We describe a procedure for isolating agonists for mammalian G protein-coupled receptors of unknown function. Human formyl peptide receptor like-1 (FPRL-1) receptor, originally identified as an orphan G protein-coupled receptor related to the formyl peptide receptor (FPR1), was expressed in Saccharomyces cells designed to couple receptor activation to histidine prototrophy. Selection for histidine prototrophs among transformants obtained with a plasmid-based library encoding random peptides identified six different agonists, each of whose production yielded autocrine stimulation of the receptor expressed in yeast. A synthetic version of each peptide promoted activation of FPRL-1 expressed in human embryonic kidney (HEK293) cells, and five of the peptides exhibited significant selectivity for activation of FPRL-1 relative to FPR1. One selective peptide was tested and found to mobilize calcium in isolated human neutrophils. This demonstrates that stimulation of FPRL-1 results in neutrophil activation and suggests that the receptor functions as a component of the inflammatory response. This autocrine selection protocol may be a generally applicable method for providing pharmacological tools to evaluate the physiological roles of the growing number of mammalian orphan G protein-coupled receptors.

The data once again emphasized that AKI following endovascular aortic repair is an infrequent but morbid complication. For both open and endovascular repair of the abdominal and thoracic aorta, acute kidney injury portends a worse short and long-term outcome even if the patient does not become dialysis dependent.

BACKGROUND: Adults with cerebral palsy (CP) have an increased risk for polypharmacy, premature mortality, and early development of several morbidities, including conditions associated with excess medication exposure, such as chronic kidney disease (CKD) and liver disease. To date, very little is known about the consequence of polypharmacy for adults with CP. OBJECTIVE:To determine if polypharmacy is associated with an increased risk for mortality, severe CKD, and liver disease among adults with CP, before and after adjusting for comorbid neurodevelopmental disabilities (NDDs) and multimorbidity. METHODS:This is an exploratory treatment effectiveness study. Data from the Optum Clinformatics Data Mart were used for this retrospective cohort study. Adults aged 18 years or older with a diagnosis of CP and without severe CKD (stages IV+) and liver disease were identified from the calendar year 2013 and were subsequently followed from January 1, 2014, to death, severe CKD, liver disease, loss to follow-up, or end of study period (December 31, 2017). Diagnosis codes were used to identify NDDs (intellectual disabilities, epilepsy, autism spectrum disorders, spina bifida) and 24 relevant morbidities at baseline (i.e., calendar year 2013). Polypharmacy was defined as ≥ 5 medications and hyperpolypharmacy was defined

Due to complex medical profiles, adults with neurodevelopmental disabilities (NDDs) may have a heightened risk for early development of chronic kidney disease (CKD) and accelerated CKD progression to advanced stages and kidney failure. The purpose of this study was to estimate the incidence rate of advanced CKD for adults with NDDs and compare the incidence rate to adults without NDDs. Patients and Methods: Data were used from the Optum Clinformatics ® Data Mart to conduct this retrospective cohort study. The calendar year 2013 was used to identify eligible participants: individuals ≥18 years of age and without advanced CKD. Participants were followed from 01/01/2014 to advanced CKD, loss to follow-up, death, or end of the study period (12/31/2017), whichever came first. Diagnostic, procedure, and diagnosis-related group codes identified NDDs (intellectual disabilities, cerebral palsy, autism spectrum disorders), incident cases of advanced CKD (CKD stages 4+), diabetes, cardiovascular diseases, and hypertension present in the year 2013. Crude incidence rates (IR) of advanced CKD and IR ratios (IRR), comparing adults with vs without NDDs (with 95% CI) were estimated. Then, Cox regression estimated the hazard ratio (HR and 95% CI) for advanced CKD, comparing adults with NDDs to adults without NDDs while adjusting for covariates. Results: Adults with NDDs (n=33,561) had greater crude IR of advanced CKD (IRR=1.32; 95% CI=1.24-1.42) compared to adults without NDDs (n=6.5M). The elevated rate of advanced CKD among adults with NDDs increased after adjusting for demographics (HR=2.19; 95% CI=2.04-2.34) and remained elevated with further adjustment for hypertension and diabetes (HR=2.01; 95% CI=1.87-2.15) plus cardiovascular disease (HR=1.84; 95% CI=1.72-1.97). Stratified analyses showed that the risk of advanced CKD was greater for all NDD subgroups. Conclusion: Study findings suggest that adults with NDDs have a greater risk of advanced CKD than do adults without NDDs, and that difference is not explained by covariates used in our analysis.

BACKGROUND: Adults with cerebral palsy (CP) have increased risk for developing various secondary chronic diseases, especially when they have other neurodevelopmental disabilities (NDDs). Multiple medications are likely prescribed to manage the greater morbidity-related burden for adults with CP; however, because health care delivery and care coordination is suboptimal for this population, adults with CP may have an increased risk for polypharmacy. To date, very little is known about the prescribing practices and extent of polypharmacy for adults with CP.