Analgesic effects of ultrasound-guided preoperative posterior Quadratus Lumborum block in laparoscopic hepatectomy: A prospective double-blinded randomized controlled trial.

STUDY OBJECTIVE: To determine if single-injection bilateral posterior quadratus lumborum block (QLB) with ropivacaine would improve postoperative analgesia in the first 24 h after laparoscopic hepatectomy, compared with 0.9% saline. DESIGN: Prospective, double blinded, randomized controlled trial. SETTING: A single tertiary care center from November 2021 and January 2023. PATIENTS: A total of 94 patients scheduled to undergo laparoscopic hepatectomy due to hepatocellular carcinoma. INTERVENTIONS: Ninety-four patients were randomized into a QLB group (receiving 20 mL of 0.375% ropivacaine on each side, 150 mg in total) or a control group (receiving 20 mL of 0.9% saline on each side). MEASUREMENTS: The primary outcome was the cumulative opioid consumption during the initial 24-h post-surgery. Secondary outcomes included pain scores and intraoperative and recovery parameters. MAIN RESULTS: The mean cumulative opioid consumption during the initial 24-h post-surgery was 30.8 ± 22.4 mg in the QLB group (n = 46) and 34.0 ± 19.4 mg in the control group (n = 46, mean differences: -3.3 mg, 95% confidence interval, -11.9 to 5.4, p = 0.457). The mean resting pain score at 1 h post-surgery was significantly lower in the QLB group than in the control group (5 [4-6.25] vs. 7 [4.75-8], p = 0.035). No significant intergroup differences were observed in the resting or coughing pain scores at other time points or in other secondary outcomes. CONCLUSIONS: Preoperative bilateral posterior QLB did not reduce cumulative opioid consumption during the first 24 h after laparoscopic hepatectomy.

Comparison of analgesic effects between programmed intermittent epidural boluses and continuous epidural infusion after cesarean section: a randomized controlled study.

BACKGROUND: This study aimed to compare the analgesic effects of programmed intermittent epidural boluses (PIEB) and continuous epidural infusion (CEI) for postoperative analgesia after elective cesarean section (CS). METHODS: Seventy-four women who underwent elective CS were randomized to receive either PIEB or CEI. The PIEB group received 4 ml-intermittent boluses of 0.11% ropivacaine every hour at a rate of 120 ml/h. The CEI group received a constant rate of 4 ml/h of 0.11% ropivacaine. The primary outcome was the pain score at rest at 36 h after CS. Secondary outcomes included the pain scores during mobilization, time-weighted pain scores, the incidence of motor blockade, and complications-related epidural analgesia during 36 h after CS. RESULTS: The pain score at rest at 36 h after CS was significantly lower in the PIEB group compared with that in the CEI group (3.0 vs. 0.0; median difference: 2, 95% CI [1, 2], P < 0.001). The mean time-weighted pain scores at rest and during mobilizations were also significantly lower in the PIEB group than in the CEI group (pain at rest; mean difference [MD]: 37.5, 95% CI [24.6, 50.4], P < 0.001/pain during mobilization; MD: 56.6, 95% CI [39.8, 73.5], P < 0.001). The incidence of motor blockade was significantly reduced in the PIEB group compared with that in the CEI group (P < 0.001). CONCLUSIONS: PIEB provides superior analgesia with less motor blockade than CEI in postpartum women after CS, without any apparent adverse events.

Quality and composition of archived nucleic acids after use in SARS-CoV-2 molecular testing.

BACKGROUND: Reverse transcription real-time PCR (rRT-PCR) has been a gold-standard method to detect SARS-CoV-2, for which quality assessment of nucleic acids (NAs) is not needed. In order to prepare for future use, we evaluated NA quality from archived SARS-CoV-2 rRT-PCR samples. METHODS: NA samples were collected in February 2021 and extracted using the QIAamp DSP Virus Spin Kit, (53 SARS-CoV-2-positive and 100 SARS-CoV-2-negative). Quality, quantity, and purity of NA were measured spectrophotometrically or fluorescently. Droplet digital PCR was used to characterize the double strand DNA (dsDNA) origin and composition by quantifying 16S rDNA and RPP30. RESULTS: The RIN and purity were not significantly different between groups (p = 0.3828). RNA quantity was significantly higher than dsDNA in both groups (p < 0.0001); both dsDNA and RNA quantity were significantly higher in positive samples (dsDNA, RNA p = 0.021). For dsDNA, 16S rDNA copies were significantly greater than RPP30 in both groups (p < 0.0001), and RPP30 were significantly higher in positive samples (p < 0.0001). CONCLUSIONS: Archived NA quality after SARS-CoV-2 rRT-PCR was guaranteed for subsequent molecular research using human or bacterial DNA, especially for short targets.

Neuroinflammation-Modulating Agent SB1617 Enhances LC3-Associated Phagocytosis to Mitigate Tau Pathology.

Tau protein aggregation and propagation in neurons and surrounding microglia are well-known risk factors for neurodegenerative diseases. Therefore, emerging therapeutic strategies that target neuroinflammatory activity in microglia have the potential to prevent tauopathy. Here, we explored the microglia-mediated neuroprotective function of SB1617 against tau aggregation. Our study revealed that SB1617-inactivated pathogenic M1-like microglia, reduced the secretion of pro-inflammatory cytokines via translational regulation, and induced microglial polarization toward the M2 phenotype and phagocytic function. Furthermore, we observed that extracellular pathogenic tau aggregates were eliminated via LC3-associated phagocytosis. The in vivo efficacy of SB1617 was confirmed in mice with traumatic brain injury in which SB1617 exerted neuroprotective effects by reducing pathogenic tau levels through microglia-mediated anti-inflammatory activity. Our results indicated that SB1617-mediated microglial surveillance with LC3-associated phagocytosis is a critical molecular mechanism in the regulation of tau proteostasis. This study provides new insights into tauopathies and directions for developing novel therapies for neurodegenerative diseases.

The utility of the perfusion index as an indicator of anesthetic depth for repeated propofol sedation in children: An observational study.

BACKGROUND: Children receiving proton therapy require repeated sedation. In this study, we aimed to investigate the utility of the perfusion index (PI) for evaluating consciousness level during repeated propofol sedation. METHODS: In this prospective observational study, children aged from birth to 19 years old scheduled for proton therapy under repeated propofol sedation were enrolled. The primary outcome was the equivalence of PI values 5 min after anesthesia induction on consecutive sedation. Total consumption of propofol during sedation, time to reach the University of Michigan sedation scale (UMSS) score 1 after end of proton therapy, and duration of post-anesthesia care unit (PACU) stay were recorded. RESULTS: The PI values measured 5 min after induction of anesthesia were not equivalent to each other in consecutive sedation except for the second versus third (1st vs. 2nd: 97.5% CI: -1.34, 0.91; p = 0.206, 0.034; 2nd vs. 3rd: 97.5% CI: -0.87, 0.94; p = 0.023, 0.036 3rd vs. 4th: 97.5% CI: -2.08, -0.26; p < 0.99, <0.001; 4th vs. 5th: 97.5% CI: 0.21, 2.28; p < 0.001, >0.99; respectively). In consecutive sedation, there was not a significantly different difference in the time to reach UMSS score 1 (p > 0.99, all) for total consumption of propofol, time to reach UMSS score 1 after the end of proton therapy, and duration of PACU stay. CONCLUSIONS: During repeated propofol sedation in children, PI was insufficient to be used as an indicator of consciousness level assessment. However, we suggest that the information related to repeated sedation provided by this study may be helpful in clinical practice.

Correlation between bispectral index and patient state index in children under sevoflurane anesthesia.

BACKGROUND: Because the unanticipated arousal or hemodynamic instability during anesthesia may adversely affect the physical and emotional welfare of children, adequate management of the anesthesia depth is required. We aimed to compare Bispectral Index (BIS) and Patient State Index (PSI) in children during sevoflurane anesthesia and evaluate PSI as depth of anesthesia monitor in children aged 6 months-12 years. METHODS: In this prospective observational study, children aged 6 months-12 years old scheduled for elective surgery under sevoflurane anesthesia were enrolled from November 2018 to June 2019. We monitored BIS and PSI at different sevoflurane concentrations. The primary outcome was the correlation between BIS and PSI. The correlation between BIS and PSI at different sevoflurane concentrations (at 1, 1.5, and 2 MACs) and at different age groups (6 months-2 years, 2-7 years, and 8-12 years) was also investigated. RESULTS: Bispectral index and PSI showed a fair correlation (r = .430; 95% confidence interval [CI], 0.297-0.546; p < .001). Two values were fairly correlated at 1, 1.5, and 2 MAC (r = .544; 95% CI, 0.314-0.716; p < .001, r = .509; 95% CI, 0.283-0.699; p < .001, and r = .315; 95% CI, 0.047-0.522; p = 0.007). BIS and PSI values showed a fair correlation in 6 months - 2 year and 8-12 year groups (r = .696; 95% CI, 0.519-0.813; p < .001 and r = .297; 95% CI, -0.017 to 0.543; p < .021), but there was not significant correlation in 2-7 years group (r = .190; 95% CI, -0.015 to 0.374; p = .052). CONCLUSIONS: There was a fair correlation between BIS and PSI in children under sevoflurane anesthesia. The use of BIS and PSI as an indicator for anesthesia depth by sevoflurane is not reliable in pediatric patients.

Inhibition of ACE2-Spike Interaction by an ACE2 Binder Suppresses SARS-CoV-2 Entry.

The emergence of SARS-CoV-2 variants is a significant concern in developing effective therapeutics and vaccines in the middle of the ongoing COVID-19 pandemic. Here, we have identified a novel small molecule that inhibited the interactions between SARS-CoV-2 spike RBDs and ACE2 by modulating ACE2 without impairing its enzymatic activity necessary for normal physiological functions. Furthermore, the identified compounds suppressed viral infection in cultured cells by inhibiting the entry of ancestral and variant SARS-CoV-2. Our study suggests that targeting ACE2 could be a novel therapeutic strategy to inhibit SARS-CoV-2 entry into host cells and prevent the development of COVID-19.

Exploration of α/ß/γ-peptidomimetics design for BH3 helical domains.

Systematic incorporation of ring-constrained ß- and γ-amino acid residues into α-helix mimetics engenders stable helical secondary structures. In this paper, functional α/ß/γ-helical peptidomimetics were explored for mimicry of BH3 helical domains, Bim as a pioneering study. The Bim-based α/ß/γ-peptides in an αγααßα-hexad repeat with five helical turns inhibited the interaction between Bak and Bcl-xL with excellent resistance towards proteolytic digestion. Further optimization of the α/ß/γ-backbone strategy will considerably expand the utility of functional α/ß/γ-peptidomimetics, in particular due to its prominent stability against proteolysis.

Effects of Increased Optic Nerve Sheath Diameter on Inadequate Emergence from Anesthesia in Patients Undergoing Robot-Assisted Laparoscopic Prostatectomy: A Prospective Observational Study.

(1) Background: Robot-assisted laparoscopic prostatectomy (RALP) is preferred over open prostatectomy because it offers superior surgical outcomes and better postoperative recovery. The steep Trendelenburg position and pneumoperitoneum required in Robot-assisted laparoscopic prostatectomy, however, increase intracranial pressure (ICP). The present study aimed to evaluate the effects of elevated ICP on the quality of emergence from anesthesia. (2) Methods: Sixty-seven patients undergoing RALP were enrolled. We measured optic nerve sheath diameter at four timepoints during surgery. Primary outcome was inadequate emergence in the operating room (OR). Secondary outcomes were postoperative neurologic deficits of dizziness, headache, delirium, cognitive dysfunction, and postoperative nausea and vomiting (PONV). (3) Results: A total of 69 patients were screened for eligibility and 67 patients completed the study and were included in the final analysis. After establishing pneumoperitoneum with the Trendelenburg position, ONSD increased compared to baseline by 11.4%. Of the 67 patients, 36 patients showed an increase of 10% or more in optic nerve sheath diameter (ONSD). Patients with ΔONSD ≥ 10% experienced more inadequate emergence in the OR than those with ΔONSD < 10% (47.2% vs. 12.9%, p = 0.003). However, other variables related to the quality of emergence from anesthesia did not different significantly between groups. Similarly, neurologic deficits, and PONV during postoperative day 3 showed no significant differences. (4) Conclusions: ICP elevation detected by ultrasonographic ONSD measurement was associated with a transient, inadequate emergence from anesthesia.

Comparison of Jaw Elevation Device vs. Conventional Airway Assist during Sedation in Chronic Kidney Diseases Undergoing Arteriovenous Fistula Surgery: A Randomized Controlled Trial.

Patients with chronic renal failure (CRF) are likely to have obstructive sleep apnea (OSA) underdiagnosed, and maintaining airway patency is important during sedation. This study compared Jaw elevation device (JED) with conventional airway interventions (head lateral rotation, neck extension, oral or nasal airway insertion, and jaw thrust maneuver) during sedation and hypothesized that JED may be effective to open the airway. A total of 73 patients were allocated to a conventional group (n = 39) and a JED group (n = 34). The number of additional airway interventions was the primary outcome. Percentage of patients with no need of additional interventions and apnea-hypopnea index (AHI) were secondary outcomes. The number of additional interventions was significantly less in the JED group compared to the conventional group (0 (0-0) vs. 1 (0-2); p = 0.002). The percentage of patients with no requirement for additional interventions was significantly higher in the JED group compared to the conventional group (76.5% vs. 43.6%; p = 0.004). AHI was significantly lower in the JED group compared to the conventional group (4.5 (1.5-11.9) vs. 9.3 (3.8-21.9), p = 0.015). In conclusion, JED seems to be effective in opening the airway patency during sedation in CRF patients.

Phenotypic Discovery of Neuroprotective Agents by Regulation of Tau Proteostasis via Stress-Responsive Activation of PERK Signaling.

Tau protein aggregates are a recognized neuropathological feature in Alzheimer's disease as well as many other neurodegenerative disorders, known as tauopathies. The development of tau-targeting therapies is therefore extremely important but efficient strategies or protein targets are still unclear. Here, we performed a cell-based phenotypic screening under endoplasmic reticulum (ER) stress conditions and identified a small molecule, SB1617, capable of suppressing abnormal tau protein aggregation. By applying label-free target identification technology, we revealed that the transient enhancement of protein kinase-like endoplasmic reticulum kinase (PERK) signaling pathway through the inhibition of stress-responsive SB1617 targets, PDIA3 and DNAJC3, is an effective strategy for regulating proteostasis in tauopathies. The molecular mechanism and the promising efficacy of SB1617 were demonstrated in neuronal cells and a mouse model with traumatic brain injury, a tauopathy known to involve ER stress.

The usefulness of endotracheal tube twisting in facilitating tube delivery to glottis opening during GlideScope intubation in infants: randomized trial.

Despite an excellent view of the glottis, technical difficulties with endotracheal tube delivery remains in GlideScope intubation. We evaluated whether a spiral-shape twisted tube can facilitate placement of the tracheal tube tip at the center of glottis opening compared to conventional tube for GlideScope intubation in infants. Eighty-six infants were randomly placed in either the conventional tube group (group C) or the twist tube group (group T). In group T, the shaft of the tube was manually twisted into a loose spiral shape. The primary outcome was the initial center location of the tube tip at the glottis opening, and the secondary outcome was total tube handling time. The initial center location rate of the tube tip at the glottis opening was significantly higher in group T than in group C (88% [38/43] vs. 47% [20/43], P < 0.001). In addition, total tube handling time (sec) was significantly shorter in group T than in group C (15.4 ± 4.7 vs. 18.2 ± 5.3, P = 0.012). In this study, the spiral shape twist tube successfully improved the rate of initial center location of the tube tip at glottis opening and facilitated tube delivery in GlideScope intubation in infants.

Effect-site concentration of remifentanil for smooth emergence from sevoflurane anesthesia in patients undergoing endovascular neurointervention.

During emergence from general anesthesia, coughing caused by the endotracheal tube frequently occurs and is associated with various adverse complications. In patients undergoing endovascular neurointervention, achieving smooth emergence from general anesthesia without coughing is emphasized since coughing is associated with intracranial hypertension. Therefore, the up-and-down method was introduced to determine the effective effect-site concentration (Ce) of remifentanil to prevent coughing in 50% and 95% (EC50 and EC95) of patients during emergence from sevoflurane anesthesia for endovascular neurointervention. A total of 43 participants, American Society of Anesthesiologists class I or II participants, aged from 20 to 70 years who were undergoing endovascular neurointervention through transfemoral catheter for cerebrovascular disease were enrolled. Using the up-and-down method with isotonic regression, the EC50 and EC95 of remifentanil to prevent coughing during emergence from sevoflurane anesthesia were determined. We also investigated differences of hemodynamic and recovery profiles between the cough suppression group and the cough group. In total, 38 of 43 patients were included for estimation of EC50 and EC95. The EC50 and EC95 of remifentanil to prevent coughing were 1.42 ng/mL (95% confidence interval [CI], 1.28-1.56 ng/mL) and 1.70 ng/mL (95% CI, 1.67-2.60 ng/mL), respectively. There was comparable emergence and recovery data between the cough suppression group (n = 22) and the cough group (n = 16). However, the Ce of remifentanil and total dose of remifentanil were significantly higher in the cough suppression group (P = 0.002 and P = 0.004, respectively). Target-controlled infusion of remifentanil at 1.70 ng/mL could effectively prevent extubation-related coughing in 95% of neurointervention patients, which could ensure smooth emergence.

Incidence and risk factors of unplanned intubation during pediatric sedation for MRI.

BACKGROUND: It is often difficult for the pediatric patient to cooperate or to remain immobile during MR scans. Therefore, sedation is usually needed for children. PURPOSE: To evaluate the incidence and contributing factors of unanticipated intubation during sedation for MRI scan in children. STUDY TYPE: Retrospective observational study. POPULATION/SUBJECTS: In all, 1165 charts were reviewed retrospectively of patients who had been sedated by anesthesiologists at a single institution from May 2015 to June 2016. ASSESSMENT: Patient's demographics, the region of the MRI scan, total amount of medication, duration of sedation, and any adverse event during MRI were assessed. The adverse events during sedation including airway obstruction, apnea, desaturation, bradycardia, and hypotension were also assessed. STATISTICAL TESTS: Risk factors of unplanned intubation during MRI sedation were identified by univariate and multivariate analysis. Firth's exact logistic regression was used for univariate and multivariate analysis. According to the results from multiple logistic regression, a nomogram was developed to predict the risk. RESULTS: A total of 1165 children aged 7 days to 18 years with sedation used during an MRI scan during the study period showed an incidence of unexpected intubation as ~2% (n = 23, 95% confidence interval [CI]; 0.0123, 0.0295). Multivariate logistic regression revealed the following risk factors of unplanned intubation: American Society of Anesthesiologists (ASA) class III patients (odds ratio [OR] 1.212, P < 0.001), premature birth (OR 2.317, P < 0.001), and the presence of gastroesophageal reflux disease (GERD) (OR 1.474, P < 0.001) or congenital heart disease (OR 1.118, P < 0.001). DATA CONCLUSION: This study identified risk factors of unplanned intubation as follows: ASA class III patients, premature birth, and the presence of GERD or congenital heart disease. The physician should screen risk factors of unexpected intubation and maintain adequate sedation during MRI scans in pediatric patients. Level of Evidence 3. Technical Efficacy Stage 5. J. Magn. Reson. Imaging 2019;49:1053-1061.

A retrospective comparison of propofol to dexmedetomidine for pediatric magnetic resonance imaging sedation in patients with mucopolysaccharidosis type II.

BACKGROUND: Mucopolysaccharidosis type II patients are reported to have an elevated incidence of difficult airway. Propofol is a commonly used sedative for magnetic resonance imaging in pediatric patients, but patients who receive it may exhibit dose-dependent upper airway obstruction and respiratory depression. Dexmedetomidine also provides adequate procedural sedation with a relatively low risk of airway obstruction. Accordingly, we introduced the use of dexmedetomidine in our practice to reduce the risk of airway obstruction during magnetic resonance imaging procedures. AIMS: The aim of this study was to evaluate the incidence of artificial airway interventions in patients sedated with propofol and compare it to that in patients sedated with dexmedetomidine in patients with mucopolysaccharidosis type II during magnetic resonance imaging procedures. METHODS: All mucopolysaccharidosis type II patients undergoing magnetic resonance imaging at our institution between April 2014 and February 2018 were included in this study. The patients were divided into two groups according to whether they were managed before and after the introduction of dexmedetomidine: those who were sedated with propofol (group P) and those who were sedated with dexmedetomidine (group D). RESULTS: Forty-six sedations were performed in 27 patients. Artificial airway interventions were significantly more frequent during propofol-based than dexmedetomidine-based sedation: 14 of 32 (43.8%) in group P and 1 of 14 (7.1%) in group D (odds ratio, 10.11; 95% confidence interval, 1.18-86.85; P = 0.018). Time to awake and time to discharge were similar between groups. Changes in hemodynamic variables also did not significantly differ between groups. CONCLUSION: Dexmedetomidine provides an adequate level of sedation and is associated with lower rates of artificial airway interventions compared to propofol. Therefore, dexmedetomidine may offer advantages for preserving the native airway compared to propofol when administered during magnetic resonance imaging scans in patients with mucopolysaccharidosis type II.

Incidence of tolerance in children undergoing repeated administration of propofol for proton radiation therapy: a retrospective study.

BACKGROUND: Propofol is an excellent hypnotic drug for use in repeated radiation procedures in young children. To date, tolerance to propofol generally does not develop in pediatric patients undergoing radiation therapy. However, several studies have suggested that there may be potential for development of tolerance to propofol. The aim of this study was to evaluate the development of a tolerance to propofol used for repeated deep sedation in children undergoing proton radiation therapy (PRT). METHODS: All children undergoing PRT at our institution between December 2015 and January 2018 were eligible for inclusion in this study. Sedation was induced by a bolus dose of propofol (2.0 mg.kg- 1) followed by a continuous infusion of 250 µg.kg- 1.min- 1 via an infusion pump to achieve deep sedation. Sedation was maintained with the propofol infusion of 200 µg.kg- 1.min- 1, which was adjusted in 25 µg.kg- 1.min- 1 increments up or down as necessary to ensure deep sedation. The primary outcome was mean doses of propofol over time. RESULTS: Fifty-eight children were analyzed. The mean (SD) age was 4.5 (2.1) years. The mean (SD) number of treatment sessions was 19 (7). Fifteen patients (26%) developed tolerance to propofol. However, there were no significant differences between the children who developed tolerance and the children who did not develop tolerance in mean propofol dose and awakening time over time (p = 0.887 and P = 0.652, respectively). Age, the number of PRT, and attending anesthesiologists was not significantly associated with the incidence of tolerance to propofol. CONCLUSION: Repeated prolonged deep sedation for PRT elicited multiple times over several weeks in young children using propofol did not develop tolerance in 74% of patients. Although the incidence of 26% tolerance to propofol may still be present, the increase in propofol dose was minimal. Therefore, the use of repeated propofol for children was safe.

Analysis of the functionally-narrowest portion of the pediatric upper airway in sedated children.

The narrowest portions of the pediatric larynx are the glottis and subglottic region. However, the pliable and paralyzed subglottic region, acting like a curtain, is no resistance when passing an endotracheal tube. Therefore, the 'functionally' portion of the pediatric upper airway, which may be the most vulnerable to damage during intubation, is the unyielding portion below the cricoid cartilage. We investigated the functionally-narrowest portion below the cricoid cartilage.Computed tomography (CT) was performed under deep sedation. CT images were used for measurement of dimensions and cross-sectional area (CSA) of the larynx at the level of the cricoid, subcricoid, and trachea. We analyzed the anteriorposterior (AP) diameter, transverse diameter, and CSA below the cricoid cartilage (at the cricoid, subcricoid, and tracheal levels).CT images of 46 children from 8 months to 96 months were reviewed from electric medical record (EMR). The mean ±â€ŠSD of AP diameter was the shortest at the subcricoid level (cricoid, 105.7 ±â€Š15.8 mm; subcricoid, 94.6 ±â€Š15.3 mm; and trachea, 101.5 ±â€Š15.7 mm; P < .001). The mean ±â€ŠSD of transverse diameter was the shortest at the trachea level (cricoid, 99.8 ±â€Š12.2 mm; subcricoid, 102.5 ±â€Š13.7 mm; and trachea, 98.8 ±â€Š10.7 mm; P = .01). The mean ±â€ŠSD of CSA was the smallest at the subcricoid level (cricoid, 8781.5 ±â€Š1963.3 mm; subcricoid, 8425.0 ±â€Š2025.7 mm; and trachea, 8523.7 ±â€Š1791.1 mm; P = .02). The AP diameter at the subcricoid level was narrower than the transverse diameter at trachea level (mean difference: 4.2 mm, 95% confidence interval [CI]: 0.7-7.7, P = .02).Since the most susceptible portion for airway damage is unyielding portion, our findings suggest that, functionally, the narrowest portion of the pediatric larynx is located in the subcricoid region.

Phenotype-Based High-Content Screening Using Fluorescent Chemical Bioprobes: Lipid Droplets and Glucose Uptake Quantification in Live Cells.

Phenotypic screening in live cells has emerged as a promising strategy for drug discovery in pharmaceutical communities. For relevant phenotype-based screening setups, it is critical to develop adequate reporters in order to selectively visualize subcellular compartments or phenotypic changes that represent disease-related characteristics during compound screening. In this chapter, we introduce two phenotype-based high-content/high-throughput assays using fluorescent bioprobes that have been designed and refined to selectively stain cellular lipid droplets (LDs) and to show cellular glucose uptake. In conjunction with target identification process for the hit compounds from phenotypic screening, these fluorescent chemical probe-based screening techniques are expected to drive a great advancement for the discovery of novel first-in-class therapeutics.

Postoperative delirium in elderly patients with critical limb ischemia undergoing major leg amputation: a retrospective study.

BACKGROUND: Critical limb ischemia has been identified as a risk factor for the incidence of postoperative delirium in elderly patients. Limb amputation is the last option in critical limb ischemia treatments. We investigated the incidence and predisposing factors of postoperative delirium in patients undergoing major leg amputation. METHODS: From January 2012 to December 2016, 121 patients aged over 60 years who had undergone major leg amputation were enrolled in this study. Various factors related to the patients' outcomes were assessed, including demographic, preoperative laboratory, anesthetic, surgical, and postoperative indicators. RESULTS: Twenty two patients were excluded and 99 patients were assigned to either the delirium group or no delirium group. Forty of them (40%) developed a delirium during 30 days postoperatively. Univariate analysis implied that end-stage renal disease on hemodialysis, alcohol consumption, C-reactive protein, staying in an intensive care unit (ICU), duration of an ICU stay, occurrence of complications, and mortality during six months, were the factors that accounted for significant differences between the two groups. In multivariate analysis, three factors were significantly related to the development of delirium: mortality during six months (odds ratio [OR] = 13.86, 95% CI [2.10-31.90]), alcohol (OR = 8.18, 95% CI [1.13-16.60]), and hemodialysis (OR = 4.34, 95% CI [2.06-93.08]). CONCLUSIONS: Approximately 40% of the elderly patients suffered from postoperative delirium in major leg amputation. Identifying those with risk factors for postoperative delirium and intervening at the early stage will be of great benefit in major leg amputations for the elderly population.

Effects of Pravastatin on Type 1 Diabetic Rat Heart with or without Blood Glycemic Control.

Although statins have been suggested to attenuate the progression of diabetic cardiomyopathy, its effect without glycemic control remains unclear. Therefore, we evaluated the effect of pravastatin on diabetic rat hearts according to glycemic control. Rats were randomly divided into five groups: control (C), diabetes (D), diabetes with insulin (I), diabetes with pravastatin (P), and diabetes with insulin and pravastatin (IP). Eight weeks after allocated treatments, the heart was extracted and analyzed following echocardiography. Cardiac fibrosis was measured using Masson's trichrome stain. Cardiac expression of collagen I/III, matrix metalloproteinase (MMP)-2, MMP-9, and angiotensin-converting enzyme (ACE)/ACE2 was evaluated by immunohistochemistry and/or Western blot. Enzyme-linked immunosorbent assay was used for measuring reactive oxygen species (ROS). Diabetic groups without glycemic control (D and P) showed significantly impaired diastolic function and increased levels of cardiac fibrosis, collagen I/III, MMP-2, MMP-9, and ROS production. However, there were little significant differences in the outcomes among the control and two glucose-controlled diabetic groups (I and IP). Groups C and IP showed more preserved ACE2 and lower ACE expressions than the other groups did (D, I, and P). Our study suggested glycemic control would be more important to attenuate the progression of diabetic cardiomyopathy than pravastatin medication.