Expert consensus on difficult airway assessment.

Background: Identifying a potentially difficult airway is crucial both in anaesthesia in the operating room (OR) and non-operation room sites. There are no guidelines or expert consensus focused on the assessment of the difficult airway before, so this expert consensus is developed to provide guidance for airway assessment, making this process more standardized and accurate to reduce airway-related complications and improve safety. Methods: Seven members from the Airway Management Group of the Chinese Society of Anaesthesiology (CSA) met to discuss the first draft and then this was sent to 15 international experts for review, comment, and approval. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) is used to determine the level of evidence and grade the strength of recommendations. The recommendations were revised through a three-round Delphi survey from experts. Results: This expert consensus provides a comprehensive approach to airway assessment based on the medical history, physical examination, comprehensive scores, imaging, and new developments including transnasal endoscopy, virtual laryngoscopy, and 3D printing. In addition, this consensus also reviews some new technologies currently under development such as prediction from facial images and voice information with the aim of proposing new research directions for the assessment of difficult airway. Conclusions: This consensus applies to anesthesiologists, critical care, and emergency physicians refining the preoperative airway assessment and preparing an appropriate intubation strategy for patients with a potentially difficult airway.

MicroRNA-503 Exacerbates Myocardial Ischemia/Reperfusion Injury via Inhibiting PI3K/Akt- and STAT3-Dependent Prosurvival Signaling Pathways.

Acute myocardial infarction is a leading cause of death worldwide, while restoration of blood flow to previously ischemic myocardium may lead to ischemia/reperfusion (I/R) injury. Accumulated evidence shows that microRNAs play important roles in cardiovascular diseases. However, the potential role of microRNA-503 (miR-503) in myocardial I/R injury is little known. Thus, this study is aimed at determining whether and how miR-503 affects myocardial I/R injury in vivo and in vitro. A mouse model of myocardial I/R injury and H9c2 cell model of hypoxia/reoxygenation (H/R) injury were established. The postischemic cardiac miR-503 was downregulated in vivo and in vitro. Mechanistically, PI3K p85 and Bcl-2 are miR-503 targets. The post-ischemic cardiac PI3K p85 protein level was decreased in vivo. Agomir-503 treatment exacerbated H/R-induced injuries manifested as decreased cell viability, increased lactate dehydrogenase activity, and cell apoptosis. Agomir-503 treatment reduced cell viability under normoxia as well and reduced both PI3K p85 and Bcl-2 protein levels under either normoxia or H/R condition. It reduced phosphorylation of Stat3 (p-Stat3-Y705) and Akt (T450) in cells subjected to H/R. In contrast, Antagomir-503 treatment attenuated H/R injury and increased p-Stat3 (Y705) under normoxia and increased p-Akt (T450) under either normoxia or H/R condition. It is concluded that miR-503 exacerbated I/R injury via inactivation of PI3K/Akt and STAT3 pathways and may become a therapeutic target in preventing myocardial I/R injury.

Environmental Enrichment in Postoperative Pain and Surgical Care: Potential Synergism With the Enhanced Recovery After Surgery Pathway.

BACKGROUND: Holistic biopsychosocial care has been underemphasized in perioperative pathway designs. The importance and a cost-effective way of implementing biopsychosocial care to improve postoperative pain and facilitate surgical convalescence are not well established, despite the recent popularization of Enhanced Recovery After Surgery (ERAS) programs. OBJECTIVE: We have explored the evidence and rationale of environmental enrichment (EE) as a complementary multimodal psychosocial care pathway to reduce postoperative pain, optimize patient recovery and improve existing weaknesses in surgical care. METHODS: We conducted a database search to identify and grade potential EE techniques for their evidence quality and consistency in the management of acute postoperative pain, perioperative anxiety and the etiologically comparable acute procedural or experimental pain. FINDINGS AND CONCLUSIONS: The introduction of music, virtual reality, educational information, mobile apps, or elements of nature into the healthcare environment can likely improve patients' experience of surgery. Compared with traditional psychological interventions, EE modalities are voluntary, therapist-sparing and more economically sustainable. We have also discussed practical strategies to integrate EE within the perioperative workflow. Through a combination of sensory, motor, social and cognitive modalities, EE is an easily implementable patient-centered approach to alleviate pain and anxiety in surgical patients, create a more homelike recovery environment and improve quality of life.

Total Intravenous Anesthesia (TIVA) With Propofol for Acute Postoperative Pain: A Scoping Review of Randomized Controlled Trials.

Total intravenous anesthesia (TIVA) with propofol may improve acute postoperative pain control compared to inhalational anesthesia. The objective of this review was to comprehensively update and evaluate the existing literature on the analgesic efficacy of propofol TIVA. A systemized literature search for randomized controlled trials in adult patients was conducted in the PubMed and Cochrane CENTRAL (EMBASE source) databases up to August 2019. Clinical trials included compared propofol TIVA against inhalational isoflurane, sevoflurane, or desflurane. Only clinical trials that studied acute postoperative pain scores or analgesic consumption as a primary outcome were included. Sixteen randomized controlled trials were included. Surgical procedures evaluated included: radical gastrectomy, open vein stripping, breast cancer surgery, laparoscopic cholecystectomy, inguinal herniotomy, abdominoplasty, bariatric surgery, lumbar spine surgery, emergency neurosurgical operations, open and laparoscopic gynecological surgeries, and dental surgery. Propofol TIVA was associated with reduced postoperative pain scores and/or decreased opioid consumption in 9 out of 16 clinical trials. There was no difference in 5 clinical trials, and propofol TIVA was associated with worse analgesic outcomes in 2 trials. Propofol TIVA may improve acute postoperative analgesia after surgery, but different factors such as surgical procedures and anesthetic/analgesic techniques may influence its effectiveness.

Anesthetic Management for Squamous Cell Carcinoma of the Esophagus.

While surgery plays a major role in the treatment and potential cure of esophageal cancers, esophagectomy remains a high-risk operation with significant perioperative morbidity and mortality compared to other oncosurgical procedures. Perioperative management for esophagectomy is complex, and close attention to detail in various areas of anesthetic and perioperative management is crucial to improve postoperative outcomes. Patients undergoing esophagectomy should be offered an evidence-based risk assessment for their postoperative outcomes to allow active participation and informed, shared-decision making. Novel perioperative risk scores have been developed to predict both short-term and long-term outcomes in patients with esophageal cancer, although independent validation of such scoring systems is still required. Apart from accurate preoperative risk assessment, further efforts to improve morbidity and mortality from esophagectomy is achieved through comprehensive Enhanced Recovery after Surgery (ERAS) protocols, which comprise an individualized bundle of care throughout the perioperative journey for each patient and should be implemented as a standard practice. Furthermore, anesthetic practice and perioperative anesthetic drug usage can potentially affect cancer progression and recurrence. This chapter reviews current evidence for various factors that contribute to the improvement of perioperative outcomes, including prehabilitation, preoperative optimization of anemia, thoracic epidural analgesia, intraoperative protective ventilatory strategies, goal-directed fluid therapy, as well as special attention to other perioperative issues that potentially reduce anastomotic and cardiopulmonary complications. In summary, it is difficult to show a measurable benefit from any one single intervention, and a multidisciplinary approach that encompasses multiple aspects of perioperative care is necessary to improve outcomes after esophagectomy.

Allopurinol reduces oxidative stress and activates Nrf2/p62 to attenuate diabetic cardiomyopathy in rats.

Allopurinol (ALP) attenuates oxidative stress and diabetic cardiomyopathy (DCM), but the mechanism is unclear. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) following the disassociation with its repressor Keap1 under oxidative stress can maintain inner redox homeostasis and attenuate DCM with concomitant attenuation of autophagy. We postulated that ALP treatment may activate Nrf2 to mitigate autophagy over-activation and consequently attenuate DCM. Streptozotocin-induced type 1 diabetic rats were untreated or treated with ALP (100 mg/kg/d) for 4 weeks and terminated after heart function measurements by echocardiography and pressure-volume conductance system. Cardiomyocyte H9C2 cells infected with Nrf2 siRNA or not were incubated with high glucose (HG, 25 mmol/L) concomitantly with ALP treatment. Cell viability, lactate dehydrogenase, 15-F2t-Isoprostane and superoxide dismutase (SOD) were measured with colorimetric enzyme-linked immunosorbent assays. ROS, apoptosis, was assessed by dihydroethidium staining and TUNEL, respectively. The Western blot and qRT-PCR were used to assess protein and mRNA variations. Diabetic rats showed significant reductions in heart rate (HR), left ventricular eject fraction (LVEF), stroke work (SW) and cardiac output (CO), left ventricular end-systolic volume (LVVs) as compared to non-diabetic control and ALP improved or normalized HR, LVEF, SW, CO and LVVs in diabetic rats (all P < .05). Hearts of diabetic rats displayed excessive oxidative stress manifested as increased levels of 15-F2t-Isoprostane and superoxide anion production, increased apoptotic cell death and cardiomyocytes autophagy that were concomitant with reduced expressions of Nrf2, heme oxygenase-1 (HO-1) and Keap1. ALP reverted all the above-mentioned diabetes-induced biochemical changes except that it did not affect the levels of Keap1. In vitro, ALP increased Nrf2 and reduced the hyperglycaemia-induced increases of H9C2 cardiomyocyte hypertrophy, oxidative stress, apoptosis and autophagy, and enhanced cellular viability. Nrf2 gene silence cancelled these protective effects of ALP in H9C2 cells. Activation of Nrf2 subsequent to the suppression of Keap1 and the mitigation of autophagy over-activation may represent major mechanisms whereby ALP attenuates DCM.

Hyperglycemia-Induced Oxidative Stress Abrogates Remifentanil Preconditioning-Mediated Cardioprotection in Diabetic Rats by Impairing Caveolin-3-Modulated PI3K/Akt and JAK2/STAT3 Signaling.

Diabetic hearts are more vulnerable to ischemia/reperfusion (I/R) injury and less responsive to remifentanil preconditioning (RPC), but the underlying mechanisms are incompletely understood. Caveolin-3 (Cav-3), the dominant isoform of cardiomyocyte caveolae, is reduced in diabetic hearts in which oxidative stress is increased. This study determined whether the compromised RPC in diabetes was an independent manifestation of hyperglycemia-induced oxidative stress or linked to impaired Cav-3 expression with associated signaling abnormality. RPC significantly attenuated postischemic infarction, cardiac dysfunction, myocardial apoptosis, and 15-F2t-isoprostane production (a specific marker of oxidative stress), accompanied with increased Cav-3 expression and enhanced Akt and STAT3 activation in control but not in diabetic rats. Pretreatment with the antioxidant N-acetylcysteine (NAC) attenuated hyperglycemia-induced reduction of Cav-3 expression and Akt and STAT3 activation and restored RPC-mediated cardioprotection in diabetes, which was abolished by cardiac-specific knockdown of Cav-3 by AAV9-shRNA-Cav-3, PI3K/Akt inhibitor wortmannin, or JAK2/STAT3 inhibitor AG490, respectively. Similarly, NAC could restore RPC protection from high glucose and hypoxia/reoxygenation-induced injury evidenced by decreased levels of LDH release, 15-F2t-isoprostane, O2 -, and JC-1 monomeric cells, which were reversed by caveolae disrupter methyl-ß-cyclodextrin, wortmannin, or AG490 in isolated primary cardiomyocytes or siRNAs of Cav-3, Akt, or STAT3 in H9C2 cells. Either methyl-ß-cyclodextrin or Cav-3 knockdown reduced Akt and STAT3 activation. Further, the inhibition of Akt activation by a selective inhibitor or siRNA reduced STAT3 activation and vice versa, but they had no effects on Cav-3 expression. Thus, hyperglycemia-induced oxidative stress abrogates RPC cardioprotection by impairing Cav-3-modulated PI3K/Akt and JAK2/STAT3 signaling. Antioxidant treatment with NAC could restore RPC-induced cardioprotection in diabetes by improving Cav-3-dependent Akt and STAT3 activation and by facilitating the cross talk between PI3K/Akt and JAK2/STAT3 signaling pathways.

Anaesthetic considerations in nonagenarians and centenarians.

PURPOSE OF REVIEW: The ageing population is a global public health issue and we can expect to encounter more and more older patients requiring anaesthetic care. Age itself is no longer the sole reason for declining a patient for anaesthesia and surgery. Undoubtedly, managing patients at the extremities of age is challenging and demanding, not only because of multiple comorbidities, but also the poorer functional status, frailty and decline in general well being that must be managed during the perioperative journey. In this article, we will focus on three important aspects of anaesthetic care for this patient group, namely, comorbidity, frailty and perioperative cognitive dysfunction; and give recommendations on how anaesthetists should tackle these aspects for the 'older old' and the 'oldest old', based on current best evidence. RECENT FINDINGS: The 'oldest old' (nonagerians and centenarians) are the fastest-growing geriatric population worldwide. Evidence has demonstrated that an enhanced care programme designed for elderly patients is safe, feasible and could diminish both complications and length of stay after surgery. Studies are emerging on frailty measurement and the association with outcomes of anaesthesia and surgery and have resulted in new recommendations on best practices for postoperative brain health and nomenclature of perioperative neurocognitive disorder. SUMMARY: Comorbidity, frailty and perioperative cognitive dysfunction are significant perioperative concerns specific to elderly patients and clearly associated with adverse outcomes after surgery. These anaesthetic concerns should be anticipated and properly managed through the perioperative pathway so that their potential complications can be mitigated.

Vascular endothelial growth factor regulation of endothelial nitric oxide synthase phosphorylation is involved in isoflurane cardiac preconditioning.

Aims: Previous studies indicate that nitric oxide derived from endothelial nitric oxide synthase (eNOS) serves as both trigger and mediator in anaesthetic cardiac preconditioning. The mechanisms underlying regulation of eNOS by volatile anaesthetics have not been fully understood. Therefore, this study examined the role of vascular endothelial growth factor (VEGF) in isoflurane cardiac preconditioning. Methods and results: Wistar rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Isoflurane given prior to ischaemia/reperfusion significantly decreased myocardial infarct size from 60 ± 1% in control to 40 ± 3% (n = 8 rats/group, P < 0.05). The beneficial effects of isoflurane were blocked by neutralizing antibody against VEGF (nVEGF). Coronary arterial endothelial cells (ECs) alone or together with cardiomyocytes (CMs) were subjected to hypoxia/reoxygenation injury. The expression of VEGF and eNOS was analysed by western blot, and nitric oxide was measured by ozone-based chemiluminescence. In co-cultured CMs and ECs, isoflurane administered before hypoxia/reoxygenation attenuated lactate dehydrogenase activity and increased the ratio of phosphorylated eNOS/eNOS and nitric oxide production. The protective effect of isoflurane on CMs was compromised by nVEGF and after VEGF in ECs was inhibited with hypoxia inducible factor-1α short hairpin RNA (shRNA). The negative effect of hypoxia inducible factor-1α shRNA was restored by recombinant VEGF. Conclusion: Isoflurane cardiac preconditioning is associated with VEGF regulation of phosphorylation of eNOS and nitric oxide production.

Anesthetic management of thoracoscopic resection of lung lesions in small children.

BACKGROUND: Video-assisted thoracoscopic surgery has dramatically increased over the last decade because of both medical and cosmetic benefits. Anesthesia for video-assisted thoracoscopic surgery in small children is more challenging compared to adults due to the considerable problems posed by small airway dimensions and ventilation. The optimal technique for one-lung ventilation has yet to be established and the use of remifentanil infusion in this setting is not well described. AIMS: This study investigated the use of extraluminal bronchial blocker placement for one-lung ventilation and the effect of infusion of remifentanil in infants and small children undergoing video-assisted thoracoscopic surgery. METHODS: We retrospectively reviewed the technique of one-lung ventilation and the hemodynamic effects of remifentanil infusion in 31 small children during elective video-assisted thoracoscopic surgery for congenital lung lesions under anesthesia with sevoflurane or isoflurane, oxygen, and air. Patients' heart rate, blood pressure, and endtidal carbon dioxide at baseline (after induction of anesthesia), immediately after one-lung ventilation, during carbon dioxide insufflation, and at the end of one-lung ventilation were extracted from the database and analyzed. The use of vasopressors or dexmedetomidine was also recorded and analyzed. RESULTS: Extraluminal placement of a bronchial blocker alongside the tracheal tube was successfully performed in 90.3% of cases (28 patients) without any serious complications or arterial oxygen desaturation. There was no significant rise in blood pressure or heart rate even with the rise of endtidal carbon dioxide concentration during video-assisted thoracoscopic surgery. In 58% of patients (18 patients), phenylephrine was administered to maintain the blood pressure within 20% of the baseline value. There was no significant change in the heart rate of all patients at each time point. CONCLUSION: One-lung ventilation with an extraluminal parallel blocker was used effectively in this series of young children undergoing thoracoscopic excision of congenital pulmonary lesions. Remifentanil infusion attenuated surgical stress effectively in infants and small children undergoing video-assisted thoracoscopic surgery.

Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic Rats.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease which has been previously shown to be associated with type 2 diabetes mellitus (T2DM). Recent research has indicated that type 1 diabetes mellitus (T1DM) is also involved in the development of nonalcoholic fatty liver disease, whereas the underlying mechanisms are largely unknown. Forkhead box O1 (FoxO1) and adiponectin (APN) have been proposed to play an important role in the processes in NAFLD in T1DM. We herein investigated the effects of FoxO1 and APN on the development of NAFLD and the underlying mechanism in streptozotocin-induced T1DM. Serum liver enzymes AST, ALT, and triglyceride (TG) were determined by commercially available kits. Blood glucose levels were measured by the OneTouch Ultra glucose meter. Relevant protein expression was tested by Western blot analysis. Results showed that serum AST, ALT, and TG were all significantly increased in T1DM rats, which was ameliorated by application of APN or selective inhibition of FoxO1 with AS1842856. Moreover, APN and AS1842856 both decreased the expression of liver nuclear FoxO1 which was significantly increased in diabetic rats. However, the inhibition of FoxO1 did not alter the expression of APN and its receptors. We also found that Akt1 expression was significantly declined in diabetic rat which was restored by APN and moderately and significantly increased by FoxO1 inhibition. It is concluded that APN ameliorates NAFLD via inhibition of FoxO1 through Akt1/FoxO1 signaling pathway.

The analgesic effects of intraoperative total intravenous anesthesia (TIVA) with propofol versus sevoflurane after colorectal surgery.

Clinical studies have shown that total intravenous anesthesia (TIVA) with propofol is associated with better postoperative pain control compared with inhalational anesthesia, while other studies have not shown any benefit. The analgesic effect of TIVA with propofol in colorectal surgery has not been studied. The aim of this study is to evaluate the postoperative analgesic effects of TIVA with propofol versus inhalational sevoflurane in colorectal surgery.This is a retrospective case-control study. Records of patients undergoing colorectal surgery from 2014 to 2016 (36 months) were retrieved. Ninety-five patients who received TIVA with propofol were matched against 95 patients who received inhalational sevoflurane. Acute postoperative numerical rating scale (NRS) pain scores, postoperative morphine consumption, patient satisfaction, and side effects were compared and analyzed for differences between TIVA with propofol and sevoflurane.There were no significant differences in NRS pain scores, incidence of side effects, and patient satisfaction between the 2 groups. Patients receiving TIVA with propofol had significantly reduced total morphine consumption (P < .001), and daily morphine consumption on postoperative days 1 (P = .031), 2 (P = .002), and 3 (P = .031) compared with those receiving sevoflurane.TIVA with propofol was not associated with improved postoperative analgesia, better patient satisfaction, or reduced side effects. It may reduce postoperative opioid consumption after colorectal surgery.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public-private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses.

AMPK Contributes to Cardioprotective Effects of Pterostilbene Against Myocardial Ischemia- Reperfusion Injury in Diabetic Rats by Suppressing Cardiac Oxidative Stress and Apoptosis.

BACKGROUND/AIMS: Pterostilbene (PT) exerts antidiabetic effects by decreasing blood glucose and modulating lipid metabolism and has been shown to attenuate myocardial ischemia-reperfusion (IR) injury in non-diabetic subjects. However, whether PT can protect against myocardial IR injury in diabetes is unknown. AMPK stimulation is indispensable in offering cardioprotection against myocardial IR injury in diabetes by limiting cardiac apoptosis. Thus, we hypothesized that PT may confer protection against myocardial IR injury in diabetes via AMPK activation. METHODS: Sprague-Dawley rats at eight weeks of diabetes induction (induced by an intravenous dose of 65 mg/kg streptozotocin) were administered with vehicle or PT (20 and 40 mg/kg/day, p.o.) for four weeks (starting from week 9 to 12). At the end of week 12, myocardial IR injury was induced by subjecting the diabetic rats to 30 minutes of coronary artery ligation and followed by 2 hours of reperfusion. In in vitro studies, rat primary cardiomyocytes were incubated with low glucose (LG, 5.5 mM) or high glucose (HG, 30 mM) and exposed to 45 minutes hypoxia and 2 hours reoxygenation in the presence or absence of PT (0.5 µM) or the AMPK inhibitor compound C (CC, 5 µM). RESULTS: PT significantly reduced post-ischemic cardiac infarct size, oxidative stress, plasma lactate dehydrogenase (LDH), creatine kinase-MB levels and apoptosis in diabetic rats. In cardiomyocytes, PT decreased hypoxia/ reoxygenation-induced oxidative stress, attenuated LDH and cleaved caspase3/caspase3 ratio and increased Bcl-2/Bax ratio and AMPK phosphorylation. However, CC administration blunted the cardioprotective effects of PT both in vivo and in vitro. CONCLUSION: Suppressing cardiac oxidative stress and apoptosis via AMPK stimulation may represent a primary mechanism whereby pterostilbene attenuates diabetic myocardial IR injury.

Repeated Non-Invasive Limb Ischemic Preconditioning Confers Cardioprotection Through PKC-Ԑ/STAT3 Signaling in Diabetic Rats.

BACKGROUND/AIMS: Protein kinase C(PKC)-ε activation is a mechanism of preconditioning cardioprotection but its role in repeated non-invasive limb ischemic preconditioning (rNLIP) mediated cardioprotection against myocardial ischemia/reperfusion (I/R) injury in diabetes is unknown. METHODS: Eight-week streptozotocin-induced diabetic and non-diabetic Sprague-Dawley rats were subjected to I/R without or with rNLIP. In vitro, H9C2 cells were cultured with high glucose (HG) and subjected to hypoxia/re-oxygenation (H/R) without or with PKC-ε or STAT3 gene knock-down in the absence or presence of remote time hypoxia preconditioning (HPC). RESULTS: Diabetic rats displayed larger post-ischemic myocardial infarct size and higher troponin-I release with concomitant cardiac PKC-ԑ overexpression and activation manifested as increased membrane translocation, while phosphorylated STAT3 (p-STAT3) and Akt (p-Akt) were lower compared to non-diabetic rats (all P<0.05). rNLIP reduced infarct size in both non-diabetic and diabetic rats. rNLIP reduced post-ischemic cardiac PKC-ԑ activation in diabetic while increased PKC-ԑ activation in non-diabetic rats, resulting in increased cardiac p-STAT3 and p-Akt. In H9C2 cells, HG increased PKC-ԑ expression and exacerbated post-H/R injury, accompanied with reduced p-STAT3 and p-Akt, which were all reverted by HPC. These HPC protective effects were abolished by either PKC-ԑ or STAT3 gene knock-down, except that PKC-ԑ gene knock-down reverted HG and H/R-induced reduction of p-STAT3. CONCLUSION: rNLIP attenuates diabetic heart I/R injury by mitigating HG-induced PKC-ԑ overexpression and, subsequently, activating STAT3.

Remifentanil preconditioning confers cardioprotection via c-Jun NH2-terminal kinases and extracellular signal regulated kinases pathways in ex-vivo failing rat heart.

Remifentanil preconditioning (RPC) exerts protection in normal hearts, but has not been investigated in heart failure. The aim of the present study was to evaluate the effect of RPC in a chronic failing rat heart model and the mechanisms involving mitogen-activated protein kinases (MAPK) and Bcl-2 protein family. The doxorubicin induced failing rat hearts were subjected to 30 min ischemia / 120 min reperfusion (IR) with or without RPC by using Langendorff apparatus. RPC was induced by three cycles of 5 min remifentanil / 5 min drug-free perfusion before IR, with three different concentrations: 25, 50 and 100 µg/l. An extracellular signal regulated kinases (ERK) inhibitor PD98059, p38MAPK inhibitor SB203580, c-Jun NH2-terminal kinases (JNK) inhibitor SP600125 were perfused at 10 min before RPC. Infarct size, cardiac function and protein kinase activity were determined. RPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by IR injury in failing heart. The JNK inhibitor SP600125 and ERK inhibitor PD98059 abolished the RPC mediated reduction effect on the infarct size and LDH activity after reperfusion. In addition, RPC increased the phosphorylation of JNK, ERK1/2 and the downstream GSK-3ß, as well as the Bcl-2/Bax ratio, while, these changes were completely reversed by SP600125 and PD98059. And of note, SB203580 had no effect. In conclusion, our results suggested that the activation of JNK and ERK pathways, by leading to inhibition of GSK-3ß and regulating Bcl-2 protein family, is a major mechanism that RPC confers cardioprotection in failing rat heart.

Siegesbeckia Orientalis L. Extract Attenuates Postoperative Cognitive Dysfunction, Systemic Inflammation, and Neuroinflammation.

A proportion of patients experience acute or even prolonged cognitive impairment after surgery, a condition known as postoperative cognitive dysfunction (POCD). It is characterized by impairment in different cognitive domains and neuroinflammation has been implicated as one of the inciting factors as strategies targeting inflammation tend to improve cognitive performance. Siegesbeckia Orientails L. (S. Orientails) is a common Chinese medicinal herb used for managing chronic inflammatory diseases. We investigated if pretreatment with S. Orientails before surgery confers any neuroprotective effects in postoperative animals in terms of reducing inflammation and mitigating cognitive impairment. Three-month-old male C57BL/6N mice were fed different doses of S. Orientails extract for 14 days before they underwent a laparotomy. After cognitive testing they were sacrificed on postoperative day (POD) 3. Our results showed that animals with extract pretreatment demonstrated memory improvement in a dose-dependent manner compared with control. Further, evidence for the attenuation of systemic and neuroinflammation was found in the pretreated animals, along with the inhibition of inflammatory pathways and significantly reduced tau phosphorylation in the hippocampus. Taken together, these results demonstrated a neuroprotective effect of S. Orientails in postoperative animals, indicating a therapeutic potential of S. Orientails in minimizing POCD and the possibility of utilizing this traditional Chinese medicine perioperatively.

Decoding telomere protein Rap1: Its telomeric and nontelomeric functions and potential implications in diabetic cardiomyopathy.

Mammalian Rap1, the most conserved telomere-interacting protein, beyond its role within nucleus for the maintenance of telomeric functions, is also well known for its pleiotropic functions in various physiological and pathological conditions associated with metabolism, inflammation and oxidative stress. For all these, nowadays Rap1 is the subject of critical investigations aimed to unveil its molecular signaling pathways and to scrutinize the applicability of its modulation as a promising therapeutic strategy with clinical relevance. However, the underlying intimate mechanisms of Rap1 are not extensively studied, but any modulation of this protein level has been associated with pathologies like inflammation, oxidative stress and deregulated metabolism. This is considerably important in light of the recent discovery of Rap1 modulation in diseases like cancer and cardiac metabolic disorders. In this review, we focus on both the telomeric and nontelomeric functions of Rap1 and its modulation in various health risks, especially on the heart.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 1 Efficacy: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and degree of pain experienced. Consistent use of the recommended outcome measures will facilitate the comprehensive reporting across sedation trials, along with meaningful comparisons among studies and interventions in systematic reviews and meta-analyses.