Complementary hydrophobic interaction of the redox enzyme maturation protein NarJ with the signal peptide of the respiratory nitrate reductase NarG.

In bacteria, NarJ plays an essential role as a redox enzyme maturation protein in the assembly of the nitrate reductase NarGHI by interacting with the N-terminal signal peptide of NarG to facilitate cofactor incorporation into NarG. The purpose of our research was to elucidate the exact mechanism of NarG signal peptide recognition by NarJ. We determined the structures of NarJ alone and in complex with the signal peptide of NarG via X-ray crystallography and verified the NarJ-NarG interaction through mutational, binding, and molecular dynamics simulation studies. NarJ adopts a curved α-helix bundle structure with a U-shaped hydrophobic groove on its concave side. This groove accommodates the signal peptide of NarG via a dual binding mode in which the left and right parts of the NarJ groove each interact with two consecutive hydrophobic residues from the N- and C-terminal regions of the NarG signal peptide, respectively, through shape and chemical complementarity. This binding is accompanied by unwinding of the helical structure of the NarG signal peptide and by stabilization of the NarG-binding loop of NarJ. We conclude that NarJ recognizes the NarG signal peptide through a complementary hydrophobic interaction mechanism that mediates a structural rearrangement.

Comparison of invasive and non-invasive measurements of cardiac index and systemic vascular resistance in living-donor liver transplantation: a prospective, observational study.

BACKGROUND: Based on the controversy surrounding pulmonary artery catheterization (PAC) in surgical patients, we investigated the interchangeability of cardiac index (CI) and systemic vascular resistance (SVR) measurements between ClearSight™ and PAC during living-donor liver transplantation (LDLT). METHODS: This prospective study included consecutively selected LDLT patients. ClearSight™-based CI and SVR measurements were compared with those from PAC at seven LDLT-stage time points. ClearSight™-based systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressures were also compared with those from femoral arterial catheterization (FAC). For the comparison and analysis of ClearSight™ and the reference method, Bland-Altman analysis was used to analyze accuracy while polar and four-quadrant plots were used to analyze the trending ability. RESULTS: From 27 patients, 189 pairs of ClearSight™ and reference values were analyzed. The CI and SVR performance errors (PEs) exhibited poor accuracy between the two methods (51.52 and 51.73%, respectively) in the Bland-Altman analysis. CI and SVR also exhibited unacceptable trending abilities in both the polar and four-quadrant plot analyses. SAP, MAP, and DAP PEs between the two methods displayed favorable accuracy (24.28, 21.18, and 26.26%, respectively). SAP and MAP exhibited acceptable trending ability in the four-quadrant plot between the two methods, but not in the polar plot analyses. CONCLUSIONS: During LDLT, CI and SVR demonstrated poor interchangeability, while SAP and MAP exhibited acceptable interchangeability between ClearSight™ and FAC.

Therapeutic Effects of Combination of Nebivolol and Donepezil: Targeting Multifactorial Mechanisms in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons in the spinal cord. Although the disease's pathophysiological mechanism remains poorly understood, multifactorial mechanisms affecting motor neuron loss converge to worsen the disease. Although two FDA-approved drugs, riluzole and edaravone, targeting excitotoxicity and oxidative stress, respectively, are available, their efficacies are limited to extending survival by only a few months. Here, we developed combinatorial drugs targeting multifactorial mechanisms underlying key components in ALS disease progression. Using data analysis based on the genetic information of patients with ALS-derived cells and pharmacogenomic data of the drugs, a combination of nebivolol and donepezil (nebivolol-donepezil) was identified for ALS therapy. Here, nebivolol-donepezil markedly reduced the levels of cytokines in the microglial cell line, inhibited nuclear factor-κB (NF-κB) nucleus translocation in the HeLa cell and substantially protected against excitotoxicity-induced neuronal loss by regulating the PI3K-Akt pathway. Nebivolol-donepezil significantly promoted the differentiation of neural progenitor cells (NPC) into motor neurons. Furthermore, we verified the low dose efficacy of nebivolol-donepezil on multiple indices corresponding to the quality of life of patients with ALS in vivo using SOD1G93A mice. Nebivolol-donepezil delayed motor function deterioration and halted motor neuronal loss in the spinal cord. Drug administration effectively suppressed muscle atrophy by mitigating the proportion of smaller myofibers and substantially reducing phospho-neurofilament heavy chain (pNF-H) levels in the serum, a promising ALS biomarker. High-dose nebivolol-donepezil significantly prolonged survival and delayed disease onset compared with vehicle-treated mice. These results indicate that the combination of nebivolol-donepezil efficiently prevents ALS disease progression, benefiting the patients' quality of life and life expectancy.

Effect of driving pressure-guided positive end-expiratory pressure on postoperative pulmonary complications in patients undergoing laparoscopic or robotic surgery: a randomised controlled trial.

BACKGROUND: Individualised positive end-expiratory pressure (PEEP) improves respiratory mechanics. However, whether PEEP reduces postoperative pulmonary complications (PPCs) remains unclear. We investigated whether driving pressure-guided PEEP reduces PPCs after laparoscopic/robotic abdominal surgery. METHODS: This single-centre, randomised controlled trial enrolled patients at risk for PPCs undergoing laparoscopic or robotic lower abdominal surgery. The individualised group received driving pressure-guided PEEP, whereas the comparator group received 5 cm H2O fixed PEEP during surgery. Both groups received a tidal volume of 8 ml kg-1 ideal body weight. The primary outcome analysed per protocol was a composite of pulmonary complications (defined by pre-specified clinical and radiological criteria) within 7 postoperative days after surgery. RESULTS: Some 384 patients (median age: 67 yr [inter-quartile range: 61-73]; 66 [18%] female) were randomised. Mean (standard deviation) PEEP in patients randomised to individualised PEEP (n=178) was 13.6 cm H2O (2.1). Individualised PEEP resulted in lower mean driving pressures (14.7 cm H2O [2.6]), compared with 185 patients randomised to standard PEEP (18.4 cm H2O [3.2]; mean difference: -3.7 cm H2O [95% confidence interval (CI): -4.3 to -3.1 cm H2O]; P<0.001). There was no difference in the incidence of pulmonary complications between individualised (25/178 [14.0%]) vs standard PEEP (36/185 [19.5%]; risk ratio [95% CI], 0.72 [0.45-1.15]; P=0.215). Pulmonary complications as a result of desaturation were less frequent in patients randomised to individualised PEEP (8/178 [4.5%], compared with standard PEEP (30/185 [16.2%], risk ratio [95% CI], 0.28 [0.13-0.59]; P=0.001). CONCLUSIONS: Driving pressure-guided PEEP did not decrease the incidence of pulmonary complications within 7 days of laparoscopic or robotic lower abdominal surgery, although uncertainty remains given the lower than anticipated event rate for the primary outcome. CLINICAL TRIAL REGISTRATION: KCT0004888 (http://cris.nih.go.kr, registration date: April 6, 2020).

Comparison of modified thoracoabdominal nerve block through perichondral approach and subcostal transversus abdominis plane block for pain management in laparoscopic cholecystectomy: a randomized-controlled trial.

Background: The modified thoracoabdominal nerve block through the perichondral approach (M-TAPA) is a novel regional analgesic technique that can provide analgesia for both the lateral and anterior abdominal walls. This study aimed to compare the analgesic effect of M-TAPA with that of the subcostal transversus abdominis plane block (TAPB) in patients undergoing laparoscopic cholecystectomy (LC). Methods: Sixty patients scheduled to undergo elective LC were randomly assigned to receive either M-TAPA or subcostal TAPB during anesthesia induction. The primary outcome was the maximum pain intensity during movement within the first 12 hours postoperatively, measured using an 11-point numeric rating scale (NRS). Secondary outcomes included changes in NRS scores during rest, coughing, and movement, which were assessed at 1, 2, 4, 6, and 12 hours postoperatively and immediately before discharge. Additionally, postoperative nausea and vomiting, and patient satisfaction were recorded as secondary outcomes. Results: Data from 56 patients were analyzed, and no significant difference was observed in the primary outcome between the two groups (M-TAPA: 5.5 [interquartile range (IQR): 5-7] vs . subcostal TAPB: 5 [IQR: 4-7], median difference: 0, 95% confidence interval: -1 to 1, P = 0.580). Furthermore, no significant differences in secondary outcomes were observed between the two groups. Conclusions: No significant difference was observed in the analgesic effect between the two techniques. Consequently, further research is necessary to compare the efficacy of M-TAPA with other well-established regional analgesic techniques.

Comparison of the recovery profile of remimazolam with flumazenil and propofol anesthesia for open thyroidectomy.

BACKGROUND: Previous studies have consistently reported a slower recovery of consciousness following remimazolam-based total intravenous anesthesia without flumazenil than with propofol. This study aimed to compare the reversal effect of flumazenil on the recovery of consciousness after remimazolam-based total intravenous anesthesia with the propofol recovery profile. METHODS: This prospective, single-blinded, randomized trial included 57 patients undergoing elective open thyroidectomy at a tertiary university hospital. Patients were randomly allocated to receive either remimazolam- or propofol-based total intravenous anesthesia (remimazolam group: 28 patients, propofol group: 29 patients). The primary outcome was the time from the end of general anesthesia to first eye opening (min). The secondary outcomes were the time from the end of the general anesthesia to extubation (min), initial modified Aldrete score measured at the post-anesthesia care unit, length of stay at the post-anesthesia care unit (min), occurrence of postoperative nausea and vomiting during the first 24 h postoperatively, and Korean version of Quality of Recovery-15 score at 24 h postoperatively. RESULTS: The remimazolam group showed significantly faster first eye opening time (2.3 [interquartile range, IQR: 1.8-3.3] min vs. 5.0 [IQR: 3.5-7.8] min, median difference:-2.7 [95% confidence interval, CI: -3.7 to -1.5] min, P < 0.001) and extubation time (3.2 [IQR: 2.4-4.2] min vs. 5.7 [IQR: 4.7-8.3] min, median difference: -2.7 [97.5% CI: -5.0 to -1.6] min, P < 0.001). There were no significant differences in other postoperative outcomes. CONCLUSIONS: The planned incorporation of flumazenil with remimazolam-based total intravenous anesthesia provided rapid and reliable recovery of consciousness.

Effects of sugammadex versus neostigmine on postoperative nausea and vomiting after general anesthesia in adult patients:a single-center retrospective study.

We aimed to compare the effect of sugammadex to that of neostigmine with respect to the occurrence of postoperative nausea and vomiting (PONV) during the first 24 h following general anesthesia. This retrospective cohort study included patients who underwent elective surgery under general anesthesia in 2020 at an academic medical center in Seoul, South Korea. The exposure groups were determined according to whether the patient received sugammadex or neostigmine as a reversal agent. The primary outcome was PONV occurrence during the first 24 h postoperatively (overall). The association between the type of reversal agent and primary outcome was investigated using logistic regression while adjusting for confounding variables using stabilized inverse probability of treatment weighting (sIPTW). Of the 10,912 patients included in this study, 5,918 (54.2%) received sugammadex. Sugammadex was associated with a significantly lower incidence of overall PONV (15.8% vs. 17.7%; odds ratio, 0.87; 95% confidence interval [CI], 0.79-0.97; P = 0.010) after sIPTW. In conclusion, compared with neostigmine/glycopyrrolate, sugammadex use has a lower risk of PONV during the first 24 h following general anesthesia.

Performance of the Hypotension Prediction Index in living donor liver transplant recipients.

BACKGROUND: The Hypotension Prediction Index (HPI) was recently introduced and clinically validated in different surgical conditions. This prospective observational study evaluated HPI's performance in living donor liver transplant recipients under the hypothesis that HPI would be inferior to the previously reported predictability in major surgery due to the surgical characteristics of liver transplantation. METHODS: Twenty adult patients undergoing living donor liver transplantation were enrolled. HPI was monitored during the surgery with the attending anesthesiologist blinded to the HPI. The mean arterial pressure and HPI were recorded at 1-minute intervals. The area under the curve (AUC) of the receiver operating characteristic curve was calculated for the whole dataset and at each phase of liver transplantation at five, 10, and 15 minutes to analyze HPI's performance. RESULTS: A total of 9173 data points were analyzed. The AUC for predicting hypotension at five minutes was 0.810 (95% confidence interval [CI]: 0.780-0.840). The AUCs for predicting hypotension at 10 and 15 minutes were 0.726 (95% CI: 0.681-0.772) and 0.689 (95% CI: 0.642-0.737), respectively. The AUCs for predicting hypotension at five minutes in the preanhepatic, anhepatic, and neohepatic phase were 0.795 (95% CI: 0.711-0.876), 0.728 (95% CI: 0.638-0.819), and 0.837 (95% CI: 0.802-0.873), respectively. The HPI's performance was inferior to that previously reported in major surgery. CONCLUSIONS: HPI in this observational study in living donor liver transplantation predicted hypotension with moderate-to-low accuracy, its predictive value being highest in the neohepatic phase and lowest in the anhepatic phase.

Unique dimeric structure of the DUF2891 family protein CJ0554 from Campylobacter jejuni.

Campylobacter jejuni is a pathogenic bacterium that causes enteritis and Guillain-Barre syndrome in humans. To identify a protein target for the development of a new therapeutic against C. jejuni infection, each gene product of C. jejuni must be functionally characterized. The cj0554 gene of C. jejuni encodes a DUF2891 family protein with unknown functions. To provide functional insights into CJ0554, we determined and analyzed the crystal structure of the CJ0554 protein. CJ0554 adopts an (α/α)6-barrel structure, which consists of an inner α6 ring and an outer α6 ring. CJ0554 assembles into a dimer in a unique top-to-top orientation that is not observed in its structural homologs, N-acetylglucosamine 2-epimerase superfamily members. Dimer formation was verified by analyzing CJ0554 and its ortholog protein through gel-filtration chromatography. The top of the CJ0554 monomer barrel harbors a cavity, which is connected to that of the second subunit in the dimer structure, generating a larger intersubunit cavity. This elongated cavity accommodates extra nonproteinaceous electron density, presumably as a pseudosubstrate, and is lined with generally catalytically active histidine residues that are invariant in CJ0554 orthologs. Therefore, we propose that the cavity functions as the active site of CJ0554.

Epithelial plasticity enhances regeneration of committed taste receptor cells following nerve injury.

Taste receptor cells are taste bud epithelial cells that are dependent upon the innervating nerve for continuous renewal and are maintained by resident tissue stem/progenitor cells. Transection of the innervating nerve causes degeneration of taste buds and taste receptor cells. However, a subset of the taste receptor cells is maintained without nerve contact after glossopharyngeal nerve transection in the circumvallate papilla in adult mice. Here, we revealed that injury caused by glossopharyngeal nerve transection triggers the remaining differentiated K8-positive taste receptor cells to dedifferentiate and acquire transient progenitor cell-like states during regeneration. Dedifferentiated taste receptor cells proliferate, express progenitor cell markers (K14, Sox2, PCNA) and form organoids in vitro. These data indicate that differentiated taste receptor cells can enter the cell cycle, acquire stemness, and participate in taste bud regeneration. We propose that dedifferentiated taste receptor cells in combination with stem/progenitor cells enhance the regeneration of taste buds following nerve injury.

Comparison of tracheal temperature and core temperature measurement in living donor liver transplant recipients: a clinical comparative study.

BACKGROUND: Body temperature is a vital sign, and temperature monitoring during liver transplantation is important. Tracheal temperature can be measured via an endotracheal tube with a temperature sensor on the cuff of the tube. This study aimed to investigate the accuracy and trending ability of tracheal temperature measurement compared to those of the core temperature measured at the esophagus and pulmonary artery (PA) in living donor liver transplant recipients. METHODS: Twenty-two patients who underwent living donor liver transplantation (LDLT) were enrolled. Patients were intubated using an endotracheal tube with a temperature sensor placed on the inner surface of the tube cuff. Tracheal, esophageal, and PA temperatures were recorded at five time points corresponding to the different phases of liver transplantation. The tracheal and esophageal, tracheal and PA, and esophageal and PA temperatures were compared using Bland-Altman analysis, four-quadrant plot/concordance analysis, and polar plot analysis. RESULTS: Bland-Altman analysis showed an overall mean bias (95% limits of agreement) between tracheal and esophageal temperatures of -0.10 °C (-0.37 °C to 0.18 °C), with a percentage error of 0.27%; between tracheal and PA temperatures, -0.05 °C (-0.91 °C to 0.20 °C), with a percentage error of -0.15%; and between esophageal and PA temperatures, 0.04 °C (-0.27 °C to 0.35 °C), with a percentage error of 0.12%. The concordance rates between tracheal and esophageal temperatures, tracheal and PA temperatures, and esophageal and PA temperatures were 96.2%, 96.2%, and 94.94%, respectively. The polar plot analysis showed a mean angular bias (radial limits of agreement) of 4° (26°), -3° (13°), and 2° (21°). CONCLUSIONS: Monitoring core temperature at the inner surface of the endotracheal tube cuff is accurate in all phases of LDLT with good trending ability; thus, it can be an excellent alternative for monitoring during LDLTs.

Influence of anesthesia type on post-reperfusion syndrome during liver transplantation: a single-center retrospective study.

BACKGROUND: Post-reperfusion syndrome (PRS) results in sudden hemodynamic instability following graft reperfusion. Although PRS is known to influence outcomes following liver transplantation, little is known regarding the effects of anesthetics on PRS. This study investigated the association between the type of anesthetic agent and PRS in liver transplantation. METHODS: This single-center retrospective cohort study included patients who underwent liver transplantation between June 2016 and December 2019. Patients were divided into sevoflurane and propofol groups according to the anesthetic agent used. Stabilized inverse probability of treatment weighting (IPTW) analysis was performed to investigate the association between PRS identified based on blood pressure recordings and the type of anesthesia. Associations between the anesthetic agent and the duration of hypotension as well as early postoperative outcomes were also investigated. RESULTS: Data were analyzed for 398 patients, 304 (76.4%) and 94 (23.6%) of whom were anesthetized with propofol and sevoflurane, respectively. PRS developed in 40.7% of the 398 patients. Following stabilized IPTW analysis, the association with PRS was lower in the sevoflurane group than in the propofol group (odds ratio, 0.47; P = 0.018). However, there was no association between the type of anesthetic used and early postoperative outcomes. CONCLUSIONS: The association of PRS was lower in the sevoflurane group than in the propofol group. However, there was no association between the type of anesthetic and the early postoperative outcomes. Further studies are required to determine the optimal anesthetic for liver transplantation.

Excitability-Independent Memory Allocation for Repeated Event.

How memory is organized in cell ensembles when an event is repeated is not well-understood. Recently, we found that retraining 24 h after the initial fear conditioning (FC) event induces turnover of neurons in the lateral amygdala (LA) that encodes fear memory. Excitability-dependent competition between eligible neurons has been suggested as a rule that governs memory allocation. However, it remains undetermined whether excitability is also involved in the allocation of a repeated event. By increasing excitability in a subset of neurons in the LA before FC, we confirmed that these neurons preferentially participated in encoding fear memory as previously reported. These neurons, however, became unnecessary for memory recall after retraining 24 h following initial FC. Consistently, the initial memory-encoding neurons became less likely to be reactivated during recall. This reorganization in cell ensembles, however, was not induced and memory was co-allocated when retraining occurred 6 h after the initial FC. In 24-h retraining condition, artificially increasing excitability right before retraining failed to drive memory co-allocation. These results suggest a distinct memory allocation mechanism for repeated events distantly separated in time.

Structural analysis of the virulence gene protein IceA2 from Helicobacter pylori.

Helicobacter pylori is a pathogenic bacterium that causes gastric ulcers and cancer. Among the diverse virulence genes of H. pylori, the IceA gene was identified to be expressed upon adherence to host cells. The IceA gene has two alleles, iceA1 and iceA2, which encode completely different proteins. IceA1 protein was shown to exert endonuclease activity, whereas IceA2 has never been analyzed at the molecular level. Based on a sequence analysis, IceA2 proteins differ in length depending on the strain and are classified into five groups (A-E). To structurally characterize IceA2, we determined the crystal structure of group-D IceA2 (IceA2sD) and performed a modeling-based comparative analysis of IceA2 groups. IceA2sD consists of three ß-sheet repeats and serially arranges them like the ß-propeller structure of the WD40 domain. However, each ß-sheet of IceA2 is stabilized using a unique structural motif that is not observed in WD40. Moreover, IceA2sD lacks an additionally appended ß-strand and does not form the Velcro-like closure of WD40. Therefore, IceA2sD adopts a curved rod-like structure rather than an enclosed circular structure in WD40. IceA2 proteins contain 1-4 ß-sheet modules depending on the groups and are modeled to be highly diverse in size and shape.

Propofol abuse among healthcare workers: an analysis of criminal cases using the database of the Supreme Court of South Korea's judgments.

BACKGROUND: Due to its abuse potential, propofol has been classified as a controlled substance since February 2011 in South Korea. Healthcare workers are exposed to propofol abuse considering their easy access to this substance in hospitals. Therefore, we aimed to investigate propofol abuse among healthcare workers through the database of the Supreme Court in South Korea. METHODS: We retrospectively analyzed adjudicated criminal cases related to propofol abuse among healthcare workers from January 1, 2013, to December 31, 2020, using the database of the Supreme Court of South Korea's judgments. We collected the clinical characteristics and punishment-related information of healthcare workers who abused propofol. RESULTS: Of the 194 cases collected using the search term 'propofol,' 20 were included in the final analysis. The most common healthcare workers who abused propofol were nursing aides (n = 15). Among them, 40% (n = 8) of the defendants had previously been punished for substance abuse, and 35% (n = 7) had a history of psychological disease. Of the defendants, 65% (n = 13) self-administered propofol more than twice, and the median number of self-administrations was three. Except for two, the defendants were sentenced to imprisonment, including suspended sentences, and the median values of their duration of prison and probation were 9 months and 24 months. CONCLUSIONS: Despite propofol being strongly regulated as a controlled substance in South Korea, its abuse among healthcare workers remains. Healthcare workers should be vigilant against its abuse among themselevs.

Structural and Biochemical Analysis of the Furan Aldehyde Reductase YugJ from Bacillus subtilis.

NAD(H)/NADP(H)-dependent aldehyde/alcohol oxidoreductase (AAOR) participates in a wide range of physiologically important cellular processes by reducing aldehydes or oxidizing alcohols. Among AAOR substrates, furan aldehyde is highly toxic to microorganisms. To counteract the toxic effect of furan aldehyde, some bacteria have evolved AAOR that converts furan aldehyde into a less toxic alcohol. Based on biochemical and structural analyses, we identified Bacillus subtilis YugJ as an atypical AAOR that reduces furan aldehyde. YugJ displayed high substrate specificity toward 5-hydroxymethylfurfural (HMF), a furan aldehyde, in an NADPH- and Ni2+-dependent manner. YugJ folds into a two-domain structure consisting of a Rossmann-like domain and an α-helical domain. YugJ interacts with NADP and Ni2+ using the interdomain cleft of YugJ. A comparative analysis of three YugJ structures indicated that NADP(H) binding plays a key role in modulating the interdomain dynamics of YugJ. Noticeably, a nitrate ion was found in proximity to the nicotinamide ring of NADP in the YugJ structure, and the HMF-reducing activity of YugJ was inhibited by nitrate, providing insights into the substrate-binding mode of YugJ. These findings contribute to the characterization of the YugJ-mediated furan aldehyde reduction mechanism and to the rational design of improved furan aldehyde reductases for the biofuel industry.

Effect of postoperative non-steroidal anti-inflammatory drugs on anastomotic leakage after pancreaticoduodenectomy.

BACKGROUND: Although the association between an increase in anastomotic leakage (AL) and non-steroidal anti-inflammatory drugs (NSAIDs) has been reported in gastrointestinal surgeries, this issue has rarely been addressed for pancreaticoduodenectomy (PD). We aimed to investigate the association between postoperative NSAIDs administration and clinically relevant AL (CR-AL) following PD. METHODS: We retrospectively evaluated 2,163 consecutive patients who underwent PD between 2007 and 2019. The patients were divided into two groups; patients who received and did not receive NSAIDs by postoperative day (POD) 5. We conducted a propensity score analysis using inverse probability of treatment weighting (IPTW) to adjust the baseline differences between both groups. We compared the occurrence of CR-AL and other postoperative outcomes before and after IPTW. Further, we used the multivariable binary logistic regression method for a sensitivity analysis for CR-AL. RESULTS: A total of 2,136 patients were included in the analysis. Of these, 222 (10.4%) received NSAIDs by POD 5. The overall occurrence rate of CR-AL was 14.9%. After IPTW, postoperative NSAIDs were significantly associated with CR-AL (odds ratio [OR]: 1.24, 95% CI [1.05, 1.47], P = 0.012), prolonged postoperative hospitalization (OR: 1.31, 95% CI [1.14, 1.50], P < 0.001), and unplanned readmission within 30 days postoperatively (OR 1.48: 95% CI [1.15, 1.91], P = 0.002). However, this association was not consistent in the sensitivity analysis. CONCLUSIONS: Postoperative NSAIDs use was significantly associated with an increase in CR-AL incidence following PD. However, sensitivity analysis failed to show its association, which precludes a firm conclusion of its detrimental effect.

Turnover of fear engram cells by repeated experience.

A sparse population of neurons active during a learning event has been identified as memory engram cells. However, cells that are recruited to support memory when experience is repeated have been scarcely explored. Evidence from previous studies provides contradictory views. To address these questions, we employed learning-dependent cell labeling in the lateral amygdala (LA) and applied electrophysiological recording, spine imaging, and optogenetic tools to the labeled neurons with or without retraining. We found that engram cells established from original fear learning became dispensable for memory retrieval specifically with relearning, and this correlated with a reduction of synaptic transmission and loss of dendritic spines in these neurons. Despite such decreased connectivity, direct activation of these neurons resulted in fear-memory recall. We further identified that repeated memory was encoded in neurons active during relearning. These results suggest a shift in neuronal ensembles encoding fear memory in the LA by relearning through disconnection of the existing engram neurons established from original experience.

Effect of sugammadex on the recovery of gastrointestinal motility after open pancreaticoduodenectomy: a single-center retrospective study.

BACKGROUND: This study aimed to investigate the association between sugammadex use and the occurrence of delayed passage of first flatus and oral intake tolerance following open pancreaticoduodenectomy (PD). METHODS: We reviewed consecutive patients who underwent open PD between 2015 and 2019; subsequently, they were divided into the sugammadex (group S) and neostigmine with anticholinergics (group N) groups based on the reversal agent used. We performed stabilized inverse probability of treatment weighting (IPTW) analysis to adjust for baseline differences between the groups. We compared the delayed passage of first flatus, oral intake tolerance, and other postoperative outcomes between the groups before and after IPTW. RESULTS: Of the 736 included patients, 309 (42.0%) received sugammadex. Stabilized IPTW revealed a significantly lower occurrence of delayed passage of first flatus in group S (19.3%) compared to group N (28.3%) (OR 0.61, 95% CI: 0.43-0.86, P=0.005). Further, there was a significantly lower occurrence of delayed oral intake tolerance in group S (19.9%) than in group N (27.7%) (OR 0.65, 95% CI: 0.46-0.92, P=0.016). CONCLUSIONS: Compared to previous reversal agents, sugammadex use was significantly associated with a decrease in the occurrence of prolonged time to first flatus and oral intake tolerance following open PD.

Synaptic plasticity-dependent competition rule influences memory formation.

Memory is supported by a specific collection of neurons distributed in broad brain areas, an engram. Despite recent advances in identifying an engram, how the engram is created during memory formation remains elusive. To explore the relation between a specific pattern of input activity and memory allocation, here we target a sparse subset of neurons in the auditory cortex and thalamus. The synaptic inputs from these neurons to the lateral amygdala (LA) are not potentiated by fear conditioning. Using an optogenetic priming stimulus, we manipulate these synapses to be potentiated by the learning. In this condition, fear memory is preferentially encoded in the manipulated cell ensembles. This change, however, is abolished with optical long-term depression (LTD) delivered shortly after training. Conversely, delivering optical long-term potentiation (LTP) alone shortly after fear conditioning is sufficient to induce the preferential memory encoding. These results suggest a synaptic plasticity-dependent competition rule underlying memory formation.