Generalized Seizure Activity in an Adult Rhesus Macaque (Macaca mulatta) during Ketamine Anesthesia and Urodynamic Studies

We report a case of a generalized seizure in an adult female rhesus macaque (Macaca mulatta) undergoing a urodynamic evaluation while she was anesthetized with continuous-infusion ketamine. The seizure presented with generalized tonic–clonic activity during bladder infusion with saline. The tonic–clonic phase was self-limited and was followed by focal facial twitching, which was interrupted by bolus administration of intravenous diazepam. The ictal event was documented as pressure oscillations during cystometrogram recordings and a period of external urethral sphincter muscle activation, which was detectable by electromyography. An acute decrease in urethral pressure was demonstrated at the end of the generalized seizures. Ketamine anesthesia combined with relatively rapid infusion of saline into the bladder may have contributed to the onset of seizures. In addition, this case highlights the value of having a fast-acting benzodiazepine agent available to stop continuous or residual seizure activity during diagnostic or experimental procedures in anesthetized nonhuman primates.Anesthetic agents are used to sedate and immobilize nonhuman primates for veterinary health care and experimental studies. For these purposes, ketamine, a dissociative general anesthetic, is the agent used most commonly in macaques. Several protocols have been developed for the safe administration of ketamine, either as a single agent or as part of a balanced anesthetic approach administered orally, per rectum, intramuscularly, or intravascularly.^9,16,18 Although ketamine and other anesthetic agents are known to suppress physiologic responses during experimental studies, reflexive micturition may still be evoked, as demonstrated by urodynamic recordings in anesthetized rats.^1,2,10 In addition, urodynamic studies have demonstrated that bladder reflexes are suppressed by anesthesia in nonhuman primates, although comparative studies on the effects of different anesthetic agents have suggested that ketamine may be a suitable anesthetic for cystometrograms in rhesus macaques.⁵Here, parenteral administration of ketamine was used to sedate and immobilize adult rhesus macaques for comprehensive urodynamic studies. In one subject, the infusion of saline into the urinary bladder was associated with the acute onset of a generalized seizure, characterized by a self-limited period of tonic–clonic activity, followed by focal facial twitching, which was relieved by prompt intravenous administration of diazepam, and voiding. The tonic–clonic phase of the event was documented by cystometrography and electromyography recordings. We suggest the administration of ketamine anesthesia and the relatively rapid infusion of saline into the bladder as possible factors that may have contributed to the ictal event in this rare case of a clinical seizure during a urodynamic study in a nonhuman primate.     

Design and structure of two new protein cages illustrate successes and ongoing challenges in protein engineering

In recent years, new protein engineering methods have produced more than a dozen symmetric, self‐assembling protein cages whose structures have been validated to match their design models with near‐atomic accuracy. However, many protein cage designs that are tested in the lab do not form the desired assembly, and improving the success rate of design has been a point of recent emphasis. Here we present two protein structures solved by X‐ray crystallography of designed protein oligomers that form two‐component cages with tetrahedral symmetry. To improve on the past tendency toward poorly soluble protein, we used a computational protocol that favors the formation of hydrogen‐bonding networks over exclusively hydrophobic interactions to stabilize the designed protein–protein interfaces. Preliminary characterization showed highly soluble expression, and solution studies indicated successful cage formation by both designed proteins. For one of the designs, a crystal structure confirmed at high resolution that the intended tetrahedral cage was formed, though several flipped amino acid side chain rotamers resulted in an interface that deviates from the precise hydrogen‐bonding pattern that was intended. A structure of the other designed cage showed that, under the conditions where crystals were obtained, a noncage structure was formed wherein a porous 3D protein network in space group I2₁3 is generated by an off‐target twofold homomeric interface. These results illustrate some of the ongoing challenges of developing computational methods for polar interface design, and add two potentially valuable new entries to the growing list of engineered protein materials for downstream applications.     

A pyritized polychaete from the Devonian of Ontario

A polychaete from the Middle Devonian Arkona Shale at Hungry Hollow, Arkona, Ontario is preserved in three dimensions in pyrite. The prostomium bears a single median antenna, a pair of lateral antennae and a pair of ventral palps. It is assumed to be fused to a reduced peristomium. The anteriormost three pairs of trunk appendages are modified as tentacular cirri, the third long and biramous. The remainder of the finely annulated trunk bears at least 21 similar biramous parapodia, some of which preserve evidence of chaetae. The postsegmental pygidium is very small and may bear up to two pairs of cirri. The polychaete, Arkonips topororum, falls within the Palpata, Aciculata, among the crown group Phyllodocida. Its remarkable preservation highlights the potential of the Arkona Shale to yield other examples of soft-tissue preservation.     

Does the correlation between schmorl's nodes and vertebral morphology extend into the lumbar spine?

Schmorl's nodes are depressions on vertebrae due to herniation of the nucleus pulposus of the intervertebral disc into the vertebral body. This study provides an extension of our previous study which analyzed the shape of the lower thoracic spine and found that vertebral morphology was associated with the presence of Schmorl's nodes. Ninety adult individuals from the late Medieval site of Fishergate House, York, and the Post‐Medieval site of Coach Lane, North Shields, Tyne and Wear, England, were analysed using 2D geometric morphometrics to identify possible relationships between vertebral morphology and Schmorl's nodes at the thoraco‐lumbar junction and in the lumbar spine. A significant correlation was found between vertebral shape and the presence of Schmorl's nodes in the twelfth thoracic vertebrae and the first to third lumbar vertebrae. The findings corroborate previous studies and suggest that vertebral shape may be an important factor in spinal health. It is hypothesized that the pedicle shape of affected vertebrae may not provide adequate structural support for the vertebral bodies, resulting in vertical disc herniation. Am J Phys Anthropol 157:526–534, 2015. © 2015 Wiley Periodicals, Inc.     

Monitoring Vital Signs: Development of a Modified Early Warning Scoring (Mews) System for General Wards in a Developing Country

Objective

The aim of the study was to develop and validate, by consensus, the construct and content of an observations chart for nurses incorporating a modified early warning scoring (MEWS) system for physiological parameters to be used for bedside monitoring on general wards in a public hospital in South Africa.

Methods

Delphi and modified face-to-face nominal group consensus methods were used to develop and validate a prototype observations chart that incorporated an existing UK MEWS. This informed the development of the Cape Town ward MEWS chart.

Participants

One specialist anaesthesiologist, one emergency medicine specialist, two critical care nurses and eight senior ward nurses with expertise in bedside monitoring (N = 12) were purposively sampled for consensus development of the MEWS. One general surgeon declined and one neurosurgeon replaced the emergency medicine specialist in the final round.

Results

Five consensus rounds achieved ≥70% agreement for cut points in five of seven physiological parameters respiratory and heart rates, systolic BP, temperature and urine output. For conscious level and oxygen saturation a relaxed rule of <70% agreement was applied. A reporting algorithm was established and incorporated in the MEWS chart representing decision rules determining the degree of urgency. Parameters and cut points differed from those in MEWS used in developed countries.

Conclusions

A MEWS for developing countries should record at least seven parameters. Experts from developing countries are best placed to stipulate cut points in physiological parameters. Further research is needed to explore the ability of the MEWS chart to identify physiological and clinical deterioration.     

Vertebral morphology influences the development of Schmorl's nodes in the lower thoracic vertebrae

Schmorl's nodes are the result of herniations of the nucleus pulposus into the adjacent vertebral body and are commonly identified in both clinical and archaeological contexts. The current study aims to identify aspects of vertebral shape that correlate with Schmorl's nodes. Two‐dimensional statistical shape analysis was performed on digital images of the lower thoracic spine (T10–T12) of adult skeletons from the late medieval skeletal assemblages from Fishergate House, York, St. Mary Graces and East Smithfield Black Death cemeteries, London, and postmedieval Chelsea Old Church, London. Schmorl's nodes were scored on the basis of their location, depth, and size. Results indicate that there is a correlation between the shape of the posterior margin of the vertebral body and pedicles and the presence of Schmorl's nodes in the lower thoracic spine. The size of the vertebral body in males was also found to correlate with the lesions. Vertebral shape differences associated with the macroscopic characteristics of Schmorl's nodes, indicating severity of the lesion, were also analyzed. The shape of the pedicles and the posterior margin of the vertebral body, along with a larger vertebral body size in males, have a strong association with both the presence and severity of Schmorl's nodes. This suggests that shape and/or size of these vertebral components are predisposing to, or resulting in, vertically directed disc herniation. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc.