Virtual ER, a Serious Game for Interprofessional Education to Enhance Teamwork in Medical and Nursing Undergraduates: Development and Evaluation Study.

BACKGROUND: Engaging students in interprofessional education for higher order thinking and collaborative problem-solving skills is challenging. This study reports the development of Virtual ER, a serious game played on a virtual platform, and how it can be an innovative way for delivering interprofessional education to medical and nursing undergraduates. OBJECTIVE: We report the development of a serious online game, Virtual ER, and evaluate its effect on teamwork enhancement and clinical competence. We also explore if Virtual ER can be an effective pedagogical tool to engage medical and nursing students with different learning styles. METHODS: Virtual ER is a custom-made, learning outcome-driven, case-based web app. We developed a game performance scoring system with specific mechanisms to enhance serious gaming elements. Sixty-two students were recruited from our medical and nursing programs. They played the games in teams of 4 or 5, followed by an instructor-led debriefing for concept consolidation. Teamwork attitudes, as measured by the Human Factors Attitude Survey, were compared before and after the game. Learning style was measured with a modified Honey and Mumford learning style questionnaire. RESULTS: Students were satisfied with Virtual ER (mean satisfaction score 5.44, SD 0.95, of a possible 7). Overall, Virtual ER enhanced teamwork attitude by 3.02 points (95% CI 1.15-4.88, P=.002). Students with higher scores as activists (estimate 9.09, 95% CI 5.17-13.02, P<.001) and pragmatists (estimate 5.69, 95% CI 1.18-10.20, P=.01) had a significantly higher degree of teamwork attitude enhancement, while students with higher scores as theorists and reflectors did not demonstrate significant changes. However, there was no difference in game performance scores between students with different learning styles. CONCLUSIONS: There was considerable teamwork enhancement after playing Virtual ER for interprofessional education, in particular for students who had activist or pragmatist learning styles. Serious online games have potential in interprofessional education for the development of 21st century life skills. Our findings also suggest that Virtual ER for interprofessional education delivery could be expanded locally and globally.

Medical teachers' experience of emergency remote teaching during the COVID-19 pandemic: a cross-institutional study.

BACKGROUND: The COVID-19 pandemic and the consequent social distancing measures caused unprecedented disruption for medical and healthcare education. This study examined medical teachers' experience with emergency remote teaching during the pandemic and their acceptance of online teaching after the pandemic. METHODS: In this sequential mixed methods study, online surveys were disseminated to teachers (n = 139) at two Asia-Pacific medical schools to evaluate their experience with emergency remote teaching during the pandemic. Subsequently, in-depth interviews were conducted with teachers from both institutions (n = 13). Each interviewee was classified into an adopter category based on Rogers' Diffusion of Innovations Theory. Interview transcripts were analyzed thematically, and the descriptive themes were mapped to broader themes partly based on the Technology Acceptance Model and these included: (i) perceived usefulness of online teaching, (ii) perceived ease of delivering online teaching, (iii) experience with institutional support and (iv) acceptance of online teaching after the pandemic. RESULTS: Our participants described accounts of successes with their emergency remote teaching and difficulties they experienced. In general, most participants found it difficult to deliver clinical skills teaching remotely and manage large groups of students in synchronous online classes. With regards to institutional support, teachers with lower technological literacy required just-in-time technical support, while teachers who were innovative in their online teaching practices found that IT support alone could not fully address their needs. It was also found that teachers' acceptance of online teaching after the pandemic was influenced by their belief about the usefulness of online teaching. CONCLUSIONS: This study demonstrated that our participants managed to adapt to emergency remote teaching during this pandemic, and it also identified a myriad of drivers and blockers to online teaching adoption for medical teachers. It highlights the need for institutes to better support their teaching staff with diverse needs in their online teaching.

Brij-functionalized chitosan nanocarrier system enhances the intestinal permeability of P-glycoprotein substrate-like drugs.

The highly expressed P-glycoprotein (Pgp) in the intestine plays a key role in preventing drugs across the intestinal epithelium, which linked by tight junctions (TJs). Thus increasing the oral bioavailability of Pgp substrate-like drugs (PSLDs) remains a great challenge. Herein, we construct a nanocarrier system derived from Brij-grafted-chitosan (BC) to enhance the oral bioavailability and therapeutic effect of berberine (BBR, a typical PLSD) against diabetic kidney disease. The developed BC nanoparticles (BC-NPs) are demonstrated to improve the intestinal permeability of BBR via transiently and reversibly modulating the intercellular TJs (paracellular pathway) and Pgp-mediated drug efflux (transcellular pathway). As compared to free BBR and chitosan nanoparticles, the BC-NPs enhanced the relative oral bioavailability of BBR in rats (4.4- and 2.7-fold, respectively), and the therapeutic potency of BBR in renal function and histopathology. In summary, such strategy may provide an effective nanocarrier system for oral delivery of BBR and PSLDs.

Impact of postoperative haemoglobin on length of stay post fractured hip repair in patients with standardised perioperative management.

INTRODUCTION:: Perioperative blood transfusion is not without risk and effort should be made to limit patients' exposure to allogeneic blood. However, there is conflicting data regarding the impact of anaemia on postoperative recovery in patients with repaired hip fractures. It is hypothesised that for a given baseline functional status and fracture type, lower postoperative haemoglobin will increase rehabilitation time and prolong total length of hospital stay. METHODS:: This is a retrospective study on data collected prospectively on patients entered into the Clinical Pathway aged >65 years admitted to Queen Mary Hospital (QMH) with a fractured neck of femur during 2011-2013. Potential predictor variables were analysed with linear regression with respect to total length of stay and those that reached a significance level of 0.05 were included in further analysis. RESULTS:: 1092 patients were admitted to QMH with a suspected fractured neck of femur; data from 747 patients were analysed. The fracture sites were neck of femur (50%), intertrochanteric (48%) and subtrochanteric fracture (2%). Approximately 30% of patients received blood transfusions. Of these only the development of postoperative medical complications statistically prolonged hospital stay. No relationship was seen with haemoglobin levels cut-off above and below 10 g/dl with the result remaining non-significant down to a cut-off of above and below 8 g/dl. DISCUSSION:: This study revealed that post-surgical haemoglobin level of between 8 g/dl and 10 g/dL did not have an impact on the total length of hospital stay. The development of postoperative medical complications was the only factor that prolonged the total length of stay.

Brij-grafted-chitosan copolymers with function of P-glycoprotein modulation: Synthesis, characterization and in vitro investigations.

Chitosan (CS), a nature-derived polysaccharide, is a promising nano-carrier material with good biocompatibility and biodegradability. However, the biomedical applications of CS are hindered because of its poor aqueous solubility. To circumvent this drawback, a series of Brij-grafted-chitosan copolymers (BCs) with various grafting degree of Brij-S20 were first developed and reported. The results indicated that the water solubility of BCs (from 9.13 to 9.54 mg/mL) were much higher than that of CS (0.32 mg/mL), due to the broken intra- and/or inter-molecular hydrogen bonds and the decreased initial crystallinity in BCs. The amphiphilic structure of BCs presented lower critical micelle concentration (0.116-0.376 mg/mL) thus facilitating its self-aggregation into micelles for drug encapsulation. Moreover, BCs markedly enhanced the intracellular uptake of rhodamine-123 in MDCK-MDR1 cells. This inhibition on Pgp-mediated efflux was also confirmed by confocal microscopy. In conclusion, BCs could be further developed as polymeric nano-carriers for those drugs with Pgp-mediated efflux.

Effects of differential-phase remote ischemic preconditioning intervention in laparoscopic partial nephrectomy: A single blinded, randomized controlled trial in a parallel group design.

STUDY OBJECTIVE: There are two windows of protection for remote ischemic preconditioning (RIPC), an early (ERIPC) and a late-phase (LRIPC). While ERIPC has been well studied, works on LRIPC are relatively scarce, especially for the kidneys. We aimed to compare the effects of early-phase versus late-phase RIPC in patients with laparoscopic partial nephrectomy (LPN). DESIGN: A randomized controlled study SETTING: The Second Affiliated Hospital of Anhui Medical University, 1 May 2012 to 30 October 2013 PATIENTS: Sixty-five ASA 1 to 2 patients scheduled for LPN were located randomly to ERIPC group, LRIPC group and CON group (control). INTERVENTIONS: Three five-minute cycles of right upper limb ischaemia and reperfusion were performed after induction of anesthesia in ERIPC group. Patients in LRIPC group received similar treatment 24h before surgery, while control patients were not subjected to preconditioning. MEASUREMENTS: Serum neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C (CysC) were evaluated before the induction of anesthesia (0h), 2h (2h) and 6h (6h) after surgery. Unilateral glomerular filtration rates (GFR) were assessed before and after surgery to evaluate overall renal function. MAIN RESULTS: Serum NGAL and CysC were significantly lower in ERIPC and LRIPC groups at 2h post-operation (P<0.001), 6h post-operation (P<0.001). Additionally, The GFR were significantly lower in ERIPC and LRIPC groups than in CON group at the 3rd month after surgery (P=0.019; P<0.001). Moreover, compared to the ERIPC group, concentration of NGAL and CysC in LRIPC group decreased to a greater extent, while GFR and the percentage of decrement was significantly less in the LRIPC group (P=0.016; P<0.001). CONCLUSIONS: Regardless of early-phase or late-phase intervention, limb remote ischemic preconditioning confers protection on renal ischemia-reperfusion injury in patients with laparoscopic partial nephrectomy, and the late-phase protection is more prominent.

Genetic Loci Conditioning Adult Plant Resistance to the Ug99 Race Group and Seedling Resistance to Races TRTTF and TTTTF of the Stem Rust Pathogen in Wheat Landrace CItr 15026.

Wheat landrace CItr 15026 previously showed adult plant resistance (APR) to the Ug99 stem rust race group in Kenya and seedling resistance to Puccinia graminis f. sp. tritici races QFCSC, TTTTF, and TRTTF. CItr 15026 was crossed to susceptible accessions LMPG-6 and Red Bobs, and 180 double haploid (DH) lines and 140 recombinant inbred lines (RIL), respectively, were developed. The 90K wheat iSelect single-nucleotide polymorphism platform was used to genotype the parents and populations. Parents and 180 DH lines were evaluated in the field in Kenya for three seasons. A major quantitative trait locus (QTL) for APR was consistently detected on chromosome arm 6AS. This QTL was further detected in the RIL population screened in Kenya for one season. Parents, F1, and the two populations were tested as seedlings against races TRTTF and TTTTF. In addition, the DH population was tested against race QFCSC. Goodness-of-fit tests indicated that the TRTTF resistance in CItr 15026 was controlled by two complementary genes whereas the TTTTF and QFCSC resistance was conditioned by one dominant gene. The TRTTF resistance loci mapped to chromosome arms 6AS and 6DS, whereas the TTTTF and QFCSC resistance locus mapped to the same region on 6DS as the TRTTF resistance. The APR identified in CItr 15026 should be useful in developing cultivars with durable stem rust resistance.

Molecular Mapping of Stem Rust Resistance Loci Effective Against the Ug99 Race Group of the Stem Rust Pathogen and Validation of a Single Nucleotide Polymorphism Marker Linked to Stem Rust Resistance Gene Sr28.

Wheat landrace PI 177906 has seedling resistance to stem rust caused by Puccinia graminis f. sp. tritici races TTKSK, TTKST, and BCCBC and field resistance to the Ug99 race group. Parents, 140 recombinant inbred lines, and 138 double haploid (DH) lines were evaluated for seedling resistance to races TTKSK and BCCBC. Parents and the DH population were evaluated for field resistance to Ug99 in Kenya. The 90K wheat single nucleotide polymorphism (SNP) genotyping platform was used to genotype the parents and populations. Goodness-of-fit tests indicated that two dominant genes in PI 177906 conditioned seedling resistance to TTKSK. Two major loci for seedling resistance were consistently mapped to the chromosome arms 2BL and 6DS. The BCCBC resistance was mapped to the same location on 2BL as the TTKSK resistance. Using field data from the three seasons, two major QTL were consistently detected at the same regions on 2BL and 6DS. Based on the mapping result, race specificity, and the infection type observed in PI 177906, the TTKSK resistance on 2BL is likely due to Sr28. One SNP marker (KASP_IWB1208) was found to be predictive for the presence of the TTKSK resistance locus on 2BL and Sr28.

Genetic mapping of resistance to the Ug99 race group of Puccinia graminis f. sp. tritici in a spring wheat landrace CItr 4311.

KEY MESSAGE: A gene for Ug99 resistance from wheat landrace CItr 4311 was detected on the long arm of chromosome 2B. Wheat landrace CItr 4311 has seedling resistance to stem rust caused by Puccinia graminis f. sp. tritici race TTKSK and field resistance to the Ug99 race group. Parents, F1 seedlings, 121 doubled haploid (DH) lines, and 124 recombinant inbred lines (RILs) developed from a cross between CItr 4311 and the susceptible line LMPG-6 were evaluated for seedling resistance to race TTKSK. Goodness-of-fit tests indicated that a single dominant gene in CItr 4311 conditioned the TTKSK resistance. The 90 K wheat iSelect SNP platform was used to genotype parents and the DH population. The seedling resistance locus was mapped to the chromosome arm 2BL. Parents and the DH population were evaluated for field resistance in Kenya. One major QTL for the field resistance was consistently detected in the same region on 2BL as the seedling resistance. Using KASP assays, five linked SNP markers were used to verify the result in the 124 RIL, 35 wheat accessions, 46 DH lines from the LMPG-6/PI 165194 cross and F1 seedlings, and susceptible bulks derived from crosses between six resistant landraces with LMPG-6. Race specificity, mapping results, and haplotype similarity with lines with Sr9h (Gabo 56, Timstein, and PI 670015), support the hypothesis that the Sr gene in CItr 4311 and the landraces is Sr9h. The KASP assays developed in this study will be useful for pyramiding the TTKSK resistance from CItr 4311 with other Sr genes effective against Ug99.

Methylglyoxal-induced neuroinflammatory response in in vitro astrocytic cultures and hippocampus of experimental animals.

Diabetes mellitus is characterized by chronic hyperglycemia and its diverse complications. Hyperglycemia is associated with inflammatory responses in different organs and diabetic patients have a higher risk of developing neurodegenerative disorders. Methylglyoxal is a reactive advanced glycation end product precursor that accumulates in diabetic patients. It induces various stress responses in the central nervous system and causes neuronal dysfunction. Astrocytes are actively involved in maintaining neuronal homeostasis and possibly play a role in protecting the brain against neurodegeneration. However it is not clear whether methylglyoxal exerts any adverse effects towards these astrocytes. In the present study we investigated the effects of methylglyoxal in astrocytic cultures and hippocampi of experimental animals. The cells from the astrocytic line DITNC1 were treated with methylglyoxal for 1 to 24 h. For the in vivo model, 3 months old C57BL/6 mice were treated with methylglyoxal solution for 6 weeks by intraperitoneal injection. Following the treatment, both astrocytes and hippocampi were harvested for MTT assay, Western blot and real time PCR analyses. We found that methylglyoxal induced astrogliosis in DITNC1 astrocytic cultures and C57BL/6 mice. Further, activation of the pro-inflammatory JNK signaling pathway and its downstream effectors c-Jun were observed. Furthermore, increased gene expression of pro-inflammatory cytokines and astrocytic markers were observed from real time PCR analyses. In addition, inhibition of JNK activities resulted in down-regulation of TNF-α gene expression in methylglyoxal treated astrocytes. Our results suggest that methylglyoxal may contribute to the progression of diabetes related neurodegeneration through JNK pathway activation in astrocytes and the subsequent neuroinflammatory responses in the central nervous system.

Dexmedetomidine Combined with General Anesthesia Provides Similar Intraoperative Stress Response Reduction When Compared with a Combined General and Epidural Anesthetic Technique.

BACKGROUND: Epidural anesthesia may attenuate the sympathetic hyperactivity and stress response from surgery. In this study, we compared the stress response, hemodynamic variables, and recovery profiles of patients undergoing total IV anesthesia (TIVA) and intraoperative dexmedetomidine with those receiving epidural anesthesia and TIVA. METHODS: Ninety patients undergoing elective open gastrectomy under TIVA were recruited. The dexmedetomidine group (group D, n = 30) received IV dexmedetomidine 0.6 µg/kg before the induction of general anesthesia, followed by dexmedetomidine 0.4 µg/kg/h until peritoneal closure. The control group (group C, n = 30) received volume-matched normal saline infusion as placebo. The epidural group (group E, n = 30) received epidural anesthesia with 0.375% ropivacaine combined with TIVA. The hemodynamic variables and recovery characteristics during emergence were evaluated. Blood samples for norepinephrine (NE), epinephrine (E), cortisol (Cor), and cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6, and IL-10) were obtained before the administration of dexmedetomidine or epidural anesthesia (baseline), immediately after tracheal intubation, upon incision, at the time of celiac exploration, and at tracheal extubation. RESULTS: Compared with group E, there were no differences in the plasma concentration levels of NE, E, Cor, and cytokines (TNF-α, IL-6, and IL-10) in group D at all time points. The levels of NE and E in groups D and E were significantly lower than that in group C, at all time points following induction (all P < 0.0001 except at incision which were P = 0.001 and P = 0.004), and the level of Cor in groups D and E was significantly lower than that in group C at celiac exploration (P = 0.017 and P = 0.019) and immediately after tracheal extubation (P < 0.0001). The levels of TNF-α, IL-6, and IL-10 increased after the celiac exploration in the 3 groups. The levels of plasma TNF-α, IL-6, and IL-6/IL-10 ratio were higher in group C than in groups D and E at celiac exploration and tracheal extubation (all P < 0.0001 except at celiac exploration which were P = 0.005 and P =0.038 for TNF-α and P = 0.049 and P = 0.038 for IL-6/IL-10 ratio). In group D, the heart rate was significantly slower after commencing dexmedetomidine and remained significantly slower throughout the operative course (all P < 0.0001 except at tracheal extubation which was P = 0.032). The number of patients who required intervention because of intraoperative hypotension was significantly higher in group E (36.7%) compared with groups D and C (13.3% and 10.0%) (P = 0.037, P = 0.015). The times to eye opening and tracheal extubation were similar in all groups. There were fewer incidences of agitation in group D (6.7 %) than in group C (26.6%) (P = 0.038). CONCLUSIONS: When used in conjunction with TIVA, intraoperative dexmedetomidine blunts surgical stress responses to an extent comparable to combined epidural and general anesthesia without compromising hemodynamic stability and with minimal adverse effects during the intraoperative period.

Rapid Identification of Resistance Loci Effective Against Puccinia graminis f. sp. tritici Race TTKSK in 33 Spring Wheat Landraces.

Wheat breeders worldwide are seeking new sources of resistance to Puccinia graminis f. sp. tritici race TTKSK. To prioritize field-resistant landraces for follow-up genetic studies to test for the presence of new resistance genes, seedling response to P. graminis f. sp. tritici race TTKSK, molecular markers linked to specific Sr genes, segregation ratios among progeny from crosses, and bulked segregant analyses (BSA) were used. In total, 33 spring wheat landraces with seedling resistance to P. graminis f. sp. tritici race TTKSK were crossed to a susceptible genotype, LMPG-6. The segregation ratios of stem rust reactions in F2 seedlings fit a single dominant gene model in 31 populations and progeny from two crosses gave ambiguous results. Using the 90K wheat single-nucleotide polymorphism genotyping platform, BSA showed that the seedling resistance in 29 accessions is probably controlled by loci on chromosome 2BL. For the three remaining accessions, BSA revealed that the seedling resistance is most likely controlled by previously unreported genes. For confirmation, two populations were advanced to the F2:3 and screened against P. graminis f. sp. tritici race TTKSK. Segregation of the F2:3 families fit a 1:2:1 ratio for a single dominant gene. Using the F2:3 families, BSA located the TTKSK locus on chromosome 6DS to the same location as Sr42.

Mapping resistance to the Ug99 race group of the stem rust pathogen in a spring wheat landrace.

KEY MESSAGE: A new gene for Ug99 resistance from wheat landrace PI 374670 was detected on the long arm of chromosome 7A. Wheat landrace PI 374670 has seedling and field resistance to stem rust caused by Puccinia graminis f. sp tritici Eriks. & E. Henn (Pgt) race TTKSK. To elucidate the inheritance of resistance, 216 BC1F2 families, 192 double haploid (DH) lines, and 185 recombinant inbred lines (RILs) were developed by crossing PI 374670 and the susceptible line LMPG-6. The parents and progeny were evaluated for seedling resistance to Pgt races TTKSK, MCCFC, and TPMKC. The DH lines were tested in field stem rust nurseries in Kenya and Ethiopia. The DH lines were genotyped with the 90K wheat iSelect SNP genotyping platform. Goodness-of-fit tests indicated that a single dominant gene in PI 374670 conditioned seedling resistance to the three Pgt races. The seedling resistance locus mapped to the long arm of chromosome 7A and this result was verified in the RIL population screened with the flanking SNP markers using KASP assays. In the same region, a major QTL for field resistance was detected in a 7.7 cM interval and explained 34-54 and 29-36% of the variation in Kenya and Ethiopia, respectively. Results from tests with specific Pgt races and the csIH81 marker showed that the resistance was not due to Sr22. Thus, a new stem rust resistance gene or allele, either closely linked or allelic to Sr15, is responsible for the seedling and field resistance of PI 374670 to Ug99.

Time to adequate oxygenation following ventilation using the Enk oxygen flow modulator versus a jet ventilator via needle cricothyrotomy in rabbits.

INTRODUCTION: Limited information is available on the management of the 'cannot intubate, cannot ventilate' (CICV) situation in infants. We compared the time to achieve adequate oxygenation following rescue ventilation using the Enk oxygen flow modulator (OFM) with a jet ventilator in a simulated CICV situation using the rabbit as an infant respiratory model. METHODS: Following institutional ethics committee approval, needle cricothyrotomy was performed under direct vision in nine anesthetized rabbits following surgical exposure of the larynx. After ensuring adequate level of anesthesia and analgesia, and confirming proper positioning of the 18G cannula, apnea was induced by the administration of myorelaxant and the SpO2 was allowed to drop to 75% before initiating rescue ventilation via either the OFM or jet ventilator. RESULTS: Five rabbits were ventilated with the OFM and four with the jet ventilator. Ventilation was maintained with either device for 15 min. All rabbits were successfully rescued using either device. There was no statistical difference in the time required for SpO2 to return to 80%, 85%, 90%, and 95%. CONCLUSIONS: Both devices facilitated successful rescue ventilation through a needle cricothyrotomy.

Effectiveness and safety of erythropoiesis-stimulating agent use in the perioperative period.

INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) are widely used in treating anemia associated with renal failure. They are also now used perioperatively to reduce the use of allogeneic blood transfusions (ABTs) in patients undergoing surgery with anticipated high blood loss. Although they can reduce the risks associated with ABT and improve quality of life, the use of ESAs is still associated with adverse effects. AREAS COVERED: A narrative review is provided on ESAs and a systematic review has been conducted to examine the current evidence for the efficacy and safety of perioperative ESAs use. A search of PubMed and Medline databases has been performed using a combination of search terms including erythropoietin, perioperative, surgical, safety and efficacy. EXPERT OPINION: Current evidence supports the use of perioperative ESAs to reduce the need for ABT. However, large studies assessing safety in anemic patients with chronic renal disease have found adverse effects including cardiovascular, stroke and thromboembolic events. However, whether these concerns can be conferred onto the surgical population remains to be seen as the perioperative dosing strategies have been more variable in timing, dose and duration in comparison with those used for chronic diseases. Future research needs to address the questions of optimal dosing strategies in order to maximize the positive effects and minimize adverse events.

High dose remifentanil increases myocardial oxidative stress and compromises remifentanil infarct-sparing effects in rats.

Chronic administration of high dose opioids such as morphine is known to create intracellular oxidative stress via an opioid receptor dependent mechanism and this can interfere with cellular function. This study aimed at examining whether such changes can occur following short term exposure to high concentration of remifentanil, a potent short acting opioid. We conducted a experimental study using rat myocardium and systematically quantified tissue levels of superoxide anions, malondialdehyde (MDA) and nitrotyrosine following exposure to increasing duration (15 min, 1 or 2 h) or escalating doses of remifentanil (1 µg, 5 µg, 10 µg or 20 µg/kg/min). Concurrently the susceptibility of the heart to ischaemia reperfusion injury was assessed under the similar conditions. For any given duration of remifentanil infusion, there was increasing superoxide anions generated as the dose of remifentanil was increased. MDA concentrations were significantly increased when the animal was exposed to 10 µg/kg/min for 2h or 20 µg/kg/min for any duration. There was a trend towards an increased nitrotyrosine concentration with increasing dose of remifentanil, becoming significant when the dose was 20 µg/kg/min. The infarct limiting ability of remifentanil was compromised when the dihydroethidium fluorescence positive cell percentage exceeded 50%, MDA concentration greater than 2 nmol/mg of protein and nitrotyrosine content exceeding 1.5 µg/mg of protein. Short term high dose opioid exposure can induce oxidative changes seen previously only with chronic opioid use and this high oxidative stress environment corrupts the heart's sensitivity to be preconditioned by opioids.

Perioperative statin therapy.

INTRODUCTION: The lipid lowering class of drugs known as "Statins" are being increasing recognized for their pleiotropic effects which include anti-inflammation, antioxidant, vasodilatation, improved endothelial function and stabilization of atherosclerotic plaques. These effects may counteract, to some extent, the deleterious impact of surgical stress on various organ systems during the perioperative period. AREAS COVERED: A literature review was undertaken to examine current evidence for the effect of perioperative statin use on postoperative morbidity and mortality. A search of PubMed, Medline and Scopus databases was performed using a combination of search terms including statins and perioperative risk reduction, outcomes, morbidity and mortality. Further searches were made on specific areas such as statins and thrombosis, kidney injury, renal protection, cancer, cost and safety. EXPERT OPINION: Current evidence supports a reduction in cardiovascular morbidity and mortality associated with perioperative statin use in high risk patients undergoing non cardiac surgery and this represents a very cost effective application of statin therapy with few adverse events reported. Data is emerging that point to other benefits such as renal protection but this requires further confirmation from prospective studies. Future research needs to address the questions of the optimal type, timing and dosage of statin therapy as well as whether there are problems associated with abrupt withdrawal and adverse effects associated with long term use.

Effects of the Mycoparasite Sphaerellopsis filum on Overwintering Survival of Stem Rust in Perennial Ryegrass.

Sphaerellopsis filum is a mycoparasite of Puccinia graminis subsp. graminicola, a rust fungus that causes widespread crop damage on perennial ryegrass grown for seed. In observations taken over the winter months, S. filum was found naturally colonizing 2% of P. graminis subsp. graminicola uredinia on first-year plantings and 25% of the uredinia on second-year plantings of perennial ryegrass. In controlled experiments conducted in glasshouses and growth chambers, S. filum applied to rust-inoculated plants reduced the lifetime spore production of P. graminis subsp. graminicola pustules by half, from 39,000 to 18,000 spores/pustule. Mist duration, temperature, and P. graminis subsp. graminicola pustule age at the time of S. filum inoculation had significant effects on the proportion of P. graminis subsp. graminicola pustules infected by S. filum. Fifty percent of all P. graminis subsp. graminicola pustules were infected when S. filum was inoculated onto erumpent pustules and incubated above 5°C for 48 h while exposed to mist. Plants inoculated with both fungi under controlled conditions and then planted into the field had a significantly greater proportion of P. graminis subsp. graminicola pustules infected with S. filum, and a significantly reduced P. graminis subsp. graminicola overwintering population, compared with plants inoculated with P. graminis subsp. graminicola only. First-year stands of perennial ryegrass treated in the field with monthly applications of S. filum had more than 10 times the proportion of pustules infected with S. filum and 50% less P. graminis subsp. graminicola disease compared with the nontreated controls. In comparison, plants with one application of fungicide during the winter had 98% lower P. graminis subsp. graminicola severity than the P. graminis subsp. graminicola-only control There were no effects of S. filum or fungicide application on rust severity in 2- or 3-year-old perennial ryegrass stands.

Remifentanil preconditioning reduces hepatic ischemia-reperfusion injury in rats via inducible nitric oxide synthase expression.

BACKGROUND: Opioid preconditioning against ischemia reperfusion injury has been well studied in myocardial and neuronal tissues. The objective of this study was to determine whether remifentanil could attenuate hepatic injury and to investigate the mechanisms. METHODS: A rat model of hepatic ischemia reperfusion injury and a hepatocyte hypoxia reoxygenation (HR) injury model were used, respectively, in two series of experiments. Remifentanil was administered before ischemia or hypoxia and the experiments were repeated with previous administration of naloxone, L-arginine and N-ω-nitro-L-arginine methyl ester, a nonselective opioid receptor antagonist, a nitric oxide donor, and nitric oxide synthase (NOS) inhibitor, respectively. Serum aminotransferase, cytokines, and hepatic lipid peroxidation were measured. Histopathology examination and apoptotic cell detection were assessed. For the in vitro study, cell viability, intracellular nitric oxide, apoptosis, and NOS expression were evaluated. RESULTS: Remifentanil and L-arginine pretreatment reduced concentrations of serum aminotransferases and cytokines, decreased the concentrations of hepatic malondialdehyde and myeloperoxidase activity, and increased superoxide dismutase, nitric oxide, and inducible NOS expression in vivo. Decreased histologic damage and apoptosis were also seen in these two groups. These changes were prevented by previous administration of N-ω-nitro-L-arginine methyl ester but not naloxone. There was an increase in inducible NOS protein expression but not endogenous NOS in remifentanil and L-arginine pretreated groups compared with control, naloxone, and N-ω-nitro-L-arginine methyl ester groups. CONCLUSION: Pretreatment with remifentanil can attenuate liver injury both in vivo and in vitro. Inducible NOS but not opioid receptors partly mediate this effect by exhausting reactive oxygen species and attenuating the inflammatory response.

Peripheral nerve injury alters the expression of NF-κB in the rat's hippocampus.

The hippocampus plays an important role in learning and memory and possibly contributes to the formation of pain-related memory and emotional responses. However, there is currently little data linking the hippocampus to neuropathic pain. It has been reported that NF-κB is an important regulatory factor in memory consolidation within the hippocampus. This study aims to examine a possible relationship between the hippocampal NF-κB expression and nerve injury-induced thermal hyperalgesia using a rat model of constriction sciatic nerve injury (CCI). Immunofluorescence and Western blot analysis were performed to detect and quantify the hippocampal NF-κB expression. Thermal hyperalgesia was examined on day 0 and postoperative days 1, 7 and 14. The nuclear portion of the p65 NF-κB expression was significantly increased on the contralateral side on days 7 and 14 as well as significantly increased on the ipsilateral side on day 14 as compared to the sham control group. Intraperitoneal administration of MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, reduced hyperalgesia and modulated the NF-κB expression in the contralateral side of hippocampus. These results suggest an association between the hippocampal NF-κB expression and the behavioral manifestation of thermal hyperalgesia, which is likely to be mediated through activation of the NMDA receptor.