Stable Zinc Electrode Reaction Enabled by Combined Cationic and Anionic Electrolyte Additives for Non-Flow Aqueous Zn─Br2 Batteries.

Aqueous zinc-bromine batteries hold immense promise for large-scale energy storage systems due to their inherent safety and high energy density. However, achieving a reliable zinc metal electrode reaction is challenging because zinc metal in the aqueous electrolyte inevitably leads to dendrite growth and related side reactions, resulting in rapid capacity fading. Here, it is reported that combined cationic and anionic additives in the electrolytes using CeCl3 can simultaneously address the multiple chronic issues of the zinc metal electrode. Trivalent Ce3+ forms an electrostatic shielding layer to prevent Zn2+ from concentrating at zinc metal protrusions, while the high electron-donating nature of Cl- mitigates H2O decomposition on the zinc metal surface by reducing the interaction between Zn2+ and H2O. These combined cationic and anionic effects significantly enhance the reversibility of the zinc metal reaction, allowing the non-flow aqueous Zn─Br2 full-cell to reliably cycle with exceptionally high capacity (>400 mAh after 5000 cycles) even in a large-scale battery configuration of 15 × 15 cm2.

Cytosolic microRNA-inducible nuclear translocation of Cas9 protein for disease-specific genome modification.

MicroRNA-dependent mRNA decay plays an important role in gene silencing by facilitating posttranscriptional and translational repression. Inspired by this intrinsic nature of microRNA-mediated mRNA cleavage, here, we describe a microRNA-targeting mRNA as a switch platform called mRNA bridge mimetics to regulate the translocation of proteins. We applied the mRNA bridge mimetics platform to Cas9 protein to confer it the ability to translocate into the nucleus via cleavage of the nuclear export signal. This system performed programmed gene editing in vitro and in vivo. Combinatorial treatment with cisplatin and miR-21-EZH2 axis-targeting CRISPR Self Check-In improved sensitivity to chemotherapeutic drugs in vivo. Using the endogenous microRNA-mediated mRNA decay mechanism, our platform is able to remodel a cell's natural biology to allow the entry of precise drugs into the nucleus, devoid of non-specific translocation. The mRNA bridge mimetics strategy is promising for applications in which the reaction must be controlled via intracellular stimuli and modulates Cas9 proteins to ensure safe genome modification in diseased conditions.

Comparison of the effects of paratracheal pressure and cricoid pressure on placement of the i-gel® supraglottic airway: a randomized clinical trial.

PURPOSE: Anesthesiologists can use supraglottic airway devices as a rescue technique for failed intubation even in patients with an increased risk of gastric regurgitation. In this randomized study, we aimed to evaluate the effects of cricoid pressure and paratracheal pressure on placement of the i-gel® (Intersurgical Ltd., Wokingham, Berkshire, UK). METHODS: After induction of anesthesia in 76 adult patients, we inserted the i-gel under paratracheal or cricoid pressure, and assessed the success rate of i-gel insertion, resistance during insertion, time required for insertion, accuracy of the insertion location, tidal volumes, and peak inspiratory pressure with or without each maneuver after i-gel insertion. RESULTS: The overall success rate of insertion was significantly higher under paratracheal pressure than under cricoid pressure (36/38 [95%] vs 27/38 [71%], respectively; difference, 24%; 95% confidence interval [CI], 8 to 40; P = 0.006]. Resistance during insertion was significantly lower under paratracheal pressure than under cricoid pressure (P < 0.001). The time required for insertion was significantly shorter under paratracheal pressure than under cricoid pressure (median [interquartile range], 18 [15-23] sec vs 28 [22-38] sec, respectively; difference in medians, -10; 95% CI, -18 to -4; P < 0.001). Fibreoptic examination of the anatomical alignment of the i-gel in the larynx revealed no significant difference in the accuracy of the insertion location between the two maneuvers (P = 0.31). The differences in tidal volume and peak inspiratory pressure with or without the maneuvers were significantly lower with paratracheal pressure than with cricoid pressure (P = 0.003, respectively). CONCLUSIONS: Insertion of the i-gel supraglottic airway was significantly more successful, easier, and faster while applying paratracheal pressure than cricoid pressure. STUDY REGISTRATION: ClinicalTrials.gov (NCT05377346); first submitted 11 May 2022.

RéSUMé: OBJECTIF: Les anesthésiologistes peuvent utiliser des dispositifs supraglottiques comme technique de sauvetage en cas d'échec de l'intubation, même chez les personnes présentant un risque accru de régurgitation gastrique. Dans cette étude randomisée, nous avons cherché à évaluer les effets de la pression cricoïdienne et de la pression paratrachéale sur le positionnement du dispositif i-gel® (Intersurgical Ltd., Wokingham, Berkshire, Royaume-Uni). MéTHODE: Après l'induction de l'anesthésie chez 76 adultes, nous avons inséré l'i-gel en utilisant une pression paratrachéale ou cricoïdienne, et avons évalué le taux de réussite de l'insertion de l'i-gel, la résistance pendant l'insertion, le temps nécessaire à l'insertion, la précision de l'emplacement d'insertion, les volumes courants ainsi que la pression inspiratoire maximale avec ou sans chacune des manœuvres après l'insertion de l'i-gel. RéSULTATS: Le taux global de réussite de l'insertion était significativement plus élevé avec une pression paratrachéale qu'avec une pression cricoïdienne (36/38 [95 %] vs 27/38 [71 %], respectivement; différence, 24 %; intervalle de confiance [IC] à 95 %, 7,6 à 39,8; P = 0,006]. La résistance lors de l'insertion était significativement plus faible en utilisant une pression paratrachéale par rapport à une pression cricoïdienne (P < 0,001). Le temps nécessaire à l'insertion était significativement plus court après avoir exercé une pression paratrachéale plutôt que cricoïdienne (médiane [écart interquartile], 18,4 [15,3­23,1] secondes vs 28,4 [22,3 à 37,8] secondes, respectivement; différence dans les médianes, −10,0; IC 95 %, −18,4 à −3,6; P < 0,001). L'examen par fibre optique de l'alignement anatomique de l'i-gel dans le larynx n'a révélé aucune différence significative dans la précision de l'emplacement d'insertion entre les deux manœuvres (P = 0,31). Les différences de volume courant et de pression inspiratoire maximale avec ou sans les manœuvres étaient significativement plus faibles avec la pression paratrachéale qu'avec la pression cricoïdienne (P = 0,003, respectivement). CONCLUSION: L'insertion du dispositif supraglottique i-gel a été significativement plus réussie, plus facile et plus rapide lors de l'application d'une pression paratrachéale que d'une pression cricoïdienne. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05377346); soumis pour la première fois le 11 mai 2022.

Effect of paratracheal pressure on the effectiveness of mask ventilation in obese anesthetized patients: a randomized, cross-over study.

Paratracheal pressure has been recently suggested to compress and occlude the upper esophagus at the lower left paratracheal region to prevent gastric regurgitation alternative to cricoid pressure. It also prevents gastric insufflation. The aim of this randomized cross-over study was to investigate the effectiveness of paratracheal pressure on mask ventilation in obese anesthetized paralyzed patients. After the induction of anesthesia, two-handed mask ventilation was initiated in a volume-controlled mode with a tidal volume of 8 mL kg‒1 based on ideal body weight (IBW), a respiratory rate of 12 breaths min- 1, and positive end-expiratory pressure of 10 cmH2O. Expiratory tidal volume and peak inspiratory pressure were recorded alternately with or without the application of 30 Newtons (approximately 3.06 kg) paratracheal pressure during a total of 16 successive breaths over 80 s. Association of patient characteristics with the effectiveness of paratracheal pressure on mask ventilation, defined as the difference in expiratory tidal volume between the presence or absence of paratracheal pressure were evaluated. In 48 obese anesthetized paralyzed patients, expiratory tidal volume was significantly higher with the application of paratracheal pressure than without paratracheal pressure [496.8 (74.1) mL kg- 1 of IBW vs. 403.8 (58.4) mL kg- 1 of IBW, respectively; P < 0.001]. Peak inspiratory pressure was also significantly higher with the application of paratracheal pressure compared to that with no paratracheal pressure [21.4 (1.2) cmH2O vs. 18.9 (1.6) cmH2O, respectively; P < 0.001]. No significant association was observed between patient characteristics and the effectiveness of paratracheal pressure on mask ventilation. Hypoxemia did not occur in any of the patients during mask ventilation with or without paratracheal pressure. The application of paratracheal pressure significantly increased both the expiratory tidal volume and peak inspiratory pressure during face-mask ventilation with a volume-controlled mode in obese anesthetized paralyzed patients. Gastric insufflation was not evaluated in this study during mask ventilation with or without paratracheal pressure.

Artificial intelligence-driven new drug discovery targeting serine/threonine kinase 33 for cancer treatment.

BACKGROUND: Artificial intelligence (AI) is capable of integrating a large amount of related information to predict therapeutic relationships such as disease treatment with known drugs, gene expression, and drug-target binding. AI has gained increasing attention as a promising tool for next-generation drug development. METHODS: An AI method was used for drug repurposing and target identification for cancer. Among 8 survived candidates after background checking, N-(1-propyl-1H-1,3-benzodiazol-2-yl)-3-(pyrrolidine-1-sulfonyl) benzamide (Z29077885) was newly selected as an new anti-cancer drug, and the anti-cancer efficacy of Z29077885 was confirmed using cell viability, western blot, cell cycle, apoptosis assay in MDA-MB 231 and A549 in vitro. Then, anti-tumor efficacy of Z29077885 was validated in an in vivo A549 xenograft in BALB/c nude mice. RESULTS: First, we discovered an antiviral agent, Z29077885, as a new anticancer drug candidate using the AI deep learning method. Next, we demonstrated that Z29077885 inhibits Serine/threonine kinase 33 (STK33) enzymatic function in vitro and showed the anticancer efficacy in various cancer cells. Then, we found enhanced apoptosis via S-phase cell cycle arrest as the mechanism underlying the anticancer efficacy of Z29077885 in both lung and breast cancer cells. Finally, we confirmed the anti-tumor efficacy of Z29077885 in an in vivo A549 xenograft. CONCLUSIONS: In this study, we used an AI-driven screening strategy to find a novel anticancer medication targeting STK33 that triggers cancer cell apoptosis and cell cycle arrest at the s phase. It will pave a way to efficiently discover new anticancer drugs.

Protomer of Imipramine Captured in Cucurbit[7]uril.

Small molecules possessing multiple proton-accessible sites are important not only to many biological systems but also to host-guest chemistry; their protonation states are causal to boosting or hindering specific host-guest interactions. However, determining the protonation site is not trivial. Herein, we conduct electrospray ionization ion mobility spectrometry-mass spectrometry to imipramine, a known molecule with two protonation sites, based on the introduction of cucurbit[7]uril as a host molecule. For protonated imipramine, the proposed strategy allows clear distinction of the two protomers as host-guest complex ions and can be leveraged to capture the energetically less preferable protomer of the protonated imipramine.

Effect of head and neck positions on tracheal intubation using a McGRATH MAC video laryngoscope: A randomised, prospective study.

BACKGROUND: Different head and neck positions may affect video laryngoscopy in terms of laryngeal exposure, intubation difficulty, advancement of the tracheal tube into the glottis and the occurrence of palatopharyngeal mucosal injury. OBJECTIVE: We investigated the effects of simple head extension, head elevation without head extension and the sniffing position on tracheal intubation using a McGRATH MAC video laryngoscope. DESIGN: A randomised, prospective study. SETTING: Medical centre governed by a university tertiary hospital. PATIENTS: A total of 174 patients undergoing general anaesthesia. METHODS: Patients were randomly allocated to one of three groups: simple head extension (neck extension without a pillow), head elevation only (head elevation with a pillow of 7 cm and no neck extension) and sniffing position (head elevation with a pillow of 7 cm and neck extension). MAIN OUTCOMES: During tracheal intubation using a McGRATH MAC video laryngoscope in three different head and neck positions, we assessed intubation difficulty by several methods: a modified intubation difficulty scale score, time taken for tracheal intubation, glottic opening, number of intubation attempts, requirements for other manoeuvres (lifting force or laryngeal pressure) for laryngeal exposure and advancement of the tracheal tube into the glottis. The occurrence of palatopharyngeal mucosal injury was evaluated after tracheal intubation. RESULTS: Tracheal intubation was significantly easier in the head elevation group than in the simple head extension ( P  = 0.001) and sniffing positions ( P  = 0.011). Intubation difficulty did not differ significantly between the simple head extension and sniffing positions ( P  = 0.252). The time taken for intubation in the head elevation group was significantly shorter than that in the simple head extension group ( P  < 0.001). A lifting force or laryngeal pressure was required less frequently for tube advancement into the glottis in the head elevation group than in the simple head extension ( P  = 0.002) and sniffing position groups ( P  = 0.012). The need for a lifting force or laryngeal pressure for tube advancement into the glottis was not significantly different between the simple head extension and sniffing positions ( P  = 0.498). Palatopharyngeal mucosal injury occurred less frequently in the head elevation group than in the simple head extension group ( P  = 0.009). CONCLUSION: The head elevation position facilitated tracheal intubation using a McGRATH MAC video laryngoscope compared with a simple head extension or sniffing position. TRIAL REGISTRY NUMBER: ClinicalTrials.gov (NCT05128968).

Comparison of the effect of sevoflurane and propofol on the optic nerve sheath diameter in patients undergoing middle ear surgery.

PURPOSE: During middle ear surgery, the patient's head is turned away from the surgical site, which may increase the intracranial pressure. Anesthetics also affect the intracranial pressure. The optic nerve sheath diameter (ONSD) measured using ultrasonography is a reliable marker for estimating the intracranial pressure. This aim of this study was to investigate the effect of sevoflurane and propofol on the ONSD in patients undergoing middle ear surgery. METHODS: Fifty-eight adult patients were randomized into sevoflurane group (n = 29) or propofol group (n = 29). The ONSD was measured using ultrasound after anesthesia induction before head rotation (T0), and at the end of surgery (T1). The occurrence and severity of postoperative nausea and vomiting (PONV) were assessed 1 h after the surgery. RESULTS: The ONSD was significantly increased from T0 to T1 in the sevoflurane group [4.3 (0.5) mm vs. 4.9 (0.6) mm, respectively; P < 0.001] and the propofol group [4.2 (0.3) mm vs. 4.8 (0.5) mm, respectively; P < 0.001]. No significant difference was observed in the ONSD at T0 (P = 0.267) and T1 (P = 0.384) between the two groups. The change in the ONSD from T0 to T1 was not significantly different between the sevoflurane and propofol groups [0.6 (0.4) mm vs. 0.6 (0.3) mm, respectively; P = 0.972]. The occurrence and severity of PONV was not significantly different between the sevoflurane and propofol groups (18% vs. 0%, respectively; P = 0.053). CONCLUSION: The ONSD was significantly increased during middle ear surgery. No significant difference was observed in the amount of ONSD increase between the sevoflurane and propofol groups.

Fast and High-Yield Anhydrous Synthesis of Ti3 C2 Tx MXene with High Electrical Conductivity and Exceptional Mechanical Strength.

2D transition metal carbides or nitrides (MXenes) have attracted considerable attention from materials scientists and engineers owing to their physicochemical properties. Currently, MXenes are synthesized from MAX-phase precursors using aqueous HF. Here, in order to enhance the production of MXenes, an anhydrous etching solution is proposed, consisting of dimethylsulfoxide as solvent with its high boiling point, NH4 HF2 as an etchant, CH3 SO3 H as an acid, and NH4 PF6 as an intercalant. The reaction temperature can be increased up to 100 °C to accelerate the etching and delamination of Ti3 AlC2 MAX crystals; in addition, the destructive side reaction of the produced Ti3 C2 Tx MXene is suppressed in the etchant. Consequently, the etching reaction is completed in 4 h at 100 °C and produces high-quality monolayer Ti3 C2 Tx with an electrical conductivity of 8200 S cm-1 and yield of over 70%. The Ti3 C2 Tx MXene fabricated via this modified synthesis exhibits different surface structures and properties arising from more F-terminations than those of Ti3 C2 Tx synthesized in aqueous HF2 T. The atypical surface structure of Ti3 C2 Tx MXene results in an exceptionally high ultimate tensile strength (167 ± 8 MPa), which is five times larger than those of Ti3 C2 Tx MXenes synthesized in aqueous HF solution (31.7 ± 7.8 MPa).

Auranofin promotes antibacterial effect of doripenem against carbapenem-resistant Acinetobacter baumannii.

AIMS: This study was performed to identify the potential for repurposing auranofin as an antibiotic adjuvant against carbapenemase-producing Acinetobacter baumannii. METHODS AND RESULTS: The clinically isolated A. baumannii strains used in this study were all resistant to carbapenems and harboured the blaOXA-23 gene. The synergistic effect of auranofin and doripenem against carbapenemase-producing A. baumannii was confirmed through checkerboard and growth kinetic analyses. This study also demonstrated the inhibitory effects of auranofin against A. baumannii biofilms. The anti-biofilm effects of auranofin were visualized by confocal laser scanning microscopy (CLSM). Furthermore, auranofin inhibited motility, one of the virulence factors. Additionally, the changes in the expression of carbapenemase-, biofilm- and efflux pump-related genes induced by auranofin were confirmed via quantitative polymerase chain reaction (qPCR). CONCLUSIONS: Our results demonstrated that auranofin has an antibacterial effect with doripenem and an inhibitory effect on several factors related to carbapenem resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that auranofin is a promising antibiotic adjuvant that can be used to prevent antibiotic resistance in carbapenem-resistant A. baumannii.

Effectiveness of Cricoid and Paratracheal Pressures in Occluding the Upper Esophagus Through Induction of Anesthesia and Videolaryngoscopy: A Randomized, Crossover Study.

BACKGROUND: Maneuvers for preventing passive regurgitation of gastric contents are applied to effectively occlude the esophagus throughout rapid sequence induction and intubation. The aim of this randomized, crossover study was to investigate the effectiveness of cricoid and paratracheal pressures in occluding the esophagus through induction of anesthesia and videolaryngoscopy. METHODS: After the induction of anesthesia in 40 adult patients, the location of the esophageal entrance relative to the glottis and location of the upper esophagus relative to the trachea at the low paratracheal region were assessed using an ultrasonography, and the outer diameter of the esophagus was measured on ultrasound before and during application of cricoid and paratracheal pressures of 30 N. Then, videolaryngoscopy was performed with the application of each pressure. During videolaryngoscopy, location of the esophageal entrance relative to the glottis under cricoid pressure was examined on the screen of videolaryngoscope, and the upper esophagus under paratracheal pressure was evaluated using ultrasound. The occlusion rate of the esophagus, and the best laryngeal view using the percentage of glottic opening scoring system were also assessed during videolaryngsocopy. Esophageal occlusion under each pressure was determined by inserting an esophageal stethoscope into the esophagus. If the esophageal stethoscope could not be advanced into the esophagus under the application of each pressure, the esophagus was regarded to be occluded. RESULTS: During videolaryngoscopy, esophagus was occluded in 40 of 40 (100%) patients with cricoid pressure and 23 of 40 (58%) patients with paratracheal pressure (difference, 42%; 95% confidence interval, 26-58; P < .001). Both cricoid and paratracheal pressures significantly decreased the diameter of the esophagus compared to no intervention in the anesthetized paralyzed state ( P < .001, respectively). Ultrasound revealed that the compressed esophagus by paratracheal pressure in the anesthetized paralyzed state was partially released during videolaryngoscopy in 17 of 40 patients, in whom esophageal occlusion was unsuccessful. The best laryngeal view was not significantly different among the no intervention, cricoid pressure, and paratracheal pressure (77 [29] % vs 79 [30] % vs 76 [31] %, respectively; P = .064). CONCLUSIONS: The occlusion of the upper esophagus defined by inability to pass an esophageal stethoscope was more effective with cricoid pressure than with paratracheal pressure during videolaryngoscopy, although both cricoid and paratracheal pressures reduced the diameter of the esophagus on ultrasound in an anesthetized paralyzed state.

Method Performance Verification of Anti-GAD65 and Anti-Insulin antibody Assays.

BACKGROUND: The aim of this study was to evaluate the performance of chemiluminescence immunoassays for anti-GAD65 and anti-insulin antibodies following user verification guidelines. METHODS: The analytical performance of anti-GAD65 and anti-insulin antibodies using a MAGLUMI 2000 analyzer was verified following user verification guidelines by the Clinical and Laboratory Standards Institute. RESULTS: Performance specifications including precision, linearity, carry-over, cutoffs for positive results, reference intervals, and comparability with pre-existing commercially available radioimmunoassays using patient specimens and certified reference material were verified (coefficients of variation for precision of anti-GAD65 and anti-insulin antibodies were 2.6% and 3.4%, respectively). Comparability assessed using clinical serum specimens showed overall agreement with radioimmunoassay of 87.2% (95% confidence interval 74.8% - 94.0%) for the anti-GAD65 antibody assay and 85.4% (95% confidence interval 71.6% - 93.1%) for the anti-insulin antibody assay. CONCLUSIONS: The results of this study verified the analytical performance of MAGLUMI anti-GAD65 and anti-insulin antibody assays for clinical use.

Assessment of the 50 % and 95 % effective paratracheal forces for occluding the esophagus in anesthetized patients.

This study aimed to evaluate the 50% and 95% effective paratracheal forces for occluding the esophagus in anesthetized patients. In 46 anesthetized patients, the upper esophagus was examined using ultrasonography, and the lower paratracheal area over the esophagus just above the clavicle was marked. Manual paratracheal force was applied over that area using a novel pressure sensing device set-up. In the first patient, a 20 N paratracheal force was applied, and the patency of the esophagus was assessed by advancing the esophageal stethoscope. Unsuccessful advancement of the esophageal stethoscope was considered an effective paratracheal force. If advancement of the esophageal stethoscope was successful, the paratracheal force was increased by 2 N for the next patient, and if it was unsuccessful, the force was decreased by 2 N for the next patient. These sequential tests were performed using 12- and 18-Fr esophageal stethoscopes, respectively. According to Dixon and Mood method, the 50% effective paratracheal force (confidence interval) was 18.4 (17.5‒19.3) N with the use of a 12-Fr esophageal stethoscope and 12.8 (11.0‒14.6) N with the use of an 18-Fr esophageal stethoscope. Using probit regression analysis, the 50% and 95% effective paratracheal forces were 18.4 (16.8‒19.6) N and 20.6 (19.4‒27.9) N, respectively, with the use of a 12-Fr esophageal stethoscope, and 12.4 (8.3‒14.4) N and 16.9 (14.7‒37.3) N, respectively, with the use of an 18-Fr esophageal stethoscope. Our findings suggest a guide for applying paratracheal force during rapid sequence induction and tracheal intubation.

Evaluation of the conventional and modified aerosol boxes during tracheal intubation in normal and difficult airways: a randomized, crossover, manikin simulation study.

The aim of this study was to evaluate conventional and modified aerosol boxes in terms of intubation time, first-pass intubation success, and mouth-to-mouth distance between the laryngoscopist and patient during tracheal intubation in simulated patients with normal and difficult airways. Sixteen anesthesiologists performed tracheal intubations with direct laryngoscope or three different videolaryngoscopes (McGRATH MAC videolaryngoscope, C-MAC videolaryngoscope, and Pentax-AWS) without an aerosol box or with a conventional or a modified aerosol boxes in simulated manikins with normal and difficult airways. Intubation time, first-pass intubation success, and mouth-to-mouth distance during tracheal intubation were recorded. Compared to no aerosol box, the use of a conventional aerosol box significantly increased intubation time in both normal and difficult airways (Bonferroni-corrected P-value (Pcorrected) = 0.005 and Pcorrected = 0.003, respectively). Intubation time was significantly shorter with the modified aerosol box than with the conventional one for both normal and difficult airways (Pcorrected = 0.003 and Pcorrected = 0.011, respectively). However, no significant differences were found in intubation time between no aerosol box and the modified aerosol box for normal and difficult airways (Pcorrected = 0.336 and Pcorrected = 0.112, respectively). The use of conventional or modified aerosol boxes significantly extended the mouth-to-mouth distances compared to not using an aerosol box during tracheal intubation with each laryngoscope (all Pcorrected < 0.05), and the distances were not different between the conventional and modified boxes in normal and difficult airways. The use of modified aerosol box did not increase intubation time and could help maintain a distance from the simulated patients with normal and difficult airways.

Anti-bacterial and Anti-biofilm Effects of Equol on Yersinia enterocolitica.

Yersinia enterocolitica has clinical significance due to its etiological role in yersiniosis and gastroenteritis. This study was designed to assess anti-bacterial and anti-biofilm effects of equol on Y. enterocolitica via phenotypic and genetic analyses. To determine its anti-bacterial activity, minimum inhibitory concentrations (MICs) of equol against clinically isolated Y. enterocolitica strains were analyzed. Subsequently, it was confirmed that the sub-MIC90 value of equol could inhibit biofilm formation and reduce preformed biofilm. Furthermore, it was found that equol could reduce the expression of biofilm-related (hmsT) gene in Y. enterocolitica. This study also demonstrated that equol not only reduced levels of bacterial motility, but also decreased the expression of a motility-related (flhDC) gene in Y. enterocolitica. XTT [2,3-bis (2-metoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction analysis revealed that equol attenuated cellular metabolic activities in Y. enterocolitica biofilm. Additionally, changes in biomass and cell density in equol-treated biofilms were visualized using a confocal laser scanning microscope. In conclusion, this study suggests that equol is a potential anti-bacterial and anti-biofilm agent to treat Y. enterocolitica.

Rare variants in MYH15 modify amyotrophic lateral sclerosis risk.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive muscular atrophy and respiratory failure. The G4C2 repeat expansion in the C9orf72 gene is the most prevalent genetic risk for ALS. Mutation carriers (C9ALS) display variability in phenotypes such as age-at-onset and duration, suggesting the existence of additional genetic factors. Here we introduce a three-step gene discovery strategy to identify genetic factors modifying the risk of both C9ALS and sporadic ALS (sALS) using limited samples. We first identified 135 candidate genetic modifiers of C9ALS using whole-genome sequencing (WGS) of extreme C9ALS cases diagnosed ~30 years apart. We then performed an unbiased genetic screen using a Drosophila model of the G4C2 repeat expansion with the genes identified from WGS analysis. This genetic screen identified the novel genetic interaction between G4C2 repeat-associated toxicity and 18 genetic factors, suggesting their potential association with C9ALS risk. We went on to test if 14 out of the 18 genes, those which were not known to be risk factors for ALS previously, are also associated with ALS risk in sALS cases. Gene-based-statistical analyses of targeted resequencing and WGS were performed. These analyses together reveal that rare variants in MYH15 represent a likely genetic risk factor for ALS. Furthermore, we show that MYH15 could modulate the toxicity of dipeptides produced from expanded G4C2 repeat. Our study presented here demonstrates the power of combining WGS with fly genetics to facilitate the discovery of fundamental genetic components of complex traits with a limited number of samples.

Comparison of the Conventional Downward and Modified Upward Laryngeal Handshake Techniques to Identify the Cricothyroid Membrane: A Randomized, Comparative Study.

BACKGROUND: Accurate identification of the cricothyroid membrane is crucial for successful cricothyroidotomy. The aim of this study was to compare the conventional downward and modified upward laryngeal handshake techniques in terms of accuracy to identify the cricothyroid membrane in nonobese female patients. METHODS: In 198 anesthetized female patients, the cricothyroid membrane was identified by either the conventional downward laryngeal handshake technique (n = 99) or the modified upward laryngeal handshake technique (n = 99). According to the conventional downward laryngeal handshake technique, the cricothyroid membrane was identified by palpating the neck downward from the greater cornu of the hyoid bone, thyroid laminae, and cricoid cartilage. According to the modified upward laryngeal handshake technique, the cricothyroid membrane was located by moving up from the sternal notch. The primary outcome was the accuracy of identifying the cricothyroid membrane. Secondary outcomes included the accuracy of midline identification and time taken to locate what participants believed to be the cricothyroid membrane. The primary and secondary outcomes according to the technique were analyzed using generalized estimating equations. RESULTS: The cricothyroid membrane could be identified more accurately by the modified upward laryngeal handshake technique than by the conventional downward technique (84% vs 56%, respectively; odds ratio [OR], 4.36; 95% confidence interval [CI], 2.13-8.93; P < .001). Identification of the midline was also more accurate by the modified laryngeal handshake than by the conventional technique (96% vs 83%, respectively; OR, 4.98; 95% CI, 1.65-15.01; P = .004). The time taken to identify the cricothyroid membrane was not different between the conventional and modified techniques (20.2 [16.2-26.6] seconds vs 19.0 [14.5-26.4] seconds, respectively; P = .83). CONCLUSIONS: The modified upward laryngeal handshake technique that involved tracing the trachea and laryngeal structures upward from the sternal notch was more accurate in identifying the cricothyroid membrane than the conventional downward technique in anesthetized female patients.

Effect of Paratracheal Pressure on the Glottic View During Direct Laryngoscopy: A Randomized Double-Blind, Noninferiority Trial.

BACKGROUND: Cricoid pressure has been used as a component of the rapid sequence induction and intubation technique. However, concerns have been raised regarding the effectiveness and safety of cricoid pressure. Paratracheal pressure, a potential alternative to cricoid pressure to prevent regurgitation of gastric contents or aspiration, has been studied to be more effective to cricoid pressure in preventing gastric insufflation during positive pressure ventilation. However, to adopt paratracheal compression into our practice, adverse effects including its effect on the glottic view during direct laryngoscopy should be studied. We conducted a randomized, double-blind, noninferiority trial comparing paratracheal and cricoid pressures for any adverse effects on the view during direct laryngoscopy, together with other secondary outcome measures. METHODS: In total, 140 adult patients undergoing general anesthesia randomly received paratracheal pressure (paratracheal group) or cricoid pressure (cricoid group) during anesthesia induction. The primary end point was the incidence of deteriorated laryngoscopic view, evaluated by modified Cormack-Lehane grade with a predefined noninferiority margin of 15%. Secondary end points included percentage of glottic opening score, ease of mask ventilation, change in ventilation volume and peak inspiratory pressure during mechanical mask ventilation, ease of tracheal intubation, and resistance encountered while advancing the tube into the glottis. The position of the esophagus was assessed by ultrasound in both groups to determine whether pressure applied to the respective area would be likely to result in esophageal compression. All secondary outcomes were tested for superiority, except percentage of glottic opening score, which was tested for noninferiority. RESULTS: Paratracheal pressure was noninferior to cricoid pressure regarding the incidence of deterioration of modified Cormack-Lehane grade (0% vs 2.9%; absolute risk difference, -2.9%; 95% confidence interval, -9.9 to 2.6, P <.0001). Mask ventilation, measured on an ordinal scale, was found to be easier (ie, more likely to have a lower score) with paratracheal pressure than with cricoid pressure (OR, 0.41; 95% confidence interval, 0.21-0.79; P = .008). The increase in peak inspiratory pressure was significantly less in the paratracheal group than in the cricoid group during mechanical mask ventilation (median [min, max], 0 [-1, 1] vs 0 [-1, 23]; P = .001). The differences in other secondary outcomes were nonsignificant between the groups. The anatomical position of the esophagus was more suitable for compression in the paratracheal region, compared to the cricoid cartilage region. CONCLUSIONS: Paratracheal pressure was noninferior to cricoid pressure with respect to the effect on glottic view during direct laryngoscopy.

Correlation of the lumbar dural sac dimension with the spread of spinal anesthesia in elderly female patients: A prospective observational study.

BACKGROUND: To test a hypothesis that the dural sac dimension would be correlated with the spinal block level, we evaluated the correlation between the lumbar dural sac dimension and the spread of spinal anesthesia in elderly women. METHODS: In 40 women over the age of 65 years, the lumbar dural sac dimensions were measured at the L2-L3, L3-L4, L4-L5, and L5-S1 intervertebral spaces using ultrasonography in the lateral decubitus position, followed by the administration of spinal anesthesia. The correlation coefficients were analyzed for the lumbar dural sac dimension at each intervertebral level, peak sensory block level, peak motor block, time to peak sensory and peak motor blockade, durations of sensory and motor blockade, and patient characteristics. We subsequently analyzed the partial correlations between the lumbar dural sac dimension and the outcomes of spinal anesthesia, while adjusting for age, body mass index, and waist circumference. RESULTS: Peak sensory block level was inversely correlated with each lumbar sac dimension: L2-L3 (ρ = -0.37, P = .029), L3-L4 (ρ = -0.57, P < .001), L4-L5 (ρ = -0.65, P < .001), and L5-S1 (ρ = -0.49, P = .002) intervertebral spaces. Partial correlation analysis with adjustment for age, body mass index, and waist circumference revealed inverse correlations between the lumbar dural sac dimension at the following intervertebral spaces and peak sensory block level: L3-L4 (r = -.52, P = .003), L4-L5 (r = -.76, P < .001), and L5-S1 (r = -.65, P < .001). CONCLUSIONS: Outcomes of ultrasonographic investigation revealed an inverse correlation between the lumbar dural sac dimension and peak sensory block level in elderly women.

Effect of head and shoulder positioning on the cross-sectional area of the subclavian vein in obese subjects.

OBJECTIVE: Head and shoulder positioning may affect cross-sectional area (CSA) and location of the subclavian vein (SCV). We investigated the CSA of the SCV and the depth of the SCV, depending on the head and shoulder positions. METHODS: In 24 healthy obese volunteers, the short axis ultrasound images of the SCV and adjacent structures were obtained in three different head positions (neutral, 30° turned to the contralateral side, and 30° turned to the ipsilateral side) and two different shoulder positions (neutral and lowered). Images of the right and left SCVs were obtained in the supine and Trendelenburg positions. Subsequently, the CSA and depth of the SCV were measured. RESULTS: Significant differences were found in the CSA of the SCV in different head positions (30° turned to contralateral side vs. neutral: -0.06 cm2, 95% confidence interval [CI], -0.10 to -0.02; Pcorrected = 0.002, 30° turned to contralateral side vs. 30° turned to ipsilateral side: -0.16 cm2, 95% CI, -0.22 to -0.11; Pcorrected < 0.001, Neutral vs. 30° turned to ipsilateral side: -0.10 cm2, 95% CI, -0.14 to -0.07; Pcorrected < 0.001). The CSA of the SCV was significantly different, depending on shoulder positions (neutral vs. lowered: 0.44 cm2, 95% CI, 0.33 to 0.54; Pcorrected < 0.001), and body position (supine vs. Trendelenburg: -0.15 cm2, 95% CI, -0.19 to -0.12; Pcorrected < 0.001). However, the depth of the SCV did not differ with respect to head, shoulder, and body positions. CONCLUSIONS: Ipsilateral 30° head rotation, neutral shoulder position, and Trendelenburg position significantly enhanced the CSA of the SCV in obese participants.