Polynitroxylated pegylated hemoglobin: a novel neuroprotective hemoglobin for acute volume-limited fluid resuscitation after combined traumatic brain injury and hemorrhagic hypotension in mice.

OBJECTIVE: Resuscitation of hemorrhagic hypotension after traumatic brain injury is challenging. A hemoglobin-based oxygen carrier may offer advantages. The novel therapeutic hemoglobin-based oxygen carrier, polynitroxylated pegylated hemoglobin (PNPH), may represent a neuroprotective hemoglobin-based oxygen carrier for traumatic brain injury resuscitation. HYPOTHESES: 1) PNPH is a unique non-neurotoxic hemoglobin-based oxygen carrier in neuronal culture and is neuroprotective in in vitro neuronal injury models. 2) Resuscitation with PNPH would require less volume to restore mean arterial blood pressure than lactated Ringer's or Hextend and confer neuroprotection in a mouse model of traumatic brain injury plus hemorrhagic hypotension. DESIGN: Prospective randomized, controlled experimental study. SETTING: University center. MEASUREMENTS AND MAIN RESULTS: In rat primary cortical neuron cultures, control bovine hemoglobin was neurotoxic (lactate dehydrogenase release; 3-[4,5-dimethylthiazol-2-yl-]-2,5-diphenyltetrazolium bromide assay) at concentrations from 12.5 to 0.625 µM, whereas polyethylene glycol-conjugated hemoglobin showed intermediate toxicity. PNPH was not neurotoxic (p<.05 vs. bovine hemoglobin and polyethylene glycol hemoglobin; all concentrations). PNPH conferred neuroprotection in in vitro neuronal injury (glutamate/glycine exposure and neuronal stretch), as assessed via lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl-]-2,5-diphenyltetrazolium bromide (all p<.05 vs. control). C57BL6 mice received controlled cortical impact followed by hemorrhagic hypotension (2 mL/100 g, mean arterial blood pressure ∼35-40 mm Hg) for 90 min. Mice were resuscitated (mean arterial blood pressure>50 mm Hg for 30 min) with lactated Ringer's, Hextend, or PNPH, and then shed blood was reinfused. Mean arterial blood pressures, resuscitation volumes, blood gasses, glucose, and lactate were recorded. Brain sections at 7 days were examined via hematoxylin and eosin and Fluoro-Jade C (identifying dying neurons) staining in CA1 and CA3 hippocampus. Resuscitation with PNPH or Hextend required less volume than lactated Ringer's (both p<.05). PNPH but not Hextend improved mean arterial blood pressure vs. lactated Ringer's (p<.05). Mice resuscitated with PNPH had fewer Fluoro-Jade C positive neurons in CA1 vs. Hextend and lactated Ringer's, and CA3 vs. Hextend (p<.05). CONCLUSIONS: PNPH is a novel neuroprotective hemoglobin-based oxygen carrier in vitro and in vivo that may offer unique advantages for traumatic brain injury resuscitation.

Interleukin-4 improves white matter integrity and functional recovery after murine traumatic brain injury via oligodendroglial PPARγ.

Long-term neurological recovery after severe traumatic brain injury (TBI) is strongly linked to the repair and functional restoration of injured white matter. Emerging evidence suggests that the anti-inflammatory cytokine interleukin-4 (IL-4) plays an important role in promoting white matter integrity after cerebral ischemic injury. Here, we report that delayed intranasal delivery of nanoparticle-packed IL-4 boosted sensorimotor neurological recovery in a murine model of controlled cortical impact, as assessed by a battery of neurobehavioral tests for up to five weeks. Post-injury IL-4 treatment failed to reduce macroscopic brain lesions after TBI, but preserved the structural and functional integrity of white matter, at least in part through oligodendrogenesis. IL-4 directly facilitated the differentiation of oligodendrocyte progenitor cells (OPCs) into mature myelin-producing oligodendrocytes in primary cultures, an effect that was attenuated by selective PPARγ inhibition. IL-4 treatment after TBI in vivo also failed to stimulate oligodendrogenesis or improve white matter integrity in OPC-specific PPARγ conditional knockout (cKO) mice. Accordingly, IL-4-afforded improvements in sensorimotor neurological recovery after TBI were markedly impaired in the PPARγ cKO mice compared to wildtype controls. These results support IL-4 as a potential novel neurorestorative therapy to improve white matter functionality and mitigate the long-term neurological consequences of TBI.

Trends in CBCT current practice within three UK paediatric dental departments.

INTRODUCTION: Cone beam computed tomography (CBCT) is used across all dental specialties and has a number of advantages compared to 2D images. The SEDENTEXCT guidelines provide a number of indications for the use, however there are currently no specific guidelines for paediatric dentistry. The aim of this study was to assess current practice of CBCT imaging within paediatric dental departments in England, audit compliance of CBCT justifications against the standards set by SEDENTEXCT and assess whether the use of CBCT affected the treatment plan for each individual patient. METHODS: From the retrospective analysis of CBCT examinations taken over a 4-year period across three dental hospitals in the north of England, the following data were collected: age at the time of exposure, clinical indication, region of interest (ROI) and diagnostic findings. Clinical notes were also used to identify whether the CBCT had an effect on the final treatment plan. RESULTS: A total of 335 CBCT examinations were performed, mean age: 11 years. The number of CBCTs increased each year with a twofold increase in the first 2 years. The main clinical indication in 46% of CBCT examinations was the assessment of localised developing dentition, 68% were in the upper anterior sextant and 61% of CBCT exams were in the mixed dentition age group. The investigations were justified in 100% of the cases. CONCLUSION: The quantity of CBCT examination in paediatric dental patients is increasing to assist treatment planning but more often to enable improved surgical planning.

Acceptability of intravenous propofol sedation for adolescent dental care.

PURPOSE: Propofol is an intravenous anaesthetic agent commonly utilised in general anaesthesia, however in sub-anaesthetic concentrations can be utilised to provide sedation through automated dosing of target-controlled infusion (TCI). TCI has been shown to provide accurate and stable predicted plasma and effect-site concentrations of propofol. A four-part mixed-method prospective study was undertaken to evaluate the safety and patient acceptability of intravenous propofol sedation in adolescent patients requiring dental care. There is a paucity in the literature on patient-reported outcomes and patient safety in the management of adolescent patients for dental treatment. METHODS: Demographics were recorded including age, gender, ASA Classification and Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) completed pre-operatively. Behaviour ratings of the Frankl and Houpt scales were recorded followed by post-operative questionnaire and telephone consultation. Consultation was completed following the procedure to determine patient satisfaction, memory of the procedure and any reported side effects of treatment. Qualitative thematic analysis was utilised. RESULTS: 55 patients were recruited for the study, of which 49 (mean age 14.67 years) completed the sedation study and were treated safely with no post-operative complications. The mean lowest oxygen saturation was 98.12% SpO2 (SD 2.6). Thematic analysis demonstrated positive patient-reported outcomes to IV sedation. CONCLUSION: Propofol TCI sedation is an effective treatment modality for the management of dentally anxious adolescents as a safe alternative to general anaesthesia, allowing the opportunity for increased provision of treatment per visit on those patients with a high dental need. Further randomised controlled trials comparing propofol TCI to other pharmacological managements are required.

Diagnostic efficacy of cone beam computed tomography in paediatric dentistry: a systematic review.

PURPOSE: To determine in which clinical situations it is indicated or contra-indicated to prescribe cone beam computed tomography (CBCT) for paediatric patients. METHODS: Systematic review of in vivo paediatric research studies of diagnostic efficacy using CBCT, with supplementary searches for guideline documents on CBCT and for systematic reviews permitting inclusion of ex vivo and adult studies. RESULTS: After screening, 190 publications were included, mostly case studies. No systematic reviews were found of in vivo paediatric research. Fourteen studies of diagnostic efficacy were identified. The supplementary searches found 18 guideline documents relevant to the review and 26 systematic reviews. The diagnostic efficacy evidence on CBCT was diverse and often of limited quality. There was ex vivo evidence for diagnostic accuracy being greater using CBCT than radiographs for root fractures. The multiplanar capabilities of CBCT are advantageous when localising dental structures for surgical planning. Patient movement during scanning is more common in children which could reduce diagnostic efficacy. CONCLUSIONS: No strong recommendations on CBCT are possible, except that it should not be used as a primary diagnostic tool for caries. Guidelines on use of CBCT in the paediatric age group should be developed cautiously, taking into account the greater radiation risk and the higher economic costs compared with radiography. CBCT should only be used when adequate conventional radiographic examination has not answered the question for which imaging was required. Clinical research in paediatric patients is required at the higher levels of diagnostic efficacy of CBCT.

Correction to: Diagnostic efficacy of cone beam computed tomography in paediatric dentistry: a systematic review.

In the original publication of the article the fifth author's name "A. Littlewood" was submitted as "A. Littewood" which was left unnoticed in the later stages. The correct name is as published in this erratum.

Clinical measures of balance in people with type two diabetes: A systematic literature review.

Approximately 422 million people have diabetes mellitus worldwide, with the majority diagnosed with type 2 diabetes mellitus (T2DM). The complications of diabetes mellitus include diabetic peripheral neuropathy (DPN) and retinopathy, both of which can lead to balance impairments. Balance assessment is therefore an integral component of the clinical assessment of a person with T2DM. Although there are a variety of balance measures available, it is uncertain which measures are the most appropriate for this population. Therefore, the aim of this study was to conduct a systematic review on clinical balance measures used with people with T2DM and DPN. Databases searched included: CINAHL plus, MEDLINE, SPORTDiscus, Dentistry and Oral Sciences source, and SCOPUS. Key terms, inclusion and exclusion criteria were used to identify appropriate studies. Identified studies were critiqued using the Downs and Black appraisal tool. Eight studies were included, these studies incorporated a total of ten different clinical balance measures. The balance measures identified included the Dynamic Balance Test, balance walk, tandem and unipedal stance, Functional Reach Test, Clinical Test of Sensory Interaction and Balance, Berg Balance Scale, Tinetti Performance-Oriented Mobility Assessment, Activity-Specific Balance Confidence Scale, Timed Up and Go test, and the Dynamic Gait Index. Numerous clinical balance measures were used for people with T2DM. However, the identified balance measures did not assess all of the systems of balance, and most had not been validated in a T2DM population. Therefore, future research is needed to identify the validity of a balance measure that assesses these systems in people with T2DM.

Effect of an inductive hydrogel composed of urinary bladder matrix upon functional recovery following traumatic brain injury.

Traumatic brain injury (TBI) is a major public health problem with no effective clinical treatment. Use of bioactive scaffold materials has been shown to be a promising strategy for tissue regeneration and repair in a number of injury models. Of these scaffold materials, urinary bladder matrix (UBM) derived from porcine bladder tissue, has demonstrated desirable properties for supporting and promoting the growth of neural cells in vitro, suggesting its potential as a scaffold for brain tissue repair in the treatment of TBI. Herein we evaluate the biocompatibility of UBM within brain tissue and the effects of UBM delivery upon functional outcome following TBI. A hydrogel form of UBM was injected into healthy rat brains for 1, 3, and 21 days to examine the tissue response to UBM. Multiple measures of tissue injury, including reactive astrocytosis, microglial activation, and neuron degeneration showed that UBM had no deleterious effects on normal brain. Following TBI, the brains were evaluated histologically and behaviorally between sham-operated controls and UBM- and vehicle-treated groups. Application of UBM reduced lesion volume and attenuated trauma-induced myelin disruption. Importantly, UBM treatment resulted in significant neurobehavioral recovery following TBI as demonstrated by improvements in vestibulomotor function; however, no differences in cognitive recovery were observed between the UBM- and vehicle-treated groups. The present study demonstrated that UBM is not only biocompatible within the brain tissue, but also can exert protective effects upon injured brain.

Element levels in snakes in South Carolina: differences between a control site and exposed site on the Savannah River site.

Levels of 18 elements, including lead, mercury, selenium, and uranium, were examined in three species of snakes from an exposed and reference site on the Department of Energy's Savannah River Site in South Carolina. We tested the hypotheses that there were no differences as a function of species, and there were no difference between the exposed and control site for blood and muscle (tail) samples for banded water snake (Nerodia fasciata), brown water snake (N. taxispilota) and cotton mouth (Akistrodon piscivorous). The banded water snakes collected were significantly smaller than the other two species. For blood, there were significant species differences only for barium, copper, selenium, uranium and zinc, while for muscle tissue there were significant interspecific differences in aluminum, arsenic, barium, cobalt, cesium, copper, iron, lead, mercury, manganese, strontium, vanadium and zinc, suggesting that muscle tissue in the tail is a better indicator of potential interspecific differences. It is also easier logistically to collect tail tissue than blood. Where one species had significantly higher levels than the other species in muscle tissue levels, cottonmouth had higher levels of five elements (aluminum, cobalt, lead, mercury, vanadium), brown water snake had two (lead, strontium), and banded water snake had only barium. There were few significant differences between the control and reference site for levels of blood, but several for muscle tissue. All three species had significantly higher levels of arsenic and manganese at Tim's Branch than the reference site, and nickel and uranium were significantly higher for banded water snake and cotton mouth, the larger species. Individuals with high exposure of one element were exposed to high levels of other elements.