Critical data‐based re‐evaluation of minocycline as a putative specific microglia inhibitor

Minocycline, a second generation broad‐spectrum antibiotic, has been frequently postulated to be a “microglia inhibitor.” A considerable number of publications have used minocycline as a tool and concluded, after achieving a pharmacological effect, that the effect must be due to “inhibition” of microglia. It is, however, unclear how this “inhibition” is achieved at the molecular and cellular levels. Here, we weigh the evidence whether minocycline is indeed a bona fide microglia inhibitor and discuss how data generated with minocycline should be interpreted. GLIA 2016;64:1788–1794     

A study of confidential unit exclusion

The effectiveness of the confidential unit exclusion (CUE) procedure recommended by the Food and Drug Administration has been questioned by the blood banking community. The purpose of this study was to determine whether donors were informing the blood center correctly regarding the disposition (transfuse or do not transfuse) of their donated blood. A letter explaining the confidential study and requesting permission to send the participant a questionnaire noting his or her self-exclusion choice was mailed to 230 donors who had chosen transfuse and 276 donors who had chosen do not transfuse. After consent was obtained, participants were sent a second packet and asked to indicate whether they had chosen correctly and, if not, to identify reasons for that incorrect choice. A seven-word terminology quiz made up of words from the CUE form was also enclosed. All participants who had chosen transfuse indicated that this was the correct choice. Approximately 50 percent of those who had chosen do not transfuse indicated that this was an incorrect choice; the most common reason was that "I was not paying attention." The most frequently misunderstood term was "confidential." Donors who chose do not transfuse had a significantly higher rate of error on the terminology quiz (p less than 0.01) than did those who chose transfuse.     

A retrospective explanatory case study of the implementation of a bleeding management quality initiative,in an Australian cardiac surgery unit

Background

Bleeding management in cardiac surgery is challenging. Many guidelines exist to support bleeding management; however, literature demonstrates wide variation in practice. In 2012, a quality initiative was undertaken at The Prince Charles Hospital, Australia to improve bleeding management for cardiac surgery patients. The implementation of the quality initiative resulted in significant reductions in the incidence of blood transfusion, re-exploration for bleeding; superficial leg and chest wound infections; length of hospital stay, and cost. Given the success of the initiative, we sought to answer the question; “How and why was the process of implementing a bleeding management quality initiative in the cardiac surgery unit successful, and sustainable?”

Alterations of action potentials and the localization of Nav1.6 sodium channels in spared axons after hemisection injury of the spinal cord in adult rats

Previously, we reported a pronounced reduction in transmission through surviving axons contralateral to chronic hemisection (HX) of adult rat spinal cord. To examine the cellular and molecular mechanisms responsible for this diminished transmission, we recorded intracellularly from lumbar lateral white matter axons in deeply anesthetized adult rats in vivo and measured the propagation of action potentials (APs) through rubrospinal/reticulospinal tract (RST/RtST) axons contralateral to chronic HX at T10. We found decreased excitability in these axons, manifested by an increased rheobase to trigger APs and longer latency for AP propagation passing the injury level, without significant differences in axonal resting membrane potential and input resistance. These electrophysiological changes were associated with altered spatial localization of Nav1.6 sodium channels along axons: a subset of axons contralateral to the injury exhibited a diffuse localization (>10 μm spread) of Nav1.6 channels, a pattern characteristic of demyelinated axons (Craner MJ, Newcombe J, Black JA, Hartle C, Cuzner ML, Waxman SG. Proc Natl Acad Sci USA 101: 8168-8173, 2004b). This result was substantiated by ultrastructural changes seen with electron microscopy, in which an increased number of large-caliber, demyelinated RST axons were found contralateral to the chronic HX. Therefore, an increased rheobase, pathological changes in the distribution of Nav1.6 sodium channels, and the demyelination of contralateral RST axons are likely responsible for their decreased conduction chronically after HX and thus may provide novel targets for strategies to improve function following incomplete spinal cord injury.     

The ortho-plastic management of Gustilo grade IIIB fractures of the tibia in children: A systematic review of the literature

Background

The challenges of managing Gustilo IIIB tibial fractures in children are unique. A multi-disciplinary, evidence based approach is needed. We aimed to evaluate the evidence for the ortho-plastic management of Gustilo grade IIIB open tibial shaft fractures in children based on a review of all published data in order to rationalise the orthopaedic and plastic surgical approach to these complex injuries.

Method

A systematic review of the literature was performed. Gustilo grade IIIB tibial shaft fractures in pre-adolescent and adolescent children were identified and evaluated with regard to both the skeletal and soft tissue management, and the outcome.

Results

Of 54 children with grade IIIB tibial fractures, a mean union time of 31 weeks included 33 weeks for 42 adolescents and 23 weeks for 12 pre-adolescents. Faster union time in pre-adolescents tended towards significance. Delayed union occurred in 22%, nonunion in 13%, mostly in adolescents. Two of 45 covered by vascularised flaps and 3 of 9 treated without flaps developed deep infection (p = 0.028). There was no correlation between method of skeletal fixation and union time.

Conclusion

Gustilo IIIB tibial shaft fractures in pre-adolescents tended towards faster healing with fewer complications, irrespective of the method of skeletal fixation. In adolescents, healing times were similar to adults. Soft tissue closure without flaps was associated with deep infection in one-third of patients, requiring debridement and flap cover. Adequate debridement and flap cover is suggested in all cases, irrespective of age.     

Drowning deaths of U.S. Service personnel associated with motor vehicle accidents occurring in Operation Iraqi Freedom and Operation Enduring Freedom, 2003-2005

OBJECTIVE: We examined common factors in vehicular drowning deaths that might lead to changes in equipment or training. METHODS: Drowning deaths among service members deployed to Operations Iraqi Freedom or Enduring Freedom, 2003 to 2005, were ascertained using the Armed Forces Medical Examiner Tracking System database. Cases were linked to Army and Navy safety and investigative files. RESULTS: Fifty-two cases of vehicular drowning deaths were identified. These occurred mostly at night, were almost always the result of a rollover, and were most frequently associated with a high-mobility medium-weight vehicle. Seat belts were rarely worn, but the majority of injuries should not have been severe enough to affect egress from the vehicle. These drowning deaths seldom occurred while engaged with the enemy and were rarely associated with bad road conditions or bad weather. CONCLUSIONS: Effective preventive strategies might focus on training and equipment to reduce rollover events and on the expeditious extrication of victims.     

Single dose intranasal immunization with ISCOMATRIX™ vaccines to elicit antibody-mediated clearance of influenza virus requires delivery to the lower respiratory tract

The effectiveness of single dose, intranasally delivered vaccines comprising detergent-disrupted inactivated influenza virus (split virus) and ISCOMATRIX™ adjuvant was examined in mice. Vaccines formulated with adjuvant required 10- to 100-fold less split virus antigen to induce pulmonary protection following viral challenge when compared to vaccines containing split virus alone. Furthermore, those formulated with ISCOMATRIX™ adjuvant elicited specific antibody in serum, saliva, vaginal, nasal and lung fluids when delivered to the entire respiratory tract. No specific antibody was detected in serum or mucosal samples, however, when the same vaccines were delivered using a procedure that restricted the inoculum to the nasal passages. Good protective responses can thus be achieved with only a single intranasal inoculation of influenza vaccine formulated with adjuvant, providing the vaccine can access sites of immune induction in the lower respiratory tract.     

Cardiac output monitoring: basic science and clinical application

Derangements in the circulation are a common feature of sepsis, trauma, major surgery and other critical illnesses. Detailed evaluation of the circulation is therefore an essential aspect of the clinical management of such patients. The use of cardiac output monitoring technology is an increasingly important aspect of evaluating patients in the operating theatre, critical care unit and elsewhere. There are now a number of different technologies available for this purpose, which use a diverse range of physiological principles. A detailed understanding of the physiological principles applied by such technology is essential for safe and effective use in clinical practice. The aim of this article is to describe the physiological principles used to measure cardiac output and their application in various monitors in common clinical use.