Polyethylene glycol fusion repair prevents reinnervation accuracy in rat peripheral nerve

Functional recovery following a peripheral nerve injury is made easier when regenerating axons correctly reinnervate their original targets. Polyethylene glycol (PEG) has recently been used in attempts to fuse severed peripheral axons during suture‐based repair, but an analysis of target selectivity following such repair has not been undertaken. The rat femoral nerve (in which muscle and cutaneous pathways comingle proximally but segregate distally into separate terminal nerve branches) is a convenient in vivo model for assessing motor neuron regeneration accuracy. The present study uses retrograde labeling of motor neurons to compare reinnervation accuracy after suture‐based nerve repair with and without PEG fusion. The results show that adding PEG to the suture repair site blocked the preference of motor neurons to reinnervate correctly the distal terminal nerve branch to muscle that was seen with suture repair. Retrograde transport and diffusion studies also determined that PEG fusion allowed passage of probes across the repair site, as has previously been seen, but did not result in motor neuron labeling in the spinal cord. The results suggest that PEG fusion disrupts the beneficial trophic influence of muscle on motor neuron reinnervation accuracy normally seen after suture repair and that such fusion‐based approaches may be best suited to nerve injuries in which accurate target reinnervation at the terminal nerve branch level is not a priority. © 2016 Wiley Periodicals, Inc.     

Impact of obesity on dialysis and transplant and its management

Obesity is increasing to unprecedented levels, including in the end-stage kidney disease population, where upwards of 60% of kidney transplant patients are overweight or obese. Obesity poses additional challenges to the care of the dialysis patient, including difficulties in creating vascular access and inserting Tenckhoff catheters, higher rates of catheter malfunction and peritonitis, the need for longer and/or more frequent dialysis (or peritoneal dialysis [PD] exchanges) to achieve adequate clearance, increased metabolic complications particularly with PD, and obesity is a barrier to kidney transplantation. In this article, we review special considerations in performing PD, hemodialysis and transplant in the obese patient, as well as the evidence behind medical and surgical management of obesity in dialysis patients.     

Neutrophil extracellular traps and thrombosis in COVID-19

Journal of Thrombosis and Thrombolysis - Studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events....     

Rapid review of virus risk communication interventions: Directions for COVID-19

ObjectiveIn response to COVID-19, we conducted a rapid review of risk communication interventions to mitigate risk from viruses to determine if such interventions are efficacious.MethodsWe searched for risk communication interventions in four databases: Medline, PsycInfo, the ProQuest Coronavirus Research Database, and CENTRAL. The search produced 1572 articles. Thirty-one articles were included in the final review.ResultsResults showed risk communication interventions can produce cognitive and behavior changes around viruses. Results were more consistently positive for interventions focused on HIV/AIDS as compared to influenza. There was no consistent best intervention approach when comparing peer health, audio/visual, and intensive multi-media interventions. Tailoring risk communication toward a target population, in comparison to not tailoring, was related to better outcomes.ConclusionThe results suggest that risk communication interventions can be efficacious at reducing risk from viruses. They also highlight the complexity of risk communication interventions. Additional research is needed to understand the mechanisms that lead risk communication to reduce risk from viruses.Practical valueResults support risk communication interventions to reduce risk from viruses.     

Positive effects of short course androgen therapy on the neurodevelopmental outcome in boys with 47,XXY syndrome at 36 and 72 months of age

The effects of early androgen treatment on neurodevelopmental performance in pre‐pubertal boys with 47,XXY have not been well investigated. The influence of hormones on brain development in humans suggests that a positive effect on neurodevelopmental outcome in young boys with XXY may be plausible with hormone replacement therapy. The aim of the study was to investigate retrospectively if an early course of androgen treatment (three injections of testosterone enanthate, 25 mg, each) had an impact on specific domains of neurodevelopmental function in boys with 47,XXY at 36 and 72 months of age. One hundred one boys with a karyotype of 47,XXY had neurodevelopmental assessments. The retrospective chart review resulted in one group (n = 34) who had received androgen treatment during infancy and the second group was untreated (N = 67). Statistical analysis was completed to determine if there was a positive effect from treatment observed at 36 and at 72 months on multiple domains of development. There were significant differences in multiple cognitive domains in the group who received androgen treatment, including multiple measures of language, intellectual, and neuromotor skills. Improved function was observed in neurodevelopmental outcome in boys with 47,XXY at 36 and 72 months who had been treated with a short course of androgen treatment in infancy. Continued research is underway to expand our understanding of the relationship of androgen, brain function, and neurobehavioral and neurodevelopmental outcome in boys with 47,XXY. © 2013 Wiley Periodicals, Inc.     

Human defensin alpha-1 causes Trypanosoma cruzi membrane pore formation and induces DNA fragmentation, which leads to trypanosome destruction

Human defensins play a fundamental role in the initiation of innate immune responses to some microbial pathogens. Here we show that human defensin alpha-1 displays a trypanocidal role against Trypanosoma cruzi, the causative agent of Chagas' disease. The toxicity of human defensin alpha-1 against T. cruzi is mediated by membrane pore formation and the induction of nuclear and mitochondrial DNA fragmentation, leading to trypanosome destruction. Exposure of trypomastigote and amastigote forms of T. cruzi to defensin alpha-1 significantly reduced parasite viability in a peptide concentration-dependent and saturable manner. The toxicity of defensin alpha-1 against T. cruzi is blocked by anti-defensin alpha-1 immunoglobulin G. Electron microscopic analysis of trypomastigotes exposed to defensin alpha-1 revealed pore formation in the cellular and flagellar membranes, membrane disorganization, and blebbing as well as cytoplasmic vacuolization. Furthermore, human defensin alpha-1 enters the trypanosome when membrane pores are present and is associated with later intracellular damage. Trypanosome membrane depolarization abolished the toxicity of defensin alpha-1 against the parasite. Preincubation of trypomastigotes with defensin alpha-1 followed by exposure to human epithelial cells significantly reduced T. cruzi infection in these cells. Thus, human defensin alpha-1 is an innate immune molecule that causes severe toxicity to T. cruzi and plays an important role in reducing cellular infection. This is the first report showing that human defensin alpha-1 causes membrane pore formation in a human parasite, leading to trypanosome destruction.