemented an Evidence Academy conference model bringing together researchers, health care professionals, advocates, and policy makers across North Carolina to discuss high-impact, life-saving study results. The overall goal is to develop dissemination and implementation strategies for translating evidence into practice and policy. Each 1-day, single-theme, regional meeting focuses on a leading community-identified health priority. The model capitalizes on the power of diverse local networks to encourage broad, common awareness of new research findings. Furthermore, it emphasizes critical reflection and active group discussion on how to incorporate new evidence within and across organizations, health care systems, and communities. During the concluding session, participants are asked to articulate action plans relevant to their individual interests, work setting, or area of expertise.

Working (out) with fitness influencers - benefits for the fitness influencer, user health, and the endorsed brand: Key factors and the role of gender and brand familiarity.

Objective: Fitness influencers have become important digital health communicators with regard to influencing consumer health behaviours, such as physical activity. We investigate how working (out) with these new communicators can generate benefits for the fitness influencer, user health, and endorsed brands. Based on the source credibility, social identity theory, and gender congruity research, this paper aims to identify the main factors that affect users' attitudes toward the fitness influencer (influencer benefit), users' exercise intentions (user health benefit) and their purchase intentions (brand benefit), considering user and influencer gender. Methods: Two studies were conducted, both with male and female influencers and users. In study 1 (n = 496), the fitness influencer endorsed an unfamiliar brand, and in study 2 (n = 529) a familiar brand was endorsed. To test the proposed models and to estimate the path coefficients, structural equation modelling was performed. Results: Key influencing factors were identified in the two studies: For attitude toward the influencer, source credibility is the most important; for exercise intention, parasocial interaction and attitude toward the behaviour are crucial; and purchase intention is largely predicted by the brand attitude. The studies revealed gender-congruent and non-congruent tendencies for female and male respondents, and different effects of unfamiliar and familiar brands. Conclusions: Working (out) with fitness influencers can improve user attitudes toward the influencer, increase users' exercise intentions, and increase brand purchase intentions, for both unfamiliar and familiar brands. Some gender congruity and some gender incongruity effects exist. The paper discusses important implications for theory and practice.

Endothelial cells are highly heterogeneous at the level of cytokine-induced insulin resistance.

The endothelial wall plays a crucial role in various diseases as it serves as the barrier between circulatory system and organ tissue. Inflammation-driven insulin resistance and subsequent endothelial dysfunction represent a pathomechanism in cardiovascular diseases such as atherosclerosis and myocardial infarction. It was recently suggested that insulin resistance also contributes to the pathogenesis of psoriasis, a chronic inflammatory disease of the skin. However, it is not clear whether similar mechanisms at the endothelium contribute to the disease. In this study, we ask which endothelial cells are most suitable to address this question. We investigated the insulin response of four cell types (primary cells and cell lines) representing different vascular beds (micro- and macrovascular cells) in the presence of different pro-inflammatory cytokines. All four cell types used responded well to insulin; however, the ability to become resistant to insulin due to an inflammatory stimulus by cytokines involved in psoriasis (e.g. IL-1ß, IL-12, IL-17, IL-23 and TNF-α) was very heterogeneous and could not be attributed to the differential expression of the cognate cytokine receptors. We conclude that this disparity is due to the different origins and properties of the endothelial cells used. Thus, endothelial cells should be carefully selected for the purpose of the respective study, particularly when it comes to analysing the pathogenesis of a disease and the search of new molecular targets for innovative therapies.

"Where There Is Light, There Is Also Darkness": Discussing Young Adults' Willingness to Disclose Data to Use Wearables and Health Applications-Results from a Focus Group Study.

In recent years, the Internet of Medical Things (IoMT) has gained momentum. This development has only been intensified by the current COVID-19 crisis, which promotes the development of applications that can help stop the virus from spreading by monitoring people's movements and their social contacts. At the same time, it has become increasingly difficult for individuals to control the use of their private data by commercial companies. While Internet users claim to be highly interested in protecting their privacy, their behaviors indicate otherwise. This phenomenon is discussed in literature as the so-called privacy paradox. The existence of the privacy paradox has also been confirmed by previous studies, which found individuals' claims and actions to contradict one another. The present study investigates the following research questions: (1) What significance do individuals attribute to protecting their privacy, with a special focus on the health sector? (2) To what extent are they willing to grant commercial parties access to their data in order to use applications in general and health applications in particular? Results from seven focus groups with 40 respondents aged 20-30 years were conducted in an urban setting in Austria in late 2019. The respondents' inputs are meant to provide answers to these questions. The results indicate that, overall, the young generation is well-informed about the growing data collection and is quite critical of it. As such, their willingness to share information in the health context is only moderately pronounced. Thus, only a moderately pronounced privacy paradox can be detected for the health sector when compared to other sectors. In conclusion, implications and directions for further research are addressed.

Motivate me to exercise with you: The effects of social media fitness influencers on users' intentions to engage in physical activity and the role of user gender.

Objective: Social media fitness influencers are evolving into a new digital form of health communicators whom consumers might turn to for assistance with more physical activity and exercise at home, especially in the current COVID-19 crisis. Drawing from source credibility theory, social cognitive theory, protection motivation theory and literature on physical activity, physical fitness and gender, we analyse how male and female users' evaluations of social media fitness influencers and user health-related variables impact intentions to exercise with the social media fitness influencer. Methods: Two consecutive studies using male and female YouTube fitness influencers were carried out. Structural equation modelling was conducted to test the proposed models and estimate the path coefficients. Results: Study 1 (N = 507) shows that the respective influencer's perceived trustworthiness, expertise and attractiveness are important for the influencer's evaluation, and that it is the perceived motivating power rather than the attitude toward the influencer that increases intentions to exercise for male and female users. Study 2 (N = 445) extends Study 1 and shows that physical fitness, training involvement with YouTube fitness videos and lower health increase behavioural intentions. A more negative body image also raises intentions to exercise, but only among female users. Conclusion: Social media fitness influencers who are perceived as trustworthy, as experts and as attractive, can be effective for increasing men's and women's physical activity. Perceived motivating power of the influencer emerged as a key variable that predicts intentions to exercise. User health-related variables have different effects on intentions to exercise for men and women.

Evolution of Investigating Informed Assent Discussions about CPR in Seriously Ill Patients.

CONTEXT: Outcomes after cardiopulmonary resuscitation (CPR) remain poor. We have spent 10 years investigating an "informed assent" (IA) approach to discussing CPR with chronically ill patients/families. IA is a discussion framework whereby patients extremely unlikely to benefit from CPR are informed that unless they disagree, CPR will not be performed because it will not help achieve their goals, thus removing the burden of decision-making from the patient/family, while they retain an opportunity to disagree. OBJECTIVES: Determine the acceptability and efficacy of IA discussions about CPR with older chronically ill patients/families. METHODS: This multi-site research occurred in three stages. Stage I determined acceptability of the intervention through focus groups of patients with advanced COPD or malignancy, family members, and physicians. Stage II was an ambulatory pilot randomized controlled trial (RCT) of the IA discussion. Stage III is an ongoing phase 2 RCT of IA versus attention control in in patients with advanced chronic illness. RESULTS: Our qualitative work found the IA approach was acceptable to most patients, families, and physicians. The pilot RCT demonstrated feasibility and showed an increase in participants in the intervention group changing from "full code" to "do not resuscitate" within two weeks after the intervention. However, Stages I and II found that IA is best suited to inpatients. Our phase 2 RCT in older hospitalized seriously ill patients is ongoing; results are pending. CONCLUSIONS: IA is a feasible and reasonable approach to CPR discussions in selected patient populations.

Platelet, not endothelial, P-selectin expression contributes to generation of immunity in cutaneous contact hypersensitivity.

Leukocyte extravasation is a prerequisite for host defense and autoimmunity alike. Detailed understanding of the tightly controlled and overlapping sequences of leukocyte extravasation might aid development of novel therapeutic strategies. Leukocyte extravasation is initiated by interaction of selectins with appropriate carbohydrate ligands. Lack of P-selectin expression leads to decreased contact hypersensitivity responses. Yet, it remains unclear if this is due to inhibition of leukocyte extravasation to the skin or due to interference with initial immune activation in lymph nodes. In line with previous data, we here report a decreased contact hypersensitivity response, induced by 2,4,-dinitrofluorobenzene (DNFB), in P-selectin-deficient mice. Eliciting an immune reaction towards DNFB in wild-type mice, followed by adoptive transfer to P-selectin-deficient mice, had no impact on inflammatory response in recipients. This was significantly reduced in wild-type recipient mice adoptively transferred with DNFB immunity generated in P-selectin-deficient mice. To investigate if platelet or endothelial P-selectin was involved, mice solely lacking platelet P-selectin expression generated by bone marrow transplantation were used. Adoptive transfer of immunity from wild-type mice reconstituted with P-selectin-deficient bone marrow led to a decrease of inflammatory response. Comparing this decrease to the one observed using P-selectin-deficient mice, no differences were observed. Our observations indicate that platelet, not endothelial, P-selectin contributes to generation of immunity in DNFB-induced contact hypersensitivity.

Microdialysis documents changes in the micromilieu of psoriatic plaques under continuous systemic therapy.

Microdialysis is a novel technique suitable to analyse soluble mediators in the skin compartment. We applied this methodical approach to monitor changes in the micromilieu of psoriatic plaques under therapy. Tissue fluid was collected from lesional and non-lesional skin of three patients with severe plaque-type psoriasis prior to as well as after 12 weeks of continuous oral therapy with fumaric acid esters. Concentrations of a spectrum of cytokines and adipokines were measured using a commercial fluorescent bead immunoassay. The procedure was well tolerated even without local anaesthesia. Prior to initiation of therapy, we found elevated levels for IL-2, IL-6, IL-18, IL-23, and resistin in lesional versus non-lesional skin, whereas adiponectin levels were higher in non-lesional skin. All patients showed significant clinical improvement under treatment, paralleled by reduced concentrations of IL-6, IL-18, IL-23, and resistin, but not IL-2 and adiponectin in lesional skin. Thus, we were able to demonstrate through microdialysis a shift in the micromilieu of psoriatic plaques, characterized by reduced levels of pro-inflammatory mediators in three patients under effective systemic anti-inflammatory therapy with fumaric acid esters. Our observations need to be confirmed by larger studies. This approach is limited by practical aspects as it is very time-consuming, but suitable to directly explore pathomechanisms causing the psoriatic phenotype in general and insulin resistance in the skin compartment in particular.

Asking mom: formative research for an HPV vaccine campaign targeting mothers of adolescent girls.

Vaccination against the types of human papillomavirus (HPV) that cause about 70% of cervical cancers is approved for use in girls and women between 9 and 26 years of age and recommended routinely in 11-12-year-old girls. This article reports on the systematic theory-based formative research conducted to develop HPV vaccine messages for a campaign targeting racially diverse mothers of nonvaccinated 11-12-year-old girls in rural Southeastern United States. A consortium of 13 county health departments concerned about high rates of cervical cancer in their region relative to state and national averages initiated the campaign. The research examined behavioral determinants for vaccination decisions as well as mothers' reactions to message frames and emotional appeals. On the basis of focus groups and intercept interviews (n = 79), the authors demonstrated how preproduction message research and production message testing were used to develop messages that would motivate mothers of preteen girls. Core emotional truths that emerged were a mother's instinct to protect her daughter from harm and to embrace aspirations for her daughter's future. Mothers also reacted more positively to text about preventing cervical cancer than about preventing HPV, a sexually transmitted disease. Mothers preferred message concepts with photos of minorities and Caucasian mothers and daughters.

An evaluation of the National Public Health Leadership Institute--1991-2006: part II. Strengthening public health leadership networks, systems, and infrastructure.

CONTEXT: The year-long National Public Health Leadership Institute's (PHLI) goals are to develop the capacity of individual leaders and networks of leaders so that both can lead improvements in public health systems, infrastructure, and population health. OBJECTIVE: To evaluate PHLI's impact on networks, systems, and infrastructure. PARTICIPANTS: Senior leaders from government, health care, associations, and other organizations who graduated from PHLI between 1992 and 2006. INTERVENTION: Retreats; readings, conference calls, and webinars; personal assessments, feedback, and coaching; and action learning projects. METHODS: A cross-sectional survey sent in 2007 to all leaders from the program's first 15 cohorts. Between 1992 and 2006, PHLI graduated 806 leaders. Of the 646 graduates located, 393 (61%) responded, for an overall response rate of 49% (393/806). Telephone interviews of 35 key informants were also conducted. RESULTS: Graduates fostered changes in systems, policies, organizations, and programs and frequently described these changes as resulting from their work as or with networks. Many graduates formed an informal national network of "thought leaders" and volunteered with professional associations to help in creating methods for improving systems and infrastructure. At the state level, graduates worked as informal networks and with associations to restructure services, reorganize agencies, catalyze new laws, and develop programs. Locally, graduates developed coalitions, fostered new laws, and improved programs, among other changes. CONCLUSION: The Centers for Disease Control and Prevention's multiyear sponsorship of a national program fostered national networks among "thought leaders" who helped to lead the development and diffusion of numerous innovations. Public health leadership development program sponsors should foster collaborative leadership by engaging leaders in systems thinking, team leadership, dialogue, conflict resolution, and negotiation, recommend using networks for sustained personal and system development, and link leaders to networks and associations. Networks provide the collective creativity and broad support needed to enact system and infrastructure changes.