Urban policy interventions to reduce traffic emissions and traffic-related air pollution: Protocol for a systematic evidence map.

INTRODUCTION: Cities are the world's engines of economic growth, innovation, and social change, but they are also hot spots for human exposure to air pollution, mainly originating from road traffic. As the urban population continues to grow, a greater quantity of people risk exposure to traffic-related air pollution (TRAP), and therefore also risk adverse health effects. In many cities, there is scope for further improvement in air quality through targeted urban policy interventions. The objective of this protocol is to detail the methods that will be used for a systematic evidence map (SEM) which will identify and characterize the evidence on policy interventions that can be implemented at the urban-level to reduce traffic emissions and/or TRAP from on-road mobile sources, thus reducing human exposures and adverse health impacts. METHODS: Articles will be searched for and selected based on a predetermined search strategy and eligibility criteria. A variety of databases will be searched for relevant articles published in English between January 1, 2000 and June 1, 2020 to encompass the interdisciplinary nature of this SEM, and articles will be stored and screened using Rayyan QCRI. Predetermined study characteristics will be extracted and coded from included studies in a Microsoft Excel sheet, which will serve as an open access, interactive database, and two authors will review the coded data for consistency. The database will be queryable, and various interactive charts, graphs, and maps will be created using Tableau Public for data visualization. The results of the evidence mapping will be detailed via narrative summary. CONCLUSION: This protocol serves to increase transparency of the SEM methods and provides an example for researchers pursuing future SEMs.

Placental membrane grafts for urethral replacement in a rabbit model: a pilot study.

PURPOSE: Several graft materials are available for use in the treatment of urethral stricture disease. Placental membrane is being used in a variety of settings as a graft in wound healing and tissue repair. We aim to evaluate the effect of implanting decellularized human placental membrane into rabbit urethras. METHODS: Dorsal onlay graft urethroplasty using prepared human placental membrane was performed in 10 New Zealand White rabbits (Oryctolagus cuniculus). After 3 months, the rabbits underwent cystourethroscopy to evaluate urethral patency. The rabbits were then euthanized and the urethras examined for pathological findings. RESULTS: All urethroplasties were performed without complication. There were no observed episodes of urinary retention, infection, or renal failure. Urethral patency was achieved in all rabbits 3 months postoperatively. Urothelial replacement of the placental membrane graft was observed in all rabbits without malignant transformation. CONCLUSION: Dorsal onlay urethroplasty using decellularized human placental membrane can safely be performed in a rabbit model. This pilot study demonstrated urothelial replacement of human placental membrane in the rabbit urethra without stricture formation. Placental membrane is a promising biomaterial for urethral reconstruction.

Characterization of the Testicular Toxicity of 3-Nitro-1,2,4-Triazol-5-One and 2,4-Dinitroanisole in Rats ( Rattus norvegicus).

Nitrotriazolone (3-nitro-1,2,4-triazol-5-one; NTO) and dinitroanisole (2,4-dinitroanisole; DNAN), insensitive energetic materials used in explosive formulations, have induced testicular toxicity and oligospermia in repeated-dose oral toxicity tests. To identify the target site of testicular toxicity of NTO and DNAN, Sprague Dawley rats were orally dosed with NTO (500 mg/kg/d) or DNAN (50 or 100 mg/kg/d) in corn oil for 1, 3, 7, or 14 days. Degeneration of germinal epithelium occurred in multiple tubule stages on days 7 and 14 in treated rats. Degeneration increased in severity with time and was characterized by degeneration/apoptosis of pachytene spermatocytes and round and elongating spermatids, depletion of step 19 spermatids, luminal spermatogenic cell sloughing, multinucleate cells, and pronounced Sertoli cell vacuolation. Serum luteinizing hormone and follicle-stimulating hormone did not differ between NTO- and DNAN-treated and control rats on any sampling day. Serum testosterone levels reduced only in rats given 50 mg/kg/d DNAN for 7 days. These results suggest that the initial site of testicular injury for both NTO and DNAN is the Sertoli cell.

Rhesus macaque and mouse models for down-selecting circumsporozoite protein based malaria vaccines differ significantly in immunogenicity and functional outcomes.

BACKGROUND: Non-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. Transgenic rodent parasites expressing genes of human Plasmodium are now routinely used for efficacy studies of human malaria vaccines. Mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are sufficient to move a vaccine candidate into the clinic. METHODS: A comparison of immunogenicity, fine-specificity and functional activity of two Alum-adjuvanted Plasmodium falciparum circumsporozoite protein (CSP)-based vaccines was conducted in mouse and rhesus models. One vaccine was a soluble recombinant protein (CSP) and the other was the same CSP covalently conjugated to the Qß phage particle (Qß-CSP). RESULTS: Mice showed different kinetics of antibody responses and different sensitivity to the NANP-repeat and N-terminal epitopes as compared to rhesus. While mice failed to discern differences between the protective efficacy of CSP versus Qß-CSP vaccine following direct challenge with transgenic Plasmodium berghei parasites, rhesus serum from the Qß-CSP-vaccinated animals induced higher in vivo sporozoite neutralization activity. CONCLUSIONS: Despite some immunologic parallels between models, these data demonstrate that differences between the immune responses induced in the two models risk conflicting decisions regarding potential vaccine utility in humans. In combination with historical observations, the data presented here suggest that although murine models may be useful for some purposes, non-human primate models may be more likely to predict the human response to investigational vaccines.