Cellular Therapy in Experimental Autoimmune Encephalomyelitis as an Adjuvant Treatment to Translate for Multiple Sclerosis.

This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 105. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.

Community coalition efforts to prevent childhood obesity: two-year results of the Shape Up Under 5 study.

BACKGROUND: Cross-sector collaborations and coalitions are promising approaches for childhood obesity prevention, yet there is little empirical evidence about how they affect change. We hypothesized that changes in knowledge of, and engagement with, childhood obesity prevention among coalition members can diffuse through social networks to influence policies, systems, and environments. METHODS: We studied a community coalition (N = 16, Shape Up Under 5 "SUU5 Committee") focused on early childhood obesity prevention in Somerville, MA from 2015-17. Knowledge, engagement, and social network data were collected from Committee members and their network contacts (n = 193) at five timepoints over two years. Policy, systems, and environment data were collected from the SUU5 Committee. Data were collected via the validated COMPACT Stakeholder-driven Community Diffusion survey and analyzed using regression models and social network analysis. RESULTS: Over 2 years, knowledge of (p = 0.0002), and engagement with (p = 0.03), childhood obesity prevention increased significantly among the SUU5 Committee. Knowledge increased among the Committee's social network (p = 0.001). Significant changes in policies, systems, and environments that support childhood obesity prevention were seen from baseline to 24 months (p = 0.003). CONCLUSION: SUU5 had positive effects on "upstream" drivers of early childhood obesity by increasing knowledge and engagement. These changes partially diffused through networks and may have changed "midstream" community policies, systems, and environments.

Three-Dimensional Bioprinting of an In Vitro Lung Model.

In December 2019, COVID-19 emerged in China, and in January 2020, the World Health Organization declared a state of international emergency. Within this context, there is a significant search for new drugs to fight the disease and a need for in vitro models for preclinical drug tests. This study aims to develop a 3D lung model. For the execution, Wharton's jelly mesenchymal stem cells (WJ-MSC) were isolated and characterized through flow cytometry and trilineage differentiation. For pulmonary differentiation, the cells were seeded in plates coated with natural functional biopolymer matrix as membrane until spheroid formation, and then the spheroids were cultured with differentiation inductors. The differentiated cells were characterized using immunocytochemistry and RT-PCR, confirming the presence of alveolar type I and II, ciliated, and goblet cells. Then, 3D bioprinting was performed with a sodium alginate and gelatin bioink in an extrusion-based 3D printer. The 3D structure was analyzed, confirming cell viability with a live/dead assay and the expression of lung markers with immunocytochemistry. The results showed that the differentiation of WJ-MSC into lung cells was successful, as well as the bioprinting of these cells in a 3D structure, a promising alternative for in vitro drug testing.

Implementing and Evaluating a Stakeholder-Driven Community Diffusion-Informed Early Childhood Intervention to Prevent Obesity, Cuyahoga County, Ohio, 2018-2020.

PURPOSE AND OBJECTIVES: The purpose of this article is to demonstrate and evaluate aspects of a Stakeholder-Driven Community Diffusion (SDCD)-informed intervention with a group of stakeholders drawn from a large coalition seeking a novel approach for promoting policy, systems, and environmental-level change. The objectives were to implement an SDCD intervention, assess changes in participants' perspectives, and evaluate where the group's actions fit within the context of a systems map that the group created during the intervention. INTERVENTION APPROACH: An SDCD-informed intervention convened 12 multisector stakeholders from the Early Ages Healthy Stages coalition in Cuyahoga County, Ohio. They participated in group model building activities to promote systems thinking related to childhood obesity prevention, reviewed evidence about topics of interest to the group, and were provided with technical assistance and seed funding to guide the selection and implementation of actions prioritized by the group. EVALUATION METHODS: Data were collected via meeting notes and group model building outputs to demonstrate implementation and action prioritization; online surveys and qualitative interviews to measure perspective change among stakeholders; and a follow-up survey to the broader coalition assessing actions coalition members were taking. RESULTS: An SDCD-informed intervention guided the development of a systems map and the selection of 4 actions: 1) develop a better understanding of the local early childcare environment; 2) assess the effectiveness and impact of Ohio Healthy Programs (OHP); 3) advocate for OHP and improved early childhood education quality; and 4) hold OHP designees accountable to high-quality programming. Data collected from surveys and interviews showed increased awareness of programs, resources, and collaboration opportunities among stakeholders. Follow-up survey results showed ongoing coalition action throughout the systems map. IMPLICATIONS FOR PUBLIC HEALTH: Using an SDCD-informed intervention among a coalition of community stakeholders provided a unique approach for implementing, assessing, and analyzing collaborative efforts to prevent childhood obesity in Cuyahoga County. Our approach can be applied to help researchers and stakeholders improve efforts to address childhood obesity in their communities.

Biodegradable Nanoparticles Loaded with Levodopa and Curcumin for Treatment of Parkinson's Disease.

Background: Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. Levodopa (L-DOPA) remains the gold-standard drug available for treating PD. Curcumin has many pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anti-amyloid, and antitumor properties. Copolymers composed of Poly (ethylene oxide) (PEO) and biodegradable polyesters such as Poly (ε-caprolactone) (PCL) can self-assemble into nanoparticles (NPs). This study describes the development of NH2-PEO-PCL diblock copolymer positively charged and modified by adding glutathione (GSH) on the outer surface, resulting in a synergistic delivery of L-DOPA curcumin that would be able to pass the blood-brain barrier. Methods: The NH2-PEO-PCL NPs suspensions were prepared by using a nanoprecipitation and solvent displacement method and coated with GSH. NPs were submitted to characterization assays. In order to ensure the bioavailability, Vero and PC12 cells were treated with various concentrations of the loaded and unloaded NPs to observe cytotoxicity. Results: NPs have successfully loaded L-DOPA and curcumin and were stable after freeze-drying, indicating advancing into in vitro toxicity testing. Vero and PC12 cells that were treated up to 72 h with various concentrations of L-DOPA and curcumin-loaded NP maintained high viability percentage, indicating that the NPs are biocompatible. Conclusions: NPs consisting of NH2-PEO-PCL were characterized as potential formulations for brain delivery of L-DOPA and curcumin. The results also indicate that the developed biodegradable nanomicelles that were blood compatible presented low cytotoxicity.

Implementing Group Model Building With the Shape Up Under 5 Community Committee Working to Prevent Early Childhood Obesity in Somerville, Massachusetts.

OBJECTIVE: To describe our process of using group model building (GMB) with the Shape Up Under 5 Committee; measure the effects on Committee members; and describe the community-wide health messaging campaign that resulted from the process. DESIGN: Pilot study. SETTING: Somerville, Massachusetts. PARTICIPANTS: Members of the Shape Up Under 5 Committee, a multisector group of professionals. INTERVENTION: Research team convened the Committee and facilitated GMB from October 2015 to June 2017. MAIN OUTCOME MEASURES: Boundary objects produced during GMB activities; committee members' perspectives on early childhood obesity in their community; and Committee members' knowledge, engagement, and trust at the conclusion of each meeting. RESULTS: Working together using GMB activities and with support from the research team, the Committee created a community-wide campaign that provided evidence-based messages to reach an entire city that emphasized diversity and reaching immigrants and community members who spoke languages other than English. More than 80% of Committee members reported changes in their perspectives related to early childhood obesity at the conclusion of the pilot test. Six perspective shift themes emerged from interviews and open-ended survey items: exposure to new perspectives about challenges community members face; increased awareness of others working on similar issues; increased knowledge about early childhood obesity; seeing value in creating a space to work across sectors; appreciating complexity and linkages between early childhood obesity prevention and other community issues; and how participation in committee influences members' priorities in their own work. Knowledge of and engagement with early childhood obesity prevention varied at the conclusion of each meeting, as did increases in trust among Committee members. CONCLUSION: Group model building is a promising approach to support multisector groups working to address early childhood obesity in their community. Meeting activities may have had differential impacts on members' knowledge of and engagement with early childhood obesity.

Implementing a stakeholder-driven community diffusion-informed intervention to create healthier, more equitable systems: a community case study in Greenville County, South Carolina.

This case study describes the application of a theory-informed, stakeholder-driven intervention with a group of 19 multi-sector stakeholders from an existing coalition to promote whole-of-community change that supports childhood obesity prevention. The intervention applied community-based system dynamics to design and implement activities that promoted insights into the systems driving childhood obesity prevalence and helped participants prioritize actions to influence those systems. This led to three new priority areas for the coalition: addressing food insecurity; building power among historically marginalized voices within the community; and supporting advocacy efforts to promote community-wide change beyond the coalition's previous focus on organizational-level policy, systems and environment change. The intervention spurred the application of community-based system dynamics to other health issues and in partner organizations, which demonstrates paradigm shifts about how to address complex public health issues in the community.

Using Agent-Based Modeling to Extrapolate Community-Wide Impact from a Stakeholder-Driven Childhood Obesity Prevention Intervention: Shape Up Under 5.

Objective: Whole-of-community interventions are a promising systems-based approach to childhood obesity prevention. A theorized driver of success is "Stakeholder-Driven Community Diffusion" (SDCD): the spread of knowledge about and engagement with obesity prevention efforts from a committee of stakeholder representatives. We focus on the potential of SDCD to affect the broader community. Methods: We use an agent-based model of SDCD to dynamically represent the interpersonal interactions that drive community diffusion of knowledge and engagement. We test its explanatory power using longitudinal data from a sample of community members and then use simulations to extrapolate from this limited sample to the unobserved community at large. We also consider counterfactual scenarios that show how changes in implementation strategy might have led to different patterns of community change. Results: Our model can reproduce real-world patterns of diffusion. Simulations show a substantial increase in knowledge (an approximate doubling) and a slight increase in engagement throughout the broader community. A relatively small amount of this change in knowledge (∼10%), and all the change in engagement is attributable to direct intervention effects on committee members. Conclusions: SDCD is premised on creating preconditions for sustainable change. Previous work has estimated impact on small samples closely linked to the stakeholder committee, but the degree to which this translates into the much broader diffusion envisioned by SDCD theory is unknown. This analysis demonstrates the potential of interventions to do just that. Additionally, the counterfactual scenarios suggest that simulation can help tailor implementation of SDCD interventions to increase impact.

Acromegaly due to an ectopic pituitary adenoma in the clivus: case report and review of literature.

Pituitary adenomas rarely originate outside the sella turcica. Ectopic locations include the suprasellar region, sphenoid sinus, cavernous sinus and clivus. We describe a 50-year-old female who presented with clinical signs and biochemical evidence of acromegaly. Pituitary MRI demonstrated a 2 mm hypointense lesion on the right side of the pituitary gland. However upon drilling of the upper clival bone to expose the sella during endoscopic transsphenoidal surgery, soft tumor-like tissue was encountered within the clivus. Exploration of the sella, including the area of hypointensity noted on preoperative imaging, did not identify any other abnormality. Immunohistochemical examination of the fully resected tumor demonstrated growth hormone immunoreactivity. Failed preoperative diagnosis of this rare ectopic GH-producing tumor was compounded by the presence of a misleading pituitary abnormality consistent with a microadenoma. The epidemiology and pertinent literature of this uncommon condition is discussed.

Validation and refinement of the Stakeholder-driven Community Diffusion Survey for childhood obesity prevention.

BACKGROUND: Whole-of-community interventions hold promise in addressing childhood obesity. The COMPACT Stakeholder-driven Community Diffusion theory posits that stakeholders' knowledge of childhood obesity prevention efforts and engagement with the issue contribute to successful intervention implementation. Building on completed formative research and pilot testing, we describe the validation and refinement of knowledge and engagement measures. METHODS: We assessed content validity using a modified Delphi process with science (n=18) and practice-based (n=16) experts. Next, we refined the survey based on input from science- and practice-based experts, cognitive response testing, and item analysis of extant survey data. Field testing of the refined survey involved community stakeholders in Greenville County, South Carolina (n=50), East Boston, Massachusetts (n=30), and Tucson, Arizona (n=84) between 2019 and 2020. Construct validity was assessed with confirmatory factor analysis (CFA). Two-week test-retest reliability was assessed among a subsample of 14 paired respondents in South Carolina. RESULTS: Experts rated existing knowledge domains (intervention factors, roles, sustainability, problem, resources) and engagement domains (dialogue/mutual learning, flexibility, influence/power, leadership/stewardship, trust) highly for their importance in addressing childhood obesity. Expert input resulted in 11 new knowledge items and 7 new engagement items that mapped onto existing domains. Correspondingly, two domain names were modified: implementation/sustainability and trust/trustworthiness. We also eliminated 8 extant items (4 knowledge and 4 engagement) and adapted item language for comprehension and consistency. Further modifications based on CFA results and item analyses resulted in 23 knowledge items across four domains (roles and resources merged) and 23 engagement items across five domains. Modified knowledge and engagement scales had adequate fit and strong item factor loadings (most >0.7 and all >0.5). Knowledge (α=0.86-0.87) and engagement (α=0.75-0.90) subscales had high internal scale consistency. Knowledge intraclass correlation coefficients (ICCs) for test-retest agreement of subscale scores ranged from 0.50 for intervention factors to 0.86 for roles/resources. For engagement subscale scores, ICCs ranged from 0.70 for trust/trustworthiness to 0.96 for leadership/stewardship. CONCLUSIONS: Findings from this multi-method survey development process increase our confidence of the knowledge and engagement measures' content validity, construct validity, and reliability.

Design and methods of Shape Up Under 5: Integration of systems science and community-engaged research to prevent early childhood obesity.

Shape Up Under 5 (SUU5) was a two-year early childhood obesity prevention pilot study in Somerville, Massachusetts (2015-2017) designed to test a novel conceptual framework called Stakeholder-driven Community Diffusion. For whole-of-community interventions, this framework posits that diffusion of stakeholders' knowledge about and engagement with childhood obesity prevention efforts through their social networks will improve the implementation of health-promoting policy and practice changes intended to reduce obesity risk. SUU5 used systems science methods (agent-based modeling, group model building, social network analysis) to design, facilitate, and evaluate the work of 16 multisector stakeholders ('the Committee'). In this paper, we describe the design and methods of SUU5 using the conceptual framework: the approach to data collection, and methods and rationale for study inputs, activities and evaluation, which together may further our understanding of the hypothesized processes within Stakeholder-driven Community Diffusion. We also present a generalizable conceptual framework for addressing childhood obesity and similar complex public health issues through whole-of-community interventions.