Chronic Sciatic Neuropathy in Rat Reduces Voluntary Wheel-Running Activity With Concurrent Chronic Mechanical Allodynia.

BACKGROUND: Animal models of peripheral neuropathy produced by a number of manipulations are assessed for the presence of pathologic pain states such as allodynia. Although stimulus-induced behavioral assays are frequently used and important to examine allodynia (ie, sensitivity to light mechanical touch; von Frey fiber test), other measures of behavior that reflect overall function are not only complementary to stimulus-induced responsive measures, but are also critical to gain a complete understanding of the effects of the pain model on quality of life, a clinically relevant aspect of pain on general function. Voluntary wheel-running activity in rodent models of inflammatory and muscle pain is emerging as a reliable index of general function that extends beyond stimulus-induced behavioral assays. Clinically, reports of increased pain intensity occur at night, a period typically characterized with reduced activity during the diurnal cycle. We therefore examined in rats whether alterations in wheel-running activity were more robust during the inactive phase compared with the active phase of their diurnal cycle in a widely used rodent model of chronic peripheral neuropathic pain, the sciatic nerve chronic constriction injury (CCI) model. METHODS: In adult male Sprague Dawley rats, baseline (BL) hindpaw threshold responses to light mechanical touch were assessed using the von Frey test before measuring BL activity levels using freely accessible running wheels (1 hour/day for 7 sequential days) to quantify the distance traveled. Running wheel activity BL values are expressed as total distance traveled (m). The overall experimental design was after BL measures, rats underwent either sham or CCI surgery followed by repeated behavioral reassessment of hindpaw thresholds and wheel-running activity levels for up to 18 days after surgery. Specifically, separate groups of rats were assessed for wheel-running activity levels (1 hour total/trial) during the onset (within first 2 hours) of either the (1) inactive (n = 8/group) or (2) active (n = 8/group) phase of the diurnal cycle. An additional group of CCI-treated rats (n = 8/group) was exposed to a locked running wheel to control for the potential effects of wheel-running exercise on allodynia. The 1-hour running wheel trial period was further examined at discrete 20-minute intervals to identify possible pattern differences in activity during the first, middle, and last portions of the 1-hour trial. The effect of neuropathy on activity levels was assessed by measuring the change from their respective BLs to distance traveled in the running wheels. RESULTS: Although wheel-running distances between groups were not different at BL from rats examined during either the inactive phase of the diurnal cycle or active phase of the diurnal cycle, sciatic nerve CCI reduced running wheel activity levels compared with sham-operated controls during the inactive phase. In addition, compared with sham controls, bilateral low-threshold mechanical allodynia was observed at all time points after surgical induction of neuropathy in rats with free-wheel and locked-wheel access. Allodynia in CCI compared with shams was replicated in rats whose running wheel activity was examined during the active phase of the diurnal cycle. Conversely, no significant reduction in wheel-running activity was observed in CCI-treated rats compared with sham controls at any time point when activity levels were examined during the active diurnal phase. Finally, running wheel activity patterns within the 1-hour trial period during the inactive phase of the diurnal cycle were relatively consistent throughout each 20-minute phase. CONCLUSIONS: Compared with nonneuropathic sham controls, a profound and stable reduction of running wheel activity was observed in CCI rats during the inactive phase of the diurnal cycle. A concurrent robust allodynia persisted in all rats regardless of when wheel-running activity was examined or whether they ran on wheels, suggesting that acute wheel-running activity does not alter chronic low-intensity mechanical allodynia as measured using the von Frey fiber test. Overall, these data support that acute wheel-running exercise with limited repeated exposures does not itself alter allodynia and offers a behavioral assay complementary to stimulus-induced measures of neuropathic pain.

Moyamoya disease, revascularisation surgery and anaesthetic considerations.

We report a case of a rare disease that requires a unique anaesthetic approach for a unique surgical procedure. Anaesthesiologists need to be familiar with different pathophysiological aspects of this disease and its perioperative management.

Comparative analysis of nucleotide translocation through protein nanopores using steered molecular dynamics and an adaptive biasing force.

The translocation of nucleotide molecules across biological and synthetic nanopores has attracted attention as a next generation technique for sequencing DNA. Computer simulations have the ability to provide atomistic-level insight into important states and processes, delivering a means to develop a fundamental understanding of the translocation event, for example, by extracting the free energy of the process. Even with current supercomputing facilities, the simulation of many-atom systems in fine detail is limited to shorter timescales than the real events they attempt to recreate. This imposes the need for enhanced simulation techniques that expand the scope of investigation in a given timeframe. There are numerous free energy calculation and translocation methodologies available, and it is by no means clear which method is best applied to a particular problem. This article explores the use of two popular free energy calculation methodologies in a nucleotide-nanopore translocation system, using the α-hemolysin nanopore. The first uses constant velocity-steered molecular dynamics (cv-SMD) in conjunction with Jarzynski's equality. The second applies an adaptive biasing force (ABF), which has not previously been applied to the nucleotide-nanpore system. The purpose of this study is to provide a comprehensive comparison of these methodologies, allowing for a detailed comparative assessment of the scientific merits, the computational cost, and the statistical quality of the data obtained from each technique. We find that the ABF method produces results that are closer to experimental measurements than those from cv-SMD, whereas the net errors are smaller for the same computational cost.

The infection risk of plastic wrap as an acute burns dressing.

BACKGROUND: Domestic plastic wrap has been recommended as an appropriate acute burn wound dressing in the Emergency Management of Severe Burns course. There remain limited studies reporting the risk of infection associated with this dressing. AIM: To determine the potential infection risk of domestic plastic wrap used to treat acute burns wounds by assessment for the presence of clinically significant micro-organisms. METHODS: Ten plastic wrap samples were collected from a roll that had been opened for several months on the burns ward at our institution. Plastic wrap was imprinted directly onto horse-blood agar plates. The plates were incubated for 72h in aerobic conditions with 5% CO2. RESULTS: We found no significant growth on any agar plate after incubation. A sufficient amount of plastic wrap was sampled to be confident that areas up to 12cm×12cm from the centre of the plastic sheet were aerobically sterile. CONCLUSIONS: Our data suggest that the potential for plastic wrap to act as a fomite when used as an acute burn wound dressing is extremely low.

Disentangling steric and electrostatic factors in nanoscale transport through confined space.

The voltage-driven passage of biological polymers through nanoscale pores is an analytically, technologically, and biologically relevant process. Despite various studies on homopolymer translocation there are still several open questions on the fundamental aspects of pore transport. One of the most important unresolved issues revolves around the passage of biopolymers which vary in charge and volume along their sequence. Here we exploit an experimentally tunable system to disentangle and quantify electrostatic and steric factors. This new, fundamental framework facilitates the understanding of how complex biopolymers are transported through confined space and indicates how their translocation can be slowed down to enable future sensing methods.

Medical management of paediatric burn injuries: best practice part 2.

Burns remain a leading cause of injury in the paediatric population in Australia despite efforts in prevention. Advances in surgical management include novel debridement methods and blood conserving techniques. Patients with severe burns (>20%) remain significantly more complex to manage as a result of extensive alterations in metabolic processes. There appears increasing evidence to support the use of pharmacological modulators of the hyper-metabolic state in these patients. The management of a child with burns involves acute, subacute and long-term planning. This holistic approach seems optimally co-ordinated by a Burns Unit in which each discipline required to provide care to these children in order to achieve optimal outcomes is represented.

Medical management of paediatric burn injuries: best practice.

Burns commonly occur in children and their first aid remains inadequate despite burn prevention programmes. While scald injuries predominate, contact and flame burns remain common. Although typically less severe injuries overall than those in adults, hypertrophic scarring complicating both the burn wound and even donor sites occur more frequently in children. The heterogeneous nature of burn wounds, coupled with the difficulties associated with the early clinical assessment of burn depth, has stimulated the application of novel technologies to predict burn wound outcome. This review explores current best practice in the management of paediatric burns, with a focus on prevention, optimal first aid, resuscitation, burn wound prediction and wound management strategies.

Severe anthrax outbreaks in Italy in 2004: considerations on factors involved in the spread of infection.

Anthrax is a disease of humans and animals caused by the encapsulated, spore-forming Bacillus anthracis. In Italy, anthrax is normally a sporadic disease. During the summer 2004, anthrax broke out in the Basilicata, in southern Italy, a region with a low prevalence of anthrax in which vaccination had been suspended since 1998. The disease involved several animals in few weeks and in a large area. Over 41 days, 81 cattle died, as well as 15 sheep, 9 goats, 11 horses and 8 deer. The Multiple-locus Variable-Number Tandem Repeats Analysis (MLVA) showed that all the 53 isolates belonged to the Cluster Ala, genotype 1. The results of the Single Nucleotide Repeats (SNRs) Analysis showed that 48/53 B. anthacis strains belonged to a single clonal lineage, the sub-genotype sgt - eB. Two sporadic mutants, sgt - eB,m1 and sgt - eB,m2, were isolated, only one managing to infect other herds. Factors that could have contributed to the spread of infection, such as the transmission of spores by insect vectors and the favourable weather conditions were evaluated.

Anthrax undervalued zoonosis.

Anthrax is a non-contagious disease, known since ancient times. However, it became a matter of global public interest after the bioterrorist attacks in the U.S.A. during the autumn of 2001. The concern of politicians and civil authorities everywhere towards this emergency necessitated a significant research effort and the prevention of new bioterrorist acts. Anthrax is primarily a disease that affects livestock and wildlife; its distribution is worldwide; and it can represent a danger to humans but especially more so when it occurs in areas considered to be free and in atypical seasons and climatic conditions. The atypicality of the phenomenon may lead health workers to misdiagnose and, consequently, an inappropriately manage of affected carcasses with a consequent and inevitable increase in the risk of human infection. This article emphasises the importance of paying increasing attention to this zoonosis. The biggest risk is its underestimation.

Introduction of new safety technologies into central venous access.

The American Society of Anesthesiologists, the Anesthesia Patient Safety Foundation, the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO), and the Patient Safety and Quality Improvement Act of 2005 encourage anesthesiology departments to institute systematic improvements in patient safety, including but not limited to integration of new safety technologies. The evaluation and method of use of the reciprocating procedure device in central venous access is presented.

Delayed cooling of an acute scald contact burn injury in a porcine model: is it worthwhile?

The current Australia and New Zealand Burn Association recommended burns first aid treatment is to place the burn under cool running water for 20 minutes. Immediate cooling of a burn wound has been shown to reduce the depth of the injury. Cooling has also been recommended as beneficial for up to 3 hours after the burn. No scientific data currently exist to support this recommendation. The aim of this study was to identify the effect of delayed cooling of an acute scald contact burn wound in a porcine model. Four partial-thickness contact scald burn injuries were induced in 12 piglets each. First aid treatment consisting of cool running water for 20 minutes was instituted randomly to each wound at different time points: immediately and at time delays of 5, 20, and 60 minutes. The group receiving immediate first aid with cool running water for 20 minutes served as the control group. At day 1 and day 9, biopsies were obtained and assessed in a blinded manner. Histologic analysis of burn depth on days 1 and 9 demonstrated no significant difference in the depth of the burn in the various treatment groups in comparison to the control group receiving immediate first aid. No significant differences in the surface areas of each burn were noted between the various treatment groups on day 9. Core body temperature did not fall below 35 degrees C throughout the cooling process. This study provides scientific evidence that in an animal model delayed cooling for up to 60 minutes postacute contact scald burn is still effective compared with immediate cooling at reducing burn depth.

Determination of Free Energy Profiles for the Translocation of Polynucleotides through α-Hemolysin Nanopores using Non-Equilibrium Molecular Dynamics Simulations.

The translocation of polynucleotides through transmembrane protein pores is a fundamental biological process with important technological and medical relevance. The translocation process is complex, and it is influenced by a range of factors including the diameter and inner surface of the pore, the secondary structure of the polymer, and the interactions between the polymer and protein. In this paper, we perform nonequilibrium constant velocity-steered molecular dynamics simulations of nucleic acid molecule translocation through the protein nanopore α-hemolysin and use Jarzynski's identity to determine the associated free energy profiles. With this approach we are able to explain the observed differences in experimental translocation time through the nanopore between polyadenosine and polydeoxycytidine. The translocation of polynucleotides and single nucleotides through α-hemolysin is investigated. These simulations are computationally intensive as they employ models with atomistic level resolution; in addition to their size, these systems are challenging to study due to the time scales of translocation of large asymmetric molecules. Our simulations provide insight into the role of the interactions between the nucleic acid molecules and the protein pore. Mutated protein pores provide confirmation of residue-specific interactions between nucleotides and the protein pore. By harnessing such molecular dynamics simulations, we gain new physicochemical insight into the translocation process.

Optimal duration of cooling for an acute scald contact burn injury in a porcine model.

The Australian and New Zealand Burn Association recommend 20 minutes of cold running tap water as burn first aid. Scientific evidence for the optimal duration of treatment is limited. Our aim was to establish the optimal duration of cooling using cold running tap water to treat the acute burn. Partial thickness contact scald burns were induced at five sites in each of 17 pigs. Treatments with cold running tap water for 5, 10, 20, and 30 minutes were randomly allocated to different sites together with an untreated control site. In the running water 5 and 10 minute treatments intradermal temperatures rose by 1 degrees C per minute when cooling was stopped, compared with 0.5 degrees C per minute for 20 and 30 minutes duration. No differences in the surface area of each burn were noted between the five treatments on day 9. Histological analysis of burn depth on days 1 and 9 revealed that a higher proportion of burns treated for 20 and 30 minutes showed improvement compared with those treated for 5 and 10 minutes only. This difference reached statistical significance (P < .05) only in the cold running water for 20 minutes treatment arm. There was a statistically significant (P < .05) improvement in burn depth in a porcine acute scald burn injury model when the burn was treated with cold running tap water for 20 minutes as opposed to the other treatment durations. This study supports the current burn first aid treatment recommendations for the optimal duration of cooling an acute scald burn.

Unusual neck sinus--first or second cleft?

A sinus tract presenting with an opening around the angle of mandible is suggestive of first cleft remnant. We present the case of a 4-year-old boy with a recurrent discharging sinus around the angle of the right mandible whose internal opening was near the tonsil on imaging. Complete excision was performed with facial nerve monitoring. We discuss technical aspects of the surgery and possible embryology.

Posttraumatic small bowel obstruction in children.

BACKGROUND: The diagnosis of intestinal injuries in children after blunt abdominal trauma can be difficult and delayed. Most children who suffer blunt abdominal trauma are managed nonoperatively, making the diagnosis of intestinal injuries more difficult. We sought to gain information about children who develop intestinal obstruction after blunt abdominal trauma by reviewing our experience. METHODS: Review of records from a pediatric tertiary care center over an 11.5-year period revealed 5 patients who developed small bowel obstruction after blunt trauma to the abdomen. The details of these patients were studied. RESULTS: All patients were previously managed nonoperatively for blunt abdominal trauma. Intestinal obstruction developed 2 weeks to 1 year (median, 21 days) after the trauma. Abdominal x-ray, computerized tomography scan, or barium meal studies were used to establish the diagnosis. The pathology was either a stricture, an old perforation, or adhesions causing the intestinal obstruction. Laparotomy with resection and anastomosis was curative. CONCLUSIONS: Posttraumatic small bowel obstruction is a clinical entity that needs to be watched for in all patients managed nonoperatively for blunt abdominal trauma.