Triggering the succinate receptor GPR91 on dendritic cells enhances immunity.

Succinate acts as an extracellular mediator signaling through the G protein-coupled receptor GPR91. Here we show that dendritic cells had high expression of GPR91. In these cells, succinate triggered intracellular calcium mobilization, induced migratory responses and acted in synergy with Toll-like receptor ligands for the production of proinflammatory cytokines. Succinate also enhanced antigen-specific activation of human and mouse helper T cells. GPR91-deficient mice had less migration of Langerhans cells to draining lymph nodes and impaired tetanus toxoid-specific recall T cell responses. Furthermore, GPR91-deficient allografts elicited weaker transplant rejection than did the corresponding grafts from wild-type mice. Our results suggest that the succinate receptor GPR91 is involved in sensing immunological danger, which establishes a link between immunity and a metabolite of cellular respiration.

Can urinary indolylacroylglycine levels be used to determine whether children with autism will benefit from dietary intervention?

BACKGROUND: An increase in urinary indolyl-3-acryloylglycine (IAG) has been reported in children with autism spectrum disorders (ASD) who suffer with bowel problems in comparison to ASD children without gastrointestinal (GI) problems. The case for dietary intervention for ASD children with GI symptoms might be strengthened were such a difference to be autism-specific. METHODS: Quantitative analysis of urinary IAG levels was performed for 53 children on the autism spectrum and 146 age-matched controls. The parents of each child were asked to provide information on bowel symptoms experienced by the child and their eating habits over a period of 2 wk. RESULTS: We find no significant difference in urinary IAG levels between the ASD children with GI problems and ASD children without GI problems. Although we see some difference between ASD children with GI problems and controls in mainstream schools with GI problems, the difference between non-autistic children with other developmental disorders and controls in mainstream schools is more significant so that any difference is not autism-specific. We find a strong correlation between bowel symptoms and diet problems in ASD children, especially idiosyncratic feeding behavior and we show that ASD children suffering from multiple bowel symptoms tend to be those who also have dietary problems. CONCLUSION: We found no evidence to support the hypothesis that children with ASD who suffer with bowel problems have increased levels of urinary IAG in comparison to children with ASD who do not have gastrointestinal problems.

Transformation of a nursing culture through actualization of a nursing professional practice model.

Leading and effecting meaningful change in a nursing division culture, such as the type required to achieve Magnet designation, entails senior nurse executives to be well-acquainted not only with the facts and figures of their business but also with the nuances, myths, and cultures that either enable or block a change from occurring. Expert nurse leaders embrace the story being told by data on dashboards and the quality outcomes achieved and look beyond those points of information out to the edges of their division. These nurse executives also seek to understand the pivotal, perhaps seemingly inconsequential things (notions, beliefs, cultural beliefs, and stories) that will block or tip a culture to change and achieve success. At the Hospital of the University of Pennsylvania (HUP), a Magnet-designated organization, the road to Magnet was not straightforward. Instead, the path was a winding, learning journey. Through authentic leadership and the conception and actualization of a professional practice model, the HUP Nursing Excellence in Professional Practice (HUP NEPP) model, Magnet designation was achieved and a nursing culture was transformed.

Integrated primary nursing: a care delivery model for the 21st-century knowledge worker.

Care delivery models are an integral component for delivering patient care. Although models may be abstract, nursing care delivery models need to be evolving and reality-based, as they serve to organize the allocation of nursing resources. How nursing resources are allocated is associated with patient and professional RN satisfaction, RN perceived autonomy, and quality outcomes. Care delivery models must be evolving within today's dynamic healthcare environment and must be structured within the context of a professional practice model. At the Hospital of the University of Pennsylvania, a Magnet-designated organization, a blend of traditional primary nursing and the updated relationship-based care has been developed and actualized. This model, Integrated Primary Nursing, exists within the framework of the Hospital of the University of Pennsylvania Nursing Excellence in Professional Practice. The coalescence of the 2 has yielded a care delivery model for the 21-st century RN knowledge worker.

Using Telehealth to Reduce All-Cause 30-Day Hospital Readmissions among Heart Failure Patients Receiving Skilled Home Health Services.

BACKGROUND: The reduction of all-cause hospital readmission among heart failure (HF) patients is a national priority. Telehealth is one strategy employed to impact this sought-after patient outcome. Prior research indicates varied results on all-cause hospital readmission highlighting the need to understand telehealth processes and optimal strategies in improving patient outcomes. OBJECTIVES: The purpose of this paper is to describe how one Medicare-certified home health agency launched and maintains a telehealth program intended to reduce all-cause 30-day hospital readmissions among HF patients receiving skilled home health and report its impact on patient outcomes. METHODS: Using the Transitional Care Model as a guide, the telehealth program employs a 4G wireless tablet-based system that collects patient vital signs (weight, heart rate, blood pressure and blood oxygenation) via wireless peripherals, and is preloaded with subjective questions related to HF and symptoms and instructional videos. RESULTS: Year one all-cause 30-day readmission rate was 19.3%. Fiscal year 2015 ended with an all-cause 30-day readmission rate of 5.2%, a reduction by 14 percentage points (a 73% relative reduction) in three years. Telehealth is now an integral part of the University of Pennsylvania Health System's readmission reduction program. CONCLUSIONS: Telehealth was associated with a reduction in all-cause 30-day readmission for one mid-sized Medicare-certified home health agency. A description of the program is presented as well as lessons learned that have significantly contributed to this program's success. Future expansion of the program is planned. Telehealth is a promising approach to caring for a chronically ill population while improving a patient's ability for self-care.

New leads of metallo-beta-lactamase inhibitors from structure-based pharmacophore design.

We have applied pharmacophore generation, database searching, docking methodologies, and experimental enzyme kinetics to discover new structures for design of di-zinc metallo-beta-lactamase inhibitors. Based on crystal structures of class B1 metallo-beta-lactamases with a succinic acid and a mercapto-carboxylic acid inhibitor bound to the enzyme, two pharmacophore models were constructed. With the Catalyst program, these pharmacophores were used to search the ACD database, which provided a total of 74 hits representing four different chemical classes of compounds: Dicarboxylic acids, phosphonic and sulfonic acid derivatives, and mercapto-carboxylic acids. All hits were docked into different metallo-beta-lactamases (from classes B1 and B3) using the GOLD docking program. A selection scheme based on the GOLD scores, the Catalyst fit and shape values, and the size of the compounds (molecular weight, surface area, and number of rotatable bonds) was developed and thirteen compounds representing all four chemical classes were selected for experimental studies. Three compounds with new scaffolds hitherto not present in metallo-beta-lactamase inhibitors have IC50 values less than 15 microM and may serve as starting points in the design of metallo-beta-lactamase inhibitors.