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1.  Prone Position Is Associated with Mild Cerebral Oxygen Desaturation in Elderly Surgical Patients 
PLoS ONE  2014;9(9):e106387.
A variety of hemodynamic and respiratory alterations accompany patients in the prone position; however the effect of the prone position on intraoperative cerebral saturation has not been studied. We sought to examine whether the incidence of cerebral oxygen desaturation in elderly patients (≥68 years of age) undergoing spine surgery in the prone position was more common than patients undergoing major surgery in the supine position.
We performed a retrospective cohort study of 205 patients; 63 patients underwent surgery in the prone position and 142 in the supine position. Patients were evaluated for cerebral desaturation with bilateral cerebral oximetry. The primary predictor was position, secondary were: length of the surgery, incidence and duration of cerebral desaturation episodes at several thresholds, average time of Bispectral index below threshold of 45 in minutes, average electroencephalogram suppression ratio >0, amount of blood transfused, and the incidence of hypotension and hypertension.
Elderly spine surgery patients in the prone position were more than twice as likely to experience mild cerebral desaturation as patients in the supine position. Patients in the prone position had longer surgeries; however cerebral desaturation in the prone position was significantly more common even when adjusted for surgery time and the occurrence of intraoperative hypotension.
Cerebral desaturation is related to the prone position in elderly surgery patients. Future studies are necessary to determine whether this translates to a higher incidence of postoperative cognitive dysfunction and delirium.
PMCID: PMC4162535  PMID: 25216265
2.  Perioperative delirium and its relationship to dementia 
A number of serious clinical cognitive syndromes occur following surgery and anesthesia. Postoperative delirium is a behavioral syndrome that occurs in the perioperative period. It is diagnosed through observation and characterized by a fluctuating loss of orientation and confusion. A distinct syndrome that requires formalized neurocognitive testing is frequently referred to as postoperative cognitive dysfunction (POCD). There are serious concerns as to whether either postoperative delirium or postoperative cognitive dysfunction lead to dementia. These concerns are reviewed in this article.
PMCID: PMC3612127  PMID: 23220565
Postoperative Delirium; Postoperative Cognitive Dysfunction; Long term cognitive impairment; Dementia
3.  Transport Distance of Invertebrate Environmental DNA in a Natural River 
PLoS ONE  2014;9(2):e88786.
Environmental DNA (eDNA) monitoring is a novel molecular technique to detect species in natural habitats. Many eDNA studies in aquatic systems have focused on lake or ponds, and/or on large vertebrate species, but applications to invertebrates in river systems are emerging. A challenge in applying eDNA monitoring in flowing waters is that a species' DNA can be transported downstream. Whether and how far eDNA can be detected due to downstream transport remains largely unknown. In this study we tested for downstream detection of eDNA for two invertebrate species, Daphnia longispina and Unio tumidus, which are lake dwelling species in our study area. The goal was to determine how far away from the source population in a lake their eDNA could be detected in an outflowing river. We sampled water from eleven river sites in regular intervals up to 12.3 km downstream of the lake, developed new eDNA probes for both species, and used a standard PCR and Sanger sequencing detection method to confirm presence of each species' eDNA in the river. We detected D. longispina at all locations and across two time points (July and October); whereas with U. tumidus, we observed a decreased detection rate and did not detect its eDNA after 9.1 km. We also observed a difference in detection for this species at different times of year. The observed movement of eDNA from the source amounting to nearly 10 km for these species indicates that the resolution of an eDNA sample can be large in river systems. Our results indicate that there may be species' specific transport distances for eDNA and demonstrate for the first time that invertebrate eDNA can persist over relatively large distances in a natural river system.
PMCID: PMC3921251  PMID: 24523940
Anesthesia has developed to the point where long term outcomes are important endpoints. Elderly patients are becoming an increasingly large part of most surgical practices, consistent with demographic shifts. Long term outcomes are particularly important for this group. In this review, we discuss functional outcomes in the elderly. We describe the areas of cognitive change and frailty, both of which are specific to the elderly. We also discuss prevention of surgical infections and emerging evidence around hemodynamic alterations in the operating room and their impact on long term outcomes.
PMCID: PMC3261586  PMID: 22238042
Geriatrics; Long term outcomes; Delirium; Postoperative Cognitive Dysfunction; Surgical Site Infection
5.  A Passerine Bird's Evolution Corroborates the Geologic History of the Island of New Guinea 
PLoS ONE  2011;6(5):e19479.
New Guinea is a biologically diverse island, with a unique geologic history and topography that has likely played a role in the evolution of species. Few island-wide studies, however, have examined the phylogeographic history of lowland species. The objective of this study was to examine patterns of phylogeographic variation of a common and widespread New Guinean bird species (Colluricincla megarhyncha). Specifically, we test the mechanisms hypothesized to cause geographic and genetic variation (e.g., vicariance, isolation by distance and founder-effect with dispersal). To accomplish this, we surveyed three regions of the mitochondrial genome and a nuclear intron and assessed differences among 23 of the 30 described subspecies from throughout their range. We found support for eight highly divergent lineages within C. megarhyncha. Genetic lineages were found within continuous lowland habitat or on smaller islands, but all individuals within clades were not necessarily structured by predicted biogeographic barriers. There was some evidence of isolation by distance and potential founder-effects. Mitochondrial DNA sequence divergence among lineages was at a level often observed among different species or even genera of birds (5–11%), suggesting lineages within regions have been isolated for long periods of time. When topographical barriers were associated with divergence patterns, the estimated divergence date for the clade coincided with the estimated time of barrier formation. We also found that dispersal distance and range size are positively correlated across lineages. Evidence from this research suggests that different phylogeographic mechanisms concurrently structure lineages of C. megarhyncha and are not mutually exclusive. These lineages are a result of evolutionary forces acting at different temporal and spatial scales concordant with New Guinea's geological history.
PMCID: PMC3089620  PMID: 21573115
6.  Is Postoperative Cognitive Decline Clinically Relevant? 
Anesthesiology  2010;112(5):1280-1285.
PMCID: PMC2871108  PMID: 20418703
7.  Erythroid progenitor renewal versus differentiation: genetic evidence for cell autonomous, essential functions of EpoR, Stat5 and the GR 
Oncogene  2006;25(20):2890-2900.
The balance between hematopoietic progenitor commitment and self-renewal versus differentiation is controlled by various transcriptional regulators cooperating with cytokine receptors. Disruption of this balance is increasingly recognized as important in the development of leukemia,by causing enhanced renewal and differentiation arrest. We studied regulation of renewal versus differentiation in primary murine erythroid progenitors that require cooperation of erythropoietin receptor (EpoR),the receptor tyrosine kinase c-Kit and a transcriptional regulator (glucocorticoid receptor (GR)) for sustained renewal. However, mice defective for GR- (GRdim/dim), EpoR- (EpoRH) or STAT5ab function (Stat5ab−/−) show no severe erythropoiesis defects in vivo. Using primary erythroblast cultures from these mutants, we present genetic evidence that functional GR, EpoR, and Stat5 are essential for erythroblast renewal in vitro. Cells from GRdim/dim, EpoRH, and Stat5ab−/− mice showed enhanced differentiation instead of renewal, causing accumulation of mature cells and gradual proliferation arrest. Stat5ab was additionally required for Epo-induced terminal differentiation: differentiating Stat5ab−/− erythroblasts underwent apoptosis instead of erythrocyte maturation, due to absent induction of the antiapoptotic protein Bcl-XL. This defect could be fully rescued by exogenous Bcl-XL. These data suggest that signaling molecules driving leukemic proliferation may also be essential for prolonged self-renewal of normal erythroid progenitors.
PMCID: PMC3035873  PMID: 16407844
erythroid progenitor self-renewal; terminal erythropoiesis; Stat5; glucocorticoid receptor; erythropoietin receptor; Bcl-XL
8.  Postoperative delirium and cognitive dysfunction 
BJA: British Journal of Anaesthesia  2009;103(Suppl 1):i41-i46.
Postoperative delirium and cognitive dysfunction (POCD) are topics of special importance in the geriatric surgical population. They are separate entities, whose relationship has yet to be fully elucidated. Although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within 6 months or postoperative institutionalization. POCD has been associated with increased mortality, risk of leaving the labour market prematurely, and dependency on social transfer payments. Here, we review their definitions and aetiology, and discuss treatment and prevention in elderly patients undergoing major non-cardiac surgery. Good basic care demands identification of at-risk patients, awareness of common perioperative aggravating factors, simple prevention interventions, recognition of the disease states, and basic treatments for patients with severe hyperactive manifestations.
PMCID: PMC2791855  PMID: 20007989
age factors; anaesthesia, geriatric; brain; complications
9.  Anesthesia for Pediatric Deep Brain Stimulation 
In patients refractory to medical therapy, deep brain stimulations (DBSs) have emerged as the treatment of movement disorders particularly Parkinson's disease. Their use has also been extended in pediatric and adult patients to treat epileptogenic foci. We here performed a retrospective chart review of anesthesia records from 28 pediatric cases of patients who underwent DBS implantation for dystonia using combinations of dexmedetomidine and propofol-based anesthesia. Complications with anesthetic techniques including airway and cardiovascular difficulties were analyzed.
PMCID: PMC2931390  PMID: 20814550
10.  Complex porcine model of atherosclerosis: Induction of early coronary lesions after long-term hyperlipidemia without sustained hyperglycemia 
The Canadian Journal of Cardiology  2009;25(4):e109-e114.
The incidence of coronary artery disease (CAD) is still increasing in industrialized countries and it is even higher in diabetic patients. For experimental studies investigating the pathophysiology of CAD, the use of an animal model comparable with the pathological situation in patients is crucial.
To develop a model of advanced coronary atherosclerosis with induction of hyperlipidemia and hyperglycemia in domestic pigs.
Six pigs were fed a standard pig chow (controls), two were fed a 2% cholesterol and 17% coconut fat diet (Chol group), and two pigs received a 4% cholesterol and 17% coconut fat diet combined with streptozotocin (STZ) injections to induce diabetes (High Chol+STZ group). Serum lipid and plasma glucose values were analyzed, and histochemical staining for morphometric analysis and immunohistochemistry were performed.
Pigs on the hyperlipidemic diet had elevated mean (± SD) serum lipid levels (total cholesterol 5.05±1.45 mmol/L [Chol] and 5.03±2.41 mmol/L [High Chol+STZ] versus 2.09±0.23 mmol/L [controls]). Histopathological evaluation revealed an initial stage of coronary atherosclerosis. None of the STZ-treated pigs showed a sustained elevation of plasma glucose (mean glucose before STZ injection was 5.11±0.94 mmol/L and thereafter was 6.03±2.39 mmol/L) or a decline in pancreatic beta cells.
The current data suggest that the domestic porcine model is not suitable to create severe CAD using an atherogenic diet in combination with STZ injections for experimental interventional vascular research. This may be due to different STZ sensitivities among species. However, hyperlipidemia induced early pathological lesions in coronary arteries resembling initial stages of atherosclerosis without severe luminal narrowing.
PMCID: PMC2706769  PMID: 19340354
Atherosclerosis; Coronary disease; Diabetes mellitus; Hyperlipoproteinemia
11.  Raf-1 Antagonizes Erythroid Differentiation by Restraining Caspase Activation 
The Journal of Experimental Medicine  2002;196(10):1347-1353.
The Raf kinases are key signal transducers activated by mitogens or oncogenes. The best studied Raf isoform, Raf-1, was identified as an inhibitor of apoptosis by conventional and conditional gene ablation in mice. c-raf-1−/− embryos are growth retarded and anemic, and die at midgestation with anomalies in the placenta and fetal liver. Here, we show that Raf-1–deficient primary erythroblasts cannot be expanded in culture due to their accelerated differentiation into mature erythrocytes. In addition, Raf-1 expression is down-regulated in differentiating wild-type cells, whereas overexpression of activated Raf-1 delays differentiation. As recently described for human erythroid precursors, we find that caspase activation is necessary for the differentiation of murine fetal liver erythroblasts. Differentiation-associated caspase activation is accelerated in erythroid progenitors lacking Raf-1 and delayed by overexpression of the activated kinase. These results reveal an essential function of Raf-1 in erythropoiesis and demonstrate that the ability of Raf-1 to restrict caspase activation is biologically relevant in a context distinct from apoptosis.
PMCID: PMC2193984  PMID: 12438425
kinase; gene inactivation; erythropoiesis; fetal liver; apoptosis
12.  Mammalian Granulocyte–Macrophage Colony-stimulating Factor Receptor Expressed in Primary Avian Hematopoietic Progenitors: Lineage-specific Regulation of Proliferation and Differentiation  
The Journal of Cell Biology  1998;141(4):1041-1051.
The cytokine Granulocyte–Macrophage Colony-Stimulating Factor (GM-CSF) regulates proliferation, differentiation, and apoptosis during myelopoiesis and erythropoiesis. Structure–function relationships of GM-CSF interactions with its receptor (GM-R), the biochemistry of GM-R signal transduction, and GM-CSF action in vivo are relatively well understood. Much less is known, however, about GM-R function in primary hematopoietic cells. In this paper we show that expression of the human GM-R in a heterologous cell system (primary avian erythroid and myeloid cells) confirms respective results in murine or human cell lines, but also provides new insights how the GM-R regulates progenitor proliferation and differentiation. As expected, the hGM-CSF stimulated myeloid progenitor proliferation and differentiation and enhanced erythroid progenitor proliferation during terminal differentiation. In the latter cells, however, the hGM-R only partially substituted for the activities of the erythropoietin receptor (EpoR). It failed to replace the EpoR in its cooperation with c-Kit to induce long-term proliferation of erythroid progenitors. Furthermore, the hGM-R α chain specifically interfered with EpoR signaling, an activity neither seen for the βc subunit of the receptor complex alone, nor for the α chain of the closely related Interleukin-3 receptor. These results point to a novel role of the GM-R α chain in defining cell type–specific functions of the GM-R.
PMCID: PMC2132768  PMID: 9585421

Results 1-12 (12)