Cerebral oximetry and its role in adult cardiac, non-cardiac surgery and resuscitation from cardiac arrest.

Monitors using near-infra red spectroscopy to assess cerebral oxygenation levels non-invasively in discrete areas of the brain have been used clinically for over 20 years. Interest has intensified recently, especially during cardiac surgery, and there are now five commercially available devices. Despite the attraction of being able to measure oxygen supply/demand in such a critical area, there has been only limited uptake of this technology in overall clinical anaesthetic practice. This narrative review aims to explore not only the rationale for using this technology but also the factors which have restricted its more widespread use.

Correction: The nanotipped hairs of gecko skin and biotemplated replicas impair and/or kill pathogenic bacteria with high efficiency.

Correction for 'The nanotipped hairs of gecko skin and biotemplated replicas impair and/or kill pathogenic bacteria with high efficiency' by X. Li, et al., Nanoscale, 2016, 8, 18860-18869.

The nanotipped hairs of gecko skin and biotemplated replicas impair and/or kill pathogenic bacteria with high efficiency.

We show that gecko microspinules (hairs) and their equivalent replicas, bearing nanoscale tips, can kill or impair surface associating oral pathogenic bacteria with high efficiency even after 7 days of repeated attacks. Scanning Electron Microscopy suggests that there is more than one mechanism contributing to cell death which appears to be related to the scaling of the bacteria type with the hair arrays and accessibility to the underlying nano-topography of the hierarchical surfaces.

Four Functionally Distinct Regions in the Left Supramarginal Gyrus Support Word Processing.

We used fMRI in 85 healthy participants to investigate whether different parts of the left supramarginal gyrus (SMG) are involved in processing phonological inputs and outputs. The experiment involved 2 tasks (speech production (SP) and one-back (OB) matching) on 8 different types of stimuli that systematically varied the demands on sensory processing (visual vs. auditory), sublexical phonological input (words and pseudowords vs. nonverbal stimuli), and semantic content (words and objects vs. pseudowords and meaningless baseline stimuli). In ventral SMG, we found an anterior subregion associated with articulatory sequencing (for SP > OB matching) and a posterior subregion associated with auditory short-term memory (for all auditory > visual stimuli and written words and pseudowords > objects). In dorsal SMG, a posterior subregion was most highly activated by words, indicating a role in the integration of sublexical and lexical cues. In anterior dorsal SMG, activation was higher for both pseudoword reading and object naming compared with word reading, which is more consistent with executive demands than phonological processing. The dissociation of these four "functionally-distinct" regions, all within left SMG, has implications for differentiating between different types of phonological processing, understanding the functional anatomy of language and predicting the effect of brain damage.

Diversification and enrichment of clinical biomaterials inspired by Darwinian evolution.

UNLABELLED: Regenerative medicine and biomaterials design are driven by biomimicry. There is the essential requirement to emulate human cell, tissue, organ and physiological complexity to ensure long-lasting clinical success. Biomimicry projects for biomaterials innovation can be re-invigorated with evolutionary insights and perspectives, since Darwinian evolution is the original dynamic process for biological organisation and complexity. Many existing human inspired regenerative biomaterials (defined as a nature generated, nature derived and nature mimicking structure, produced within a biological system, which can deputise for, or replace human tissues for which it closely matches) are without important elements of biological complexity such as, hierarchy and autonomous actions. It is possible to engineer these essential elements into clinical biomaterials via bioinspired implementation of concepts, processes and mechanisms played out during Darwinian evolution; mechanisms such as, directed, computational, accelerated evolutions and artificial selection contrived in the laboratory. These dynamos for innovation can be used during biomaterials fabrication, but also to choose optimal designs in the regeneration process. Further evolutionary information can help at the design stage; gleaned from the historical evolution of material adaptations compared across phylogenies to changes in their environment and habitats. Taken together, harnessing evolutionary mechanisms and evolutionary pathways, leading to ideal adaptations, will eventually provide a new class of Darwinian and evolutionary biomaterials. This will provide bioengineers with a more diversified and more efficient innovation tool for biomaterial design, synthesis and function than currently achieved with synthetic materials chemistry programmes and rational based materials design approach, which require reasoned logic. It will also inject further creativity, diversity and richness into the biomedical technologies that we make. All of which are based on biological principles. Such evolution-inspired biomaterials have the potential to generate innovative solutions, which match with existing bioengineering problems, in vital areas of clinical materials translation that include tissue engineering, gene delivery, drug delivery, immunity modulation, and scar-less wound healing. STATEMENT OF SIGNIFICANCE: Evolution by natural selection is a powerful generator of innovations in molecular, materials and structures. Man has influenced evolution for thousands of years, to create new breeds of farm animals and crop plants, but now molecular and materials can be molded in the same way. Biological molecules and simple structures can be evolved, literally in the laboratory. Furthermore, they are re-designed via lessons learnt from evolutionary history. Through a 3-step process to (1) create variants in material building blocks, (2) screen the variants with beneficial traits/properties and (3) select and support their self-assembly into usable materials, improvements in design and performance can emerge. By introducing biological molecules and small organisms into this process, it is possible to make increasingly diversified, sophisticated and clinically relevant materials for multiple roles in biomedicine.

Bioinspired materials for regenerative medicine: going beyond the human archetypes.

The evolution of life has given rise to innumerable biomaterials with high levels of functional sophistication and performance among many thousands of different environments. The inexhaustible range of strategies and the intrinsic good design they possess can be readily included in the design of biomedical devices and materials, such as wound healing bandages and antibacterial surface coating implants. We highlight topical examples where various ingenious design strategies from biological models, originating more broadly from zoology and botany, have been appropriated into novel synthetic materials and structures for regenerative and material-based tissue engineering. Bioinspired materials engineering informed and enriched by the vast array of adaptations and strategies in nature, beyond human biology, will be instrumental in the future evolution of new more clinically acceptable pan-functional materials and structures with a broad range of uses in the regenerative sciences.

Strontium- and magnesium-enriched biomimetic ß-TCP macrospheres with potential for bone tissue morphogenesis.

During the last two decades, biogenic mineral ions have become important additives in treatments for bone regeneration and repair. Prominent among these is strontium, which is a potent suppressor of osteoclast bone resorption. Another is magnesium, which has a key influence in mineralization processes. The shells of benthic foraminiferans, hydrothermally converted into ß-TCP, have been shown to effectively release a number of bone-promoting drugs at clinically relevant levels. In this study we characterized the effects of converted foraminiferan calcium dissolution and the concomitant release profile of intrinsic strontium and magnesium. We tested the effects of strontium- and magnesium-enriched macrospheres on human osteoblast (SaOS-2) and monocytoid (U937) cell lines, which can be induced to express equivalent phagocytic activities to osteoclasts. On dissolution in a biomimetic physiological solution, the macrospheres released biologically significant quantities of calcium and phosphate ions in the first 18 days. At 3 days, during which biogenic mineral ions are released, the number of U937 osteoclast-like monocyte cells decreased, while 4 days later the osteoblast cell number increased. These results show that strontium and magnesium naturally enriched macrospheres are capable of altering the metabolic activities of the cells regulating bone homeostasis. These unique macrospheres are natural origin bone void filler particles that resorb, and release physiologically significant levels of incorporated strontium, magnesium and calcium, which together make a uniquely multifunctional in situ remedy for bone regeneration and repair and the treatment of bone-wasting diseases.

Structural correlates for lexical efficiency and number of languages in non-native speakers of English.

We used structural magnetic resonance imaging (MRI) and voxel based morphometry (VBM) to investigate whether the efficiency of word processing in the non-native language (lexical efficiency) and the number of non-native languages spoken (2+ versus 1) were related to local differences in the brain structure of bilingual and multilingual speakers. We dissociate two different correlates for non-native language processing. Firstly, multilinguals who spoke 2 or more non-native languages had higher grey matter density in the right posterior supramarginal gyrus compared to bilinguals who only spoke one non-native language. This is interpreted in relation to previous studies that have shown that grey matter density in this region is related to the number of words learnt in bilinguals relative to monolinguals and in monolingual adolescents with high versus low vocabulary. Our second result was that, in bilinguals, grey matter density in the left pars opercularis was positively related to lexical efficiency in second language use, as measured by the speed and accuracy of lexical decisions and the number of words produced in a timed verbal fluency task. Grey matter in the same region was also negatively related to the age at which the second language was acquired. This is interpreted in terms of previous findings that associated the left pars opercularis with phonetic expertise in the native language.

Comparison of cardiac outputs during major surgery using the Deltex CardioQ oesophageal Doppler monitor and the Novametrix-Respironics NICO: a prospective observational study.

INTRODUCTION: Recent studies have emphasised the importance of optimisation of intraoperative fluid administration in patients undergoing major abdominal surgery. A variety of non-invasive devices capable of measuring cardiac output are available for this purpose. Most studies have used the Deltex CardioQ Oesophageal Doppler monitor (DCQ ODM, Deltex, Chichester, Sussex, UK). A relatively new, totally non-invasive cardiac monitor is now available, the Novametrix-Respironics NICO machine (Novametrix-Respironics, USA). AIMS: This pilot study compared cardiac output values obtained during major abdominal surgery from the simultaneous use of these two devices. OBJECTIVES: To assess the reproducibility and consistency of the readings obtained to determine whether these monitors can be used interchangeably for optimising perioperative fluid administration. METHODS: 182 simultaneous paired cardiac output readings were obtained from 12 consecutive patients undergoing prolonged major abdominal surgery. These were analysed using correlation coefficients, scattergrams and Bland Altman plots. RESULTS: Although the r value obtained for correlation was 0.3639 (p<0.0001), the Bland Altman plot showed significant differences of between -4.1 and +5.1 lpm between the readings means with a bias of 0.5 lpm for the NICO over the DCQ ODM. In addition, a sequential plot of simultaneous cardiac outputs showed great disparity between the two devices in some patients. CONCLUSION: Caution should be exercised before using these monitors to optimise intraoperative fluid administration as potentially very large volumes of fluid may be administered to achieve surrogate endpoints. These devices need to be compared side by side with a gold standard method of determining cardiac output before they can be used interchangeably for optimising intraoperative fluid administration in abdominal surgery.

Exploring cross-linguistic vocabulary effects on brain structures using voxel-based morphometry.

Given that there are neural markers for the acquisition of a non-verbal skill, we review evidence of neural markers for the acquisition of vocabulary. Acquiring vocabulary is critical to learning one's native language and to learning other languages. Acquisition requires the ability to link an object concept (meaning) to sound. Is there a region sensitive to vocabulary knowledge? For monolingual English speakers, increased vocabulary knowledge correlates with increased grey matter density in a region of the parietal cortex that is well-located to mediate an association between meaning and sound (the posterior supramarginal gyrus). Further this region also shows sensitivity to acquiring a second language. Relative to monolingual English speakers, Italian-English bilinguals show increased grey matter density in the same region.Differences as well as commonalities might exist in the neural markers for vocabulary where lexical distinctions are also signalled by tone. Relative to monolingual English, Chinese multilingual speakers, like European multilinguals, show increased grey matter density in the parietal region observed previously. However, irrespective of ethnicity, Chinese speakers (both Asian and European) also show highly significant increased grey matter density in two right hemisphere regions (the superior temporal gyrus and the inferior frontal gyrus). They also show increased grey matter density in two left hemisphere regions (middle temporal and superior temporal gyrus). Such increases may reflect additional resources required to process tonal distinctions for lexical purposes or to store tonal differences in order to distinguish lexical items. We conclude with a discussion of future lines of enquiry.

A retrospective study of changes in cerebral oxygenation using a cerebral oximeter in older patients undergoing prolonged major abdominal surgery.

BACKGROUND AND OBJECTIVE: The objective was to carry out a retrospective study of changes in regional cerebral oxygen saturation (rSO2) using the Somanetics Invos Cerebral Oximeter (SICO) in older patients undergoing prolonged major abdominal surgery. Since evidence is accumulating that detection and correction of falls in rSO2 may be associated with a reduced incidence of postoperative cognitive dysfunction, the study assessed the incidence and possible predisposing factors for significant falls in rSO2 and strategies for correction. METHODS: Data from 46 consecutive patients aged 55 yr or above undergoing major abdominal surgery were collected and studied. A SICO electrode was placed over the right forehead prior to commencement of anaesthesia and values of rSO2 were recorded automatically on a floppy disk at 20 s intervals throughout the procedure and until transfer of the patient to the postanaesthesia care unit. Anaesthesia and physiological data were routinely collected by the author on an anaesthetic record computer and transferred to an Excel spreadsheet for analysis. RESULTS: Average duration of the surgery exceeded 7 h. Average blood loss was 1363 mL (interquartile range 500-2000). In 11 of the 46 patients the rSO2 drop exceeded 20%, and in six, there was a significant temporal association of rSO2 drop with ongoing major haemorrhage. In 23 of the 46 patients, a maximum drop in rSO2 occurred, which was about 15% or more. Fall in rSO2 in the 46 patients significantly correlated with blood loss (P < 0.05) and percentage fall in haemoglobin (Hb) (P = 0.01) but not with lowest Hb. Despite maintenance of conventional haemodynamic parameters such as systolic blood pressure (BP) in most patients, the fall in rSO2 seemed only reversible by blood transfusion. In five of the six patients who experienced the greatest decline in rSO2 during haemorrhage, there was no correlation between fall in rSO2 and systolic BP. CONCLUSIONS: This retrospective study confirms that a significant reduction in rSO2 is a common accompaniment to prolonged major abdominal surgery in elderly patients, especially if associated with blood loss, and is correctable by blood transfusion. In most cases, these changes would have gone unnoticed with conventional monitoring.

Invos Cerebral Oximeter compared with the transcranial Doppler for monitoring adequacy of cerebral perfusion in patients undergoing carotid endarterectomy.

AIM: The aim of this prospective study was to assess the correlation between signals obtained during carotid endarterectomy (CEA) under local (LA) or general anesthesia from the Somanetics Invos cerebral oximeter (CO) and transcranial Doppler (TCD). METHODS: Forty patients were enrolled in the study. The percentages fall in TCD mean flow velocity (FVm) and CO regional oxygen saturation (rSO2) on the ipsilateral side following clamping were recorded and the correlation coefficient and Spearman's coefficient of rank correlation were calculated. RESULTS: Fourteen patients were not included in the statistical analysis because either no TCD window or reliable TCD signal was obtained. The remaining 26 patients had a fall in either FVm, rSO2 or both during carotid clamping. There was a highly statistically significant correlation between the percentage fall in FVm and rSO2 with a correlation coefficient of 0.73, P<0.0001, with a 95% confidence interval (CI) for r=0.48 to 0.87; Spearman's coefficient of rank correlation (rho) =0.67, P=0.0008, with a 95% CI for rho=0.384 to 0.84. A significant decline in both TCD and rSO2 was noted in 3 patients under LA out of which 2 required shunts for alteration in conscious level. In 2 LA patients there was a significant decline in TCD but not in rSO2 and the endarterectomy was completed without a shunt. CONCLUSIONS: Regional oxygen saturation correlates well with FVm during carotid clamping. However, the inability to obtain reliable TCD FVm readings in 35% of patients is a serious disadvantage for this monitor. It appears that CO is a satisfactory and possibly superior device for monitoring adequacy of cerebral perfusion and oxygenation during CEA in comparison with the TCD.

Language control in the bilingual brain.

How does the bilingual brain distinguish and control which language is in use? Previous functional imaging experiments have not been able to answer this question because proficient bilinguals activate the same brain regions irrespective of the language being tested. Here, we reveal that neuronal responses within the left caudate are sensitive to changes in the language or the meaning of words. By demonstrating this effect in populations of German-English and Japanese-English bilinguals, we suggest that the left caudate plays a universal role in monitoring and controlling the language in use.

The treatment of large (>70 degrees) thoracic idiopathic scoliosis curves with posterior instrumentation and arthrodesis: when is anterior release indicated?

STUDY DESIGN: Retrospective clinical study from 2 centers. OBJECTIVE: To analyze the efficacy of posterior instrumentation and arthrodesis for thoracic idiopathic scoliosis curves more than 70 degrees. SUMMARY OF BACKGROUND INFORMATION: The increasing use of thoracoscopic techniques in deformity surgery has led several investigators to advocate anterior release followed by posterior instrumentation when treating "stiff" thoracic curves 60 degrees-70 degrees. To our knowledge, no study has been published to define indications for anterior surgery in thoracic idiopathic scoliosis. METHODS: This is a retrospective review of patients 20 years and younger, with idiopathic scoliosis and thoracic curves more than 70 degrees treated with isolated posterior instrumentation and arthrodesis at 2 institutions from 1989 to 1999. A total of 50 patients were identified, and 46 were available for minimum 2-year radiographic follow-up. Of the 50 patients, 44 had bend films taken before surgery. All patients were treated with third-generation segmental spinal instrumentation using a varied combination of hooks, wires, and screws. RESULTS: Average patient age at surgery was 14.4 years (range 10-20), and average radiographic follow-up was 4.4 years (range 2-11.5). Average preoperative thoracic curve was 75 degrees (range 70 degrees-88 degrees), and average bend was 47 degrees (range 28 degrees-60 degrees), a flexibility of 37%. Average postoperative curve was 25 degrees (range 10 degrees-46 degrees), and it was 27 degrees (range 11 degrees-46 degrees) at latest follow-up, a correction of 64%. The average length of surgery was 6.15 hours, mean hospital stay was 8 days, and average blood loss was 1100 cc. The Scoliosis Research Society 22 or 24 was available at a minimum of 2 years in 46 of 50 patients. Mean domain scores were: pain 4.4, self-image 4.3, function 4.3, mental health 4.3, satisfaction 4.7, and total 4.4. Complications included 1 pseudarthrosis, 1 implant removal for prominence, and 1 implant removal for late operative site pain. CONCLUSION: Using posterior surgery only, we have been able to at least equal the results reported in the literature by investigators using combined approaches. Isolated posterior instrumentation and arthrodesis achieve satisfactory cosmetic, radiographic, and patient-based outcomes in adolescents with idiopathic scoliosis with thoracic curves 70 degrees-90 degrees, without the added expense and morbidity of anterior release.

Novel osteoinductive biomimetic scaffolds stimulate human osteoprogenitor activity--implications for skeletal repair.

The development of new bone formation strategies offers tremendous therapeutic implications in a variety of musculoskeletal diseases. One approach involves harnessing the regenerative capacity of osteoprogenitor bone cells in combination with biomimetic scaffolds generated from appropriate scaffold matrices and osteoinductive factors. The aims of our study were to test the efficacy of two innovative osteoinductive agents: the osteoblast stimulating factor-1 (osf-1), an extracellular matrix-associated protein, and osteoinductive extracts of Saos-2 cells on human osteoprogenitor cells. Saos-2 extracted osteoinductive factors significantly stimulated alkaline phosphatase specific activity in basal and osteogenic conditions. Osf-1 significantly stimulated chemotaxis, total colony formation, alkaline phosphatase-positive colony formation, and alkaline phosphatase specific activity at concentrations as low as 10 pg/ml compared with control cultures. Osteoinductive factors present in Saos-2 cell extracts and osf-1 promoted adhesion, migration, expansion, and differentiation of human osteoprogenitor cells on 3-D scaffolds. The successful generation of 3-D biomimetic structures incorporating osf-1 or osteoinductive factors from Saos-2 cells indicates their potential for de novo bone formation that exploits cell-matrix interactions.

The choice of inhalation anaesthetic for major abdominal surgery in children with liver disease.

Many children with liver disease undergo major abdominal surgery. Maintenance of anaesthesia is thus an important consideration in this surgical population. Despite a comprehensive and painstaking review of the literature, a sound evidence base, on which a choice of inhalation anaesthetic may be made, is lacking due to limited research in these patients. Differences between the more recent agents such as isoflurane, sevoflurane and desflurane are minor. Sevoflurane is favoured in paediatric practice for gaseous induction, but desflurane or isoflurane are marginally the preferred agents for maintenance of anaesthesia in children with liver disease undergoing major abdominal surgery. However, on the evidence that exists, much of it admittedly in animals and in adults, all three are preferable to halothane in this group of patients. More work is needed in this area before sound conclusions can be drawn and one agent proved to be definitely superior to the others.

Beta-catenin antisense treatment decreases beta-catenin expression and tumor growth rate in colon carcinoma xenografts.

BACKGROUND: Loss of the adenomatous polyposis coli (APC) tumor suppressor gene plays a significant role in colorectal carcinogenesis. One function of the APC gene product is to regulate beta-catenin, a protein that plays a role in cell adhesion and also regulates the activity of certain transcription factors. To more precisely delineate the role of beta-catenin signaling in colon cancer growth, we treated mice bearing APC-mutant SW480 colon cancer xenografts with antisense oligonucleotides (ODNs) directed against beta-catenin mRNA and examined effects on beta-catenin expression and tumor growth. METHODS: Balb/C nude mice underwent subcutaneous injection of 1 x 10(6) SW480 cells to establish tumor xenografts. In one experiment, tumors were allowed to grow for 7 days, after which time animals were randomized to undergo daily intraperitoneal injections of either antisense beta-catenin ODN at doses of 5, 10, or 20 mg/kg, scrambled sequence beta-catenin ODN control, or saline control for 7 days. Tumors were excised and homogenized, and tumor lysates subjected to gel electrophoresis and Western blotting for beta-catenin protein quantification. In a second experiment, tumor-bearing animals began receiving daily intraperitoneal injections of either antisense beta-catenin ODN at doses of 5, 10, or 20 mg/kg, scrambled sequence beta-catenin ODN control, or saline control. Tumor growth was quantitated by measuring tumor volumes twice weekly. A third experiment evaluated the antitumor effects of daily bolus dosing versus continuous infusion of beta-catenin antisense ODNs (20 mg/kg). RESULTS: Treatment of APC-mutant colorectal carcinoma xenografts with beta-catenin antisense resulted in a dose-dependent down-regulation in beta-catenin protein expression as shown by Western blotting. Treatment of tumor-bearing mice with antisense directed at beta-catenin also demonstrated a dose-dependent inhibition of tumor growth. There appears to be little difference in the antitumor effects of antisense ODNs administered by continuous infusion or bolus dosing schedules. CONCLUSIONS: beta-Catenin expression plays a critical role in the tumorigenic growth of APC-mutant colon cancer xenografts. Strategies targeting beta-catenin, including the use of antisense ODNs, may be of use in the treatment of human colon cancer.