Microbes and Parkinson's disease: from associations to mechanisms.

Parkinson's disease (PD) is a neurodegenerative disorder influenced by both genetic and environmental factors. The mechanisms leading to neurodegeneration in PD are still under investigation, with several mechanistic models currently proposed. A number of microorganisms have been associated with increased risk of PD in humans, and recent research using newly developed models has begun to elucidate how these microbes may factor into disease development. Newly identified roles for PD-associated genes in host-microbe interactions and response to infections have also recently been uncovered, providing further evidence for microbial contributions to PD. Here we summarize these recent advances in the field and discuss them in the context of both historical and emerging hypotheses for PD development, with a particular focus on the application of rodent models as systems allowing for mechanistic hypothesis testing.

Characterization of the intestinal microbiota during Citrobacter rodentium infection in a mouse model of infection-triggered Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that has been shown to be influenced by the intestinal milieu. The gut microbiota is altered in PD patients, and murine studies have begun suggesting a causative role for the gut microbiota in progression of PD. We have previously shown that repeated infection with the intestinal murine pathogen Citrobacter rodentium resulted in the development of PD-like pathology in Pink1-/- mice compared to wild-type littermates. This addendum aims to expand this work by characterizing the gut microbiota during C. rodentium infection in our Pink1-/- PD model. We observed little disturbance to the fecal microbiota diversity both between infection timepoints and between Pink1-/- and wild-type control littermates. However, the level of short-chain fatty acids appeared to be altered over the course of infection with butyric acid significantly increasing in Pink1-/- mice and isobutyric acid increasing in wild-type mice.

Intestinal infection triggers Parkinson's disease-like symptoms in Pink1-/- mice.

Parkinson's disease is a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the substantia nigra compacta. Although the mechanisms that trigger the loss of dopaminergic neurons are unclear, mitochondrial dysfunction and inflammation are thought to have key roles1,2. An early-onset form of Parkinson's disease is associated with mutations in the PINK1 kinase and PRKN ubiquitin ligase genes3. PINK1 and Parkin (encoded by PRKN) are involved in the clearance of damaged mitochondria in cultured cells4, but recent evidence obtained using knockout and knockin mouse models have led to contradictory results regarding the contributions of PINK1 and Parkin to mitophagy in vivo5-8. It has previously been shown that PINK1 and Parkin have a key role in adaptive immunity by repressing presentation of mitochondrial antigens9, which suggests that autoimmune mechanisms participate in the aetiology of Parkinson's disease. Here we show that intestinal infection with Gram-negative bacteria in Pink1-/- mice engages mitochondrial antigen presentation and autoimmune mechanisms that elicit the establishment of cytotoxic mitochondria-specific CD8+ T cells in the periphery and in the brain. Notably, these mice show a sharp decrease in the density of dopaminergic axonal varicosities in the striatum and are affected by motor impairment that is reversed after treatment with L-DOPA. These data support the idea that PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson's disease, which highlights the relevance of the gut-brain axis in the disease10.

High-pressure Injection Injuries of the Hand.

High-pressure injection hand injuries are often overlooked, with severe complications owing to the acute inflammatory response. Prognosis for depends on the type of material injected, location of injection, involved pressure, and timing to surgical decompression and debridement. Acute management involves broad-spectrum antibiotics, tetanus prophylaxis, emergent decompression within 6 hours, and complete removal of the injected material. Most patients have residual sequelae of stiffness, pain, sensation loss, and difficulties in returning to work. The hand surgeon's role is prompt surgical intervention, early postoperative motion, and education of patient and staff regarding short- and long-term expectations.

Pronator-sparing technique for volar plating of distal radius fractures.

Acute distal radius fractures are commonly treated by volar locking plate fixation and typically involve reflection of the pronator quadratus for adequate exposure of the fracture. Recently, attention has been centered on the role and repair of the pronator quadratus. This article presents an alternative approach to fixation of distal radius fractures with a pronator-sparing technique that offers similar short-term radiographic outcomes to the conventional volar plating approach.

Characterization of radiation exposure in early-onset scoliosis patients treated with the vertical expandable prosthetic titanium rib.

BACKGROUND: The evaluation and treatment of patients with early-onset scoliosis requires multiple imaging studies and involves potential exposure to high cumulative lifetime doses of ionizing radiation. The Vertical Expandable Prosthetic Titanium Rib (VEPTR) used in the treatment of early-onset scoliosis requires numerous lengthening procedures and frequent radiographic follow-up. The purpose of this study was to quantify the ionizing radiation exposure in pediatric patients undergoing VEPTR treatment and to identify factors that place patients with early-onset scoliosis at greater risk of radiation exposure. METHODS: Data were collected by retrospective review of the records of all patients with early-onset scoliosis who were treated with a VEPTR over a 4-year period (2007 to 2010). Diagnostic radiographs, computed tomography, intraoperative fluoroscopy, and nuclear medicine studies were identified and analyzed for ionizing radiation exposure. Total radiation exposure was determined and compared for risk factors such as etiology (eg, neuromuscular or congenital) and surgeon experience. In addition, radiographic studies directly related and unrelated to scoliosis treatment were compared. RESULTS: Twenty-four patients had 121 surgical procedures (mean 5.0/patients) and 962 imaging studies (mean 40/patients). The mean estimated cumulative radiation dose per patient during follow-up was 86.7 mSv (range, 42.6 to 174.9 mSv) with a mean dose per year of 34 mSv (range, 22.9 to 47.1 mSv). Patients with congenital scoliosis received greater mean amounts of radiation (35.2 mSv) than patients with neuromuscular scoliosis (31.9 mSv). Patients treated within the first 2 years of the study period had higher radiation exposure (42.4 mSv) compared with patients treated in the last 2 years (24.9 mSv) (P<0.001). CONCLUSIONS: Ionizing radiation is an inevitable side effect of the VEPTR treatment for early-onset scoliosis. There are differences in the amount and sources of radiation exposure between patients with early-onset scoliosis secondary to congenital and neuromuscular causes. Surgeon experience is correlated with decreased levels of radiation exposure. Awareness of the potential for high levels of radiation exposure, as well as patient and surgeon-related factors involved, may lead to more effective radiation-reduction strategies. LEVEL OF EVIDENCE: Level IV--retrospective case study.