Parkinson’s disease is a neurodegenerative disorder that reduces a patients’ quality of life by the relentless progression of motor and non-motor symptoms. Among the non-motor symptoms is a condition called neurogenic bladder that is associated with detrusor muscle underactivity or overactivity occurring from neurologic damage. In Parkinson’s disease, Lewy-body-like protein aggregation inside neurons typically contributes to pathology. This is associated with dopaminergic neuron loss in substantia nigra pars compacta (SNc) and in ventral tegmental area (VTA), both of which play a role in micturition. GM1 gangliosides are mature glycosphingolipids that enhance normal myelination and are reduced in Parkinson’s brain. To explore the role of mature gangliosides in vivo, we obtained GM2 Synthase knockout (KO) mice, which develop parkinsonian pathology including a loss of SNc dopaminergic neurons, which we reconfirmed. However, bladder function and innervation have never been assessed in this model. We compared GM2 Synthase KO and wild type (WT) littermates’ urination patterns from 9–19 months of age by counting small and large void spots produced during 1 hour tests. Because male and female mice had different patterns, we evaluated data by sex and genotype. Small void spots were significantly increased in 12–16 month GM2 Synthase KO females, consistent with overactive bladder. Similarly, at 9–12 month GM2 KO males tended to have more small void spots than WT males. As GM2 Synthase KO mice aged, both females and males had fewer small and large void spots, consistent with detrusor muscle underactivity. Ultrasounds confirmed bladder enlargement in GM2 Synthase KO compared to WT mice. Tyrosine hydroxylase (TH) immunohistochemistry revealed significant dopaminergic loss in GM2 Synthase KO VTA and SNc, and a trend toward TH loss in GM2 KO periaqueductal gray (PAG) micturition center. Levels of the nerve growth factor precursor, proNGF, were significantly increased in GM2 Synthase KO bladders and transmission electron micrographs established atypical myelination of pelvic ganglion innervation in GM2 Synthase KO bladders. Cumulatively, our findings provide the first evidence that mature ganglioside loss affects micturition center TH neurons as well as proNGF dysregulation and innervation of the bladder. Thus, identifying therapies that will counteract these effects could be beneficial for those suffering from Parkinson’s disease and related disorders.
Background Hemorrhage is the leading cause of death in trauma patients with most fatalities occurring before reaching a higher level of care—this applies to both the civilian setting and the military combat setting. Hemostatic resuscitation with increased emphasis on blood transfusion while limiting use of crystalloids has become routine in trauma care. However, the prehospital setting—especially in combat—presents unique challenges with regard to storage, transport, and administration. We sought to evaluate available technology on the market for storage and administration technology that is relevant to the prehospital setting. Study design and methods We conducted a market review of available technology through subject–matter expert inquiry, reviews of published literature, reviews of Federal Drug Administration databases, internal military publications, and searches of Google. Results We reviewed and described a total of 103 blood transporters, 22 infusers, and 6 warmers. Conclusions The risk of on‐scene fatality in trauma patients and recent developments in trauma care demonstrate the need for prehospital transfusion. These transfusions have been logistically prohibited in many operations. We have reviewed the current commercially available equipment and recommended pursuit of equipment that improves accessibility to field transfusion. Current technology has limited applicability for the prehospital setting and is further limited for the military setting.
AimsTo assess the viability of a peripheral extremity amputation and haemorrhage model for testing topical haemostatic dressings, and secondarily to test whether a topical haemostatic dressing would arrest bleeding and maintain haemostasis without a tourniquet in this model.MethodsAn animal model was used during proof of principle model development. Bilateral through-elbow amputations were performed on a single swine under anaesthetic and treated with application of Celox Rapid topical haemostatic dressing (Celox gauze) to the stump after 30 seconds of free bleeding. Following initial haemostasis, the wound sites were bandaged using standard trauma dressings. Vital signs were monitored throughout the study.ResultsThe animal survived and, in both amputations, haemorrhage was successfully controlled. There was no evidence of re-bleeding during the 30 minutes post-injury or following removal of the packed Celox gauze from the wound sites.ConclusionTopical haemostatic dressings could be considered alongside tourniquets for use as a primary treatment of peripheral extremity haemorrhage due to traumatic amputation. It may be useful in prolonged field care where evacuation is delayed or where tourniquet alone does not provide adequate haemorrhage control.
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